•• Shimoni A. Second malignancies after allogeneic stem cell transplantation with reduced-intensity conditioning: is the incidence reduced? Biol Blood Marrow Transplant. 2014;20(11):1669–70. This is our opinion of second malignancies after RIC is based on our single-center analysis. The records of 931 consecutive patients given allogeneic SCT with MAC (n = 257), RIC (n = 449) or RTC (n = 225), in a single institution over a 13-year period, were reviewed. Twenty-seven patients had secondary malignancy, diagnosed a median of 43 months (7 months–11.5 years) after SCT. This study is very important because it showed that the risk of secondary malignancies is not reduced and is even possibly increased in the era of fludarabine-based RIC/RTC. ArticlePubMed Google Scholar
Majhail NS, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18(3):348–71. ArticlePubMed Google Scholar
• Ringden O, et al. Second solid cancers after allogeneic hematopoietic cell transplantation using reduced-intensity conditioning. Biol Blood Marrow Transplant. 2014;20(11):1777–84. In this study was examined risk of second solid cancers after allo-SCT using RIC/NMC for recipients with leukemia/MDS (n = 2833) and lymphoma (n = 1436) between 1995 and 2006. In addition, RIC/NMC recipients 40 to 60 years of age (n = 2138) were compared with patients of the same age receiving myeloablative conditioning (MAC, n = 6428). In this study the overall risks of second solid cancers in RIC/NMC recipients were similar to the general population, although there is an increased risk of cancer at some sites. ArticlePubMedPubMed Central Google Scholar
Armenian SH, et al. Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the bone marrow transplant survivor study (BMTSS) and childhood cancer survivor study (CCSS). Blood. 2011;118(5):1413–20. ArticleCASPubMedPubMed Central Google Scholar
•• Chow EJ, et al. Morbidity and mortality differences between hematopoietic cell transplantation survivors and other cancer survivors. J Clin Oncol. 2017;35(3):306–13. This study compared the risks of serious health outcomes among hematopoietic SCT survivors (n = 1792) and a matched population of patients with cancer who did not undergo SCT (n = 5455) and the general population (n = 16,340). History of SCT was associated with late morbidity and mortality among cancer survivors, in particular, high rates of late respiratory and infectious complications. Interesting, during the median follow-up of 7 years the two groups had similar risks of circulatory complications and second cancers. ArticlePubMed Google Scholar
•• Inamoto Y, et al. Secondary solid cancer screening following hematopoietic cell transplantation. Bone Marrow Transplant. 2015;50(8):1013–23. A working group was established through the CIBMTR and the EBMT with the goal to facilitate implementation of cancer screening appropriate to SCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after SCT. A consensus approach was used to establish recommendations for individual secondary cancers. This study is the guidelines to help clinicians in providing screening and preventive care for secondary cancers among SCT recipients. ArticleCASPubMedPubMed Central Google Scholar
Wingard JR, et al. Long-term survival and late deaths after allogeneic hematopoietic cell transplantation. J Clin Oncol. 2011;29(16):2230–9. ArticlePubMedPubMed Central Google Scholar
Majhail NS, et al. Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning. Blood. 2011;117(1):316–22. ArticleCASPubMedPubMed Central Google Scholar
Atsuta Y, 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(2):435–41. ArticleCASPubMed Google Scholar
Yokota A, et al. Secondary solid tumors after allogeneic hematopoietic SCT in Japan. Bone Marrow Transplant. 2012;47(1):95–100. ArticleCASPubMed Google Scholar
