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1
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Goto H, Sawa M, Fujiwara SI, Ri M, Ishida T, Takeuchi M, Ishitsuka K, Toyosaki M, Sunami K, Tsukada J, Sonoki T, Shimogomi A, Ichihashi Y, Ouchi Y, Miyamoto T, Hino M, Maeda Y, Teshima T. Impact of single dose of pegfilgrastim on peripheral blood stem cell harvest in patients with multiple myeloma or malignant lymphoma. Sci Rep 2025; 15:14523. [PMID: 40281003 PMCID: PMC12032086 DOI: 10.1038/s41598-025-98453-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 04/11/2025] [Indexed: 04/29/2025] Open
Abstract
This phase 2 study evaluated the impact of pegfilgrastim, a single-dose, long-acting granulocyte colony-stimulating factor, on the steady-state mobilization of hematopoietic stem cells into peripheral blood in patients with multiple myeloma (MM) or malignant lymphoma (ML). Efficacy and safety, along with CD34-positive cell mobilization outcomes were assessed in patients with MM, who were randomly assigned to pegfilgrastim (n = 30) or daily filgrastim (n = 31), and ML (pegfilgrastim only, n = 13) cohorts. In the MM cohort, CD34-positive cell counts ≥ 2 × 106/kg were achieved in 100% of patients in the pegfilgrastim group and 96.7% in the filgrastim group (difference: 3.3%; 80% confidence interval: -0.9-7.5%), demonstrating the non-inferiority of pegfilgrastim to filgrastim. All patients in the ML cohort achieved ≥ 2 × 106/kg CD34-positive cell counts. The plerixafor administration rates in the MM cohort were 50.0% and 63.3% in the pegfilgrastim and filgrastim groups, respectively, and 91.7% in the ML cohort. There were no major differences in safety measures between the two groups. Although the sample size was small, particularly in the ML cohort, a single dose of pegfilgrastim demonstrated comparable efficacy and safety to daily doses of filgrastim, indicating its potential for clinical use while reducing patient burden.Trial Registration: jRCT2011210029, NCT05007652.
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Affiliation(s)
- Hideki Goto
- Department of Hematology, Graduate School of Medicine, Hokkaido University Faculty of Medicine, Sapporo, Japan
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan
| | - Masashi Sawa
- Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan
| | - Shin-Ichiro Fujiwara
- Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan
| | - Masaki Ri
- Department of Hematology and Oncology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Tadao Ishida
- Department of Hematology, Japanese Red Cross Medical Center, Tokyo, Japan
| | | | - Kenji Ishitsuka
- Department of Hematology and Rheumatology, Kagoshima University, Kagoshima, Japan
| | - Masako Toyosaki
- Department of Hematology and Oncology, School of Medicine, Tokai University, Isehara, Japan
| | - Kazutaka Sunami
- Department of Hematology, NHO Okayama Medical Center, Okayama, Japan
| | - Junichi Tsukada
- Department of Hematology, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Takashi Sonoki
- Department of Hematology/Oncology, Wakayama Medical University, Wakayama, Japan
| | | | | | | | - Toshihiro Miyamoto
- Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
| | - Masayuki Hino
- Department of Hematology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yoshinobu Maeda
- Department of Hematology and Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
| | - Takanori Teshima
- Department of Hematology, Graduate School of Medicine, Hokkaido University Faculty of Medicine, Sapporo, Japan.
- Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Japan.
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Avigan ZM, Arinsburg S, Pan D, Mark T, Fausel C, Bubalo J, Milkovich G, Moshier E, Fu W, Chari A, Richter J. Mobilization strategies with and without plerixafor for autologous stem cell transplant in patients with multiple myeloma. Bone Marrow Transplant 2024; 59:1440-1448. [PMID: 39085373 DOI: 10.1038/s41409-024-02385-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 07/17/2024] [Accepted: 07/25/2024] [Indexed: 08/02/2024]
Abstract
Autologous stem cell transplantation is a standard treatment strategy for patients with multiple myeloma that requires effective mobilization and apheresis of peripheral blood progenitor cells; however, in the current era of novel myeloma induction therapies, the optimal mobilization regimen to enhance stem cell yield while limiting toxicity and resource utilization remains unknown. In this multicenter retrospective study, we assessed apheresis and transplant outcomes in myeloma patients mobilized with granulocyte colony stimulating factor (G-CSF) alone (n = 62), G-CSF with chemotherapy (n = 43), or G-CSF with the CXCR4 antagonist plerixafor (n = 417). Compared to patients treated with G-CSF alone, the plerixafor group required significantly fewer median apheresis sessions (1 vs 2, p = 0.0023) with higher CD34+ stem cell yield (9.9 vs 5.8 × 106 cells/kg, p < 0.001) and had significantly faster engraftment of neutrophils (HR 1.54, 95% CI 1.17-2.03) and platelets (HR 2.24, 95% CI 1.69-2.96) after transplant. Additionally, the plerixafor group showed a significantly better toxicity profile and lower adverse event rate than patients treated with G-CSF alone (p = 0.0028) or chemomobilization (p < 0.0001), with a trend toward reduced survival in chemomobilization patients. Taken together, these data support the routine use of plerixafor-based mobilization to increase apheresis efficiency and reduce toxicity in myeloma patients undergoing transplant.
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Affiliation(s)
- Zachary M Avigan
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Suzanne Arinsburg
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Darren Pan
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Tomer Mark
- University of Colorado - Anschutz Medical Center, Aurora, CO, 80045, USA
| | - Christopher Fausel
- Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN, 46202, USA
| | - Joseph Bubalo
- Pharmacy Services, Division of Hematology and Medical Oncology, Oregon Health & Science University Hospital and Clinics, Portland, OR, 97239, USA
| | - Gary Milkovich
- RJM Group, LLC, 13028 Smoketown Road, Woodbridge, VA, 22192, USA
| | - Erin Moshier
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Weijia Fu
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Ajai Chari
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94143, USA
| | - Joshua Richter
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
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3
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Li Y, Liu J, Huang B, Chen M, Gu J, Li J. Prolonged infusion time of cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) as a mobilization regimen may improve mobilization efficiency in newly diagnosed multiple myeloma patients: a single center experience. Ann Med 2023; 55:2289603. [PMID: 38104533 PMCID: PMC10732221 DOI: 10.1080/07853890.2023.2289603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 11/24/2023] [Indexed: 12/19/2023] Open
Abstract
OBJECTIVES This study aimed to clarify the effectiveness and safety of two different infusion durations of cyclophosphamide (CTX) plus granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell mobilization in patients with newly diagnosed multiple myeloma (NDMM). METHODS One hundred and fifty-six consecutive NDMM patients receiving CTX plus G-CSF mobilization and autologous stem cell transplantation during the period of September 2008 to May 2020 were selected for retrospective analysis. According to differences in prolonged infusion time of CTX, they were divided into a 24-h group (24-h continuous infusion) and a control group (4-6 h of infusion). Mobilization and safety of infusion were analyzed. Flow cytometry was used to detect the peripheral blood CD34+ cell count. Multivariate analysis was performed to determine the factors influencing the number of CD34+ cells. RESULTS The mean CD34+ cell counts collected in 24-h and control groups were 6.78 (interquartile range [IQR] 3.59-11.69) and 4.48 (IQR 2.39-6.30) ×106/kg, respectively (p < 0.001). Meanwhile, the target number of CD34+ cells/kg (defined as ≥4 × 106/kg) was collected from 51 (75%) of cases in 24-h group vs. 45 (51%) in the control group (p = 0.002). Multivariate analysis identified the independence of CTX infusion time as a factor influencing the target number of CD34+ cells/kg [odds ratio OR, 4.045; 95% CI: 1.630-10.038, p = 0.003]. The post-transplantation time to neutrophil engraftment was 10 (IQR 9-11) in 24-h group and 11 (IQR 10-12) in control group (p < 0.001). Finally, no statistical differences were identified between groups in terms of hematologic and non-hematologic toxicities. CONCLUSIONS For patients with NDMM, 24-h continuous infusion of CTX plus G-CSF contributes to improved mobilization efficiency and equivalent toxicity as a stem cell mobilization regimen.
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Affiliation(s)
- Yanjuan Li
- Department of Haematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Junru Liu
- Department of Haematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Beihui Huang
- Department of Haematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Meilan Chen
- Department of Haematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jingli Gu
- Department of Haematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Juan Li
- Department of Haematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Jantunen E, Partanen A, Turunen A, Varmavuo V, Silvennoinen R. Mobilization Strategies in Myeloma Patients Intended for Autologous Hematopoietic Cell Transplantation. Transfus Med Hemother 2023; 50:438-447. [PMID: 37899993 PMCID: PMC10603622 DOI: 10.1159/000531940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 06/21/2023] [Indexed: 10/31/2023] Open
Abstract
Background Multiple myeloma is currently the leading indication for autologous hematopoietic cell transplantation (AHCT). A prerequisite for AHCT is mobilization and collection of adequate blood graft to support high-dose therapy. Current mobilization strategies include granulocyte colony-stimulating factor (G-CSF) alone or in combination with chemotherapy most commonly cyclophosphamide (CY). More recently, plerixafor has become into agenda especially in patients who mobilize poorly. In the selection of a mobilization method, several factors should be considered. Summary Preplanned collection target is important as G-CSF plus plerixafor is more effective in the mobilization of CD34+ cells than G-CSF alone. On the other hand, CY plus G-CSF is superior to G-CSF only mobilization. Previous therapy and age of the patients are important considerations as G-CSF alone may not be effective enough in patients with risk factors for poor mobilization. These factors include extensive lenalidomide exposure, irradiation to bone marrow-bearing sites, higher age, or a previous mobilization failure. Also, local preferences and experiences as well as the number of apheresis needed are important issues as well as cost-effectiveness considerations. Mobilization method used may have implication for cellular composition of collected grafts, which might have an impact on posttransplant events such as hematologic and immune recovery in addition to also potential long-term outcomes. Key Message Currently, G-CSF alone and preemptive plerixafor if needed might be considered as a standard mobilization strategy in MM patients intended for AHCT.
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Affiliation(s)
- Esa Jantunen
- Institute of Clinical Medicine/Internal Medicine, University of Eastern Finland, Kuopio, Finland
- Department of Medicine, Kuopio University Hospital, Kuopio, Finland
| | - Anu Partanen
- Department of Medicine, Kuopio University Hospital, Kuopio, Finland
| | - Antti Turunen
- Department of Medicine, Kuopio University Hospital, Kuopio, Finland
| | - Ville Varmavuo
- Department of Medicine, Kymenlaakso Central Hospital, Kotka, Finland
| | - Raija Silvennoinen
- Department of Hematology, Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
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João C, Bergantim R, Santos J, Afonso C, Bernardo P, Coelho H, Costa C, Esteves G, Freitas JG, Gerivaz R, Jorge A, Macedo A, Montalvão A, Neves M, Pedrosa CL, Pereira S, Roque A, Seabra P, M Silva H, Silveira MP, Tomé A, Trigo F, Sarmento AB, Lúcio P, Geraldes C. [Multiple Myeloma Treatment Guidelines by the Portuguese Group of Multiple Myeloma]. ACTA MEDICA PORT 2023; 36:517-526. [PMID: 37429590 DOI: 10.20344/amp.19037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 04/11/2023] [Indexed: 07/12/2023]
Abstract
The treatment of multiple myeloma has profoundly changed with the introduction of several innovative therapies. The optimization of therapeutic sequencing through the combined use of the various drugs developed in recent years and the attention given to the characteristics of patients have allowed the reduction of toxicities and increased survival and quality of life of patients with multiple myeloma. These treatment recommendations from the Portuguese Multiple Myeloma Group offer guidance for first-line treatment and progression/relapse situations. These recommendations are given highlighting the data that justify each choice and referring to the respective levels of evidence that support these options. Whenever possible, the respective national regulatory framework is presented. These recommendations constitute an advance towards the best treatment of multiple myeloma in Portugal.
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Affiliation(s)
- Cristina João
- Serviço de Hemato-Oncologia. Fundação Champalimaud. Lisboa; NOVA Medical School. Universidade NOVA de Lisboa. Lisboa. Portugal
| | - Rui Bergantim
- Serviço de Hematologia. Centro Hospitalar São João. Porto; i3S - Instituto de Investigação e Inovação em Saúde. Universidade do Porto. Porto; Cancer Drug Resistance Group. IPATIMUP - Instituto the Patologia Molecular e Imunologia. Universidade do Porto. Porto. Portugal
| | - Joana Santos
- Serviço de Hematologia. Centro Hospitalar Lisboa Central. Lisboa. Portugal
| | - Celina Afonso
- Serviço de Hematologia Clínica. Centro Hospitalar Lisboa Ocidental. Lisboa. Portugal
| | - Paulo Bernardo
- Serviço de Hematologia Clínica. Hospital da Luz Lisboa. Lisboa. Portugal
| | - Henrique Coelho
- Serviço de Hematologia Clínica. Centro Hospitalar Vila Nova Gaia. Gaia. Portugal
| | - Carlos Costa
- Hematologia Clínica. Instituto CUF Oncologia. Lisboa. Portugal
| | - Graça Esteves
- Serviço de Hematologia e Transplante de Medula. Centro Hospitalar Universitário Lisboa Norte. Lisboa. Portugal
| | | | - Rita Gerivaz
- Serviço de Hematologia. Hospital Garcia de Orta. Almada. Portugal
| | - Ana Jorge
- Serviço de Hematologia Clínica. Centro Hospitalar Lisboa Ocidental. Lisboa. Portugal
| | - Ana Macedo
- Serviço de Hematologia. Centro Hospitalar Universitário do Algarve. Algarve; Faculdade de Ciências da Saúde. Universidade da Beira Interior. Covilhã. Portugal
| | - Ana Montalvão
- Unidade de Hematologia-Oncologia. Unidade Local de Saúde do Baixo Alentejo. Beja; Hospital de José Joaquim Fernandes. Beja. Portugal
| | - Manuel Neves
- Serviço de Hemato-Oncologia. Fundação Champalimaud. Lisboa. Portugal
| | - Claúdia L Pedrosa
- Serviço de Hematologia Clínica. Centro Hospitalar Universitário do Porto. Porto. Portugal
| | - Susana Pereira
- Serviço de Hematologia. Hospital Santo António dos Capuchos. Centro Hospitalar Universitário Lisboa Central. Lisboa. Portugal
| | - Adriana Roque
- Serviço de Hematologia Clínica. Centro Hospitalar e Universitário de Coimbra. Coimbra; Instituto de Fisiologia. Faculdade de Medicina. Universidade de Coimbra. Coimbra. Portugal
| | - Patrícia Seabra
- Serviço de Hematologia Clínica. Centro Hospitalar Universitário do Porto. Porto. Portugal
| | - Helena M Silva
- Serviço de Hematologia. Centro Hospitalar Tondela-Viseu. Viseu. Portugal
| | - Maria P Silveira
- Hematologia Clínica. Clínica de Oncologia e Radioterapia. Centro Clínico SAMS. Lisboa; Serviço de Imuno-Hemoterapia. Hospital Prof. Doutor Fernando da Fonseca. Amadora. Portugal
| | - Ana Tomé
- Serviço de Hematologia. Hospital Garcia de Orta. Almada. Portugal
| | - Fernanda Trigo
- Serviço de Hematologia. Centro Hospitalar São João. Porto. Portugal
| | - Ana Bela Sarmento
- Serviço de Hematologia Clínica. Centro Hospitalar e Universitário de Coimbra. Coimbra; Laboratório de Oncobiologia e Hematologia. Clínica Universitária de Hematologia e Instituto de Investigação Clínica e Biomédica de Coimbra. Grupo de Investigação em Ambiente, Genética e Oncobiologia. Faculdade de Medicina. Universidade de Coimbra. Coimbra; Centro Académico Clínico de Coimbra. Coimbra. . Portugal
| | - Paulo Lúcio
- Serviço de Hemato-Oncologia. Fundação Champalimaud. Lisboa. Portugal
| | - Catarina Geraldes
- Serviço de Hematologia Clínica. Centro Hospitalar e Universitário de Coimbra. Coimbra; Laboratório de Oncobiologia e Hematologia. Clínica Universitária de Hematologia e Instituto de Investigação Clínica e Biomédica de Coimbra. Grupo de Investigação em Ambiente, Genética e Oncobiologia. Faculdade de Medicina. Universidade de Coimbra. Coimbra; Centro Académico Clínico de Coimbra. Coimbra. Portugal
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6
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Li J, Zhang R, Chen LJ, Qu XY, Lu H, Li JY, Jin YY. [Comparison of etoposide combined with G-CSF and cyclophosphamide combined with G-CSF in mobilization of autologous peripheral hematopoietic stem cells in patients with newly diagnosed multiple myeloma]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2022; 43:781-784. [PMID: 36709174 PMCID: PMC9613493 DOI: 10.3760/cma.j.issn.0253-2727.2022.09.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/19/2021] [Indexed: 11/26/2022]
Affiliation(s)
- J Li
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
| | - R Zhang
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
| | - L J Chen
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
| | - X Y Qu
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
| | - H Lu
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
| | - J Y Li
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
| | - Y Y Jin
- Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China
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7
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Zhu Z, Li X, Liu Y, Chen P, Chen X, Li H, Huang J, Chen Y, Li N. High Efficacy of Stem Cell Mobilization With Etoposide+Cytarabine Plus G-CSF in Patients With Multiple Myeloma. Front Oncol 2022; 12:825550. [PMID: 35155259 PMCID: PMC8828636 DOI: 10.3389/fonc.2022.825550] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 01/10/2022] [Indexed: 11/24/2022] Open
Abstract
Background Efficient mobilization of CD34+ hematopoietic stem cells plays a vital role in successful autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM), especially in cases with high-risk cytogenetic recommended for tandem ASCT. However, the optimal mobilization strategy remains a matter of debate in the era of lenalidomide. The combination of etoposide with Cytarabine plus G-CSF as a novel mobilization regimen in MM has not been reported previously. Methods This research retrospectively studied mobilization efficacy and safety using etoposide combined with Cytarabine (etoposide 50–100 mg/m2, qd d1–3; AraC 0.5 g/m2, q12h d1~3) plus G-CSF (5 µg/kg/day, from d5 until the day of apheresis) in 128 patients with MM. 70(54.7%) patients received lenalidomide-based induction regimens treatment Results A median of 27.75×106 CD34+ cells/kg was collected in the first apheresis, and 28.23×106 CD34+ cells/kg were collected overall. Of the 128 patients, all achieved adequate collection (≥2×106 CD34+ cells/kg), 121(94.5%) achieved optimal collection for single ASCT (≥5×106 CD34+ cells/kg), and 114(89.1%) harvested optimal collection for tandem ASCT (≥10×106 CD34+ cells/kg). In particular, the target yield of optimal collection for tandem ASCT was reached in 82.8% (106/128) by a single apheresis procedure. 14 patients obtained deeper response post mobilization. In multivariate analysis, cycles of prior chemotherapy independently affected the optimal achievement of CD34+ cells (p=0.004, OR 0.695, 95% CI 0.544~0.888). Previous lenalidomide exposure did not significantly impair CD34+ cells collection. Although 68% episodes of antibiotic usage were observed, no severe infection or treatment-related mortality occurred. Conclusion Stem cell mobilization with Etoposide + Cytarabine plus G-CSF was highly efficient and safe in patients with MM, which could be considered in high-risk MM patients who were referred for tandem ASCT.
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Affiliation(s)
- Zhijuan Zhu
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaofan Li
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.,Translational Medicine Center on Hematology, Fujian Medical University, Fuzhou, China
| | - Yiping Liu
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Ping Chen
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xianling Chen
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Hua Li
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jiafu Huang
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yuanzhong Chen
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.,Translational Medicine Center on Hematology, Fujian Medical University, Fuzhou, China
| | - Nainong Li
- Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.,Translational Medicine Center on Hematology, Fujian Medical University, Fuzhou, China
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8
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Rees MJ, Mollee P, Ng JY, Murton A, Gonsalves JF, Panigrahi A, Beer H, Loh J, Nguyen P, Hunt S, Jina H, Wayte R, Sutrave G, Tan J, Abeyakoon C, Chee A, Augustson B, Kalro A, Lee C, Agrawal S, Churilov L, Chua CC, Lim ABM, Zantomio D, Grigg A. The association of mobilising regimen on immune reconstitution and survival in myeloma patients treated with bortezomib, cyclophosphamide and dexamethasone induction followed by a melphalan autograft. Bone Marrow Transplant 2021; 56:2152-2159. [PMID: 33911199 DOI: 10.1038/s41409-021-01300-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/24/2021] [Accepted: 04/08/2021] [Indexed: 02/05/2023]
Abstract
G-CSF only mobilisation has been shown to enhance immune reconstitution early post-transplant, but its impact on survival remains uncertain. We undertook a retrospective review of 12 transplant centres to examine overall survival (OS) and time to next treatment (TTNT) following melphalan autograft according to mobilisation method (G-CSF only vs. G-CSF and cyclophosphamide [CY]) in myeloma patients uniformly treated with bortezomib, cyclophosphamide and dexamethasone induction. Six centres had a policy to use G-CSF alone and six to use G-CSF + CY. Patients failing G-CSF only mobilisation were excluded. 601 patients were included: 328: G-CSF + CY, 273: G-CSF only. Mobilisation arms were comparable in terms of age, Revised International Staging System (R-ISS) groups and post-transplant maintenance therapy. G-CSF + CY mobilisation generated higher median CD34 + yields (8.6 vs. 5.5 × 106/kg, p < 0.001). G-CSF only mobilisation was associated with a significantly higher lymphocyte count at day 15 post-infusion (p < 0.001). G-CSF only mobilisation was associated with significantly improved OS (aHR = 0.60, 95%CI 0.39-0.92, p = 0.018) and TTNT (aHR = 0.77, 95%CI 0.60-0.97, p = 0.027), when adjusting for R-ISS, disease-response pre-transplant, age and post-transplant maintenance therapy. This survival benefit may reflect selection bias in excluding patients with unsuccessful G-CSF only mobilisation or may be due to enhanced autograft immune cell content and improved early immune reconstitution.
