Pulmonary complications after autologous hematopoietic cell transplantation
- Robert J Kaner, MD
Robert J Kaner, MD
- Associate Professor of Clinical Medicine
- Weill Medical College of Cornell University
- Dana Zappetti, MD
Dana Zappetti, MD
- Assistant Professor of Medicine
- Weill Cornell Medical College
- Section Editors
- Talmadge E King, Jr, MD
Talmadge E King, Jr, MD
- Editor-in-Chief — Pulmonary and Critical Care Medicine
- Section Editor — Interstitial Lung Disease
- Dean, School of Medicine
- Vice Chancellor, Medical Affairs
- University of California San Francisco
- Robert S Negrin, MD
Robert S Negrin, MD
- Section Editor — Bone Marrow Transplantation
- Professor of Medicine
- Stanford University School of Medicine
Autologous hematopoietic cell transplantation is performed with increasing frequency, particularly as salvage therapy after high dose chemotherapy for recurrent lymphoma, leukemia, multiple myeloma, germ cell tumors, and neuroblastoma. A variety of pulmonary complications have been described with these procedures, occurring either early (within the first 30 days or pre-engraftment) or late (more than one month or post-engraftment) after transplantation. This distinction can guide the differential diagnosis and clinical evaluation of these disorders.
The term "hematopoietic cell transplantation" (HCT) will be used throughout this review as a general term to cover transplantation of progenitor cells from any source (eg, bone marrow, peripheral blood, umbilical cord blood). Otherwise, the source of such cells will be specified (eg, autologous peripheral blood progenitor cell transplantation). (See "Sources of hematopoietic stem cells".)
Significant pulmonary complications are a leading cause of morbidity and mortality following HCT . The pulmonary complications of autologous HCT will be reviewed here. The pulmonary complications of allogeneic HCT are discussed separately. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation".)
TECHNIQUE OF AUTOLOGOUS HCT
Autologous HCT refers to collection of hematopoietic progenitor cells from the patient prior to the administration of high dose chemotherapy designed to target an underlying malignancy, followed by reinfusion of these cells. In the past, autologous bone marrow was obtained from the patient by multiple iliac crest aspirations under general anesthesia. However, most transplant centers now exclusively utilize peripheral blood progenitor cells (PBPCs) mobilized by hematopoietic growth factor administration for autologous transplantation. The cells are collected by leukapheresis, avoiding the need for general anesthesia. (See "Sources of hematopoietic stem cells".)
COMPARISON WITH ALLOGENEIC HCT
The pulmonary complications of autologous HCT share many of the features associated with allogeneic HCT, but there are also important differences. (See "Pulmonary complications after allogeneic hematopoietic cell transplantation".)
- Afessa B, Abdulai RM, Kremers WK, et al. Risk factors and outcome of pulmonary complications after autologous hematopoietic stem cell transplant. Chest 2012; 141:442.
- Slavin MA, Meyers JD, Remington JS, Hackman RC. Toxoplasma gondii infection in marrow transplant recipients: a 20 year experience. Bone Marrow Transplant 1994; 13:549.
- Geissmann F, Derouin F, Marolleau JP, et al. Disseminated toxoplasmosis following autologous bone marrow transplantation. Clin Infect Dis 1994; 19:800.
- Patel NR, Lee PS, Kim JH, et al. The influence of diagnostic bronchoscopy on clinical outcomes comparing adult autologous and allogeneic bone marrow transplant patients. Chest 2005; 127:1388.
- Gilbert CR, Lerner A, Baram M, Awsare BK. Utility of flexible bronchoscopy in the evaluation of pulmonary infiltrates in the hematopoietic stem cell transplant population -- a single center fourteen year experience. Arch Bronconeumol 2013; 49:189.
- Jain P, Sandur S, Meli Y, et al. Role of flexible bronchoscopy in immunocompromised patients with lung infiltrates. Chest 2004; 125:712.
- Hayes-Jordan A, Benaim E, Richardson S, et al. Open lung biopsy in pediatric bone marrow transplant patients. J Pediatr Surg 2002; 37:446.
- 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.
- Todd K, Wiley F, Landaw E, et al. Survival outcome among 54 intubated pediatric bone marrow transplant patients. Crit Care Med 1994; 22:171.
- Bojko T, Notterman DA, Greenwald BM, et al. Acute hypoxemic respiratory failure in children following bone marrow transplantation: an outcome and pathologic study. Crit Care Med 1995; 23:755.