Sureda A, et al. Autologous stem-cell transplantation for Hodgkin’s disease: results and prognostic factors in 494 patients from the Grupo Espanol de Linfomas/Transplante Autologo de Medula Osea Spanish Cooperative Group. J Clin Oncol. 2001;19(5):1395–404. ArticleCASPubMed Google Scholar
Smeland KB, et al. A national study on conditional survival, excess mortality and second cancer after high dose therapy with autologous stem cell transplantation for non-Hodgkin lymphoma. Br J Haematol. 2016;173(3):432–43. ArticleCASPubMed Google Scholar
Forrest DL, et al. High-dose therapy and autologous hematopoietic stem-cell transplantation does not increase the risk of second neoplasms for patients with Hodgkin’s lymphoma: a comparison of conventional therapy alone versus conventional therapy followed by autologous hematopoietic stem-cell transplantation. J Clin Oncol. 2005;23(31):7994–8002. ArticleCASPubMed Google Scholar
Goodman KA, et al. Long-term effects of high-dose chemotherapy and radiation for relapsed and refractory Hodgkin’s lymphoma. J Clin Oncol. 2008;26(32):5240–7. ArticlePubMed Google Scholar
Czyz A, et al. Second malignancies after autologous hematopoietic stem cell transplantation following modified BEAM conditioning regimen in patients with Hodgkin lymphoma—characteristics and risk factor analysis. Contemp Oncol (Pozn). 2013;17(2):200–4. Google Scholar
Miller JS, et al. Myelodysplastic syndrome after autologous bone marrow transplantation: an additional late complication of curative cancer therapy. Blood. 1994;83(12):3780–6. CASPubMed Google Scholar
Del Canizo M, et al. Incidence and characterization of secondary myelodysplastic syndromes following autologous transplantation. Haematologica. 2000;85(4):403–9. PubMed Google Scholar
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(11):3273–9. CASPubMed Google Scholar
Friedman DL, 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(2):939–44. ArticleCASPubMedPubMed Central Google Scholar
Micallef IN, et al. Therapy-related myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies. J Clin Oncol. 2000;18(5):947–55. ArticleCASPubMed Google Scholar
Brown JR, 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(10):2208–14. ArticleCASPubMed Google Scholar
Akpek G, et al. Long-term results of blood and marrow transplantation for Hodgkin’s lymphoma. J Clin Oncol. 2001;19(23):4314–21. ArticleCASPubMed Google Scholar
Tarella C, 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(7):814–24. ArticleCASPubMed Google Scholar
Curtis RE, et al. Solid cancers after bone marrow transplantation. N Engl J Med. 1997;336(13):897–904. ArticleCASPubMed Google Scholar
Witherspoon RP, et al. Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia. N Engl J Med. 1989;321(12):784–9. ArticleCASPubMed Google Scholar
Themeli M, et al. Alloreactive microenvironment after human hematopoietic cell transplantation induces genomic alterations in epithelium through an ROS-mediated mechanism: in vivo and in vitro study and implications to secondary neoplasia. Leukemia. 2010;24(3):536–43. ArticleCASPubMed Google Scholar
Savani BN, et al. Increased risk of cervical dysplasia in long-term survivors of allogeneic stem cell transplantation--implications for screening and HPV vaccination. Biol Blood Marrow Transplant. 2008;14(9):1072–5. ArticlePubMedPubMed Central Google Scholar
van Leeuwen FE, et al. Leukemia risk following Hodgkin’s disease: relation to cumulative dose of alkylating agents, treatment with teniposide combinations, number of episodes of chemotherapy, and bone marrow damage. J Clin Oncol. 1994;12(5):1063–73. ArticlePubMed Google Scholar
Le Deley MC, et al. Risk of secondary leukemia after a solid tumor in childhood according to the dose of epipodophyllotoxins and anthracyclines: a case-control study by the Societe Francaise d’Oncologie Pediatrique. J Clin Oncol. 2003;21(6):1074–81. ArticlePubMed Google Scholar
Shimoni A, et al. Secondary malignancies after allogeneic stem-cell transplantation in the era of reduced-intensity conditioning; the incidence is not reduced. Leukemia. 2013;27(4):829–35. ArticleCASPubMed Google Scholar
