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1
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Alvarez-Payares JC, Ribero Vargas DA, Suárez EU, Barrera-Correa D, Vélez Aguirre JD, Hernandez-Rodriguez JC, Ramirez-Urrea SI. Pulmonary Manifestations in Patients With Hematologic Malignancies: In Pursuit of an Accurate Diagnosis. Cureus 2025; 17:e77418. [PMID: 39949462 PMCID: PMC11822728 DOI: 10.7759/cureus.77418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/12/2025] [Indexed: 02/16/2025] Open
Abstract
Pulmonary involvement is common in patients with hematologic malignancies (HMs) and varies depending on the underlying condition, including lymphoproliferative disorders, acute leukemia, myelodysplastic syndrome, and allogeneic stem cell transplantation. Pulmonary complications are a frequent cause of morbidity and mortality in these patients, often resulting from the immunosuppressive effects of the disease or its treatment. The clinical manifestations of these complications are nonspecific, and their differential diagnosis is broad, encompassing both infectious and noninfectious causes. A thorough clinical assessment requires consideration of factors such as the patient's history, baseline immune status, treatment regimens, time since the last chemotherapy, and environmental exposures. Radiographic imaging, particularly high-resolution CT, plays a critical role in evaluating these complications, helping clinicians identify distinct patterns of pulmonary involvement. Therefore, a personalized diagnostic approach is essential, and multidisciplinary management is crucial for optimal patient care.
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Affiliation(s)
| | | | - E U Suárez
- Hematology, Fundación Jiménez Díaz University Hospital, Madrid, ESP
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2
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Cortes-Santiago N, Deutsch G, Patel KR, Silva-Carmona M, Henderson C, Sartain SE, Bhar S, Pogoriler J. The Pathology of Pulmonary Disease After Pediatric Hematopoietic Stem Cell Transplantation. Am J Surg Pathol 2024; 48:1201-1214. [PMID: 39072367 DOI: 10.1097/pas.0000000000002267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
Abstract
Pulmonary complications continue to cause significant morbidity and mortality in posthematopoietic stem cell transplantation (HSCT) settings. The histopathology of pulmonary diseases in the post-HSCT context is poorly characterized, especially in the pediatric population. We sought to characterize the pathologic spectrum of pulmonary disease post-HSCT in a pediatric cohort. Fifty-six specimens, including 53 biopsy specimens, corresponding to 53 patients, were identified. Biopsy slides were reviewed and assigned to diagnostic categories (infectious, graft-versus-host disease, vasculopathy, indeterminate, and others) by consensus among 3 pediatric pulmonary pathologists, taking into consideration pathologic, clinical, radiologic, and laboratory findings. The most common diagnostic category was infection (n=20). Vasculopathy, mostly in the form of fibromyxoid intimal expansion, was very common in the entire cohort (n=26) and was the sole finding in a small subset of patients (n=5), with particularly poor outcomes. A subset of biopsies remained indeterminate (n=10), and the findings in this cohort were dominated by acute lung injury. The latter group had a poor prognosis, with a short biopsy-to-death interval. The overall clinicopathologic concordance was 40%, most commonly agreeing in the infectious category. Finally, wedge biopsies led to a change in management in 69% of cases versus 23% of limited procedures (i.e., core needle biopsies). Our results suggest that while infectious complications continue to be common post-HSCT, other findings such as vasculopathy and acute lung injury portend a particularly poor prognosis and should be actively sought and reported.
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Affiliation(s)
- Nahir Cortes-Santiago
- Department of Pediatrics, Section of Hematology, Baylor College of Medicine; Texas Children's Hospital, Houston, TX
| | - Gail Deutsch
- Department of Laboratory Medicine and Pathology, University of Washington School of Medicine; Department of Laboratories, Seattle Children's Hospital, Seattle, WA
| | - Kalyani R Patel
- Department of Pediatrics, Section of Hematology, Baylor College of Medicine; Texas Children's Hospital, Houston, TX
| | - Manuel Silva-Carmona
- Department of Pediatrics, Division of Pulmonary Medicine, Baylor College of Medicine; Texas Children's Hospital, Houston, TX
| | - Carolyn Henderson
- Department of Pediatric Pulmonology, Emory University, Children's Healthcare of Atlanta, Atlanta, GA
| | - Sarah E Sartain
- Department of Pediatrics, Section of Hematology, Baylor College of Medicine; Texas Children's Hospital, Houston, TX
| | - Saleh Bhar
- Department of Pediatrics, Divisions of Hematology-Oncology and Critical Care Medicine, Pediatric Bone Marrow Transplantation and Cellular Therapy, Baylor College of Medicine; Texas Children's Hospital, Houston, TX
| | - Jennifer Pogoriler
- Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA
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3
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Cortes-Santiago N, Patel KR, Wu H, Sartain SE, Bhar S, Silva-Carmona M, Pogoriler J. Pulmonary Histopathologic Findings in Pediatric Patients After Hematopoietic Stem Cell Transplantation: An Autopsy Study. Pediatr Dev Pathol 2023; 26:362-373. [PMID: 37165556 DOI: 10.1177/10935266231170101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
BACKGROUND Pathologic characterization of pulmonary complications following hematopoietic stem cell transplantation (HSCT) is limited. We describe lung findings in pediatric patients who died following HSCT and attempt to identify potential clinical associations. METHODS Pathology databases at Texas Children's Hospital and the Children's Hospital of Philadelphia were queried (2013-2018 CHOP and 2017-2018 TCH). Electronic medical records and slides were reviewed. RESULTS Among 29 patients, 19 received HSCT for hematologic malignancy, 8 for non-malignant hematologic disorders, and 2 for metastatic solid tumors. Twenty-five patients (86%) showed 1 or more patterns of acute and organizing lung injury. Sixty-two percent had microvascular sclerosis, with venous involvement noted in most cases and not correlating with clinical history of pulmonary hypertension, clinical transplant-associated thrombotic microangiopathy, irradiation, or graft-versus-host disease. Features suggestive of graft-versus-host-disease were uncommon: 6 patients had lymphocytic bronchiolitis, and only 2 patients had evidence of bronchiolitis obliterans (both clinically unexpected), both with a mismatched unrelated donor transplant. CONCLUSIONS Acute and subacute alveolar injury (diffuse alveolar damage or organizing pneumonia) is common in pediatric patients who died following HSCT and is difficult to assign to a specific etiology. Microvascular sclerosis was frequent and did not correlate with a single distinct clinical feature.
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Affiliation(s)
- Nahir Cortes-Santiago
- Department of Pathology and Immunology, Texas Children's Hospital, Houston, TX, USA
- Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA
| | - Kalyani R Patel
- Department of Pathology and Immunology, Texas Children's Hospital, Houston, TX, USA
- Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA
| | - Hao Wu
- Department of Pathology, Yale School of Medicine and Yale New Haven Hospital, New Haven, CT, USA
| | - Sarah E Sartain
- Department of Pediatrics, Section of Hematology/Oncology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA
| | - Saleh Bhar
- Department of Pediatrics, Section of Hematology/Oncology and Critical Care Medicine, Bone Marrow Transplantation, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA
| | - Manuel Silva-Carmona
- Department of Pediatrics, Section of Pulmonology, Texas Children's Hospital/Baylor College of Medicine, Houston, TX, USA
| | - Jennifer Pogoriler
- Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA
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4
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Tanaka TD, Ishizawar DC, Saito T, Yoshii A, Yoshimura M. Successful treatment of pulmonary hypertension following hematopoietic stem cell transplant with a single oral tadalafil: a case report. Pulm Circ 2021; 11:20458940211027791. [PMID: 34262695 PMCID: PMC8243114 DOI: 10.1177/20458940211027791] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 06/05/2021] [Indexed: 02/02/2023] Open
Abstract
A 46-year-old man who had undergone hematopoietic stem cell transplant twice
because of acute lymphoblastic leukemia with recurrence presented with dyspnea,
leading to a diagnosis of pulmonary arterial hypertension which was quickly and
effectively treated with the phosphodiesterase type 5 inhibitor tadalafil. To
our knowledge, pulmonary arterial hypertension related to hematologic
malignancies requiring hematopoietic stem cell transplant is rarely reported.