- Murdych T, Weisdorf DJ. Serious cardiac complications during bone marrow transplantation at the University of Minnesota, 1977-1997. Bone Marrow Transplant 2001; 28:283.
- Rapoport AP, Rowe JM, Packman CH, Ginsberg SJ. Cardiac arrest after autologous marrow infusion. Bone Marrow Transplant 1991; 7:401.
- Corso S, Vukelja SJ, Wiener D, Baker WJ. Diffuse alveolar hemorrhage following autologous bone marrow infusion. Bone Marrow Transplant 1993; 12:301.
- Maiolino A, Biasoli I, Lima J, et al. Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteria. Bone Marrow Transplant 2003; 31:393.
- Carreras E, Fernández-Avilés F, Silva L, et al. Engraftment syndrome after auto-SCT: analysis of diagnostic criteria and risk factors in a large series from a single center. Bone Marrow Transplant 2010; 45:1417.
- Dispenzieri A, Lacy MQ, Hayman SR, et al. Peripheral blood stem cell transplant for POEMS syndrome is associated with high rates of engraftment syndrome. Eur J Haematol 2008; 80:397.
- Capizzi SA, Kumar S, Huneke NE, et al. Peri-engraftment respiratory distress syndrome during autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 27:1299.
- Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 27:893.
- Schmid I, Stachel D, Pagel P, Albert MH. Incidence, predisposing factors, and outcome of engraftment syndrome in pediatric allogeneic stem cell transplant recipients. Biol Blood Marrow Transplant 2008; 14:438.
- Foncillas MA, Diaz MA, Sevilla J, et al. Engraftment syndrome emerges as the main cause of transplant-related mortality in pediatric patients receiving autologous peripheral blood progenitor cell transplantation. J Pediatr Hematol Oncol 2004; 26:492.
- Lopes da Silva R, Costa F, Ferreira G, de Sousa AB. Post-autologous hematopoietic SCT engraftment syndrome: a single center experience. Bone Marrow Transplant 2012; 47:456.
- Afessa B, Tefferi A, Litzow MR, Peters SG. Outcome of diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients. Am J Respir Crit Care Med 2002; 166:1364.
- Majhail NS, Parks K, Defor TE, Weisdorf DJ. Diffuse alveolar hemorrhage and infection-associated alveolar hemorrhage following hematopoietic stem cell transplantation: related and high-risk clinical syndromes. Biol Blood Marrow Transplant 2006; 12:1038.
- Robbins RA, Linder J, Stahl MG, et al. Diffuse alveolar hemorrhage in autologous bone marrow transplant recipients. Am J Med 1989; 87:511.
- Witte RJ, Gurney JW, Robbins RA, et al. Diffuse pulmonary alveolar hemorrhage after bone marrow transplantation: radiographic findings in 39 patients. AJR Am J Roentgenol 1991; 157:461.
- Cortese G, Nicali R, Placido R, et al. Radiological aspects of diffuse alveolar haemorrhage. Radiol Med 2008; 113:16.
- Afessa B, Tefferi A, Litzow MR, et al. Diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients. Am J Respir Crit Care Med 2002; 166:641.
- Jules-Elysee K, Stover DE, Yahalom J, et al. Pulmonary complications in lymphoma patients treated with high-dose therapy autologous bone marrow transplantation. Am Rev Respir Dis 1992; 146:485.
- Grimwade DJ, Chopra R, King A, et al. Detection and significance of pulmonary Hodgkin's disease at autologous bone marrow transplantation. Bone Marrow Transplant 1994; 13:173.
- Vaughan WP, Linder J, Robbins R, et al. Pulmonary surveillance using bronchoscopy and bronchoalveolar lavage during high-dose antineoplastic therapy. Chest 1991; 99:105.
- Gupta S, Jain A, Warneke CL, et al. Outcome of alveolar hemorrhage in hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2007; 40:71.
- Chao NJ, Duncan SR, Long GD, et al. Corticosteroid therapy for diffuse alveolar hemorrhage in autologous bone marrow transplant recipients. Ann Intern Med 1991; 114:145.
- Metcalf JP, Rennard SI, Reed EC, et al. Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation. University of Nebraska Medical Center Bone Marrow Transplant Group. Am J Med 1994; 96:327.
- Ip MS, Yuen KY, Chiu EK, et al. Pulmonary infections in bone marrow transplantation: the Hong Kong experience. Respiration 1995; 62:80.
- Pecego R, Hill R, Appelbaum FR, et al. Interstitial pneumonitis following autologous bone marrow transplantation. Transplantation 1986; 42:515.
