Two hundred forty-two patients with
Philadelphia chromosome-positive
chronic myelogenous leukemia in
blast crisis were reviewed to identify significant
biologic and prognostic associations. Twenty percent of patients had lymphoid
blast crisis. Clonal evolution was present in 60 percent of patients at
blast crisis and involved most frequently the development of a double
Philadelphia chromosome, trisomy 8, or
isochromosome 17. The overall median survival from
blast crisis was 18 weeks. Patient characteristics demonstrated to have significant association with short survival were:
anemia;
thrombocytopenia; myeloid or undifferentiated blast cell morphology; clonal evolution involving the presence of a double
Philadelphia chromosome, trisomy 8, or
isochromosome 17; and low marrow blast percentage. Of 195 patients who received
therapy for
blast crisis, complete remission was achieved in 44 (23 percent) patients, and 24 (13 percent) patients had a partial remission or hematologic improvement. Lower complete remission rates were associated with old age,
thrombocytopenia, myeloid or undifferentiated blast cell morphology, clonal evolution--especially
isochromosome 17 and
trisomy 8--and long interval from diagnosis to onset of
blast crisis. A multivariate analysis identified two characteristics to have independent prognostic importance for both survival and remission: platelet counts and blast cell morphology. In addition, clonal evolution had additive prognostic value for survival (double
Philadelphia chromosome) and for response (
isochromosome 17). The beneficial association of
therapy with survival was demonstrated by the significantly longer median survival of patients treated since 1981 compared with those treated earlier, even after accounting for the pretreatment prognostic factors, and by the significant improvement in survival of patients achieving remission using the "landmark" analysis technique.