Importantly, the present case suggests that early diagnosis and treatment with a
pulmonary vasodilator, such as tadalafil, can greatly decrease pulmonary
vascular resistance in patients with severe pulmonary arterial hypertension
after hematopoietic stem cell transplant and can then improve other symptoms.
Accordingly, pulmonary vascular disease should be considered if respiratory
symptoms develop following hematopoietic stem cell transplant, because treatment
with pulmonary vasodilator may lead to significant improvement in pulmonary
arterial hypertension.
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Affiliation(s)
- Toshikazu D Tanaka
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - David C Ishizawar
- Division of Cardiology, Department of Medicine, Medical College of Wisconsin, Wauwatosa, WI, USA
| | - Takeshi Saito
- Division of Hematology and Oncology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Akira Yoshii
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Michihiro Yoshimura
- Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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5
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He Y, Xie M, Liu X. Dyspnoea and diffuse pulmonary nodules in a patient with pulmonary veno-occlusive disease: a case report and literature review. J Int Med Res 2021; 49:300060520986689. [PMID: 33478317 PMCID: PMC7841870 DOI: 10.1177/0300060520986689] [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] [Indexed: 11/15/2022] Open
Abstract
Pulmonary veno-occlusive disease (PVOD) is a rare type of pulmonary hypertension characterized by capillary damage or arterial pulmonary hypertension. Early lung transplantation is the only effective treatment for PVOD because of the lack of specificity in its clinical manifestations and its rapid progression and poor prognosis. A 28-year-old woman presented with exertional dyspnoea. A chest computed tomography scan revealed diffuse centrilobular ground glass opacities in both lungs, a ratio of the transverse diameter of the main pulmonary trunk to the ascending aorta of >1, and enlargement of the right ventricle and right atrium. A right atrial floating catheter test showed right ventricular pressure of 82/0/4 mmHg, mean pulmonary artery pressure of 83/34/53 mmHg, and pulmonary artery wedge pressure of 15/8/12 mmHg. A mutation was found in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) gene. Thus, the patient was diagnosed with PVOD and subsequently given standard bosentan treatment (62.5 mg twice a day). However, after 6 months of follow-up, there was no significant improvement in the pulmonary artery pressure or activity tolerance (6-minute walking test). Therefore, cardiopulmonary transplantation was performed. Early diagnosis and timely treatment of PVOD may improve the patient’s prognosis.
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Affiliation(s)
- Yuanzhou He
- Department of Respiratory Diseases, Tongji Hospital, Key Lab of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Xie
- Department of Respiratory Diseases, Tongji Hospital, Key Lab of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiansheng Liu
- Department of Respiratory Diseases, Tongji Hospital, Key Lab of Pulmonary Diseases of Health Ministry, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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6
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Levy M, Moshous D, Szezepanski I, Galmiche L, Castelle M, Lesage F, Dupic L, Neven B, Fischer A, Blanche S, Bonnet D. Pulmonary hypertension after bone marrow transplantation in children. Eur Respir J 2019; 54:13993003.00612-2019. [PMID: 31649064 DOI: 10.1183/13993003.00612-2019] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Accepted: 08/13/2019] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Pulmonary hypertension is a rare but important cause of mortality after haematopoietic stem cell transplantation (HSCT) in children. This complication is poorly characterised in the literature. We report here a series of children who developed pulmonary hypertension after HSCT. METHODS Between January 2008 and December 2015, we retrospectively analysed 366 children who underwent HSCT (age range 0.5-252 months; median 20.3 months). During the post-HSCT course, echocardiography scans motivated by respiratory symptoms identified 31 patients with elevated tricuspid regurgitation velocity (>2.8 m·s-1), confirmed when possible by right heart catheterisation (RHC). RESULTS 22 patients had confirmed pulmonary hypertension with mean±sd pulmonary arterial pressure 40.1±10 mmHg (range 28-62 mmHg) and pulmonary vascular resistance 17.3±9.2 Wood Units (range 8-42 Wood Units). Among the 13 responders at reactivity test, only one patient responded to calcium channel blockers. Seven patients (32%) died. 15 pulmonary hypertension patients were alive after a mean±sd follow-up of 6.5±2.3 years (range 2-10 years). All survivors could be weaned off pulmonary hypertension treatment after a median follow-up of 5 months (range 3-16). The delay between clinical symptoms and initiation of pulmonary hypertension therapy was significantly longer in patients who subsequently died (mean±sd 33.5±23 days; median 30 days) than in survivors (mean±sd 7±3 days) (p<0.001). CONCLUSION Pulmonary hypertension is a severe complication of HSCT with an underestimated incidence and high mortality. Aggressive and timely up-front combination therapy allowed normalisation of pulmonary pressure and improved survival.
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Affiliation(s)
- Marilyne Levy
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France .,M3C-Unité Médico-Chirurgicale de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.,UE3C-Unité d'Explorations Cardiologiques-Cardiopathies Congénitales, Paris, France
| | - Despina Moshous
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Pediatric Haematology-Immunology and Rheumatology Unit, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.,INSERM U1163 and Institut Imagine, Paris, France
| | - Isabelle Szezepanski
- M3C-Unité Médico-Chirurgicale de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
| | - Louise Galmiche
- Service d'Anatomopathologie, Hôpital Necker-Enfants Malades, Paris, France
| | - Martin Castelle
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Pediatric Haematology-Immunology and Rheumatology Unit, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
| | - Fabrice Lesage
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Pediatric Intensive Care Unit, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
| | - Laurent Dupic
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Pediatric Intensive Care Unit, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
| | - Bénédicte Neven
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Pediatric Haematology-Immunology and Rheumatology Unit, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.,INSERM U1163 and Institut Imagine, Paris, France
| | - Alain Fischer
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Pediatric Haematology-Immunology and Rheumatology Unit, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.,INSERM U1163 and Institut Imagine, Paris, France.,Collège de France, Paris, France
| | - Stéphane Blanche
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Pediatric Haematology-Immunology and Rheumatology Unit, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
| | - Damien Bonnet
- Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,M3C-Unité Médico-Chirurgicale de Cardiologie Pédiatrique, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
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7
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Price LC, Seckl MJ, Dorfmüller P, Wort SJ. Tumoral pulmonary hypertension. Eur Respir Rev 2019; 28:28/151/180065. [DOI: 10.1183/16000617.0065-2018] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Accepted: 11/23/2018] [Indexed: 12/15/2022] Open
Abstract
Tumoral pulmonary hypertension (PH) comprises a variety of subtypes in patients with a current or previous malignancy. Tumoral PH principally includes the tumour-related pulmonary microvascular conditions pulmonary tumour microembolism and pulmonary tumour thrombotic microangiopathy. These inter-related conditions are frequently found inpost mortemspecimens but are notoriously difficult to diagnoseante mortem. The outlook for patients remains extremely poor although there is some emerging evidence that pulmonary vasodilators and anti-inflammatory approaches may improve survival. Tumoral PH also includes pulmonary macroembolism and tumours that involve the proximal pulmonary vasculature, such as angiosarcoma; both may mimic pulmonary embolism and chronic thromboembolic PH. Finally, tumoral PH may develop in response to treatments of an underlying malignancy. There is increasing interest in pulmonary arterial hypertension induced by tyrosine kinase inhibitors, such as dasatanib. In addition, radiotherapy and chemotherapeutic agents such as mitomycin-C can cause pulmonary veno-occlusive disease. Tumoral PH should be considered in any patient presenting with unexplained PH, especially if it is poorly responsive to standard approaches or there is a history of malignancy. This article will describe subtypes of tumoral PH, their pathophysiology, investigation and management options in turn.
