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


METHODS
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.


CONCLUSIONS
Limiting exposure to alkylating agents and eliminating TBI from transplantation conditioning regimens may reduce the relative risk of tMDS/AML.
Armitage
James O
JO
University of Nebraska College of Medicine, Omaha, NE 68198-3332, USA. joarmita@unmc.edu
Carbone
Paul P
PP
Connors
Joseph M
JM
Levine
Alexandra
A
Bennett
John M
JM
Kroll
Stewart
S
D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007167:Immunotherapy; D015994:Incidence; D007951:Leukemia, Myeloid / Q000139:chemically induced* / Q000175:diagnosis; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced*; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D011878:Radiotherapy; D012307:Risk Factors; D015996:Survival Rate; D014182:Transplantation, Autologous / Q000009:adverse effects; D014916:Whole-Body Irradiation