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Affiliation(s)
- Matthew J Rees
- Department of Clinical Haematology, Austin Health, Melbourne, VIC, Australia.
| | - Peter Mollee
- Department of Haematology, Princess Alexandra Hospital, and School of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Jun Yen Ng
- Department of Haematology, Princess Alexandra Hospital, and School of Medicine, University of Queensland, Brisbane, QLD, Australia
| | - Alex Murton
- Department of Haematology, Royal Hobart Hospital, Hobart, TAS, Australia
| | | | - Ashish Panigrahi
- Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Hayley Beer
- Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
| | - Joanna Loh
- Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, VIC, Australia
| | - Philip Nguyen
- Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, VIC, Australia
| | - Sam Hunt
- Department of Haematology, Eastern Health, Melbourne, VIC, Australia
| | - Hayden Jina
- Department of Haematology, Eastern Health, Melbourne, VIC, Australia
| | - Rebecca Wayte
- Department of Clinical Haematology, Westmead Hospital, Sydney, NSW, Australia
| | - Gaurav Sutrave
- Department of Clinical Haematology, Westmead Hospital, Sydney, NSW, Australia
| | - Jocelyn Tan
- Department of Haematology, University Hospital Geelong, Geelong, VIC, Australia
| | - Chathuri Abeyakoon
- Department of Haematology, University Hospital Geelong, Geelong, VIC, Australia
| | - Ashlyn Chee
- Department of Haematology, Sir Charles Gairdner Hospital, Perth, WA, Australia
| | - Bradley Augustson
- Department of Haematology, Sir Charles Gairdner Hospital, Perth, WA, Australia
| | - Akash Kalro
- Department of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Cindy Lee
- Department of Haematology, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Shivam Agrawal
- Department of Haematology, Princes of Wales Hospital, Sydney, NSW, Australia
| | - Leonid Churilov
- Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia
| | - Chong Chyn Chua
- Department of Clinical Haematology, Austin Health, Melbourne, VIC, Australia
| | | | - Daniela Zantomio
- Department of Clinical Haematology, Austin Health, Melbourne, VIC, Australia
| | - Andrew Grigg
- Department of Clinical Haematology, Austin Health, Melbourne, VIC, Australia
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9
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Sarıcı A, Erkurt MA, Bahçecioğlu ÖF, Gök S, Kuku İ, Biçim S, Berber İ, Kaya E, Özgül M. Filgrastim alone versus cyclophosphamide and filgrastim for mobilization in multiple myeloma patients. Transfus Apher Sci 2021; 60:103159. [PMID: 34034961 DOI: 10.1016/j.transci.2021.103159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 05/13/2021] [Accepted: 05/17/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND AND OBJECTIVE High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is standard treatment approach in most multiple myeloma (MM) patients. Before ASCT, chemomobilization or only granulocyte-colony stimulating factor (G-CSF) mobilization can be preferred in stem cell mobilization. The primary aim of the study is to compare the effect of the two mobilization regimens on hematopoietic engraftment times, CD34+cell counts and number of apheresis required to harvest stem cells. MATERIALS AND METHODS The records of MM patients who applied to our hospital between 2010 and 2020 were analysed retrospectively. Patients were divided into two groups (Group A: Cyclophosphamide plus filgrastim, Group B: Filgrastim alone) according to the mobilization regimen. RESULTS A total of 223 MM patients were included in this study (Group A:153, Group B:70 patients). When the patients in Group A and Group B were compared, the number of collected CD34+ cells were higher in Group A (p < 0.001). However, there was no significant difference between the two groups in terms of median times to neutrophil and platelet engraftment, and number of apheresis required to harvest stem cells (p > 0.05). The rate of infection development during mobilization in the patients in group A and the duration of hospitalization of these patients were higher than the patients in group B (p < 0.001). Patients receiving >6 cycles of chemotherapy and immunomodulatory treatment had lower collected CD34+ cells than other patients (p = 0.012 and p = 0.054). CONCLUSION Based on our findings, filgrastim alone seems to provide a sufficient amount of stem cells in MM patients.
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Affiliation(s)
- Ahmet Sarıcı
- İnönü University, Turgut Özal Medical Center, Adult Haematology Department, Malatya, Turkey.
| | - Mehmet Ali Erkurt
- İnönü University, Turgut Özal Medical Center, Adult Haematology Department, Malatya, Turkey.
| | - Ömer Faruk Bahçecioğlu
- İnönü University, Faculty of Pharmacy, Department of Clinical Pharmacy, Malatya, Turkey.
| | - Selim Gök
- İnönü University, Faculty of Pharmacy, Department of Clinical Pharmacy, Malatya, Turkey.
| | - İrfan Kuku
- İnönü University, Turgut Özal Medical Center, Adult Haematology Department, Malatya, Turkey.
| | - Soykan Biçim
- İnönü University, Turgut Özal Medical Center, Adult Haematology Department, Malatya, Turkey.
| | - İlhami Berber
- İnönü University, Turgut Özal Medical Center, Adult Haematology Department, Malatya, Turkey.
| | - Emin Kaya
- İnönü University, Turgut Özal Medical Center, Adult Haematology Department, Malatya, Turkey.
| | - Mustafa Özgül
- İnönü University, Turgut Özal Medical Center, Adult Haematology Department, Malatya, Turkey.
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10
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Johnsrud A, Ladha A, Muffly L, Shiraz P, Goldstein G, Osgood V, Shizuru JA, Johnston L, Arai S, Weng WK, Lowsky R, Rezvani AR, Meyer EH, Frank MJ, Negrin RS, Miklos DB, Sidana S. Stem Cell Mobilization in Multiple Myeloma: Comparing Safety and Efficacy of Cyclophosphamide +/- Plerixafor versus Granulocyte Colony-Stimulating Factor +/- Plerixafor in the Lenalidomide Era. Transplant Cell Ther 2021; 27:590.e1-590.e8. [PMID: 33915323 DOI: 10.1016/j.jtct.2021.04.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 04/05/2021] [Accepted: 04/18/2021] [Indexed: 11/17/2022]
Abstract
Growth factor and chemotherapy-based stem cell mobilization strategies are commonly used to treat patients with multiple myeloma. We retrospectively compared 398 patients mobilized between 2017 and 2020 using either cyclophosphamide (4 g/m2) plus granulocyte colony-stimulating factor (G-CSF) or G-CSF alone, with on demand plerixafor (PXF) in both groups. Although total CD34+ yield was higher after chemomobilization compared with G-CSF +/- PXF (median, 13.6 × 106/kg versus 4.4 × 106/kg; P < .01), achievement of ≥2 × 106 CD34+ cells (95% versus 93.7%; P = .61) and rates of mobilization failure (5% versus 6.3%; P = .61) were similar. Fewer patients required PXF with chemomobilization (12.3% versus 49.5%; P < .01), and apheresis sessions were fewer (median, 1 [range, 1 to 4] versus 2 [range, 1 to 5]). The rate of complications, including neutropenic fever, emergency department visits, and hospitalizations, was higher after chemomobilization (30% versus 7.4%; P < .01). Previous use of ≤6 cycles of lenalidomide did not impair cell yield in either group. The median cost of mobilization was 17.4% lower in the G-CSF +/- PXF group (P = .01). Between group differences in time to engraftment were not clinically significant. Given similar rates of successful mobilization, similar engraftment time, and less toxicity and lower costs compared with chemomobilization, G-CSF with on-demand PXF may be preferable in myeloma patients with adequate disease control and limited lenalidomide exposure.
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Affiliation(s)
- Andrew Johnsrud
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Abdullah Ladha
- Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California; Division of Hematology, University of Southern California, Los Angeles, California
| | - Lori Muffly
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Parveen Shiraz
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Gary Goldstein
- Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Victoria Osgood
- Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Judith A Shizuru
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Laura Johnston
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Sally Arai
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Wen-Kai Weng
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Robert Lowsky
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Andrew R Rezvani
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Everett H Meyer
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Matthew J Frank
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Robert S Negrin
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - David B Miklos
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California
| | - Surbhi Sidana
- Stanford Cancer Institute, Stanford, California; Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University, Stanford, California.
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11
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Lazzaro C, Castagna L, Lanza F, Laszlo D, Milone G, Pierelli L, Saccardi R. Chemotherapy-based versus chemotherapy-free stem cell mobilization (± plerixafor) in multiple myeloma patients: an Italian cost-effectiveness analysis. Bone Marrow Transplant 2021; 56:1876-1887. [PMID: 33753907 PMCID: PMC8338551 DOI: 10.1038/s41409-021-01251-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 02/03/2021] [Accepted: 02/18/2021] [Indexed: 12/21/2022]
Abstract
Given the availability and efficacy of the mobilizing agent plerixafor in augmenting hematopoietic progenitor cell mobilization with granulocyte colony-stimulating factor (G-CSF), there is a strong case for comparing the cost-effectiveness of mobilization with G-CSF + cyclophosphamide versus G-CSF alone. This study investigated the cost and effectiveness (i.e., successful 4 million-CD34+ collection) of G-CSF alone versus high-dose cyclophosphamide (4 g/m2) + G-CSF mobilization (± on-demand plerixafor) in patients with multiple myeloma (MM) eligible for autograft in Italy. A decision tree-supported cost-effectiveness analysis (CEA) model in MM patients was developed from the societal perspective. The CEA model compared G-CSF alone with cyclophosphamide 4 g/m2 + G-CSF (± on-demand plerixafor) and was populated with demographic, healthcare and non-healthcare resource utilization data collected from a questionnaire administered to six Italian oncohematologists. Costs were expressed in Euro (€) 2019. The CEA model showed that G-CSF alone was strongly dominant versus cyclophosphamide + G-CSF ( ± on-demand plerixafor), with incremental savings of €1198.59 and an incremental probability of a successful 4 million-CD34+ apheresis (+0.052). Sensitivity analyses confirmed the robustness of the base-case results. In conclusion, chemotherapy-free mobilization (± on-demand plerixafor) is a “good value for money” option for MM patients eligible for autograft.
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Affiliation(s)
- Carlo Lazzaro
- Health Economist and Research Director, Studio di Economia Sanitaria, Milan, Italy.
| | - Luca Castagna
- Oncology and Haematology Unit, BMT section, Istituto Clinico Humanitas, Rozzano, Italy
| | - Francesco Lanza
- Hematology Section, Romagna Transplant Network, University Hospital "Santa Maria delle Croci", Ravenna, Italy
| | - Daniele Laszlo
- Stem Cell Mobilization and Collection Unit, IEO IRCCS, Milan, Italy
| | - Giuseppe Milone
- Hematology and BMT Unit, Azienda Policlinico Vittorio Emanuele, Catania, Italy
| | - Luca Pierelli
- Department of Experimental Medicine, University "Sapienza", Rome, Immune-hematology and Transfusion Medicine Unit, Azienda Ospedaliera San Camillo, Rome, Italy
| | - Riccardo Saccardi
- Department of Cellular Therapy and Transfusion Medicine, Careggi University Hospital, Florence, Italy
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12
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Low-Dose Cyclophosphamide versus Intermediate-High-Dose Cyclophosphamide versus Granulocyte Colony-Stimulating Factor Alone for Stem Cell Mobilization in Multiple Myeloma in the Era of Novel Agents: A Multicenter Retrospective Study. Transplant Cell Ther 2021; 27:244.e1-244.e8. [PMID: 33781522 DOI: 10.1016/j.jtct.2020.12.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 11/13/2020] [Accepted: 12/06/2020] [Indexed: 12/11/2022]
Abstract
The optimal stem cell (SC) mobilization strategy for patients with multiple myeloma (MM) remains a matter of debate. Possible approaches include low or high doses of cyclophosphamide (Cy), other chemotherapeutic agents, or granulocyte colony-stimulating factor (G-CSF) alone. The scope of the study was to compare low-dose Cy plus G-CSF versus intermediate-high-dose Cy plus G-CSF versus G-CSF alone for SC mobilization in MM, in terms of efficacy and safety. We retrospectively analyzed 422 MM patients undergoing SC mobilization in 6 Italian centers, including 188 patients who received low-dose Cy (LD-Cy group, defined as 2 g/m2), 163 patients who received intermediate-high-dose Cy (HD-Cy group, defined as ≥ 3 g/m2), and 71 patients who received G-CSF alone (G-CSF group). The median peak of circulating CD34+ cells was 77/µL in the LD-Cy group, 92/µL in the HD-Cy group, and 55/µL in the G-CSF group (P = .0001). The median amount of SCs collected was 9.1 × 106/kg, 9.7 × 106/kg, and 5.6 × 106/kg in the 3 groups, respectively (P = .0001). The rate of mobilization failure (defined as failure to collect ≥2 × 106/kg) was 3.7% in the LD-Cy group, 3.4% in the HD-Cy group, and 4.3% in the G-CSF group (P = .9). The target SC dose of at least 4 × 106/kg was reached in 90.4%, 91.1%, and 78.6% of the patients in these 3 groups, respectively (P = .014). The "on demand" use of plerixafor was higher in the G-CSF group (76%) compared with the LD-Cy group (19%) and the HD-Cy group (6%). In multivariate analysis, G-CSF mobilization and previous use of melphalan or radiotherapy were independently associated with failure to collect the target SC dose of ≥4 × 106/kg. No impacts of age, blood counts, or previous treatment with lenalidomide, bortezomib, or carfilzomib were observed. Our results suggest that LD-Cy may be considered for successful SC mobilization in patients with MM.
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13
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Wang L, Xiang H, Yan Y, Deng Z, Li H, Li X, Liu J. Comparison of the efficiency, safety, and survival outcomes in two stem cell mobilization regimens with cyclophosphamide plus G-CSF or G-CSF alone in multiple myeloma: a meta-analysis. Ann Hematol 2021; 100:563-573. [PMID: 33404694 PMCID: PMC7817584 DOI: 10.1007/s00277-020-04376-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 12/08/2020] [Indexed: 12/29/2022]
Abstract
Autologous stem cell transplantation as a frontline treatment for patients with multiple myeloma (MM) requires an adequate peripheral blood stem cell (PBSC) collection before processing. Granulocyte-colony stimulating factor (G-CSF) with or without cyclophosphamide (CTX) is a common regimen for PBSC mobilization; their benefits and risks are controversial. To compare the efficiency, safety, and survival outcomes between the two regimens, we conducted a meta-analysis including 18 studies with 4 prospective and 14 retrospective studies; a total of 2770 patients with MM were analyzed. The CTX plus G-CSF regimen had higher yields of total CD34+ cells (SMD = 0.39, 95% CI (0.30, 0.49)), and higher mobilization rates of the target ⩾ 2 × 106/kg (OR = 3.34, 95% CI (1.82, 6.11)) and 4 × 106/kg (OR = 2.16, 95% CI (1.69, 2.76)) cells. A favorable event-free survival (EFS) (HR = 0.73, 95% CI (0.58, 0.93), p = 0.01) and better 3-year EFS rate (OR = 1.65, 95% CI (1.1, 2.47), p = 0.02) were also reached in the patients with CTX plus G-CSF mobilization, although the risks of admission (OR = 26.49, 95% CI (7.31, 95.97)) and fever (OR = 13.66, 95% CI (6.21, 30.03)) during mobilization were increased, the treatment-related mortality was consistent (p = 0.26). The CTX plus G-CSF regimen was superior to the G-CSF-alone regimen for PBSC mobilization in patients with MM.
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Affiliation(s)
- Liwen Wang
- Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China
- Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan Province, China
| | - Hongxian Xiang
- Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China
- Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan Province, China
| | - Yuhan Yan
- Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China
- Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan Province, China
| | - Zuqun Deng
- Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China
- Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan Province, China
| | - Hui Li
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, Zhejiang Province, China
| | - Xin Li
- Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China
| | - Jing Liu
- Department of Hematology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan Province, China.
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14
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Milone G, Conticello C, Leotta S, Michieli MG, Martino M, Marco ALD, Spadaro A, Cupri A, Condorelli A, Milone GA, Markovic U, Sciortino R, Schininà G, Moschetti G, Villari L, Saccardi R. Plerixafor on-demand in association with low-dose cyclophosphamide and G-CSF in the mobilization of patients with multiple myeloma: High effectiveness, low toxicity, and affordable cost. Leuk Res Rep 2020; 14:100227. [PMID: 33204611 PMCID: PMC7649636 DOI: 10.1016/j.lrr.2020.100227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 10/10/2020] [Accepted: 10/25/2020] [Indexed: 11/18/2022] Open
Abstract
In CD34 mobilization of Multiple Myeloma patients, Cyclophosphamide at the dose of 4 gr/m2 is usually administered. A lower dose of Cyclophosphamide (1.5–2.0 gr/m2) has a lower mobilizing effect and, for this reason, this dose is not widely used in CD34+ cells mobilization. The use of Plerixafor on demand, however, could have changed these conclusions. We hypothesized that when used in conjunction with on-demand Plerixafor, low lose CTX is more advantageous than the higher dose. The results of this prospective trial support, indeed, the view that low dose Cyclophosphamide in association to on-demand PLX allows the reaching efficacy and low toxicity. In CD34+ cells mobilization of patients with multiple myeloma (MM), the use of Cyclophosphamide (CTX) at a dose of 2 g/m2 has low efficacy although also lower toxicity. The suboptimal mobilizing effect of low-dose CTX, however, may be overcome by plerixafor (PLX) on demand. We conducted a prospective multicenter study in 138 patients with MM to evaluate CTX 2 g/m2 in association with granulocyte-colony stimulating factor (G-CSF) and on-demand PLX. We compared results with a historical group of MM patients (n = 138) mobilized using CTX at a dose of 4 g/m2. CD34+ cells greater than 2 × 106/kg in max three aphereses were harvested in 98.6% of patients in the on-demand PLX study group while in 84.0% in the historical group, (p = 0.0001). In the on-demand-PLX study group, a successful harvest greater than 5 × 106/kg in max three aphereses was observed in 85.5% of patients versus 62.3% of patients in the historical control group, (p=0.0001). In the on-demand-PLX study group, 4.3% (6/138) of patients had febrile complications. Salvage mobilization in the on-demand PLX study group was 1.4%. In conclusions, on-demand PLX + CTX 2 g/m2 + G-CSF 10 μg/kg has higher efficacy and lower toxicity compared with CTX 4 g/m2 + G-CSF. An analysis of costs is presented.
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Affiliation(s)
- Giuseppe Milone
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Concetta Conticello
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Salvatore Leotta
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | | | - Massimo Martino
- Centro Unico Regionale per il Trapianto di Midollo, Grande Ospedale Metropolitano BMM, Reggio Calabria, Italy
| | - Anna Lia Di Marco
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Andrea Spadaro
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Alessandra Cupri
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Annalisa Condorelli
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Giulio Antonio Milone
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Uros Markovic
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Roberta Sciortino
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Giovanni Schininà
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | | | - Loredana Villari
- Division of Hematology and Program for Hematopoietic Transplantation, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy.,Department of Pathology, Azienda Ospedaliera Policlinico Vittorio Emanuele Catania, Italy
| | - Riccardo Saccardi
- SODc Terapie Cellulari e Medicina Trasfusionale, Azienda Ospedaliera Careggi, Firenze, Italy.,GITMO Gruppo Italiano Trapianto di Midollo Osseo
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15
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Laszlo D, Marcacci GP, Martino M, Radice D, Rabascio C, Lucchetti B, Magarò A, Caime A, Menna S, Lionetti MT, Bertolini F. A comparison of chemo-free strategy with G-CSF plus plerixafor on demand versus intermediate-dose cyclophosphamide and G-CSF as PBSC mobilization in newly diagnosed multiple myeloma patients: An Italian explorative cost Analysis. Transfus Apher Sci 2020; 59:102819. [PMID: 32499108 DOI: 10.1016/j.transci.2020.102819] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Revised: 05/06/2020] [Accepted: 05/07/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND Upfront single or tandem ASCT still represents an integral part of treatment for patients with multiple myeloma. The combination of intermediate dose (ID) - cyclophosphamide plus G-CSF, has been considered the standard method as mobilization regimen. No prospective randomized clinical trials have compared efficacy and costs using ID - cyclophosphamide against a chemo-free mobilization strategy with G-CSF and plerixafor on demand. METHODS A prospective single arm of 20 patients enrolled in three Italian Centers mobilized with G-CSF plus plerixafor on demand was compared with a retrospective historical control arm of 30 patients mobilized with ID - cyclophosphamide (4 g/sqm) and G-CSF. Costs of the prospective arm was compared with the ones of the retrospective control arm with the aim to collect ≥4 × 106/kg CD34 + . The exploratory cost analysis was performed using microcosting specific inputs of G-CSF plus plerixafor on demand versus ID - cyclophosphamide + G-CSF considering pre-apheresis, peri-apheresis and post-apheresis session. RESULTS Mobilization with ID - cyclophosphamide and G-CSF resulted in a significantly higher CD34+ peak mean on day 1 yield (119 CD34+ μL vs 67.3; p = 0.06) and in total average CD34+ yield (mean collection 10.6 × 106/kg vs 5.8 × 106/kg; p = 0.004) compared to patients mobilized with G-CSF and plerixafor. There was no significant differences (p = 0.36) in the two groups of patients collecting ≥ 4 million CD34+/Kg with ID - cyclophosphamide and G-CSF (93.3 %) vs G-CSF and plerixafor (90.0 %). None of the patients undergoing G-CSF and plerixafor mobilization had febrile neutropenia compared with 7 patients who received ID - cyclophosphamide and G-CSF (0% vs 23 %, p = 0.03) who had a median of 5 days hospitalization (range 4-6). All patients proceeded to ASCT with a mean of 3.6 CD34+/kg infused for G-CSF and plerixafor arm and 4.4 CD34+/kg for the ID - cyclophosphamide + GCSF group (p = 0.37) with a median time to ANC and PLT engraftment not different in the two groups. Total costs of a mobilizing strategy using a combination of G-CSF and plerixafor on demand was 12.690 euros compared to 16.088 euros with ID - cyclophosphamide and G-CSF (p = 0.07); in particular, mobilization cost components were significantly lower for G-CSF and plerixafor vs G-CSF and ID - cyclophosphamide for hospital stay (3080 euros vs 9653 euros; p < 0.001) whereas for mobilizing agent, there was a significative difference with 5470 euros for G-CSF and plerixafor use due to the cost of plerixafor compared with 1140 euros for ID - cyclophosphamide and G-CSF treatment (P = 0.001). CONCLUSIONS Our data demonstrate that in patients with multiple myeloma eligible for ASCT, a chemo-free mobilization with G-CSF and plerixafor on demand is associated with efficacy in PBSC collection and optimal safety profile with similar average costs when compared to a chemo-mobilization with ID - cyclophosphamide. A prospective randomized multicenter study could address which is the most cost-effective strategy for this setting of patients. CLINICAL TRIAL REGISTRY Eudract Number EudraCT 2013-004690-27.
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Affiliation(s)
- D Laszlo
- Unità Di Mobilizzazione e Raccolta CSE, Divisione Di Laboratorio Di Ematoncologia Clinica, Istituto Europeo Di Oncologia IRCCS- Milano, Italy.
| | - G P Marcacci
- SS UTIE e Trapianto CSE, Dipartimento Ematologico, IRCCS, Istituto Nazionale Dei Tumori Fondazione "Sen G. Pascale" - Napoli, Italy
| | - M Martino
- UOC Centro Trapianti Midollo Osseo, Grande Ospedale BMM - Reggio Calabria, Italy
| | - D Radice
- Divisione Di Epidemiologia e Biostatistica, Italy
| | - C Rabascio
- Unità Di Mobilizzazione e Raccolta CSE, Divisione Di Laboratorio Di Ematoncologia Clinica, Istituto Europeo Di Oncologia IRCCS- Milano, Italy
| | - B Lucchetti
- Unità Di Mobilizzazione e Raccolta CSE, Divisione Di Laboratorio Di Ematoncologia Clinica, Istituto Europeo Di Oncologia IRCCS- Milano, Italy
| | - A Magarò
- Unità Di Mobilizzazione e Raccolta CSE, Divisione Di Laboratorio Di Ematoncologia Clinica, Istituto Europeo Di Oncologia IRCCS- Milano, Italy
| | - A Caime
- Unità Di Mobilizzazione e Raccolta CSE, Divisione Di Laboratorio Di Ematoncologia Clinica, Istituto Europeo Di Oncologia IRCCS- Milano, Italy
| | - S Menna
- Data Management - Istituto Europeo Di Oncologia IRCCS - Milano, Italy
| | - M T Lionetti
- Data Management - Istituto Europeo Di Oncologia IRCCS - Milano, Italy
| | - F Bertolini
- Unità Di Mobilizzazione e Raccolta CSE, Divisione Di Laboratorio Di Ematoncologia Clinica, Istituto Europeo Di Oncologia IRCCS- Milano, Italy
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16
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Van de Wyngaert Z, Nerich V, Fouquet G, Chrétien ML, Caillot D, Azar N, Garderet L, Lenain P, Macro M, Bourhis JH, Belhocine R, Jaccard A, Karlin L, Bobin A, Moya N, Systchenko T, Gruchet C, Giraud C, Guidez S, Darras C, Princet I, Touzeau C, Moreau P, Hulin C, Deconinck E, Limat S, Leleu X. Cost and efficacy of peripheral stem cell mobilization strategies in multiple myeloma. Bone Marrow Transplant 2020; 55:2254-2260. [PMID: 32447348 DOI: 10.1038/s41409-020-0940-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 04/27/2020] [Accepted: 04/30/2020] [Indexed: 11/09/2022]
Abstract
Mobilization of peripheral blood stem cells (PBSC) can be performed using plerixafor, which is expensive, or high-dose cyclophosphamide (HDCy). We hypothesized that the overall cost of mobilization with plerixafor might not be greater if the cost of complication management was considered. We performed a cost analysis of these two strategies. This multicentric observational study recruited patients with myeloma who underwent a first PBSC mobilization. We considered direct medical costs, including hospitalization, mobilization agents, apheresis, and supportive treatments. We included 111 patients, 54 and 57 in the HDCy and plerixafor groups, respectively. Cost of mobilization with HDCy was 5097 ± 2982€ vs. 10958 ± 1789€ for plerixafor (p < 0.0001). Cost of agents used was 1287 ± 779€ vs. 6552 ± 509€, respectively (p = 0.0009). The mean number of days of hospitalization was 2 and 2.1 days, respectively (p = 0.035). All patients achieved the minimum PBSC collection target (p = 1.0); however, ASCT was performed with HDCy in 67% patients and with plerixafor in 86% (p = 0.02). Plerixafor mobilization incurred a greater cost, mostly due to the greater cost of the drug. Hospitalization length in the two groups was similar in our series. Interestingly, plerixafor appeared to be a very effective and safe mobilizing approach translating into a greater ASCT success.
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Affiliation(s)
- Zoé Van de Wyngaert
- CHU Lille, Service des Maladies du Sang, F-59000, Lille, France.,Hématologie et thérapie cellulaire, Hôpital Saint Antoine, APHP, Université Paris-Sorbonne, INSERM UMRs 938, Paris, France
| | - Virginie Nerich
- Department of Pharmacy, University Hospital of Besançon, Univ. Bourgogne Franche-Comté, Besançon, France.,INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
| | | | | | | | - Nabih Azar
- Hôpital Pitié Salpêtrière, Service d'Hématologie, F-75013, Paris, France
| | - Laurent Garderet
- Hématologie et thérapie cellulaire, Hôpital Saint Antoine, APHP, Université Paris-Sorbonne, INSERM UMRs 938, Paris, France.,Hôpital Pitié Salpêtrière, Service d'Hématologie, F-75013, Paris, France
| | | | | | | | - Ramdane Belhocine
- Hématologie et thérapie cellulaire, Hôpital Saint Antoine, APHP, Université Paris-Sorbonne, INSERM UMRs 938, Paris, France
| | - Arnaud Jaccard
- Hématologie clinique et thérapie cellulaire, CHU, Limoges, France
| | - Lionel Karlin
- Service d'Hématologie, Hospices Civils de Lyon, Lyon Sud, France
| | - Arthur Bobin
- Hematology and Inserm CIC 1402, CHU, Poitiers, France
| | - Niels Moya
- Hematology and Inserm CIC 1402, CHU, Poitiers, France
| | | | | | | | | | - Claire Darras
- Hematology and Inserm CIC 1402, CHU, Poitiers, France
| | | | - Cyrille Touzeau
- Hematology Department, University Hospital Hotel-Dieu, Nantes, France
| | - Philippe Moreau
- Hematology Department, University Hospital Hotel-Dieu, Nantes, France
| | | | | | - Samuel Limat
- Department of Pharmacy, University Hospital of Besançon, Univ. Bourgogne Franche-Comté, Besançon, France.,INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France
| | - Xavier Leleu
- Hematology and Inserm CIC 1402, CHU, Poitiers, France.
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17
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Park Y, Kim DS, Jeon MJ, Lee B, Yu ES, Kang K, Lee SR, Sung HJ, Nam M, Yoon S, Choi CW, Kang E, Cho D, Kim K, Kim BS, Kim D, Kim SJ. Single‐dose etoposide is an effective and safe protocol for stem cell mobilization in patients with multiple myeloma. J Clin Apher 2019; 34:579-588. [DOI: 10.1002/jca.21734] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 06/20/2019] [Accepted: 06/26/2019] [Indexed: 01/24/2023]
Affiliation(s)
- Yong Park
- Division of Hematology‐Oncology, Department of Internal MedicineAnam Hospital, Korea University School of Medicine Seoul South Korea
| | - Dae Sik Kim
- Division of Hematology‐Oncology, Department of Internal MedicineGuro Hospital, Korea University School of Medicine Seoul South Korea
| | - Min Ji Jeon
- Division of Hematology‐Oncology, Department of Internal MedicineGuro Hospital, Korea University School of Medicine Seoul South Korea
| | - Byung‐Hyun Lee
- Division of Hematology‐Oncology, Department of Internal MedicineAnam Hospital, Korea University School of Medicine Seoul South Korea
| | - Eun Sang Yu
- Division of Hematology‐Oncology, Department of Internal MedicineGuro Hospital, Korea University School of Medicine Seoul South Korea
| | - Ka‐Won Kang
- Division of Hematology‐Oncology, Department of Internal MedicineAnam Hospital, Korea University School of Medicine Seoul South Korea
| | - Se Ryeon Lee
- Division of Hematology‐Oncology, Department of Internal MedicineAnsan Hospital, Korea University School of Medicine Seoul South Korea
| | - Hwa Jung Sung
- Division of Hematology‐Oncology, Department of Internal MedicineAnsan Hospital, Korea University School of Medicine Seoul South Korea
| | - Myung‐Hyun Nam
- Division of Hematology‐Oncology, Department of Laboratory MedicineAnsan Hospital, Korea University School of Medicine Seoul South Korea
| | - Soo‐Young Yoon
- Department of Laboratory Medicine, Guro HospitalKorea University School of Medicine Seoul South Korea
| | - Chul Won Choi
- Division of Hematology‐Oncology, Department of Internal MedicineGuro Hospital, Korea University School of Medicine Seoul South Korea
| | - Eun‐Suk Kang
- Department of Laboratory Medicine and Genetics, Samsung Medical CenterSungkyunkwan University School of Medicine Seoul South Korea
| | - Duck Cho
- Department of Laboratory Medicine and Genetics, Samsung Medical CenterSungkyunkwan University School of Medicine Seoul South Korea
| | - Kihyun Kim
- Division of Hematology‐Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine Seoul South Korea
| | - Byung Soo Kim
- Division of Hematology‐Oncology, Department of Internal MedicineAnam Hospital, Korea University School of Medicine Seoul South Korea
| | - Dae‐Won Kim
- Department of Laboratory MedicineAnam Hospital, Korea University School of Medicine Seoul South Korea
| | - Seok Jin Kim
- Division of Hematology‐Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine Seoul South Korea
- Department of Health Sciences and TechnologySAIHST, Sungkyunkwan University Seoul 06351 South Korea
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18
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Hematopoietic Progenitor Cell Mobilization for Autologous Stem Cell Transplantation in Multiple Myeloma in Contemporary Era. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2019; 19:200-205. [DOI: 10.1016/j.clml.2018.12.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 12/10/2018] [Accepted: 12/12/2018] [Indexed: 11/21/2022]
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19
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Kang J, Hong JY, Yoon DH, Kim JE, Kim KP, Kim S, Lee KM, Park JS, Lee JS, Suh C. Pharmacokinetic and pharmacodynamic study of lenograstim for hematopoietic stem cell mobilization: a prospective randomized study for optimal apheresis. Transfusion 2019; 59:1781-1788. [PMID: 30924165 DOI: 10.1111/trf.15265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 01/14/2019] [Accepted: 01/17/2019] [Indexed: 11/30/2022]
Abstract
BACKGROUND This study evaluated the correlation between the pharmacokinetics and pharmacodynamics of granulocyte colony-stimulating factor (lenograstim) and the impact of initiation time of apheresis on stem cell mobilization in patients with multiple myeloma. STUDY DESIGN AND METHODS Twenty-four patients with multiple myeloma were randomized into one of the two groups (early vs. late). Lenograstim at 10 μg/kg/day once daily was injected for at least 4 consecutive days. Apheresis was initiated 2 hours after the fourth dose of lenograstim in the early collection group and 16 hours after the fourth dose of lenograstim in the late collection group. Blood sampling for pharmacokinetics was performed within 30 minutes before, and 1, 2, 6, and 24 hours after the fourth dose of lenograstim. RESULTS Overall, the two groups (early vs. late, n = 10 vs. 14) exhibited similar baseline characteristics including age, sex, subtype of myeloma, stage distribution, and myeloma-associated symptoms. No correlation was found between plasma lenograstim concentration and peripheral blood (PB) CD34+ cell counts or hematopoietic progenitor cells. In the late collection group, the median number of apheresis procedures for minimal collection was significantly lower (early vs. late: 2 vs. 1; p = 0.04) and there was a higher number of total collected PB CD34+ cells in a single session of apheresis (1.4 vs. 3.1; p = 0.06). There were no differences in median overall PB stem cell collection efficiency. CONCLUSION Late collection positively impacted the number of apheresis procedures for minimal collection, with numerically improved PB stem cell collection efficiency at first apheresis in patients with multiple myeloma.
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Affiliation(s)
- Jihoon Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.,Division of Hematology/Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jung Yong Hong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Dok Hyun Yoon
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jeong Eun Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kyu-Pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Shin Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Kyoung Min Lee
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Jung Sun Park
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Ji Sung Lee
- Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, South Korea
| | - Cheolwon Suh
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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20
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Gonsalves WI, Buadi FK, Ailawadhi S, Bergsagel PL, Chanan Khan AA, Dingli D, Dispenzieri A, Fonseca R, Hayman SR, Kapoor P, Kourelis TV, Lacy MQ, Larsen JT, Muchtar E, Reeder CB, Sher T, Stewart AK, Warsame R, Go RS, Kyle RA, Leung N, Lin Y, Lust JA, Russell SJ, Zeldenrust SR, Fonder AL, Hwa YL, Hobbs MA, Mayo AA, Hogan WJ, Rajkumar SV, Kumar SK, Gertz MA, Roy V. Utilization of hematopoietic stem cell transplantation for the treatment of multiple myeloma: a Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus statement. Bone Marrow Transplant 2019; 54:353-367. [PMID: 29988062 PMCID: PMC6463224 DOI: 10.1038/s41409-018-0264-8] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 05/10/2018] [Accepted: 05/11/2018] [Indexed: 12/22/2022]
Abstract
Over the last two decades, the utilization of various novel therapies in the upfront or salvage settings has continued to improve survival outcomes for patients with Multiple Myeloma (MM). Thus, the conventional role for hematopoietic stem cell transplantation (HSCT) in MM either in the form of an autologous stem cell transplant (ASCT) or an allogeneic stem cell transplant (Allo-SCT) warrants re-evaluation, given the aforementioned clinical advances. Here, we present a consensus statement of our multidisciplinary group of over 30 Mayo Clinic physicians with a special interest in the care of patients with MM and provide evidence-based recommendations on the use of HSCT in MM. We specifically address topics that include the role and timing of an ASCT for MM in the era of novel agents, eligibility for an ASCT, post-ASCT consolidation, and maintenance options, and finally the utility of an upfront tandem ASCT, salvage second ASCT, and an allo-SCT in MM.
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Affiliation(s)
| | - Francis K Buadi
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Sikander Ailawadhi
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida, USA
| | - P Leif Bergsagel
- Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Asher A Chanan Khan
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida, USA
| | - David Dingli
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Rafael Fonseca
- Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Susan R Hayman
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Prashant Kapoor
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Martha Q Lacy
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jeremy T Larsen
- Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Eli Muchtar
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Craig B Reeder
- Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Taimur Sher
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida, USA
| | - A Keith Stewart
- Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Rahma Warsame
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ronald S Go
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Robert A Kyle
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Nelson Leung
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Yi Lin
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - John A Lust
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | | | | | - Amie L Fonder
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Yi L Hwa
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Miriam A Hobbs
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Angela A Mayo
- Division of Hematology and Medical Oncology, Mayo Clinic, Scottsdale, Arizona, USA
| | - William J Hogan
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | | | - Shaji K Kumar
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Morie A Gertz
- Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA
| | - Vivek Roy
- Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida, USA
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21
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Vinorelbine-Cyclophosphamide compared to cyclophosphamide in peripheral blood stem cell mobilization for multiple myeloma. Hematol Oncol Stem Cell Ther 2018; 11:225-232. [PMID: 29705566 DOI: 10.1016/j.hemonc.2018.04.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 03/19/2018] [Accepted: 04/09/2018] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND High dose Cyclophosphamide (Cy) and Vinorelbine Cyclophosphamide (Vino-Cy) are stem cell (SC) mobilisation options for patients with multiple myeloma (MM). We present a comparison of mobilisation outcomes using these regimens. PATIENTS AND METHODS Vino-Cy patients received Vinorelbine 25 mg/m2 on day 1, cyclophosphamide 1500 mg/m2 on day 2, and pegylated GCSF on day 4 or GCSF 10 mcg/kg/day from day 4 onwards. Cy patients were given cyclophosphamide 4000 mg/m2 on day 1 and GCSF10 mcg/kg/day from day 5 onwards. The target CD34 + SC collection was 5 × 106 per kg/BW. RESULTS 149 patients were included. SC collection was lower in the Vino-Cy group (8.20 × 106/Kg BW) compared to the Cy group (11.43 × 106/Kg BW), with adjusted geometric mean ratio of 0.59 (95% CI 0.41 to 0.86, p = 0.006). Time taken to achieve an adequate PB SC count was shorter for Vino-Cy (9 ± 1 day compared to 12 ± 2 days for Cy, adjusted absolute mean difference -3.95, 95% CI -4.85 to -3.06, P < .001). Mobilisation related toxicities (in particular, neutropaenic fever) were greater for Cy. CONCLUSION Vino-Cy is a potential alternative to Cy given the need for effective mobilisation protocols with acceptable toxicity.
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22
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Oyekunle A, Shumilov E, Kostrewa P, Burchert A, Trümper L, Wuchter P, Wulf G, Bacher U, Kröger N. Chemotherapy-Based Stem Cell Mobilization Does Not Result in Significant Paraprotein Reduction in Myeloma Patients in the Era of Novel Induction Regimens. Biol Blood Marrow Transplant 2018; 24:276-281. [PMID: 29037891 DOI: 10.1016/j.bbmt.2017.10.008] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 10/03/2017] [Indexed: 11/17/2022]
Abstract
Novel induction agents markedly improved remission rates in multiple myeloma (MM), and the continued use of chemotherapy for CD34+ stem cell mobilization (SCM) has been questioned. We examined the additional effect of chemotherapy in SCM regarding remission status/morbidity. We reviewed 236 consecutive MM patients (aged 36 to 75 years) with first autologous stem cell transplantation from January 2009 to March 2016 after chemotherapy-based SCM. Responses were measured by changes in intact Ig and free light chain levels before and after chemomobilization (International Myeloma Working Group [IMWG] criteria). Most patients (225/236, 95.3%) received novel induction regimens, which were bortezomib-based (n = 223) and/or lenalidomide-based (n = 19). Most patients (170/190, 89.5%) achieved at least partial remission postinduction and pre-SCM. Stem cells were mobilized with granulocyte colony-stimulating factor and cyclophosphamide-based (212/227, 93.4%) or etoposide-based (15/227, 6.6%) regimens. There were insignificant changes in serum Ig and free light chain levels before and after chemomobilization either in the whole cohort or subgroups. Significant improvements of the IMWG remission status were documented in only 7 of 236 patients (3.0%). Sixty-seven patients (28.4%) developed chemotherapy-related complications (neutropenic fever, sepsis, and others), resulting in 9 hospitalizations (3.8%). Our study suggests that although causing significant morbidity, chemotherapy-based mobilization fails to improve remission status. The value of incorporating additional chemotherapy for SCM is thus not evident.
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Affiliation(s)
- Anthony Oyekunle
- Department for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany; Department of Internal Medicine, University of Botswana, Botswana
| | - Evgenii Shumilov
- Department of Hematology and Medical Oncology, Medical Center University of Göttingen, Germany
| | - Philippe Kostrewa
- Department of Hematology and Oncology, University Hospital Giessen and Marburg, Germany
| | - Andreas Burchert
- Department of Hematology and Oncology, University Hospital Giessen and Marburg, Germany
| | - Lorenz Trümper
- Department of Hematology and Medical Oncology, University Medicine Göttingen (UMG), Göttingen, Germany
| | - Patrick Wuchter
- Department of Internal Medicine V, University of Heidelberg, Germany; Institute of Transfusion Medicine, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service Baden-Württemberg - Hessen, Mannheim, Germany
| | - Gerald Wulf
- Department of Hematology and Medical Oncology, Medical Center University of Göttingen, Germany
| | - Ulrike Bacher
- Department of Hematology, Inselspital Bern, Bern, Switzerland
| | - Nicolaus Kröger
- Department for Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Germany.
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23
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Tanimura A, Hirai R, Nakamura M, Takeshita M, Hagiwara S, Miwa A. Improved progression-free and event-free survival in myeloma patients undergoing PBSCH receiving a cyclophosphamide + G-CSF regimen than G-CSF alone. Int J Hematol 2018; 107:559-567. [PMID: 29388164 DOI: 10.1007/s12185-018-2408-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 01/22/2018] [Accepted: 01/22/2018] [Indexed: 12/22/2022]
Abstract
Two regimens are commonly used for peripheral blood hematopoietic stem cell harvesting (PBSCH) in multiple myeloma: high-dose cyclophosphamide (HD-CY) + granulocyte-colony stimulating factor (G-CSF), and G-CSF alone. The objective of the present study was to evaluate the anti-myeloma effect of the PBSCH regimen including HD-CY. We retrospectively assessed harvesting efficiency, complications, and anti-myeloma effects in 115 patients receiving HD-CY + G-CSF (HD-CY group) and 32 patients receiving G-CSF alone (G-alone group). We collected > 2 × 106 CD34-positive cells/kg from 93 and 75% of patients in the HD-CY and G-alone groups, respectively (P = 0.0079). The mean HSC count was also higher in the HD-CY group. No severe complications were observed in the G-alone group, whereas 66% of patients in the HD-CY group were treated with intravenous antibiotics. The median progression-free and event-free survival (PFS and EFS) were longer in the HD-CY group than in the G-alone group (28 vs. 18 months and 25 vs. 13 months, respectively; P = 0.0127 and 0.0139), with no difference in median overall survival. HD-CY showed anti-myeloma effect, as verified by prolonged EFS and PFS, when a vincristine, doxorubicin, and dexamethasone regimen was administered as induction before PBSCH.
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Affiliation(s)
- Akira Tanimura
- Department of Hematology, Tokyo-Kita Medical Center, 4-17-56 Akabanedai, Kita-ku, Tokyo, Japan.
| | - Risen Hirai
- Department of Hematology, Tokyo-Kita Medical Center, 4-17-56 Akabanedai, Kita-ku, Tokyo, Japan
| | - Miki Nakamura
- Division of Hematology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Masataka Takeshita
- Department of Hematology, Tokyo-Kita Medical Center, 4-17-56 Akabanedai, Kita-ku, Tokyo, Japan
| | - Shotaro Hagiwara
- Division of Hematology, Tokyo Women's Medical University, Tokyo, Japan
| | - Akiyoshi Miwa
- Department of Hematology, Tokyo-Kita Medical Center, 4-17-56 Akabanedai, Kita-ku, Tokyo, Japan
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24
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Dulamea AO, Lupescu IG. Neurological complications of hematopoietic cell transplantation in children and adults. Neural Regen Res 2018; 13:945-954. [PMID: 29926815 PMCID: PMC6022482 DOI: 10.4103/1673-5374.233431] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Hematopoietic cell transplantation (HCT) is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen (HLA)-matched donor (allogeneic) or from the patient (autologous). Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease (GvHD). Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, GvHD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT: (1) early complications (in the first month) - related to harvesting of stem cells, during conditioning (drug toxicity, posterior reversible encephalopathy syndrome), related to pancytopenia, (2) intermediate phase complications (second to sixth month) - central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus, (3) late phase complications (after sixth month) - neurological complications of GvHD, second neoplasms and relapses of the original disease.
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Affiliation(s)
- Adriana Octaviana Dulamea
- University of Medicine and Pharmacy Carol Davila; Department of Neurology, Fundeni Clinical Institute, Bucharest, Romania
| | - Ioana Gabriela Lupescu
- University of Medicine and Pharmacy Carol Davila; Radiology and Medical Imaging Department, Fundeni Clinical Institute, Bucharest, Romania
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25
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Sevindik OG, Korkmaz S, Altuntas F. Current status of art mobilization in Myeloma. Transfus Apher Sci 2017; 56:850-853. [DOI: 10.1016/j.transci.2017.11.028] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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26
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Wallis WD, Qazilbash MH. Peripheral blood stem cell mobilization in multiple myeloma: Growth factors or chemotherapy? World J Transplant 2017; 7:250-259. [PMID: 29104859 PMCID: PMC5661122 DOI: 10.5500/wjt.v7.i5.250] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 06/30/2017] [Accepted: 09/13/2017] [Indexed: 02/05/2023] Open
Abstract
High-dose therapy followed by autologous hematopoietic stem cell (HSC) transplant is considered standard of care for eligible patients with multiple myeloma. The optimal collection strategy should be effective in procuring sufficient HSC while maintaining a low toxicity profile. Currently available mobilization strategies include growth factors alone, growth factors in combination with chemotherapy, or growth factors in combination with chemokine receptor antagonists; however, the optimal strategy has yet to be elucidated. Herein, we review the risks and benefits of each approach.
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Affiliation(s)
- Whitney D Wallis
- the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Muzaffar H Qazilbash
- the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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Lisenko K, Wuchter P, Hansberg M, Mangatter A, Benner A, Ho AD, Goldschmidt H, Hegenbart U, Schönland S. Comparison of Different Stem Cell Mobilization Regimens in AL Amyloidosis Patients. Biol Blood Marrow Transplant 2017; 23:1870-1878. [PMID: 28754546 DOI: 10.1016/j.bbmt.2017.07.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 07/14/2017] [Indexed: 12/14/2022]
Abstract
High-dose melphalan (HDM) and autologous blood stem cell transplantation (ABSCT) is an effective treatment for transplantation-eligible patients with systemic light chain (AL) amyloidosis. Whereas most centers use granulocyte colony-stimulating factor (G-CSF) alone for mobilization of peripheral blood stem cells (PBSC), the application of mobilization chemotherapy might offer specific advantages. We retrospectively analyzed 110 patients with AL amyloidosis who underwent PBSC collection. Major eligibility criteria included age <70 years and cardiac insufficiency New York Heart Association ≤III°. Before mobilization, 67 patients (61%) had been pretreated with induction therapy, including 17 (15%) patients who had received melphalan. Chemo-mobilization was performed with either cyclophosphamide, doxorubicin, dexamethasone (CAD)/G-CSF (n = 78, 71%); ifosfamide/G-CSF (n = 14, 13%); or other regimens (n = 8, 7%). AL amyloidosis patients with predominant heart involvement and/or status post heart transplantation were mobilized with G-CSF only (n = 10, 9%). PBSC collection was successful in 101 patients (92%) at first attempt. The median number of CD34+ cells was 8.7 (range, 2.1 to 45.5) × 106 CD34+/kg collected in a median of 1 leukapheresis (LP) session. Compared with G-CSF-only mobilization, a chemo-mobilization with CAD/G-CSF or ifosfamide/G-CSF had a positive impact on the number of collected CD34+ cell number/kg per LP (P <.001, multivariate). Melphalan-containing previous therapy and higher age had a significant negative impact on quantity of collected CD34+ cells. Median common toxicity criteria (CTC) grade of nonhematologic toxicity was II (range, 0 to IV). Life-threatening CTC grade IV adverse events were observed in 3 patients with no fatalities. Cardiovascular events were observed in 17 patients (22%) upon CAD/G-CSF mobilization (median CTC: grade 3; range, 1 to 4). Toxicity in patients undergoing ifosfamide/G-CSF mobilization was higher than in with those who received G-CSF-only mobilization. HDM and ABSCT were performed in 100 patients. Compared with >6.5 × 106 transplanted CD34+ cells/kg, an ABSCT with <3 × 106 CD34+ cells/kg was associated with a longer duration to leukocyte reconstitution >1 × 109/L and a reduced platelet count <150 × 109/L 1 year after ASCT. Our results show that CAD chemotherapy is very effective in PBSC mobilization and has a tolerable toxicity profile in AL amyloidosis patients. A further toxicity reduction by omission of doxorubicin might be considered. Because of advanced nonhematologic toxicity, ifosfamide administration cannot be recommended. However, G-CSF mobilization alone is also safe and effective. Considering the hematopoietic reconstitution and long-term stem cell function, our results provide a rationale to collect and transplant as many as >6.5 × 106 CD34+ cells/kg, if feasible with reasonable effort.
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Affiliation(s)
- Katharina Lisenko
- Department of Hematology, Oncology and Rheumatology, Heidelberg University, Germany
| | - Patrick Wuchter
- Department of Hematology, Oncology and Rheumatology, Heidelberg University, Germany; Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service Baden-Württemberg-Hessen, Medical Faculty Mannheim, Heidelberg University, Germany
| | - Marion Hansberg
- Department of Hematology, Oncology and Rheumatology, Heidelberg University, Germany
| | - Anja Mangatter
- Department of Hematology, Oncology and Rheumatology, Heidelberg University, Germany
| | - Axel Benner
- Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany
| | - Anthony D Ho
- Department of Hematology, Oncology and Rheumatology, Heidelberg University, Germany
| | - Hartmut Goldschmidt
- Department of Hematology, Oncology and Rheumatology, Heidelberg University, Germany; National Center for Tumor Diseases, University Hospital, Heidelberg, Germany
| | - Ute Hegenbart
- Department of Hematology, Oncology and Rheumatology, Heidelberg University, Germany; Amyloidosis Center, Heidelberg University, Germany.