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8
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Duncan CN, Talano JAM, McArthur JA. Acute Respiratory Failure and Management. CRITICAL CARE OF THE PEDIATRIC IMMUNOCOMPROMISED HEMATOLOGY/ONCOLOGY PATIENT 2019. [PMCID: PMC7123688 DOI: 10.1007/978-3-030-01322-6_11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Acute respiratory failure is a common reason for admission to the pediatric intensive care unit in oncology patients. Acute respiratory complications are also common after pediatric hematopoietic stem cell transplant (HSCT), accounting for a high proportion of HSCT-related morbidity and mortality. Evaluation of these patients requires a thorough workup that includes identification and treatment of infectious etiologies, and treatment for noninfectious causes once infectious causes are ruled out. These patients should be closely monitored for development of pediatric acute respiratory distress syndrome (PARDS) with early escalation of respiratory support. Patients undergoing a trial of noninvasive ventilation (NIV) should be continuously monitored to ensure they are responding. Prolonged delay of endotracheal intubation in patients who do not improve or worsen on NIV could worsen their outcome. Optimal treatment of immunocompromised patients with acute lung failure requires early and aggressive lung protective ventilation, prevention of fluid overload, and rapid diagnosis of underlying causes to facilitate prompt disease-directed therapy.
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Affiliation(s)
| | - Julie-An M. Talano
- Children’s Hospital of Wisconsin-Milwaukee, Medical College of Wisconsin, Milwaukee, WI USA
| | - Jennifer A. McArthur
- Department of Pediatric Medicine, St. Jude Children’s Research Hospital, Memphis, TN USA
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9
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Wieruszewski PM, Herasevich S, Gajic O, Yadav H. Respiratory failure in the hematopoietic stem cell transplant recipient. World J Crit Care Med 2018; 7:62-72. [PMID: 30370228 PMCID: PMC6201323 DOI: 10.5492/wjccm.v7.i5.62] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 09/04/2018] [Accepted: 10/10/2018] [Indexed: 02/06/2023] Open
Abstract
The number of patients receiving hematopoietic stem cell transplantation (HSCT) is rapidly rising worldwide. Despite substantial improvements in peri-transplant care, pulmonary complications resulting in respiratory failure remain a major contributor to morbidity and mortality in the post-transplant period, and represent a major barrier to the overall success of HSCT. Infectious complications include pneumonia due to bacteria, viruses, and fungi, and most commonly occur during neutropenia in the early post-transplant period. Non-infectious complications include idiopathic pneumonia syndrome, peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, pulmonary veno-occlusive disease, delayed pulmonary toxicity syndrome, cryptogenic organizing pneumonia, bronchiolitis obliterans syndrome, and post-transplant lymphoproliferative disorder. These complications have distinct clinical features and risk factors, occur at differing times following transplant, and contribute to morbidity and mortality.
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Affiliation(s)
- Patrick M Wieruszewski
- Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, United States
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
| | - Svetlana Herasevich
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States
| | - Ognjen Gajic
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
| | - Hemang Yadav
- Multidisciplinary Epidemiology and Translational Research in Intensive Care Group, Mayo Clinic, Rochester, MN 55905, United States
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, United States
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10
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Vande Vusse LK, Madtes DK. Early Onset Noninfectious Pulmonary Syndromes after Hematopoietic Cell Transplantation. Clin Chest Med 2017; 38:233-248. [PMID: 28477636 PMCID: PMC7126669 DOI: 10.1016/j.ccm.2016.12.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Lisa K Vande Vusse
- Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Mailstop D5-360, Seattle, WA 98109, USA; Division of Pulmonary and Critical Care Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.
| | - David K Madtes
- Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Mailstop D5-360, Seattle, WA 98109, USA
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11
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Zinter MS, Melton A, Sabnis AJ, Dvorak CC, Elicker BM, Nawaytou HM, Kameny RJ, Fineman JR. Pulmonary veno-occlusive disease in a pediatric hematopoietic stem cell transplant patient: a cautionary tale. Leuk Lymphoma 2017; 59:1494-1497. [PMID: 28958195 DOI: 10.1080/10428194.2017.1382697] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Affiliation(s)
- M S Zinter
- a Benioff Children's Hospital , University of California , San Francisco , CA , USA.,b Department of Pediatrics, Division of Critical Care Medicine , University of California , San Francisco , CA , USA
| | - A Melton
- a Benioff Children's Hospital , University of California , San Francisco , CA , USA.,c Department of Pediatrics, Division of Allergy, Immunology, and Blood and Marrow Transplantation , University of California , San Francisco , CA , USA
| | - A J Sabnis
- a Benioff Children's Hospital , University of California , San Francisco , CA , USA.,d Department of Pediatrics, Division of Hematology and Oncology , University of California , San Francisco , CA , USA
| | - C C Dvorak
- a Benioff Children's Hospital , University of California , San Francisco , CA , USA.,c Department of Pediatrics, Division of Allergy, Immunology, and Blood and Marrow Transplantation , University of California , San Francisco , CA , USA
| | - B M Elicker
- e Department of Radiology , University of California , San Francisco , CA , USA
| | - H M Nawaytou
- a Benioff Children's Hospital , University of California , San Francisco , CA , USA.,f Department of Pediatrics, Division of Cardiology , University of California , San Francisco , CA , USA
| | - R J Kameny
- a Benioff Children's Hospital , University of California , San Francisco , CA , USA.,b Department of Pediatrics, Division of Critical Care Medicine , University of California , San Francisco , CA , USA
| | - J R Fineman
- a Benioff Children's Hospital , University of California , San Francisco , CA , USA.,b Department of Pediatrics, Division of Critical Care Medicine , University of California , San Francisco , CA , USA
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12
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Gazourian L, Spring L, Meserve E, Hwang D, Diaz AA, Ash SY, Ho VT, Sholl LM, Washko GR. Pulmonary Clinicopathological Correlation after Allogeneic Hematopoietic Stem Cell Transplantation: An Autopsy Series. Biol Blood Marrow Transplant 2017; 23:1767-1772. [PMID: 28668489 DOI: 10.1016/j.bbmt.2017.06.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Accepted: 06/16/2017] [Indexed: 01/24/2023]
Abstract
Pulmonary complications are a significant cause of morbidity, mortality, and resource utilization after hematopoietic stem cell transplantation (HSCT). The objective of this study was to compare antemortem clinical suspicion of pulmonary complications and postmortem findings in a modern HSCT cohort. All patients who underwent allogeneic HSCT at our institution (n = 1854) between January 1, 2000 and June 30, 2010 were reviewed and patients who died of any cause greater than 1 year after HSCT and had an unrestricted autopsy available for analysis were included. Presence of pulmonary graft-versus-host disease (GVHD) was assessed by a pathologist blinded to the autopsy report, as previously described by Yousem (1995). A total of 35 (1.9%) patients had autopsies available for review. Airway disease, vascular disease, and interstitial disease were all clinically under-recognized compared with the pathological findings on autopsy. Varying degrees of pathological changes were detected, including 10 (28.6%) patients having bronchiolitis obliterans (BO) and 12 (34.3%) patients having pulmonary veno-occlusive disease (PVOD). Pulmonary manifestations of chronic GVHD, particularly BO and PVOD, were clinically under-recognized in our cohort. Our results suggest that PVOD, which has traditionally been considered a rare complication, may be clinically and histologically under-recognized.
