|
1
|
Prolonged Lenalidomide Therapy Does Not Impact Autologous Peripheral Blood Stem Cell Mobilization and Collection in Multiple Myeloma Patients: A Single-Center Retrospective Analysis. Transplant Cell Ther 2021; 27:661.e1-661.e6. [PMID: 33895403 DOI: 10.1016/j.jtct.2021.04.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 03/22/2021] [Accepted: 04/13/2021] [Indexed: 12/22/2022]
Abstract
Since the introduction of lenalidomide into induction therapy for multiple myeloma (MM), there have been conflicting reports about its impact on autologous peripheral blood stem cell (PBSC) mobilization. We evaluated the impact of previous lenalidomide exposure in a large cohort of patients with MM undergoing mobilization and collection at a tertiary stem cell transplantation center. We hypothesized that collection of PBSCs is feasible even with a prolonged duration of previous lenalidomide therapy. We examined patients with MM who attempted stem cell mobilization and collection, seen at our center between January 2012 and July 2015. The patients were categorized into 3 groups for analysis: (1) patients with previous receipt of >6 cycles lenalidomide, (2) patients with previous receipt of ≤6 cycles of lenalidomide, and (3) patients without previous lenalidomide exposure. We compared collection yields and days of apheresis among the 3 groups using linear regression analysis. We identified 297 patients with MM who underwent mobilization of PBSCs. Of these, 35 had received >6 cycles of lenalidomide (median, 8 cycles; range, 7 to 25 cycles), 156 had received ≤6 cycles of lenalidomide (median, 4 cycles; range, 1 to 6 cycles), and 106 had received no lenalidomide. Prior lenalidomide exposure did not have a statistically significant impact on the absolute number of CD34+ cells collected or on the duration of collection based on a multivariate linear regression analysis for association between receipt of >6 cycles of lenalidomide. In this retrospective analysis of MM patients undergoing autologous PBSC transplantation, we show that the duration of previous lenalidomide exposure does not impact the total number of PBSCs collected or the number of days of apheresis. These data suggest that longer courses of induction therapy with lenalidomide-containing regimens to achieve a maximum response can be safe without impairing the ability to collect PBSCs, and that limiting lenalidomide use before mobilization does not appear warranted in all cases.
Collapse
|
|
2
|
Pan J, Ghimire S, Alpdogan SO, Chapman A, Carabasi M, DiMeglio M, Gong J, Martinez-Outschoorn U, Rose L, Ramirez M, Wagner JL, Weiss M, Flomenberg N, Pro B, Porcu P, Filicko-OHara J, Gaballa S. Phase I/II study of bendamustine in combination with ofatumumab, carboplatin, etoposide (BOCE) for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma. Leuk Lymphoma 2020; 62:590-597. [PMID: 33146052 DOI: 10.1080/10428194.2020.1842400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
We developed an outpatient salvage chemotherapy regimen using bendamustine, ofatumumab, carboplatin and etoposide (BOCE) to treat relapsed/refractory non-Hodgkin lymphoma (RR NHL) in a single-center phase I/II study. Primary objectives were safety, tolerability and overall response rate (ORR). Thirty-five RR NHL patients (57% de novo large cell [DLBCL] or grade 3B follicular [FL], 26% transformed DLBCL, 9% grade 3A FL, 3% mantle cell; median age = 62, median prior therapies = 1) were treated. Median follow-up was 24.1 months. ORR was 69% (CR = 49%, PR = 20% [ORR = 70%, CR = 50%, PR = 20% in the de novo DLBCL/grade 3B FL subgroup]). Median progression-free survival was 5.1 months and overall-survival 26.2 months. Twelve patients subsequently underwent stem cell transplantation. The most common non-hematologic grade 3-4 toxicities were neutropenic fever and hypophosphatemia. There were no treatment-related deaths. In conclusion, BOCE is a safe and effective outpatient salvage regimen for patients with RR NHL and serves as an effective bridge to stem cell transplantation.
