Imatinib mesylate therapy of chronic phase chronic myeloid leukemia resistant or intolerant to interferon: results and prognostic factors for response and progression-free survival in 150 patients.
OBJECTIVE
Imatinib mesylate has recently been shown to be highly effective in chronic-phase chronic myeloid leukemia (CML). The results of imatinib treatment in chronic-phase CML patients resistant or intolerant to interferon (IFN) and the factors predicting therapeutic response and progression-free survival were analyzed.


METHODS
One hundred and fifty patients with chronic-phase CML resistant (n=111) or intolerant (n=39) to IFN were treated with imatinib. Prognostic factors for response and disease progression were assessed by multivariate analysis.


RESULTS
The median time from diagnosis was 43 months (0.5-188), median IFN therapy 21.5 months (0.5-140) and median follow-up from starting imatinib 13.6 months (range: 3-23). Complete hematologic response was achieved in 96 of 97 patients. Complete, partial and minor cytogenetic responses were present in 44%, 22%, and 8% of patients at 12 months. Grade III-IV neutropenia, thrombocytopenia, and anemia developed in 33%, 16%, and 6% of patients, respectively. Sixty-five patients discontinued treatment for a median of 4 weeks (1-36) due to toxicity. The rate of progression-free survival (lack of accelerated/blastic phase with persistent response) was 89.2% (95% CI: 84-94.4) at 12 months and 80.2% (95% CI: 72.2-88.2) at 18 months. Platelets > 450x10(9)/L and treatment discontinuation > 4 weeks were associated with a lower rate of major (complete plus partial) cytogenetic response. Patients in Sokal's high-risk group and those who did not achieve a major cytogenetic response had significantly shorter progression-free survival.


CONCLUSIONS
Imatinib is highly effective in chronic-phase CML patients resistant or intolerant to IFN, especially in those with normal platelet counts and in those not requiring prolonged treatment discontinuation due to neutropenia.
Cervantes
Francisco
F
Hematology Department, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.
Hernández-Boluda
Juan-Carlos
JC
Steegmann
Juan-Luis
JL
Conde
Eulogio
E
Alvarez-Larrán
Alberto
A
López-Jiménez
Javier
J
Osorio
Santiago
S
Villalón
Lucía
L
Camós
Mireia
M
García-Conde
Javier
J
Odriozola
Jesús
J
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007372:Interferons / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D013030:Spain; D016896:Treatment Outcome
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D007372:Interferons