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Affiliation(s)
- Lee Gazourian
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Lahey Hospital and Medical Center, Burlington, Massachusetts.
| | - Laura Spring
- Department of Medical Oncology, Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Emily Meserve
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
| | - David Hwang
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Alejandro A Diaz
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Samuel Y Ash
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Vincent T Ho
- Department of Medical Oncology, Division of Hematologic Malignancies, Dana Farber Cancer Institute, Boston, Massachusetts
| | - Lynette M Sholl
- Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts
| | - George R Washko
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts
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13
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Abstract
OPINION STATEMENT Pulmonary hypertension is caused by cancer and its therapeutic agents including chemotherapy, radiotherapy, and even the targeted therapies. Ironically, some of the cancer therapies that cause one type of pulmonary hypertension (PH) could potentially be employed in the treatment of another PH type. Greater awareness on the role of cancer therapeutic agents in causing PH is required. Conversely, since PH is mostly incurable, the potential role of some of these cancer therapeutic agents in the cure of PH should be recognized. In short, the relationship between cancer, cancer therapy, and PH is an interesting one requiring further attention, education, and research.
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14
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Nikolic I, Yu PB. The Role of Bone Marrow-derived Cells in Pulmonary Arterial Hypertension. What Lies Beneath? Am J Respir Crit Care Med 2016; 193:822-4. [PMID: 27082534 DOI: 10.1164/rccm.201511-2293ed] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Ivana Nikolic
- 1 Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston, Massachusetts
| | - Paul B Yu
- 1 Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston, Massachusetts
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15
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Montani D, Lau EM, Dorfmüller P, Girerd B, Jaïs X, Savale L, Perros F, Nossent E, Garcia G, Parent F, Fadel E, Soubrier F, Sitbon O, Simonneau G, Humbert M. Pulmonary veno-occlusive disease. Eur Respir J 2016; 47:1518-34. [DOI: 10.1183/13993003.00026-2016] [Citation(s) in RCA: 155] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 02/04/2016] [Indexed: 12/11/2022]
Abstract
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterised by preferential remodelling of the pulmonary venules. In the current PH classification, PVOD and pulmonary capillary haemangiomatosis (PCH) are considered to be a common entity and represent varied expressions of the same disease. The recent discovery of biallelic mutations in the EIF2AK4 gene as the cause of heritable PVOD/PCH represents a major milestone in our understanding of the molecular pathogenesis of PVOD. Although PVOD and pulmonary arterial hypertension (PAH) share a similar clinical presentation, with features of severe precapillary PH, it is important to differentiate these two conditions as PVOD carries a worse prognosis and life-threatening pulmonary oedema may occur following the initiation of PAH therapy. An accurate diagnosis of PVOD based on noninvasive investigations is possible utilising oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest. No evidence-based medical therapy exists for PVOD at present and lung transplantation remains the preferred definitive therapy for eligible patients.
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16
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Ljungman P, Snydman D, Boeckh M. Pneumonia After Hematopoietic Stem Cell Transplantation. TRANSPLANT INFECTIONS 2016. [PMCID: PMC7153442 DOI: 10.1007/978-3-319-28797-3_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Pneumonia is the main cause of morbidity and mortality after hematopoietic stem cell transplantation. Two thirds of pneumonias observed after both autologous and allogeneic stem cell transplantations are of infectious origin, and coinfections are frequent. One third is due to noninfectious process, such as alveolar hemorrhage, alveolar proteinosis, or alloimmune pulmonary complications such as bronchiolitis obliterans or idiopathic interstitial pneumonitis. Most of these noninfectious complications may require treatment with corticosteroids which may be deleterious in infection. On the other hand, these complications either mimic or may be complicated with infections. Therefore, a precise diagnosis of pneumonia is of crucial importance to decide of the optimal treatment. CT scan is the best procedure for imaging of the lung. Although several indirect biomarkers, such as serum or plasma galactomannan or (1-3) β(beta)-G-glucan, can help in the etiological diagnosis, only direct invasive investigations provide the best chance to identify the cause(s) of pneumonia. Bronchoalveolar lavage (BAL) under fiberoptic bronchoscopy is the procedure of choice to identify the cause of pulmonary infection. It is safe and reproducible, and its diagnostic yield is around 50 % if the BAL fluid is processed at the laboratory according to a prespecified protocol established between the transplanter, the infectious diseases’ specialist, the pneumologist, and the laboratory, allowing the identification of the most likely hypotheses. Transbronchial biopsy does not provide significant additional information to BAL in most cases and more often complicates with bleeding and pneumothorax. In case of a noncontributory BAL, the decision to proceed to a second BAL, a transthoracic biopsy, or a surgical biopsy should be cautiously weighted in a multidisciplinary approach in regard to the benefits and risks of invasive procedures versus empirical treatment.
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Affiliation(s)
- Per Ljungman
- Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - David Snydman
- Tufts University School of Medicine Tufts Medical Center, Boston, Massachusetts USA
| | - Michael Boeckh
- University of Washington Fred Hutchinson Cancer Research Center, Seattle, Washington USA
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17
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Hematopoietic Stem Cell Transplantation. PATHOLOGY OF TRANSPLANTATION 2016. [PMCID: PMC7124099 DOI: 10.1007/978-3-319-29683-8_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
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18
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Elbahlawan L, Srinivasan A, Morrison RR. A Critical Care and Transplantation-Based Approach to Acute Respiratory Failure after Hematopoietic Stem Cell Transplantation in Children. Biol Blood Marrow Transplant 2015; 22:617-626. [PMID: 26409244 PMCID: PMC5033513 DOI: 10.1016/j.bbmt.2015.09.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 09/16/2015] [Indexed: 12/11/2022]
Abstract
Acute respiratory failure contributes significantly to nonrelapse mortality after allogeneic hematopoietic stem cell transplantation. Although there is a trend of improved survival over time, mortality remains unacceptably high. An understanding of the pathophysiology of early respiratory failure, opportunities for targeted therapy, assessment of the patient at risk, optimal use of noninvasive positive pressure ventilation, strategies to improve alveolar recruitment, appropriate fluid management, care of the patient with chronic lung disease, and importantly, a team approach between critical care and transplantation services may improve outcomes.
Outcomes from acute respiratory failure after hematopoietic stem cell transplantation remain unacceptably high. The review focuses on strategies to improve these outcomes.
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Affiliation(s)
- Lama Elbahlawan
- Department of Pediatric Medicine, Division of Critical Care, St. Jude Children's Research Hospital, Memphis, Tennessee.,Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee
| | - Ashok Srinivasan
- Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.,Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee
| | - R Ray Morrison
- Department of Pediatric Medicine, Division of Critical Care, St. Jude Children's Research Hospital, Memphis, Tennessee.,Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee
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19
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Ranchoux B, Günther S, Quarck R, Chaumais MC, Dorfmüller P, Antigny F, Dumas SJ, Raymond N, Lau E, Savale L, Jaïs X, Sitbon O, Simonneau G, Stenmark K, Cohen-Kaminsky S, Humbert M, Montani D, Perros F. Chemotherapy-induced pulmonary hypertension: role of alkylating agents. THE AMERICAN JOURNAL OF PATHOLOGY 2014; 185:356-71. [PMID: 25497573 DOI: 10.1016/j.ajpath.2014.10.021] [Citation(s) in RCA: 132] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Revised: 10/06/2014] [Accepted: 10/14/2014] [Indexed: 01/16/2023]
Abstract
Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents.
