Chronic myelogenous leukemia in nonlymphoid blastic phase: analysis of the results of first salvage therapy with three different treatment approaches for 162 patients.
BACKGROUND
The prognoses of patients with chronic myelogenous leukemia in blastic phase (CML-BP) are extremely poor. Treatment of patients with nonlymphoid CML-BP is associated with very low response rates, a median survival of 2-3 months, and significant toxicities. The aim of this study was to evaluate the results of therapy in CML-BP with different treatments in relation to response rate, survival, and toxicity.


METHODS
A total of 162 adults patients with a diagnosis of nonlymphoid CML-BP referred from 1986 to 1997 were included in this analysis. Only first salvage therapy was considered for the purpose of this analysis. The blastic phase of CML was defined by the presence of 30% or more blasts in the blood or bone marrow, or extramedullary disease. Ninety patients were treated with intensive chemotherapy, 31 with decitabine, and 41 with other single agents.


RESULTS
Thirty-six patients (22%) had an objective response. Response rates were similar among patients treated with intensive chemotherapy (28%) or with decitabine (26%). In aggregate, other single agents showed objective response rates of 7%. The median duration of remission for all patients was 29 weeks and the median overall survival 22 weeks. Patients treated with decitabine showed a trend toward better survival, despite a higher percentage of older patients (P < 0.004). The median survival times were 29 weeks with decitabine, 21 weeks with intensive chemotherapy, and 22 weeks with other agents. When only older patients were considered, survival was significantly better with decitabine versus other treatments (P < 0.01). A multivariate analysis of prognostic factors for survival confirmed the independent, significant favorable effect of decitabine therapy (P = 0.047). In all groups complications of myelosuppression were the most significant side effects. Severe nonhematologic toxicities were not observed in patients treated with decitabine; they occurred in 20% and 17% of patients treated with intensive chemotherapy or other single agents, respectively.


CONCLUSIONS
Compared with intensive chemotherapy, decitabine showed favorable results, with similar objective response rates, a better nonhematologic toxicity profile, and a trend for better survival, particularly among older patients. Studies will now attempt to combine decitabine with other promising approaches, such as homoharringtonine, low dose cytarabine, and interferon-alpha, in all CML phases.
Sacchi
S
S
Department of Leukemia, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Kantarjian
H M
HM
O'Brien
S
S
Cortes
J
J
Rios
M B
MB
Giles
F J
FJ
Beran
M
M
Koller
C A
CA
Keating
M J
MJ
Talpaz
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001374:Azacitidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001752:Blast Crisis / Q000188:drug therapy* / Q000473:pathology; D000077209:Decitabine; D005260:Female; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012074:Remission Induction; D016879:Salvage Therapy; D016019:Survival Analysis
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine