K. Takeyama et al., Therapy-related leukemia and myelodysplastic syndrome: A large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors, INT J HEMAT, 71(2), 2000, pp. 144-152
It is known that alkylating agents and topoisomerase II inhibitors can caus
e distinct forms of therapy-related leukemia and myelodysplastic syndrome (
TRL/MDS). Although several reports have been made on each of these agents s
eparately, no study has yet been conducted to evaluate the effect of these
two types of agents in the same population. In a nationwide, large-scale po
pulation study, the clinical and cytogenetic features as well as the progno
stic factors in 256 patients with TRL/MDS were assessed. Median age was 61
years, and the median period of latency from primary malignancies was 47.9
months. The latency period was significantly shorter in patients undergoing
chemotherapy, especially that of topoisomerase II inhibitors, for primary
cancer. The morphological diagnosis of TRL/MDS was acute myeloid leukemia i
n 59% and MDS in 41% of patients. Chromosome abnormalities that frequently
involved chromosomes 5, 7, or 11 were documented in 77% of the 189 patients
examined. MLL gene rearrangements were detected in 11 of 58 subjects and w
ere correlated with a borderline significance (P = 0.072) with topoisomeras
e II inhibitor administration. Overall median survival was only 9.7 months.
Survival was similar in cases with or without MLL gene rearrangement. Mult
ivariate analysis identified chromosome 5 abnormalities, hypoproteinemia, p
oor therapy outcomes for primary cancer, C-reactive protein, and thrombocyt
openia as being significantly poor prognostic factors (P < 0.05). This larg
e-population study provided a comprehensive update of TRL/MDS status in Jap
an, identified significant prognostic factors, and enabled the clinical sig
nificance of MLL gene rearrangement to be assessed. (C) 2000 The Japanese S
ociety of Hematology.