Gandhi V, Plunkett W. Cellular and clinical pharmacology of fludarabine. Clin Pharmacokinet. 2002;41(2):93–103. ArticleCASPubMed Google Scholar
Sacchi S, et al. Secondary malignancies after treatment for indolent non-Hodgkin’s lymphoma: a 16-year follow-up study. Haematologica. 2008;93(3):398–404. ArticlePubMed Google Scholar
Tam CS, et al. Treatment-related myelodysplasia following fludarabine combination chemotherapy. Haematologica. 2006;91(11):1546–50. CASPubMed Google Scholar
Smith MR, et al. Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: long-term follow-up of US Intergroup Study E2997. Blood. 2011;118(13):3525–7. ArticleCASPubMedPubMed Central Google Scholar
Majhail NS. Secondary cancers following allogeneic hematopoietic cell transplantation in adults. Br J Haematol. 2011;154(3):301–10. ArticlePubMed Google Scholar
Baker KS, et al. New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol. 2003;21(7):1352–8. ArticlePubMed Google Scholar
Leisenring W, et al. Nonmelanoma skin and mucosal cancers after hematopoietic cell transplantation. J Clin Oncol. 2006;24(7):1119–26. ArticlePubMed Google Scholar
Schwartz JL, et al. Basal cell skin cancer after total-body irradiation and hematopoietic cell transplantation. Radiat Res. 2009;171(2):155–63. ArticleCASPubMedPubMed Central Google Scholar
Curtis RE, 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(10):3802–11. ArticleCASPubMedPubMed Central Google Scholar
Bhatia S, et al. Solid cancers after bone marrow transplantation. J Clin Oncol. 2001;19(2):464–71. ArticleCASPubMed Google Scholar
Cohen A, et al. Risk for secondary thyroid carcinoma after hematopoietic stem-cell transplantation: an EBMT late effects working party study. J Clin Oncol. 2007;25(17):2449–54. ArticlePubMed Google Scholar
•• Ehrhardt MJ, et al. Survival of patients who develop solid tumors following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2016;51(1):83–8. Most reports address risk factors for second cancers after hematopoietic SCT; however, outcomes after secondary solid cancer development are incompletely described. This study estimated survival probabilities for transplant recipients dependent on secondary solid cancer subtype. Overall survival varied by secondary cancer type. Secondary cancer was the cause of death in most patients who died following development of melanoma, central nervous system, oral cavity, thyroid, lung, lower gastrointestinal tract and bone cancers. ArticleCASPubMed Google Scholar
Akhtari M, et al. Therapy-related myeloid neoplasms after autologous hematopoietic stem cell transplantation in lymphoma patients. Cancer Biol Ther. 2013;14(12):1077–88. ArticlePubMedPubMed Central Google Scholar
Gilliland DG, Gribben JG. Evaluation of the risk of therapy-related MDS/AML after autologous stem cell transplantation. Biol Blood Marrow Transplant. 2002;8(1):9–16. ArticleCASPubMed Google Scholar
Seshadri T, et al. Incidence and risk factors for second cancers after autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma. Leuk Lymphoma. 2009;50(3):380–6. ArticlePubMed Google Scholar
Harrison CN, et al. High-dose BEAM chemotherapy with autologous haemopoietic stem cell transplantation for Hodgkin’s disease is unlikely to be associated with a major increased risk of secondary MDS/AML. Br J Cancer. 1999;81(3):476–83. ArticleCASPubMedPubMed Central Google Scholar
Pedersen-Bjergaard J, et al. High risk of therapy-related leukemia after BEAM chemotherapy and autologous stem cell transplantation for previously treated lymphomas is mainly related to primary chemotherapy and not to the BEAM-transplantation procedure. Leukemia. 1997;11(10):1654–60. ArticleCASPubMed Google Scholar
Lillington DM, et al. Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-Hodgkin’s lymphoma. J Clin Oncol. 2001;19(9):2472–81. ArticleCASPubMed Google Scholar