| | - Stefan Schönland
- Department of Hematology, Oncology and Rheumatology, Heidelberg University, Germany; Amyloidosis Center, Heidelberg University, Germany
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Varmavuo V, Silvennoinen R, Anttila P, Säily M, Sankelo M, Putkonen M, Ahonen J, Mahlamäki E, Mäntymaa P, Savolainen ER, Remes K, Jantunen E. Cost analysis of a randomized stem cell mobilization study in multiple myeloma. Ann Hematol 2016; 95:1653-9. [DOI: 10.1007/s00277-016-2772-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 07/26/2016] [Indexed: 02/07/2023]
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Hematopoietic Progenitor Cell Mobilization with Ifosfamide, Carboplatin, and Etoposide Chemotherapy versus Plerixafor-Based Strategies in Patients with Hodgkin and Non-Hodgkin Lymphoma. Biol Blood Marrow Transplant 2016; 22:1773-1780. [PMID: 27345140 DOI: 10.1016/j.bbmt.2016.06.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Accepted: 06/17/2016] [Indexed: 11/22/2022]
Abstract
Studies comparing the efficacy and safety of chemo-mobilization with ifosfamide, carboplatin, and etoposide (ICE) ± rituximab with plerixafor-based approaches in lymphoma patients have not been performed. We analyzed hematopoietic progenitor cell mobilization outcomes in lymphoma patients undergoing chemo-mobilization with ICE (n = 35) compared with either routine plerixafor (n = 30) or "just in time" (JIT) plerixafor-based mobilization (n = 33). Chemo-mobilization provided a significantly higher total CD34(+) cell yield (median collection, 5.35 × 10(6) cells/kg for ICE versus 3.15 × 10(6) cells/kg for routine plerixafor and 3.6 × 10(6) cells/kg for JIT plerixafor, P < .001). The median day 1 yield of CD34(+) cells was not significantly different (median, 2.2 × 10(6) cells/kg in ICE versus 1.9 × 10(6) cells/kg in upfront plerixafor versus 1.7 × 10(6) cells/kg in JIT plerixafor, P = .20). There was no significant difference in the 3 groups in terms of total number of apheresis sessions performed (median, 2 in each group; P = .78). There were no mobilization failures (inability to collect at least 2 × 10(6) cells/kg) in the chemo-mobilization group, whereas 5 patients (16.7%) in the routine plerixafor and 3 patients (9.1%) in JIT group had mobilization failure (P = .04). Mean time to neutrophil engraftment was faster in the chemo-mobilization group, 10.3 days (±1.2) compared with 12.1 days (±3.6) in the routine plerixafor group and 11.6 days (±3.0) in the JIT group (P < .001) and mean time to platelet engraftment was 13.7 days (±.7) in ICE versus 20.3 days (±1.6) in routine plerixafor versus 17.1 days (± .9) in JIT group (P < .001). Red blood cell transfusions were significantly higher in the chemo-mobilization group (34.3% versus 0 versus 3.2% versus 1, P < .001) and so were the platelet transfusions (22.9% versus 0 versus 0, P < .001). Excluding the cost of chemotherapy administration, chemo-mobilization was associated with significantly less mobilization cost (average cost $17,601.76 in ICE versus $28,963.05 in routine and $25,679.81 in JIT, P < .001). Our data suggests that chemo-mobilization with ICE provides a higher total CD34(+) cell yield, lower rates of mobilization failure, faster engraftment, and lower cost compared to plerixafor-based approaches with comparable toxicity profile between the groups, except for higher transfusion requirements with chemo-mobilization.
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Cooper DL, Medoff E, Patel N, Baker J, Pratt K, Foss F, Seropian SE, Perreault S, Wu Y. Autologous Stem Cell Mobilization in the Age of Plerixafor. CLINICAL LYMPHOMA MYELOMA & LEUKEMIA 2016; 16:411-6. [PMID: 27245311 DOI: 10.1016/j.clml.2016.04.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 03/30/2016] [Accepted: 04/26/2016] [Indexed: 12/22/2022]
Abstract
BACKGROUND Autologous stem cell transplantation remains important in the treatment of myeloma and relapsed lymphoma. Plerixafor has been shown to significantly enhance stem cell mobilization but is very expensive. PATIENTS AND METHODS We evaluated plerixafor use in the 3-year period after its approval in December 2008. RESULTS A total of 277 patients with myeloma and lymphoma had stem cell mobilization; 97.5% were successfully mobilized, including 41.5% who received plerixafor. Plerixafor was generally used for rescue after suboptimal granulocyte-colony stimulating factor (G-CSF) mobilization ("just in time") or for remobilization after an unsuccessful attempt with chemotherapy plus G-CSF. In addition, 10% of patients received planned G-CSF plus plerixafor because of high risk factors for inadequate collection. Rescue plerixafor was more effective in patients with myeloma than lymphoma as after 1 dose of plerixafor; 85% versus 55% collected a minimum number of stem cells (2 × 10E6 CD34 cells/kg) for 1 transplant and 51% versus 15% collected > 5 × 10E6 CD34 cells/kg. After transplantation, there were no significant differences in engraftment as a consequence of plerixafor use. Among all patients, there were less platelet transfusions in patients provided ≥ 3.5 × 10E6 CD34(+) cells/kg. CONCLUSION With the judicious use of plerixafor, nearly all patients can collect enough stem cells to proceed to transplantation. Further studies, including hematologic tolerance to posttransplantation therapy, are required to determine the cost-effectiveness of using plerixafor to convert adequate to more optimal mobilizers.
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Affiliation(s)
- Dennis L Cooper
- Section of Hematologic Malignancies, Yale Cancer Center, New Haven, CT; Rutgers-Cancer Institute of New Jersey, New Brunswick, NJ.
| | - Erin Medoff
- Section of Hematologic Malignancies, Yale Cancer Center, New Haven, CT
| | - Natalie Patel
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT
| | - Julie Baker
- Section of Hematologic Malignancies, Yale Cancer Center, New Haven, CT
| | - Kathryn Pratt
- Department of Nursing, Smilow Cancer Hospital, Yale-New Haven Children's Hospital, New Haven, CT
| | - Francine Foss
- Section of Hematologic Malignancies, Yale Cancer Center, New Haven, CT
| | - Stuart E Seropian
- Section of Hematologic Malignancies, Yale Cancer Center, New Haven, CT
| | - Sarah Perreault
- Department of Pharmacy, Smilow Cancer Hospital, Yale-New Haven Children's Hospital, New Haven, CT
| | - Yanyun Wu
- Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT; Bloodworks, Seattle, WA
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Valtola J, Silvennoinen R, Ropponen A, Siitonen T, Säily M, Sankelo M, Terävä V, Putkonen M, Kuittinen T, Pelkonen J, Mäntymaa P, Remes K, Varmavuo V, Jantunen E. Blood graft cellular composition and posttransplant outcomes in myeloma patients mobilized with or without low-dose cyclophosphamide: a randomized comparison. Transfusion 2016; 56:1394-401. [PMID: 27041692 DOI: 10.1111/trf.13574] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 01/28/2016] [Accepted: 02/02/2016] [Indexed: 12/19/2022]
Abstract
BACKGROUND Autologous stem cell transplantation is a standard treatment in multiple myeloma (MM). Blood grafts are usually collected after mobilization with granulocyte-colony-stimulating factor (G-CSF) alone or in a combination with cyclophosphamide (CY). There is limited knowledge of the possible effects of different mobilization regimens on blood graft characteristics and posttransplant outcomes. STUDY DESIGN AND METHODS Thirty-eight patients with MM were included in this study. The patients were randomly assigned at registration to mobilization with either low-dose CY plus G-CSF (Arm A) or G-CSF alone (Arm B) and received three cycles of lenalidomide, bortetzomib, and dexamethasone induction. Flow cytometry analysis of lymphocyte subsets in the blood grafts after cryopreservation was performed. Hematologic and immune recovery were evaluated up to 12 months posttransplant. RESULTS The blood grafts in Arm A contained significantly more CD34+ cells but in Arm B there was a greater proportion of CD34+CD38- cells and higher numbers of T and B lymphocytes as well as natural killer (NK) cells. The engraftment was comparable but lymphocyte count at 15 days posttransplant was higher in Arm B (0.8 × 10(9) /L vs. 0.5 × 10(9) /L, p = 0.033). At 3 and 6 months posttransplant the total number of NK cells was also higher in G-CSF-mobilized patients. There was no difference in progression-free survival between the study arms. CONCLUSION CY plus G-GSF yields more CD34+ cells but seems to diminish lymphocyte and NK cell counts in the grafts and hampers immune recovery after transplantation. Thus G-CSF alone might be a preferred mobilization method due to more rapid immune recovery posttransplant.
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Affiliation(s)
- Jaakko Valtola
- Department of Medicine, Kuopio University Hospital, Kuopio, Finland
| | - Raija Silvennoinen
- Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland
| | - Antti Ropponen
- Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland
| | - Timo Siitonen
- Department of Medicine, Oulu University Hospital, Oulu, Finland
| | - Marjaana Säily
- Department of Medicine, Oulu University Hospital, Oulu, Finland
| | - Marja Sankelo
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Venla Terävä
- Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
| | - Mervi Putkonen
- Department of Medicine, Turku University Hospital, Turku, Finland
| | | | - Jukka Pelkonen
- Department of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland.,Laboratory Center of Eastern Finland, Kuopio, Finland
| | | | - Kari Remes
- Department of Medicine, Turku University Hospital, Turku, Finland.,University of Turku, Turku, Finland
| | - Ville Varmavuo
- Department of Medicine, Kuopio University Hospital, Kuopio, Finland
| | - Esa Jantunen
- Department of Medicine, Kuopio University Hospital, Kuopio, Finland
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Stem Cell Mobilization with G-CSF versus Cyclophosphamide plus G-CSF in Mexican Children. Stem Cells Int 2016; 2016:4078215. [PMID: 26880960 PMCID: PMC4736431 DOI: 10.1155/2016/4078215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Accepted: 11/16/2015] [Indexed: 11/17/2022] Open
Abstract
Fifty-six aphaereses were performed in 23 pediatric patients with malignant hematological and solid tumors, following three different protocols for PBPC mobilization and distributed as follows: A: seventeen mobilized with 4 g/m2 of cyclophosphamide (CFA) and 10 μg/kg/day of granulocyte colony stimulating factor (G-CSF), B: nineteen with CFA + G-CSF, and C: twenty only with G-CSF when the WBC count exceeded 10 × 109/L. The average number of MNC/kg body weight (BW)/aphaeresis was 0.4 × 108 (0.1–1.4), 2.25 × 108 (0.56–6.28), and 1.02 × 108 (0.34–2.5) whereas the average number of CD34+ cells/kg BW/aphaeresis was 0.18 × 106/kg (0.09–0.34), 1.04 × 106 (0.19–9.3), and 0.59 × 106 (0.17–0.87) and the count of CFU/kg BW/aphaeresis was 1.11 × 105 (0.31–2.12), 1.16 × 105 (0.64–2.97), and 1.12 × 105 (0.3–6.63) in groups A, B, and C, respectively. The collection was better in group B versus group A (p = 0.007 and p = 0.05, resp.) and in group C versus group A (p = 0.08 and p = 0.05, resp.). The collection of PBPCs was more effective in the group mobilized with CFM + G-CSF when the WBC exceeded 10 × 103/μL in terms of MNC and CD34+ cells and there was no toxicity of the chemotherapy.
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Mobilization policy in multiple myeloma: minimum target or law of redundancy? Two different approaches by the two sides of the Atlantic Ocean. Bone Marrow Transplant 2015; 51:348-50. [DOI: 10.1038/bmt.2015.317] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2015] [Revised: 10/31/2015] [Accepted: 11/06/2015] [Indexed: 11/08/2022]
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