Malignancy after hematopoietic cell transplantation
- Robert S Negrin, MD
Robert S Negrin, MD
- Section Editor — Bone Marrow Transplantation
- Professor of Medicine
- Stanford University School of Medicine
The success of hematopoietic cell transplantation (HCT) has led to the unfortunate complication of secondary malignancies in patients who would otherwise be long-term survivors. Among the malignancies are solid tumors, acute leukemia, myelodysplastic syndromes, and post-transplant lymphoproliferative disease (PTLD). While the former occur late in the post-transplant course (>3 years post transplant), PTLD usually occurs in the first year after transplantation . (See "Epidemiology, clinical manifestations, and diagnosis of post-transplant lymphoproliferative disorders".)
The risk for development of secondary malignancies following HCT will be reviewed here. Other complications of HCT and the development of secondary malignancies following solid organ transplantation are discussed separately. (See "The approach to hematopoietic cell transplantation survivorship" and "Hematopoietic support after hematopoietic cell transplantation" and "Management of the hematopoietic cell transplant recipient in the immediate post-transplant period" and "Development of malignancy following solid organ transplantation".)
Patients treated with chemotherapy and/or radiotherapy followed by hematopoietic cell transplantation (HCT) have an increased risk of developing myelodysplastic syndrome, acute leukemia, post-transplant lymphoproliferative disease, and solid tumors when compared with the general population [2-11]. These cancers are expected to have a significant impact upon survival in this patient population. The relative risk of developing a malignancy following HCT has varied greatly among studies and is dependent upon a number of patient and treatment factors, including:
●Radiation dose and fields
●Chemotherapy agents and doses administered
- Lowe T, Bhatia S, Somlo G. Second malignancies after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2007; 13:1121.
- Bhatia S, Louie AD, Bhatia R, et al. Solid cancers after bone marrow transplantation. J Clin Oncol 2001; 19:464.
- Baker KS, DeFor TE, Burns LJ, et al. New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol 2003; 21:1352.
- Gallagher G, Forrest DL. Second solid cancers after allogeneic hematopoietic stem cell transplantation. Cancer 2007; 109:84.
- Majhail NS, Brazauskas R, Rizzo JD, et al. Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood 2011; 117:316.
- Curtis RE, Rowlings PA, Deeg HJ, et al. Solid cancers after bone marrow transplantation. N Engl J Med 1997; 336:897.
- Rizzo JD, Curtis RE, Socié G, et al. Solid cancers after allogeneic hematopoietic cell transplantation. Blood 2009; 113:1175.
- Kolb HJ, Socié G, Duell T, et al. Malignant neoplasms in long-term survivors of bone marrow transplantation. Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group. Ann Intern Med 1999; 131:738.
- Cohen A, Rovelli A, Merlo DF, et al. Risk for secondary thyroid carcinoma after hematopoietic stem-cell transplantation: an EBMT Late Effects Working Party Study. J Clin Oncol 2007; 25:2449.
- Tarella C, Passera R, Magni M, et al. Risk factors for the development of secondary malignancy after high-dose chemotherapy and autograft, with or without rituximab: a 20-year retrospective follow-up study in patients with lymphoma. J Clin Oncol 2011; 29:814.
- Danner-Koptik KE, Majhail NS, Brazauskas R, et al. Second malignancies after autologous hematopoietic cell transplantation in children. Bone Marrow Transplant 2013; 48:363.
- Forrest DL, Nevill TJ, Naiman SC, et al. Second malignancy following high-dose therapy and autologous stem cell transplantation: incidence and risk factor analysis. Bone Marrow Transplant 2003; 32:915.
- Leisenring W, Friedman DL, Flowers ME, et al. Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol 2006; 24:1119.
- Lishner M, Patterson B, Kandel R, et al. Cutaneous and mucosal neoplasms in bone marrow transplant recipients. Cancer 1990; 65:473.
- Curtis RE, Metayer C, Rizzo JD, et al. Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood 2005; 105:3802.
- Atsuta Y, Suzuki R, Yamashita T, et al. Continuing increased risk of oral/esophageal cancer after allogeneic hematopoietic stem cell transplantation in adults in association with chronic graft-versus-host disease. Ann Oncol 2014; 25:435.
- Janin A, Murata H, Leboeuf C, et al. Donor-derived oral squamous cell carcinoma after allogeneic bone marrow transplantation. Blood 2009; 113:1834.
- Friedman DL, Rovo A, Leisenring W, et al. Increased risk of breast cancer among survivors of allogeneic hematopoietic cell transplantation: a report from the FHCRC and the EBMT-Late Effect Working Party. Blood 2008; 111:939.
- Metayer C, Curtis RE, Vose J, et al. Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study. Blood 2003; 101:2015.
- Gustafsson B, Moell J, Leblanc K, et al. Donor cell-derived acute myeloid leukemia after second allogenic cord blood transplantation in a patient with Fanconi anemia. Pediatr Transplant 2012; 16:E241.
- Yamazaki R, Nakasone H, Wada H, et al. Recurrence of monoclonal gammopathy associated with donor-derived myelodysplastic syndrome after cord blood stem cell transplantation. Exp Hematol 2011; 39:1119.
- Alpár D. Recurrent disease or donor cell leukemia?: Brain teaser after allogeneic bone marrow transplantation. Chimerism 2011; 2:19.
- Nakamizo A, Akagi Y, Amano T, et al. Donor-derived adult T-cell leukaemia. Lancet 2011; 377:1124.
- Sala Torra O, Loeb KR. Donor cell-derived leukemia and myelodysplastic neoplasm: unique forms of leukemia. Am J Clin Pathol 2011; 135:501.
- Wiseman DH. Donor cell leukemia: a review. Biol Blood Marrow Transplant 2011; 17:771.
- Straathof KC, Savoldo B, Heslop HE, Rooney CM. Immunotherapy for post-transplant lymphoproliferative disease. Br J Haematol 2002; 118:728.
- Socié G, Henry-Amar M, Bacigalupo A, et al. Malignant tumors occurring after treatment of aplastic anemia. European Bone Marrow Transplantation-Severe Aplastic Anaemia Working Party. N Engl J Med 1993; 329:1152.
- Deeg HJ, Socié G, Schoch G, et al. Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Blood 1996; 87:386.
- Pedersen-Bjergaard J, Andersen MK, Christiansen DH. Therapy-related acute myeloid leukemia and myelodysplasia after high-dose chemotherapy and autologous stem cell transplantation. Blood 2000; 95:3273.
- Miller JS, Arthur DC, Litz CE, et al. Myelodysplastic syndrome after autologous bone marrow transplantation: an additional late complication of curative cancer therapy. Blood 1994; 83:3780.
- Stone RM, Neuberg D, Soiffer R, et al. Myelodysplastic syndrome as a late complication following autologous bone marrow transplantation for non-Hodgkin's lymphoma. J Clin Oncol 1994; 12:2535.
- Bhatia S, Ramsay NK, Steinbuch M, et al. Malignant neoplasms following bone marrow transplantation. Blood 1996; 87:3633.
- André M, Henry-Amar M, Blaise D, et al. Treatment-related deaths and second cancer risk after autologous stem-cell transplantation for Hodgkin's disease. Blood 1998; 92:1933.
- Armitage JO, Carbone PP, Connors JM, et al. Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients. J Clin Oncol 2003; 21:897.
- Brown JR, Yeckes H, Friedberg JW, et al. Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma. J Clin Oncol 2005; 23:2208.
- Milligan DW, Ruiz De Elvira MC, Kolb HJ, et al. Secondary leukaemia and myelodysplasia after autografting for lymphoma: results from the EBMT. EBMT Lymphoma and Late Effects Working Parties. European Group for Blood and Marrow Transplantation. Br J Haematol 1999; 106:1020.
- Chao NJ, Nademanee AP, Long GD, et al. Importance of bone marrow cytogenetic evaluation before autologous bone marrow transplantation for Hodgkin's disease. J Clin Oncol 1991; 9:1575.
- Govindarajan R, Jagannath S, Flick JT, et al. Preceding standard therapy is the likely cause of MDS after autotransplants for multiple myeloma. Br J Haematol 1996; 95:349.
- Kalaycio M, Rybicki L, Pohlman B, et al. Risk factors before autologous stem-cell transplantation for lymphoma predict for secondary myelodysplasia and acute myelogenous leukemia. J Clin Oncol 2006; 24:3604.
- Krishnan A, Bhatia S, Slovak ML, et al. Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood 2000; 95:1588.
- Majhail NS, Rizzo JD, Lee SJ, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biol Blood Marrow Transplant 2012; 18:348.
- Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004; 351:427.
- Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
- GENERAL OBSERVATIONS
- Solid tumors
- - Nonmelanoma skin cancer
- Squamous cell cancers
- - Breast cancer
- Secondary myelodysplasia/acute leukemia
- Post-transplant lymphoproliferative disease
- Donor-derived tumors
- RISK ACCORDING TO REASON FOR HCT
- HCT for aplastic anemia
- HCT for malignancy
- HCT for nonmalignant hematologic disease
- SCREENING AND PREVENTATIVE MEASURES