Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients

J Clin Oncol. 2003 Mar 1;21(5):897-906. doi: 10.1200/JCO.2003.07.113.


Purpose: Standard therapies for non-Hodgkin's lymphoma (NHL) are associated with an increased risk of developing treatment-related myelodysplastic syndrome or acute myelogenous leukemia (tMDS/AML). However, there is considerable debate over the incidence or risk of tMDS/AML in NHL patients treated with any particular modality and the factors that contribute to malignant transformation.

Design: Conclusions were based on thorough analysis of data reported in the peer-reviewed literature and careful examination of the statistical methodology and methods for identifying cases of tMDS/AML. Unless noted, data are reported only for NHL patients, excluding Hodgkin's disease patients.

Results: Despite differences in methods used to identify cases and to estimate the cumulative incidence over time (actuarial v cumulative calculations), up to 10% of NHL patients treated with either conventional-dose chemotherapy or high-dose therapy and autologous stem-cell transplantation may develop tMDS/AML within 10 years of primary therapy. Kaplan-Meier estimates of the actuarial incidence, which are based on censoring of patients who died without developing tMDS/AML, can lead to artificially high estimates with large confidence intervals at later time points. Although there is much debate about the cause(s) of tMDS/AML, there is compelling evidence that alkylating agents, certain other leukemogenic agents, and total-body irradiation (TBI) cause chromosomal damage that can lead to tMDS/AML.

Conclusion: Limiting exposure to alkylating agents and eliminating TBI from transplantation conditioning regimens may reduce the relative risk of tMDS/AML.

Publication types

  • Review

MeSH terms

  • Acute Disease
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Clinical Trials as Topic
  • Combined Modality Therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Immunotherapy
  • Incidence
  • Leukemia, Myeloid / chemically induced*
  • Leukemia, Myeloid / diagnosis
  • Lymphoma, Non-Hodgkin / therapy*
  • Myelodysplastic Syndromes / chemically induced*
  • Neoplasms, Radiation-Induced / etiology
  • Radiotherapy
  • Risk Factors
  • Survival Rate
  • Transplantation, Autologous / adverse effects
  • Whole-Body Irradiation