Collapse
Affiliation(s)
- Jonathan Pan
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Sushil Ghimire
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - S Onder Alpdogan
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Andrew Chapman
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Matthew Carabasi
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Martina DiMeglio
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Jerald Gong
- Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | | | - Lewis Rose
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Michael Ramirez
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - John L Wagner
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Mark Weiss
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Neal Flomenberg
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Barbara Pro
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA.,Robert H. Lurie Comprehensive Cancer Center, Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Pierluigi Porcu
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Joanne Filicko-OHara
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Sameh Gaballa
- Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA, USA.,Division of Malignant Hematology, Moffitt Cancer Center, Tampa, FL, USA
| |
Collapse
|
|
3
|
Reale A, Khong T, Mithraprabhu S, Savvidou I, Hocking J, Bergin K, Ramachandran M, Chen M, Dammacco F, Ria R, Silvestris F, Vacca A, Reynolds J, Spencer A. TOP2A expression predicts responsiveness to carfilzomib in myeloma and informs novel combinatorial strategies for enhanced proteasome inhibitor cell killing. Leuk Lymphoma 2020; 62:337-347. [PMID: 33131357 DOI: 10.1080/10428194.2020.1832659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Microarray was utilized to determine if a genetic signature associated with resistance to carfilzomib (CFZ) could be identified. Twelve human myeloma (MM) cell lines (HMCLs) were treated with CFZ and a cell-viability profile was assessed categorizing HMCLs as sensitive or resistant to CFZ. The gene expression profiles (GEP) of untreated resistant versus sensitive HMCLs revealed 29 differentially expressed genes. TOP2A, an enzyme involved in cell cycle and proliferation, was overexpressed in carfilzomib-resistant HMCLs. TOP2A protein expression levels, evaluated utilizing trephine biopsy specimens acquired prior to treatment with proteasome inhibitors, were higher in patients failing to achieve a response when compared to responding patients. Logistic-regression analysis confirmed that TOP2A protein expression was a highly significant predictor of response to PIs (AUC 0.738). Further, the combination of CFZ with TOP2A inhibitors, demonstrated synergistic cytotoxic effects in vitro, providing a rationale for combining topoisomerase inhibitors with CFZ to overcome resistance in MM.
Collapse
Affiliation(s)
- Antonia Reale
- Myeloma Research Group, Australian Centre for Blood Diseases, The Alfred Hospital/Monash University, Melbourne, Australia
| | - Tiffany Khong
- Myeloma Research Group, Australian Centre for Blood Diseases, The Alfred Hospital/Monash University, Melbourne, Australia
| | - Sridurga Mithraprabhu
- Myeloma Research Group, Australian Centre for Blood Diseases, The Alfred Hospital/Monash University, Melbourne, Australia
| | - Ioanna Savvidou
- Myeloma Research Group, Australian Centre for Blood Diseases, The Alfred Hospital/Monash University, Melbourne, Australia
| | - Jay Hocking
- Myeloma Research Group, Australian Centre for Blood Diseases, The Alfred Hospital/Monash University, Melbourne, Australia.,Department of Clinical Haematology, Box Hill, Melbourne, Australia.,Myeloma Clinic, The Alfred Centre, Melbourne, Australia
| | - Krystal Bergin
- Myeloma Research Group, Australian Centre for Blood Diseases, The Alfred Hospital/Monash University, Melbourne, Australia
| | - Malarmathy Ramachandran
- Myeloma Research Group, Australian Centre for Blood Diseases, The Alfred Hospital/Monash University, Melbourne, Australia
| | - Maoshan Chen
- Myeloma Research Group, Australian Centre for Blood Diseases, The Alfred Hospital/Monash University, Melbourne, Australia
| | - Francesco Dammacco
- Department of Internal Medicine and Human Oncology, University of Bari 'Aldo Moro', Bari, Italy
| | - Roberto Ria
- Department of Internal Medicine and Human Oncology, University of Bari 'Aldo Moro', Bari, Italy
| | - Francesco Silvestris
- Department of Internal Medicine and Human Oncology, University of Bari 'Aldo Moro', Bari, Italy
| | - Angelo Vacca
- Department of Internal Medicine and Human Oncology, University of Bari 'Aldo Moro', Bari, Italy
| | - John Reynolds
- Biostatistics Consulting Platform, Faculty of Medicine, Nursing and Health Sciences, Monash University, The Alfred Centre, Melbourne, Australia
| | - Andrew Spencer
- Myeloma Research Group, Australian Centre for Blood Diseases, The Alfred Hospital/Monash University, Melbourne, Australia.,Malignant Haematology and Stem Cell Transplantation, The Alfred Hospital, Melbourne, Australia.,Department of Clinical Haematology, Monash University, Melbourne, Australia
| |
Collapse
|
|
4
|
Martino M, Naso V, Porto G, Paviglianiti A, Ferreri A, Loteta B, Moscato T, Console G, Gentile M, Rossi M, Provenzano PF, Gori M, Pitino AL, Morabito A, Tripepi G. Granisetron transdermal system and dexamethasone for the prevention of nausea and vomiting in multiple myeloma patients receiving chemo-mobilization: An observational real-world study of effectiveness and safety. Transfus Apher Sci 2020; 59:102911. [PMID: 32859502 DOI: 10.1016/j.transci.2020.102911] [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: 05/24/2020] [Revised: 08/06/2020] [Accepted: 08/06/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE Cyclophosphamide (CY) in a dose of 2-4 g/m2 is widely used for hemopoietic progenitor stem cells mobilization. CY administration is associated with several adverse effects, including chemotherapy-induced nausea and vomiting (CINV). This study aimed to evaluate the efficacy and tolerability of granisetron transdermal system (GTDS) plus dexamethasone in the management of CINV in MM patients undergoing chemo-mobilization with CY. METHODS In this single-center, prospective, observational, real world study, GTDS plus dexamethasone was administered to MM patients receiving chemo-mobilization based on CY 2 g/m2 plus G-CSF in an outpatient setting. The rate of complete response was evaluated as the main outcome. Other outcomes were rate of complete control of CINV, incidence of nausea/vomiting of any grade and safety. RESULTS A total of 88 patients were enrolled. A complete response was achieved in 45.5 % of patients; among them, 39.77 % attained complete control of CINV. Nausea and vomiting never occurred in 34.1 % and 45.5 % of patients, respectively. No episodes of grade 3-4 nausea and/or vomiting were documented. GTDS was safe and well tolerated. CONCLUSION In real world, GTDS provided an innovative, effective, and well-tolerated control of CINV in MM patients after chemo-mobilization with CY. The study found out effectiveness of a non-invasive delivery system of antiemetic.
Collapse
Affiliation(s)
- Massimo Martino
- Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.
| | - Virginia Naso
- Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Gaetana Porto
- Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Annalisa Paviglianiti
- Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Anna Ferreri
- Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Barbara Loteta
- Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Tiziana Moscato
- Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Giuseppe Console
- Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Massimo Gentile
- Hematology Unit, Department of Onco-Hematology, A.O. of Cosenza, Cosenza, Italy
| | - Marco Rossi
- Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, Catanzaro, Italy
| | - Pasquale Fabio Provenzano
- Stem Cell Transplantation and Cellular Therapies Unit, Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | | | | | - Antonella Morabito
- Pharmacy Unit, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Giovanni Tripepi
- CNR-IFC, Research Unit of Reggio Calabria, Reggio Calabria, Italy
| |
Collapse
|
|
5
|
Abstract
Enforced egress of hematopoietic stem cells (HSCs) out of the bone marrow (BM) into the peripheral circulation, termed mobilization, has come a long way since its discovery over four decades ago. Mobilization research continues to be driven by the need to optimize the regimen currently available in the clinic with regard to pharmacokinetic and pharmacodynamic profile, costs, and donor convenience. In this review, we describe the most recent findings in the field and how we anticipate them to affect the development of mobilization strategies in the future. Furthermore, the significance of mobilization beyond HSC collection, i.e. for chemosensitization, conditioning, and gene therapy as well as a means to study the interactions between HSCs and their BM microenvironment, is reviewed. Open questions, controversies, and the potential impact of recent technical progress on mobilization research are also highlighted.
Collapse
Affiliation(s)
- Darja Karpova
- Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, 69120, Germany
| | - Michael P Rettig
- Division of Oncology, Department of Medicine, Washington University School of Medicine,, St. Louis, Missouri, 63110, USA
| | - John F DiPersio
- Division of Oncology, Department of Medicine, Washington University School of Medicine,, St. Louis, Missouri, 63110, USA
| |
Collapse
|
|
6
|
Yin X, Han L, Mu S, Mu W, Liang S, Wang T, Liu Y, Zhang N. Preparation and evaluation of etoposide-loaded lipid-based nanosuspensions for high-dose treatment of lymphoma. Nanomedicine (Lond) 2019; 14:1403-1427. [PMID: 31180263 DOI: 10.2217/nnm-2018-0502] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Aim: High-dose administration of etoposide (VP16) was limited by its poor aqueous solubility and severe systemic toxicity on lymphoma therapy. Herein, a novel VP16-loaded lipid-based nanosuspensions (VP16-LNS) was developed for improving drug solubility, enhancing antitumor effect and reducing systemic toxicity. Materials & methods: VP16-LNS with soya lecithin and D-α-tocopheryl PEG 1000 succinate (TPGS) as stabilizers were prepared by nanoprecipitation method. Results: VP16-LNS exhibited uniform spherical morphology, small particle size and favorable colloidal stability. The concentration of VP16 in VP16-LNS was high enough (1017.67 μg/ml) for high-dose therapy on lymphoma. Moreover, VP16-LNS displayed long blood circulation time, selective intratumoral accumulation, remarkable antitumor effect and upregulated safety. Conclusion: VP16-LNS would be an efficient nanoformulation for clinical intravenous application against lymphoma.
Collapse
Affiliation(s)
- Xiaolan Yin
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Culture Road, Ji’nan, Shandong Province 250012, PR China
| | - Leiqiang Han
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Culture Road, Ji’nan, Shandong Province 250012, PR China
| | - Shengjun Mu
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Culture Road, Ji’nan, Shandong Province 250012, PR China
| | - Weiwei Mu
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Culture Road, Ji’nan, Shandong Province 250012, PR China
| | - Shuang Liang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Culture Road, Ji’nan, Shandong Province 250012, PR China
| | - Tianqi Wang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Culture Road, Ji’nan, Shandong Province 250012, PR China
| | - Yongjun Liu
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Culture Road, Ji’nan, Shandong Province 250012, PR China
| | - Na Zhang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 West Culture Road, Ji’nan, Shandong Province 250012, PR China
| |
Collapse
|
|
7
|
Budde LE, Wu D, Martin DB, Philip M, Shustov AR, Smith SD, Gooley TA, Chen TL, Libby EN, Chen EY, Kojouri K, Langerak A, Roden JE, Press OW, Gopal AK. Bendamustine with rituximab, etoposide and carboplatin (T(R)EC) in relapsed or refractory aggressive lymphoma: a prospective multicentre phase 1/2 clinical trial. Br J Haematol 2018; 183:601-607. [PMID: 30596402 PMCID: PMC6314205 DOI: 10.1111/bjh.15585] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 05/25/2018] [Indexed: 01/21/2023]
Abstract
We sought to develop a safe and effective outpatient salvage regimen by replacing ifosfamide within the (R)ICE (rituximab, ifosfomide, carboplatin, etoposide) regimen with bendamustine (T(R)EC) via a multicentre phase I/II study for patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) and classic Hodgkin lymphoma (HL). Therapy consisted of 60-120 mg/m2 per day bendamustine on days 1 and 2 in combination with carboplatin, etoposide and rituximab (only for CD20+ lymphoma) used in the (R)ICE regimen for up to 2 cycles. The objectives were to define a maximally tolerated dose (MTD) of bendamustine, determine safety and toxicity, assess efficacy, and evaluate impact on stem cell collection. Forty-eight patients were treated of which 71% had refractory disease. No dose-limiting toxicities were observed. The recommended phase II dose of bendamustine was 120 mg/m2 per day on days 1 and 2. Response rates were 85% (70% complete response, CR) in HL, and 65% (40% CR) in DLBCL. Stem cell collection was successful in 30 of 32 patients. The most common non-haematological toxicities ≥grade 3 were febrile neutropenia (8%) and dehydration (8%). The T(R)EC regimen safely yields high response rates, successfully mobilizes peripheral blood stem cells and compares favourably to RICE, offering an effective outpatient treatment option for patients with relapsed or refractory DLBCL and HL.
Collapse
Affiliation(s)
- Lihua. E. Budde
- Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
| | - David Wu
- Department of Laboratory Medicine, University of Washington, Seattle, WA
| | - Daniel B. Martin
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Mary Philip
- Department of Medicine, Divisions of Medical Oncology and Hematology, University of Washington, Seattle, WA
| | - Andrei R. Shustov
- Department of Medicine, Divisions of Medical Oncology and Hematology, University of Washington, Seattle, WA
| | - Stephen. D. Smith
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Ted. A. Gooley
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Tara L. Chen
- Department of Medicine, Divisions of Medical Oncology and Hematology, University of Washington, Seattle, WA
| | - Edward N. Libby
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | | | | | | | - Jennifer E. Roden
- Department of Medicine, Divisions of Medical Oncology and Hematology, University of Washington, Seattle, WA
| | - Oliver W. Press
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Ajay K. Gopal
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
- Department of Medicine, Divisions of Medical Oncology and Hematology, University of Washington, Seattle, WA
| |
Collapse
|
|
8
|
Greenbaum AM, Green DJ, Holmberg LA, Gooley T, Till BG, Budde LE, Rasmussen H, Press OW, Gopal AK. Bendamustine, etoposide, and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in non-Hodgkin lymphoma. Blood Res 2018; 53:223-226. [PMID: 30310789 PMCID: PMC6170297 DOI: 10.5045/br.2018.53.3.223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2018] [Revised: 03/15/2018] [Accepted: 05/10/2018] [Indexed: 12/03/2022] Open
Abstract
Background Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may adversely affect stem cell collection. Here we describe the lymphoma subset of a prospective, non-randomized phase II study of bendamustine, etoposide, and dexamethasone (BED) as a mobilization agent for lymphoid malignancies. Methods This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m2 IV d 1, 2), etoposide (200 mg/m2 IV d 1–3), and dexamethasone (40 mg PO d 1–4) followed by filgrastim (10 mcg/kg/d sc. through collection). Results We successfully collected stem cells from all patients, with a median of 7.9×106/kg of body weight (range, 4.4 to 17.3×106/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). Conclusion For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.
Collapse
Affiliation(s)
- Adam M Greenbaum
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Damian J Green
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Leona A Holmberg
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Ted Gooley
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Brian G Till
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Lihua E Budde
- Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA
| | - Heather Rasmussen
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Oliver W Press
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Ajay K Gopal
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| |
Collapse
|
|
9
|
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.
Collapse
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
| |
Collapse
|