title: Therapy-related myelodysplasia and acute myeloid leukemia.
abstract: Therapy-related leukemia (myelodysplasia and acute myeloid leukemia-t-MDS/AML) is a well-known complication of conventional chemoradiotherapy used to treat a variety of primary malignancies including Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), sarcoma, and ovarian and testicular cancers. The median time to development of t-MDS/AML is 3-5 years, with the risk decreasing markedly after the first decade. t-MDS/AML is the major cause of non-relapse mortality after autologous hematopoietic cell transplantation (HCT) for HL or NHL. The magnitude of risk of t-MDS/AML is higher, and the latency is shorter after HCT, compared to conventional therapy. Two types of t-MDS/AML are recognized depending on the causative therapeutic exposure: an alkylating agent/radiation-related type and a topoisomerase II inhibitor-related type. Inter-individual variability in the risk for development of t-MDS/AML suggests a role for genetic variation in susceptibility to genotoxic exposures. Treatment of t-MDS/AML with conventional therapy is associated with a uniformly poor prognosis, with a median survival of 6 months. Because of the poor response to conventional chemotherapy, allogeneic HCT is recommended. Current research is focused on developing risk prediction and risk reduction strategies.
authors: Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA. Electronic address: sbhatia@coh.org.
authors: Smita
authors: S
authors: Bhatia
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000378:metabolism; D059248:Chemoradiotherapy / Q000009:adverse effects*; D004260:DNA Repair / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000453:epidemiology / Q000209:etiology*; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D009190:Myelodysplastic Syndromes / Q000145:classification / Q000453:epidemiology / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000145:classification / Q000453:epidemiology / Q000209:etiology*; D010051:Ovarian Neoplasms / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D012509:Sarcoma / Q000628:therapy; D013736:Testicular Neoplasms / Q000628:therapy; D013997:Time Factors; D059005:Topoisomerase II Inhibitors / Q000009:adverse effects / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D059005:Topoisomerase II Inhibitors