- Carlson K, Bäcklund L, Smedmyr B, et al. Pulmonary function and complications subsequent to autologous bone marrow transplantation. Bone Marrow Transplant 1994; 14:805.
- Badier M, Guillot C, Delpierre S, et al. Pulmonary function changes 100 days and one year after bone marrow transplantation. Bone Marrow Transplant 1993; 12:457.
- Cerveri I, Zoia MC, Fulgoni P, et al. Late pulmonary sequelae after childhood bone marrow transplantation. Thorax 1999; 54:131.
- Arvidson J, Bratteby LE, Carlson K, et al. Pulmonary function after autologous bone marrow transplantation in children. Bone Marrow Transplant 1994; 14:117.
- Wilczynski SW, Erasmus JJ, Petros WP, et al. Delayed pulmonary toxicity syndrome following high-dose chemotherapy and bone marrow transplantation for breast cancer. Am J Respir Crit Care Med 1998; 157:565.
- Seiden MV, Elias A, Ayash L, et al. Pulmonary toxicity associated with high dose chemotherapy in the treatment of solid tumors with autologous marrow transplant: an analysis of four chemotherapy regimens. Bone Marrow Transplant 1992; 10:57.
- Panoskaltsis-Mortari A, Griese M, Madtes DK, et al. 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.
- Grañena A, Carreras E, Rozman C, et al. Interstitial pneumonitis after BMT: 15 years experience in a single institution. Bone Marrow Transplant 1993; 11:453.
- Clark JG, Hansen JA, Hertz MI, et al. NHLBI workshop summary. Idiopathic pneumonia syndrome after bone marrow transplantation. Am Rev Respir Dis 1993; 147:1601.
- Bilgrami SF, Metersky ML, McNally D, et al. Idiopathic pneumonia syndrome following myeloablative chemotherapy and autologous transplantation. Ann Pharmacother 2001; 35:196.
- Rubio C, Hill ME, Milan S, et al. Idiopathic pneumonia syndrome after high-dose chemotherapy for relapsed Hodgkin's disease. Br J Cancer 1997; 75:1044.
- Lane AA, Armand P, Feng Y, et al. Risk factors for development of pneumonitis after high-dose chemotherapy with cyclophosphamide, BCNU and etoposide followed by autologous stem cell transplant. Leuk Lymphoma 2012; 53:1130.
- Doran HM, Sheppard MN, Collins PW, et al. Pathology of the lung in leukaemia and lymphoma: a study of 87 autopsies. Histopathology 1991; 18:211.
- Paz HL, Crilley P, Patchefsky A, et al. Bronchiolitis obliterans after autologous bone marrow transplantation. Chest 1992; 101:775.
- Frankovich J, Donaldson SS, Lee Y, et al. High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin's disease: atopy predicts idiopathic diffuse lung injury syndromes. Biol Blood Marrow Transplant 2001; 7:49.
- Neier M, Jin Z, Kleinman C, et al. Pericardial effusion post-SCT in pediatric recipients with signs and/or symptoms of cardiac disease. Bone Marrow Transplant 2011; 46:529.
- Kansu E. Thrombosis in stem cell transplantation. Hematology 2012; 17 Suppl 1:S159.
- Bhatia S, Robison LL, Francisco L, et al. Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study. Blood 2005; 105:4215.
- Kalaycio M, Pohlman B, Kuczkowski E, et al. High-dose busulfan and the risk of pulmonary mortality after autologous stem cell transplant. Clin Transplant 2006; 20:783.
- Chien JW, Sullivan KM. Carbon monoxide diffusion capacity: how low can you go for hematopoietic cell transplantation eligibility? Biol Blood Marrow Transplant 2009; 15:447.
- Ho VT, Weller E, Lee SJ, et al. Prognostic factors for early severe pulmonary complications after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001; 7:223.
- TECHNIQUE OF AUTOLOGOUS HCT
- COMPARISON WITH ALLOGENEIC HCT
- APPROACH TO THE PATIENT WITH RESPIRATORY SYMPTOMS OR SIGNS
- EARLY COMPLICATIONS
- Pre-engraftment respiratory infections
- Pulmonary edema
- Engraftment syndrome and PERDS
- Diffuse alveolar hemorrhage
- LATE COMPLICATIONS
- Respiratory infections
- Abnormal pulmonary function tests
- Idiopathic pneumonia syndrome
- Toxicity from chemotherapy and/or radiotherapy
- Bronchiolitis obliterans
- Cardiac and pulmonary vascular
- PREDICTING COMPLICATIONS
- SUMMARY AND RECOMMENDATIONS