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Affiliation(s)
- Benoît Ranchoux
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France
| | - Sven Günther
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Assistance Publique des Hôpitaux de Paris (AP-HP), the Reference Center for Severe Pulmonary Hypertension, Pneumology and Respiratory Intensive Care Service, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France
| | - Rozenn Quarck
- Respiratory Division, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium
| | - Marie-Camille Chaumais
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; AP-HP, Pharmacy Service, Département Hospitalo-Universitaire Thorax Innovation, Hôpital Antoine Béclère, Clamart, France
| | - Peter Dorfmüller
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Pathology Service, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France
| | - Fabrice Antigny
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France
| | - Sébastien J Dumas
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France
| | - Nicolas Raymond
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Pathology Service, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France
| | - Edmund Lau
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Assistance Publique des Hôpitaux de Paris (AP-HP), the Reference Center for Severe Pulmonary Hypertension, Pneumology and Respiratory Intensive Care Service, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France
| | - Laurent Savale
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Assistance Publique des Hôpitaux de Paris (AP-HP), the Reference Center for Severe Pulmonary Hypertension, Pneumology and Respiratory Intensive Care Service, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France
| | - Xavier Jaïs
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Assistance Publique des Hôpitaux de Paris (AP-HP), the Reference Center for Severe Pulmonary Hypertension, Pneumology and Respiratory Intensive Care Service, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France
| | - Olivier Sitbon
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Assistance Publique des Hôpitaux de Paris (AP-HP), the Reference Center for Severe Pulmonary Hypertension, Pneumology and Respiratory Intensive Care Service, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France
| | - Gérald Simonneau
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Assistance Publique des Hôpitaux de Paris (AP-HP), the Reference Center for Severe Pulmonary Hypertension, Pneumology and Respiratory Intensive Care Service, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France
| | - Kurt Stenmark
- Department of Pediatrics, University of Colorado at Denver, Aurora, Colorado
| | - Sylvia Cohen-Kaminsky
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France
| | - Marc Humbert
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Assistance Publique des Hôpitaux de Paris (AP-HP), the Reference Center for Severe Pulmonary Hypertension, Pneumology and Respiratory Intensive Care Service, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France
| | - David Montani
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France; Assistance Publique des Hôpitaux de Paris (AP-HP), the Reference Center for Severe Pulmonary Hypertension, Pneumology and Respiratory Intensive Care Service, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France
| | - Frédéric Perros
- Faculty of Medicine, Université Paris-Sud, Faculté de Médecine, Hôpital de Bicêtre, Le Kremlin-Bicêtre, Paris, France; INSERM U999, Pulmonary Arterial Hypertension: Pathophysiology and Therapeutic Innovation, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, Paris, France.
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20
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Dai Z, Matsui Y. Pulmonary veno-occlusive disease: an 80-year-old mystery. ACTA ACUST UNITED AC 2014; 88:148-57. [PMID: 24853728 DOI: 10.1159/000359973] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Accepted: 01/20/2014] [Indexed: 11/19/2022]
Abstract
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension which occurs in 0.1-0.2 people per million. Its etiology is still poorly understood but is related to several risk factors. The histopathology of PVOD is characterized by intimal fibrosis narrowing or the occlusion of small pulmonary veins or venules. A definitive diagnosis requires a surgical biopsy, which is a risky procedure. Thus, the diagnosis must be based on high clinical suspicion and the results of various diagnostic tests, mainly high-resolution computed tomography, pulmonary function tests, bronchoalveolar lavage, and right heart catheterization. The definitive treatment is limited to lung transplantation. Several pulmonary arterial hypertension-specific agents may cause pulmonary edema in PVOD. However, the cautious use of such medications in selected patients, and surgical or mechanical supports, may successfully bridge patients to transplantation. Given the scant knowledge regarding this entity, future studies with a focus on elucidating the etiology and establishing the optimal treatment are required, as is further development in diagnosis.
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Affiliation(s)
- Zhehao Dai
- Tohoku University School of Medicine, Sendai, Japan
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21
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Peña E, Souza CA, Escuissato DL, Gomes MM, Allan D, Tay J, Dennie CJ. Noninfectious Pulmonary Complications after Hematopoietic Stem Cell Transplantation: Practical Approach to Imaging Diagnosis. Radiographics 2014; 34:663-83. [DOI: 10.1148/rg.343135080] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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22
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Huertas A, Girerd B, Dorfmuller P, O’Callaghan D, Humbert M, Montani D. Pulmonary veno-occlusive disease: advances in clinical management and treatments. Expert Rev Respir Med 2014; 5:217-29; quiz 230-1. [DOI: 10.1586/ers.11.15] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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23
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Pulmonary hypertension after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19:1546-56. [PMID: 23891748 DOI: 10.1016/j.bbmt.2013.07.017] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Accepted: 07/16/2013] [Indexed: 12/17/2022]
Abstract
Pulmonary hypertension (PH) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Given its nonspecific clinical presentation, it is likely that this clinical entity is underdiagnosed after HSCT. Data describing the incidence, risk factors, and etiology of PH in HSCT recipients are minimal. Physicians caring for HSCT recipients should be aware of this severe post-transplant complication because timely diagnosis and treatment may allow improved clinical outcomes. We summarize the pathophysiology, clinical presentation, diagnosis, and management of PH in HSCT recipients.
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24
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Miller CR. Pulmonary veno-occlusive disease: a misnomer? Pediatr Radiol 2012; 42:647-52; quiz 773-4. [PMID: 22311592 DOI: 10.1007/s00247-012-2350-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2011] [Revised: 11/23/2011] [Accepted: 01/06/2012] [Indexed: 10/14/2022]
Abstract
Pulmonary veno-occlusive disease (PVOD) is a rare entity with non-specific signs and symptoms and is nearly always associated with a dismal prognosis. This review will first consider pulmonary hypertension in general and then will focus on PVOD specifically with particular attention to the pathophysiology of the disease. Classically PVOD is described as a disease primarily involving obstructed venules, with the arterial side of the circulation involved to a lesser degree. This article discusses the demographics of affected individuals; the ways in which an accurate diagnosis can be made, including imaging features; predisposing diseases and associated disorders; and potential treatment.
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Affiliation(s)
- Cindy R Miller
- Department of Radiology, Yale University School of Medicine, 20 York St, CB-363G, New Haven, CT 06504, USA.
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25
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Hosokawa K, Yamazaki H, Nishitsuji M, Kobayashi S, Takami A, Fujimura M, Nakao S. Pulmonary veno-occlusive disease following reduced-intensity allogeneic bone marrow transplantation for acute myeloid leukemia. Intern Med 2012; 51:195-8. [PMID: 22246490 DOI: 10.2169/internalmedicine.51.6302] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
We report a case of pulmonary veno-occlusive disease (PVOD) following allogeneic bone marrow transplantation (BMT) for the treatment of acute myeloid leukemia (AML) from an HLA mismatched mother using a reduced-intensity conditioning (RIC) regimen including gemtuzumab ozogamicin. The patient was a 21-year-old male who complained of dyspnea with hypoxemia followed by loss of consciousness. The abnormalities in chest CT and echocardiography were compatible with a diagnosis of PVOD. Treatment with 1 mg/kg of oral prednisolone resolved dyspnea and hypoxemia within a few days, and chest CT abnormalities disappeared in a week. This report is the first to describe PVOD following RIC stem cell transplantation.
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Affiliation(s)
- Kohei Hosokawa
- Kanazawa University Graduate School of Medical Science, Japan.