Abruzzese E, et al. Detection of abnormal pretransplant clones in progenitor cells of patients who developed myelodysplasia after autologous transplantation. Blood. 1999;94(5):1814–9. CASPubMed Google Scholar
Amigo ML, et al. Diagnosis of secondary myelodysplastic syndromes (MDS) following autologous transplantation should not be based only on morphological criteria used for diagnosis of de novo MDS. Bone Marrow Transplant. 1999;23(10):997–1002. ArticleCASPubMed Google Scholar
Laurenti L, et al. Secondary myelodysplastic syndromes following peripheral blood stem cell transplantation: morphological, cytogenetic and clonality evaluation and the limitation of FAB criteria. Bone Marrow Transplant. 2000;26(2):241–2. ArticleCASPubMed Google Scholar
Keung YK, et al. Possible role of engraftment syndrome and autologous graft-versus-host disease in myelodysplastic syndrome after autologous stem cell transplantations: retrospective analysis and review of the literature. Clin Lymphoma Myeloma Leuk. 2010;10(2):129–33. ArticlePubMed Google Scholar
Traweek ST, et al. Clonal karyotypic hematopoietic cell abnormalities occurring after autologous bone marrow transplantation for Hodgkin’s disease and non-Hodgkin’s lymphoma. Blood. 1994;84(3):957–63. CASPubMed Google Scholar
Krishnan A, et al. Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors. Blood. 2000;95(5):1588–93. CASPubMed Google Scholar
Darrington DL, et al. Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies. J Clin Oncol. 1994;12(12):2527–34. ArticleCASPubMed Google Scholar
Milligan DW, et al. Secondary leukemia 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(4):1020–6. ArticleCASPubMed Google Scholar
Hosing C, et al. Risk of therapy-related myelodysplastic syndrome/acute leukemia following high-dose therapy and autologous bone marrow transplantation for non-Hodgkin’s lymphoma. Ann Oncol. 2002;13(3):450–9. ArticleCASPubMed Google Scholar
Metayer C, et al. Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study. Blood. 2003;101(5):2015–23. ArticleCASPubMed Google Scholar
Armitage JO, et al. Treatment-related myelodysplasia and acute leukemia in non-Hodgkin’s lymphoma patients. J Clin Oncol. 2003;21(5):897–906. ArticlePubMed Google Scholar
Bhatia S, et al. Malignant neoplasms following bone marrow transplantation. Blood. 1996;87(9):3633–9. CASPubMed Google Scholar
Majhail NS. Old and new cancers after hematopoietic-cell transplantation. Hematol Am Soc Hematol Educ Program. 2008;142–9.
Landgren O, et al. Risk factors for lymphoproliferative disorders after allogeneic hematopoietic cell transplantation. Blood. 2009;113(20):4992–5001. ArticleCASPubMedPubMed Central Google Scholar
Curtis RE, et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood. 1999;94(7):2208–16. CASPubMed Google Scholar
Heslop HE, et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010;115(5):925–35. ArticleCASPubMedPubMed Central Google Scholar
• Styczynski J, et al. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica. 2016;101(7):803–11. EBV-related PTLDs are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic SCT. To better define current understanding of PTLD in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of PTLDs exclusively in the stem cell transplant setting. ArticleCASPubMedPubMed Central Google Scholar
Sanz J, et al. EBV-associated post-transplant lymphoproliferative disorder after umbilical cord blood transplantation in adults with hematological diseases. Bone Marrow Transplant. 2014;49(3):397–402. ArticleCASPubMed Google Scholar
Kanakry JA, et al. Absence of post-transplantation lymphoproliferative disorder after allogeneic blood or marrow transplantation using post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis. Biol Blood Marrow Transplant. 2013;19(10):1514–7. ArticlePubMedPubMed Central Google Scholar
