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

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.