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26
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Panoskaltsis-Mortari A, Griese M, Madtes DK, Belperio JA, Haddad IY, Folz RJ, Cooke KR. An official American Thoracic Society research statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome. Am J Respir Crit Care Med 2011; 183:1262-79. [PMID: 21531955 DOI: 10.1164/rccm.2007-413st] [Citation(s) in RCA: 211] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
RATIONALE Acute lung dysfunction of noninfectious etiology, known as idiopathic pneumonia syndrome (IPS), is a severe complication following hematopoietic stem cell transplantation (HSCT). Several mouse models have been recently developed to determine the underlying causes of IPS. A cohesive interpretation of experimental data and their relationship to the findings of clinical research studies in humans is needed to better understand the basis for current and future clinical trials for the prevention/treatment of IPS. OBJECTIVES Our goal was to perform a comprehensive review of the preclinical (i.e., murine models) and clinical research on IPS. METHODS An ATS committee performed PubMed and OVID searches for published, peer-reviewed articles using the keywords "idiopathic pneumonia syndrome" or "lung injury" or "pulmonary complications" AND "bone marrow transplant" or "hematopoietic stem cell transplant." No specific inclusion or exclusion criteria were determined a priori for this review. MEASUREMENTS AND MAIN RESULTS Experimental models that reproduce the various patterns of lung injury observed after HSCT have identified that both soluble and cellular inflammatory mediators contribute to the inflammation engendered during the development of IPS. To date, 10 preclinical murine models of the IPS spectrum have been established using various donor and host strain combinations used to study graft-versus-host disease (GVHD). This, as well as the demonstrated T cell dependency of IPS development in these models, supports the concept that the lung is a target of immune-mediated attack after HSCT. The most developed therapeutic strategy for IPS involves blocking TNF signaling with etanercept, which is currently being evaluated in clinical trials. CONCLUSIONS IPS remains a frequently fatal complication that limits the broader use of allogeneic HSCT as a successful treatment modality. Faced with the clinical syndrome of IPS, one can categorize the disease entity with the appropriate tools, although cases of unclassifiable IPS will remain. Significant research efforts have resulted in a paradigm shift away from identifying noninfectious lung injury after HSCT solely as an idiopathic clinical syndrome and toward understanding IPS as a process involving aspects of both the adaptive and the innate immune response. Importantly, new laboratory insights are currently being translated to the clinic and will likely prove important to the development of future strategies to prevent or treat this serious disorder.
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27
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Azoulay E. What Has Been Learned from Postmortem Studies? PULMONARY INVOLVEMENT IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES 2011. [PMCID: PMC7123032 DOI: 10.1007/978-3-642-15742-4_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Infectious and noninfectious pulmonary diseases are commonly found on postmortem autopsy studies in patients with hematological malignancy. Despite the technological advances in diagnostic testing and imaging modalities, obtaining an accurate clinical diagnosis remains difficult and often not possible until autopsy. Major diagnostic discrepancies between clinical premortem diagnoses and postmortem autopsy findings have been reported in these patients. The most common missed diagnoses are due to opportunistic infections and cardiopulmonary complications. These findings underscore the importance of enhanced surveillance, monitoring and treatment of infections and cardiopulmonary disorders in these patients. Autopsies remain important in determining an accurate cause of death and for improved understanding of diagnostic deficiencies, as well as for medical education and quality assurance.
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Affiliation(s)
- Elie Azoulay
- Service de Réanimation Médicale, Hôpital Saint Louis, Avenue Claude Vellefaux 1, Paris, 75010 France
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28
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Gutman JA, Allen CT, Madtes DK, Schramm J, Delaney C. Pulmonary veno-occlusive disease following reduced-intensity cord blood transplantation. Bone Marrow Transplant 2008; 42:559-61. [DOI: 10.1038/bmt.2008.210] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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29
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Yoshihara S, Yanik G, Cooke KR, Mineishi S. Bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans organizing pneumonia (BOOP), and other late-onset noninfectious pulmonary complications following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2008; 13:749-59. [PMID: 17580252 DOI: 10.1016/j.bbmt.2007.05.001] [Citation(s) in RCA: 106] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2007] [Accepted: 05/01/2007] [Indexed: 12/19/2022]
Abstract
Pulmonary dysfunction is a significant complication following allogeneic hematopoietic stem cell transplantation (HSCT), and is associated with significant morbidity and mortality. Effective antimicrobial prophylaxis and treatment strategies have increased the incidence of noninfectious lung injury, which can occur in the early posttransplant period or in the months and years that follow. Late-onset noninfectious pulmonary complications are frequently encountered, but diagnostic criteria and terminology for these disorders can be confusing and therapeutic approaches are suboptimal. As a consequence, inaccurate diagnosis of these conditions may hamper the appropriate data collection, enrollment into clinical trials, and appropriate patient care. The purpose of this review is to clarify the pathogenesis and diagnostic criteria of representative conditions, such as bronchiolitis obliterans syndrome and bronchiolitis obliterans organizing pneumonia, and to discuss the appropriate diagnostic strategies and treatment options.
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Affiliation(s)
- Satoshi Yoshihara
- Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
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30
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Pulmonary veno-occlusive disease following hematopoietic stem cell transplantation: a rare model of endothelial dysfunction. Bone Marrow Transplant 2008; 41:677-86. [PMID: 18223697 DOI: 10.1038/sj.bmt.1705990] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Veno-occlusive disease is among the most serious complications following hematopoietic stem cell transplantation. While hepatic veno-occlusive disease occurs more commonly, the pulmonary variant remains quite rare and often goes unrecognized antemortem. Endothelial damage may represent the pathophysiologic foundation of these clinical syndromes. Recent advances in the treatment of hepatic veno-occlusive disease may have application to its pulmonary counterpart.
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31
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Gower WA, Collaco JM, Mogayzel PJ. Pulmonary dysfunction in pediatric hematopoietic stem cell transplant patients: non-infectious and long-term complications. Pediatr Blood Cancer 2007; 49:225-33. [PMID: 17029245 DOI: 10.1002/pbc.21060] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Pulmonary complications are among the most frequently encountered sequelae of pediatric hematopoietic stem cell transplantation (HSCT). Non-infectious complications are becoming increasingly more common in this unique population. This review addresses the diagnosis and management of non-infectious manifestations of lung disease in pediatric HSCT patients and briefly discusses the long-term pulmonary function of childhood HSCT survivors.
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Affiliation(s)
- W Adam Gower
- Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-2533, USA
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Cordonnier C, Pautas C, Kuentz M, Maitre B, Maury S. Complications pulmonaires précoces des allogreffes de cellules souches hématopoïétiques. Rev Mal Respir 2007; 24:523-34. [PMID: 17468708 DOI: 10.1016/s0761-8425(07)91574-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
INTRODUCTION Pneumonia is one of the main causes of mortality following allogenic stem cell transplantation, especially in the first months after the transplant has been performed. STATE OF THE ART Pneumonia is the most common infection occurring after transplant and the infection with the highest mortality. Following the classical, myeloablative approach to transplant, two thirds of the pneumonias that occur are of infectious origin. Their causes roughly follow the timing of the immune reconstitution, and may depend on the type of transplant, the match between donor and recipient, and, overall, the occurrence of graft-versus-host disease. Most bacterial pneumonias occur during the initial neutropenic phase. The 2nd and 3rd month post transplant are mainly complicated by viral pneumonia, especially respiratory virus and adenovirus pneumonia in deeply immunosuppressed patients. Preemptive and prophylactic strategies have considerably reduced the incidence of cytomegalovirus pneumonia. Pneumonia due to encapsulated bacteria, such as Haemophilus influenzae and Streptococcus pneumoniae, usually considered to be late infections, may actually be observed from the second month post-transplant. PERSPECTIVES The increasing use of reduced-intensity conditioning regimens has modified the time course of the main adverse events following transplantation, including the timing of the infectious pneumonias. The pneumonias that are specifically related to allogenic transplant are idiopathic interstitial pneumonia, bronchiolitis obliterans, and bronchiolitis obliterans organizing pneumonia, which are all considered to be pulmonary manifestations of graft-versus-host disease, and treated as such. Prophylaxis for many of these infectious pneumonias (i.e., P jiroveci, S pneumoniae, toxoplasmosis) are well standardized. CONCLUSIONS Much remains to be done to decrease the incidence of pneumonia in these patients and to understand their mechanisms.
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Affiliation(s)
- C Cordonnier
- Service d'Hématologie Clinique, CHU Henri Mondor, Assistance Publique-Hôpitaux de Paris et Université Paris 12, France.
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Abstract
Paediatric haematopoietic cell transplantation has experienced significant advances in the last few decades. However, pulmonary complications are an important limitation to the efficacy of this intervention, contributing to post-transplantation morbidity and mortality. Such complications persist even in experienced centres and occur in adult and paediatric recipients. This review identifies the paediatric pulmonary complications that are commonly seen following haematopoietic cell transplantation and addresses both infectious and non-infectious aetiologies and their clinical manifestations, evaluation, and potential therapy. Ultimately, improvement in outcomes will require attention to immunosuppression as well as traditional diagnostic procedures and treatment. This article aims to review the current state of pulmonary complications post-transplantation, to examine the impact of our recent advances and changes in treatment, and to identify potential future therapies and hypothesise what role these might have on long-term survival.
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Abstract
Among the various deleterious effects of cancer chemotherapy, vascular toxicity is the least well recognized. This lack of recognition may be because the vasculotoxic phenomena are not unique to antineoplastic agents, can occur in patients without exposure to these agents, and the fact cancer itself may produce a hypercoagulable state. As a result, many vascular events either go unnoticed, are ignored, and/or are attributed to the underlying malignancy. Many antineoplastic therapies are associated with various vascular phenomena that range from simple phelibitis to lethal microangiopathy. Recognition of these events is important to minimize the morbidity and even prevent unnecessary deaths. Herein we review the vascular syndromes that have been reported in association with antineoplastic agents.
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Affiliation(s)
- Nasir Shahab
- Department of Medicine, Division of Hematology-Medical Oncology, Ellis Fischel Cancer Center, University of Missouri-Columbia, Columbia, MO 65203, USA.
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Abstract
Tens of thousands of patients undergo hematopoietic stem cell transplantation (HSCT) each year, mainly for hematologic disorders. In addition to the underlying diseases, the chemotherapy and radiation therapy that HSCT recipients receive can result in damage to multiple organ systems. Pulmonary complications develop in 30% to 60% of HSCT recipients. With the widespread use of prophylaxis for certain infections, the spectrum of pulmonary complications after HSCT has shifted from more infectious to noninfectious complications. This article reviews some of the noninfectious, chronic pulmonary complications.
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Affiliation(s)
- Bekele Afessa
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
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Shankar S, Choi JK, Dermody TS, Head DR, Bunin N, Iannone R. Pulmonary hypertension complicating bone marrow transplantation for idiopathic myelofibrosis. J Pediatr Hematol Oncol 2004; 26:393-7. [PMID: 15167356 DOI: 10.1097/00043426-200406000-00013] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Idiopathic myelofibrosis is a rare hematologic disorder that is occasionally associated with pulmonary hypertension and has been cured with bone marrow transplantation (BMT). Most cases occur in older adults, but children with similar clinical and pathologic findings have been described. The authors describe a critically ill male infant with idiopathic myelofibrosis and subtle findings suggestive of pulmonary hypertension who was treated with BMT after failing to respond to chemotherapy. After BMT, the patient's clinical course improved in all respects, but he ultimately died of progressive pulmonary hypertension.
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Affiliation(s)
- Sadhna Shankar
- Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6310, USA.
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37
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Kotloff RM, Ahya VN, Crawford SW. Pulmonary complications of solid organ and hematopoietic stem cell transplantation. Am J Respir Crit Care Med 2004; 170:22-48. [PMID: 15070821 DOI: 10.1164/rccm.200309-1322so] [Citation(s) in RCA: 231] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The ability to successfully transplant solid organs and hematopoietic stem cells represents one of the landmark medical achievements of the twentieth century. Solid organ transplantation has emerged as the standard of care for select patients with severe vital organ dysfunction and hematopoietic stem cell transplantation has become an important treatment option for patients with a wide spectrum of nonmalignant and malignant hematologic disorders, genetic disorders, and solid tumors. Although advances in surgical techniques, immunosuppressive management, and prophylaxis and treatment of infectious diseases have made long-term survival an achievable goal, transplant recipients remain at high risk for developing a myriad of serious and often life-threatening complications. Paramount among these are pulmonary complications, which arise as a consequence of the immunosuppressed status of the recipient as well as from such factors as the initial surgical insult of organ transplantation, the chemotherapy and radiation conditioning regimens that precede hematopoietic stem cell transplantation, and alloimmune mechanisms mediating host-versus-graft and graft-versus-host responses. As the population of transplant recipients continues to grow and as their care progressively shifts from the university hospital to the community setting, knowledge of the pulmonary complications of transplantation is increasingly germane to the contemporary practice of pulmonary medicine.
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Affiliation(s)
- Robert M Kotloff
- Section of Advanced Lung Disease and Lung Transplantation, Pulmonary, Allergy, and Critical Care Division, University of Pennsylvania Medical Center, 838 West Gates, 3400 Spruce Street, Philadelphia, PA 19027, USA.
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38
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Abstract
Current and past drug intake is essential in the evaluation of a patient who has DAH. Simple treatments, such as reversal of a coagulation defect or withdrawal of the drug, can reverse a life-threatening situation. DAO may result in DAH, and depending on the severity of the drug withdrawl, will not be adequate and corticosteroid therapy is recommended.
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Affiliation(s)
- Marvin I Schwarz
- Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, C272, Denver, CO 80262, USA.
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39
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Trobaugh-Lotrario AD, Greffe B, Deterding R, Deutsch G, Quinones R. Pulmonary veno-occlusive disease after autologous bone marrow transplant in a child with stage IV neuroblastoma: case report and literature review. J Pediatr Hematol Oncol 2003; 25:405-9. [PMID: 12759629 DOI: 10.1097/00043426-200305000-00011] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Pulmonary veno-occlusive disease (PVOD) is a rare, almost universally fatal complication of chemotherapy and bone marrow transplantation with few treatment options. A 19-month-old boy with stage 4 neuroblastoma with fatal PVOD following high-dose chemotherapy with autologous peripheral blood stem cell rescue is described here. A comprehensive literature review revealed 40 case reports of PVOD in oncology patients. Various therapeutic modalities were attempted, with four survivors. PVOD should be considered in patients with dyspnea and cardiomegaly. Less invasive diagnostic methods and more effective therapies are needed.
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Affiliation(s)
- Angela D Trobaugh-Lotrario
- Section of Pediatric Hematology/Oncology/Bone Marrow Transplantation, Children's Hospital of Denver, Colorado, USA
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40
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Seguchi M, Hirabayashi N, Fujii Y, Azuno Y, Fujita N, Takeda K, Sato Y, Nishimura M, Yamada K, Oka Y. Pulmonary hypertension associated with pulmonary occlusive vasculopathy after allogeneic bone marrow transplantation. Transplantation 2000; 69:177-9. [PMID: 10653399 DOI: 10.1097/00007890-200001150-00030] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Pulmonary vasculature abnormalities, including pulmonary veno-occlusive disease, have been demonstrated in marrow allograft recipients. However, it is often difficult to make a correct diagnosis of pulmonary lesions. METHODS An open lung biopsy was performed on a patient who developed severe pulmonary hypertension after bone marrow transplantation for T-cell lymphoma. RESULTS An open lung biopsy specimen demonstrated pulmonary arterial occlusion due to intimal fibrosis and veno-occlusion. The most striking alteration was partial to complete occlusion of the small arteries by fibrous proliferation of the intima. CONCLUSION High-dose preparative chemotherapy and radiation before transplantation are thought to have contributed to the development of vasculopathy in this patient, because arterial occlusion by intimal fibrosis and atypical veno-occlusion are often associated with lung injury due to chemoradiation. An open lung biopsy is essential for diagnosing pulmonary vascular disease presenting signs compatible with posttransplantation pulmonary hypertension.
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Affiliation(s)
- M Seguchi
- Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan
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41
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Williams LM, Fussell S, Veith RW, Nelson S, Mason CM. Pulmonary veno-occlusive disease in an adult following bone marrow transplantation. Case report and review of the literature. Chest 1996; 109:1388-91. [PMID: 8625695 DOI: 10.1378/chest.109.5.1388] [Citation(s) in RCA: 62] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Pulmonary veno-occlusive disease (PVOD) was diagnosed in an adult following chemotherapy and bone marrow transplantation (BMT) for acute lymphoblastic leukemia. A medical literature review showed only three previous reports of PVOD following BMT occurring in children but no prior cases in adults.
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Affiliation(s)
- L M Williams
- Department of Medicine, Louisiana State University School of Medicine, New Orleans, USA
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42
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Affiliation(s)
- R A Zager
- Fred Hutchinson Cancer Research Center, University of Washington, Seattle
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43
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Affiliation(s)
- R Breuer
- Institute of Pulmonology, Hadassah University Hospital, Hebrew University Medical School, Jerusalem, Israel
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44
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Kramer MR, Estenne M, Berkman N, Antoine M, de Francquen P, Lipski A, Jacobovitz D, Lafair J. Radiation-induced pulmonary veno-occlusive disease. Chest 1993; 104:1282-4. [PMID: 8404211 DOI: 10.1378/chest.104.4.1282] [Citation(s) in RCA: 53] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Late occurrence of radiation-induced pulmonary pneumonitis and fibrosis is well documented. We report an unusual case of radiation induced veno-occlusive disease (VOD) occurring six years following mantle irradiation for Hodgkin's lymphoma. The patient developed severe pulmonary hypertension and cor pulmonale. A left lung transplantation was performed successfully and pathologic examination of the explanted lung showed severe changes compatible with VOD. In the absence of exposure to alternate therapeutic or toxic agents that may cause VOD, it is likely that radiation caused damage to the venular endothelium and caused progressive obliteration of the pulmonary vessels. Review of the literature reveals only a few similar reports of VOD mostly following radiation for bone marrow transplantation. We conclude that previous irradiation (even several years earlier) should be considered as a possible cause of pulmonary VOD.
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Affiliation(s)
- M R Kramer
- Institute of Pulmonology, Hadassah University Hospital, Jerusalem, Israel
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45
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Bentur L, Cullinane C, Wilson P, Greenberg M, O'Brodovich H, Silver MM. Fatal pulmonary arterial occlusive vascular disease following chemotherapy in a 9-month-old infant. Hum Pathol 1991; 22:1295-8. [PMID: 1748437 DOI: 10.1016/0046-8177(91)90116-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Fatal pulmonary hypertension developed in an infant during the 7-month period in which he received, via a central venous catheter, combination chemotherapy for stage IV neuroblastoma as well as intermittent parenteral feeding. In a lung biopsy and at autopsy, small pulmonary arteries showed diffuse medial hypertrophy and peripheral muscularization, very extensive concentric intimal fibrosis, and focal eccentric fibrosis evolving from organizing thrombi. Pulmonary veins were normal. Hypothetically, chemotherapeutic drug therapy (possibly potentiated either by the parenteral nutrition or simply by the vehicular fluids causing volume loading of the pulmonary circulation) could cause occlusive pulmonary arterial disease by several mechanisms, but the association has not been described previously, although use of such drugs has been reported with pulmonary veno-occlusive disease.
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Affiliation(s)
- L Bentur
- Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada
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46
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Ettinger NA, Trulock EP. Pulmonary considerations of organ transplantation. Part 2. THE AMERICAN REVIEW OF RESPIRATORY DISEASE 1991; 144:213-23. [PMID: 2064131 DOI: 10.1164/ajrccm/144.1.213] [Citation(s) in RCA: 62] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- N A Ettinger
- Respiratory and Critical Care Division, Washington University School of Medicine, St. Louis, Missouri 63110
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47
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Gilroy RJ, Teague MW, Loyd JE. Pulmonary veno-occlusive disease. Fatal progression of pulmonary hypertension despite steroid-induced remission of interstitial pneumonitis. THE AMERICAN REVIEW OF RESPIRATORY DISEASE 1991; 143:1130-3. [PMID: 2024825 DOI: 10.1164/ajrccm/143.5_pt_1.1130] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
This report describes a 28-yr-old patient with pulmonary veno-occlusive disease (PVOD). She presented with pulmonary hypertension, hypoxemia, and interstitial pneumonitis. We report the discordance between the response of her hypoxemia and interstitial pneumonitis, which resolved with corticosteroid therapy, and her progressive pulmonary hypertension, which caused fatal right heart failure. This report emphasizes that the radiographic interstitial shadowing of PVOD may be caused by either (1) an inflammatory interstitial pneumonitis (which may be responsive to anti-inflammatory therapy) or (2) interstitial pulmonary edema, or both.
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Affiliation(s)
- R J Gilroy
- Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-2650
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48
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Marraro G, Uderzo C, Marchi P, Castagnini G, Vaj PL, Masera G. Acute respiratory failure and pulmonary thrombosis in leukemic children. Cancer 1991; 67:696-702. [PMID: 1985761 DOI: 10.1002/1097-0142(19910201)67:3<696::aid-cncr2820670328>3.0.co;2-v] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Acute respiratory failure (ARF) in an 11-year-old child with pre-T acute lymphoblastic leukemia (ALL) at the beginning of induction therapy was observed, connected with a pulmonary thrombosis and not with an infective origin. A systematic search for this pathology identified six other children with the same pulmonary complication, five of whom where in the early phase of acute nonlymphoblastic leukemia (ANLL) and one in induction therapy for ALL in marrow relapse. At the beginning of the symptomatology, all children presented severe hypoxia and hypercapnia, with no or minimal chest radiograph abnormalities and no clear hemodynamic involvement. In all patients the arteriography and nuclear imaging studies confirmed the diagnosis. The causes of the thrombi could be connected with neoplastic emboli after cell lysis and/or with the vascular damage resulting from antiblastic therapy. Intravenous urokinase treatment and respiratory assistance had been successfully carried out in six of seven children.
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Affiliation(s)
- G Marraro
- Anaesthesia and Intensive Care Department, L. Mandic Hospital, Merate (CO), Italy
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49
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Brückmann C, Lindner W, Roos R, Permanetter W, Haas RJ, Haworth SG, Belohradsky BH. Severe pulmonary vascular occlusive disease following bone marrow transplantation in Omenn syndrome. Eur J Pediatr 1991; 150:242-5. [PMID: 2029913 DOI: 10.1007/bf01955521] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
A 5-month-old infant presented with severe combined immunodeficiency disease, reticuloendotheliosis, and hypereosinophilia (Omenn syndrome) resulting in recurrent infections and endomyocardial disease. Bone marrow transplantation from an HLA-identical donor after chemotherapeutic conditioning led to both immunological and clinical recovery. Bone marrow transplantation, however, was followed by severe pulmonary occlusive disease. The patient gradually recovered while on increased inspiratory oxygen and the calcium channel blocker nifedipine.
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Affiliation(s)
- C Brückmann
- Universitäts-Kinderklinik München, Federal Republic of Germany
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50
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Palevsky HI, Pietra GG, Fishman AP. Pulmonary veno-occlusive disease and its response to vasodilator agents. THE AMERICAN REVIEW OF RESPIRATORY DISEASE 1990; 142:426-9. [PMID: 2382906 DOI: 10.1164/ajrccm/142.2.426] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Pulmonary veno-occlusive disease (PVOD) is an uncommon form of unexplained (primary) pulmonary hypertension (PPH) rarely diagnosed during life and generally associated with a progressively deteriorating course. We describe three patients with PVOD; in two of them, diagnosis was established by open lung biopsy. All three patients underwent right heart catheterization and acute vasodilator testing, and each responded favorably to at least one test agent. One patient did not receive chronic vasodilator therapy and died seven months after his initial evaluation. The other two patients were treated with chronic vasodilator therapy; one initially improved, but then experienced progressive right heart failure and died 23 months after the start of therapy, the third patient is alive and clinically improved 72 months after beginning vasodilator therapy. Details of the vasodilator studies, and the rationale for treating this uncommon disorder, are provided.
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Affiliation(s)
- H I Palevsky
- Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia
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