Therapy-related myelodysplasia and acute myeloid leukemia

Semin Oncol. 2013 Dec;40(6):666-75. doi: 10.1053/j.seminoncol.2013.09.013.


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.

MeSH terms

  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Agents, Alkylating / metabolism
  • Chemoradiotherapy / adverse effects*
  • DNA Repair / genetics
  • Female
  • Genetic Predisposition to Disease
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hodgkin Disease / therapy
  • Humans
  • Leukemia, Myeloid, Acute / classification
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / etiology*
  • Lymphoma, Non-Hodgkin / therapy
  • Male
  • Myelodysplastic Syndromes / classification
  • Myelodysplastic Syndromes / epidemiology
  • Myelodysplastic Syndromes / etiology*
  • Neoplasms, Second Primary / classification
  • Neoplasms, Second Primary / epidemiology
  • Neoplasms, Second Primary / etiology*
  • Ovarian Neoplasms / therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Sarcoma / therapy
  • Testicular Neoplasms / therapy
  • Time Factors
  • Topoisomerase II Inhibitors / adverse effects
  • Topoisomerase II Inhibitors / metabolism


  • Antineoplastic Agents, Alkylating
  • Topoisomerase II Inhibitors