Courville EL, et al. EBV-negative monomorphic B-cell post-transplant lymphoproliferative disorders are pathologically distinct from EBV-positive cases and frequently contain TP53 mutations. Mod Pathol. 2016;29(10):1200–11. ArticleCASPubMed Google Scholar
Xuan L, et al. Spectrum of Epstein-Barr virus-associated diseases in recipients of allogeneic hematopoietic stem cell transplantation. Transplantation. 2013;96(6):560–6. ArticleCASPubMed Google Scholar
Fox CP, et al. EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplant. 2014;49(2):280–6. ArticleCASPubMed Google Scholar
Nash RA, et al. Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases. Biol Blood Marrow Transplant. 2003;9(9):583–91. ArticlePubMedPubMed Central Google Scholar
Uhlin M, et al. Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation. Haematologica. 2014;99(2):346–52. ArticlePubMedPubMed Central Google Scholar
van Esser JW, et al. Prevention of Epstein-Barr virus-lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation. Blood. 2002;99(12):4364–9. ArticlePubMed Google Scholar
Ahmad I, et al. Preemptive management of Epstein-Barr virus reactivation after hematopoietic stem-cell transplantation. Transplantation. 2009;87(8):1240–5. ArticleCASPubMed Google Scholar
Stevens SJ, et al. Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients. Blood. 2001;97(5):1165–71. ArticleCASPubMed Google Scholar
Omar H, et al. Targeted monitoring of patients at high risk of post-transplant lymphoproliferative disease by quantitative Epstein-Barr virus polymerase chain reaction. Transpl Infect Dis. 2009;11(5):393–9. ArticleCASPubMed Google Scholar
Styczynski J, et al. Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Clin Infect Dis. 2013;57(6):794–802. ArticleCASPubMed Google Scholar
van der Velden WJ, et al. Reduced PTLD-related mortality in patients experiencing EBV infection following allo-SCT after the introduction of a protocol incorporating pre-emptive rituximab. Bone Marrow Transplant. 2013;48(11):1465–71. ArticlePubMed Google Scholar
Worth A, et al. Pre-emptive rituximab based on viraemia and T cell reconstitution: a highly effective strategy for the prevention of Epstein-Barr virus-associated lymphoproliferative disease following stem cell transplantation. Br J Haematol. 2011;155(3):377–85. ArticleCASPubMed Google Scholar
Cesaro S, et al. A prospective study on modulation of immunosuppression for Epstein-Barr virus reactivation in pediatric patients who underwent unrelated hematopoietic stem-cell transplantation. Transplantation. 2010;89(12):1533–40. ArticleCASPubMed Google Scholar
Doubrovina E, et al. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood. 2012;119(11):2644–56. ArticleCASPubMedPubMed Central Google Scholar
Schouten HC, et al. Large-cell anaplastic non-Hodgkin’s lymphoma originating in donor cells after allogenic bone marrow transplantation. Br J Haematol. 1995;91(1):162–6. ArticleCASPubMed Google Scholar
Rowlings PA, et al. Increased incidence of Hodgkin’s disease after allogeneic bone marrow transplantation. J Clin Oncol. 1999;17(10):3122–7. ArticleCASPubMed Google Scholar
Hertenstein B, et al. Development of leukemia in donor cells after allogeneic stem cell transplantation--a survey of the European Group for Blood and Marrow Transplantation (EBMT). Haematologica. 2005;90(7):969–75. PubMed Google Scholar
Wiseman DH. Donor cell leukemia: a review. Biol Blood Marrow Transplant. 2011;17(6):771–89. ArticlePubMed Google Scholar
Rizzo JD, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, the Center for International Blood and Marrow Transplant Research, and the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2006;12(2):138–51. ArticlePubMed Google Scholar
Saslow D, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57(2):75–89. ArticlePubMed Google Scholar
Chao NJ, et al. Importance of bone marrow cytogenetic evaluation before autologous bone marrow transplantation for Hodgkin’s disease. J Clin Oncol. 1991;9(9):1575–9. ArticleCASPubMed Google Scholar