Imatinib mesylate as treatment for blastic transformation of Philadelphia chromosome positive chronic myelogenous leukemia.
OBJECTIVE
Imatinib mesylate (STI571) is a selective inhibitor of the bcr/abl tyrosine kinase with therapeutic potential in the blast crisis (BC) of chronic myelogenous leukemia (CML).


METHODS
We report the characteristics and clinical outcome of 30 patients [16 males and 14 females, median age 50 (range, 18 to 72) years] with CML in BC included in a phase II international multicenter extended trial of treatment with imatinib. The initially administered dose of imatinib was 600 mg orally once daily.


RESULTS
Eighteen patients (60%) achieved a sustained hematologic remission (SHR) at a median time of 4 weeks (range, 2-14) after starting therapy. The median duration of SHR was 5 months (range, 4-13). Four patients (13%) achieved a cytogenetic remission at a median time of 8 weeks (range, 6-10) after beginning imatinib therapy. The rates of event-free survival (EFS) and overall survival (OS) at 1 year were 29%+/-8% and 36%+/-13%, respectively. In univariate analysis, the achievement of a SHR was more frequent in patients without a complex karyotype and in those receiving imatinib without having had previous chemotherapy. A long interval between the diagnosis of BC and imatinib therapy (> or = 9.5 weeks) (p=0.0011), the presence of additional cytogenetic abnormalities (p=0.015), and extramedullary involvement (p=0.02) were associated with significantly shorter EFS. In contrast, longer OS was observed in patients treated with imatinib shortly after the diagnosis of BC (p=0.0003) and in those without additional cytogenetic abnormalities (p=0.0043). Multivariate analyses indicated that the time interval between the diagnosis of BC and the beginning of imatinib therapy was the only significant prognostic factor for both EFS and OS.


CONCLUSIONS
STI571 therapy produces a high percentage of SHR in patients with CML in BC; a minority of the patients also obtain some degree of cytogenetic response. Nevertheless, these responses are transient and additional therapy should be offered.
Sureda
Anna
A
Clinical Hematology Division, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. asureda@hsp.santpau.es
Carrasco
Marina
M
de Miguel
Miguel
M
Martínez
Jesùs A
JA
Conde
Eulogio
E
Sanz
Miguel A
MA
Díaz-Mediavilla
Joaquin
J
Sierra
Jorge
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000097:blood; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000097:blood; D009503:Neutropenia / Q000139:chemically induced; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl