Abstract

With the introduction of imatinib (IM) as first-line therapy for chronic myeloid leukemia (CML) as well as in advanced phases of the disease, the long-term outcome of this hematologic malignancy has dramatically changed.. The aim of this study has been to analyse the experience of our centre with IM therapy in CML patients, focusing on the cytogenetic and molecular responses according to the phase of the disease in which IM was given, as well as the treatment failures and the results of the mutational analysis performed in these situations. Between January 2000 and March 2008, 77 patients with CML [47 men and 30 women, median age 49 years (range, 18–78)] were treated with IM. 33 of them received IM at a dose of 400 mg qd as first-line treatment in de novo chronic-phase (CP), 32 patients received it in late chronic-phase [time from diagnosis to IM, 51 (12–157) months]. Of these 32 patients in late CP, all of them received prior therapy with interferon-alpha, 10 patients received an autologous transplant and 3 of them an allogeneic transplant. Five patients were initially treated with IM 600mg qd because of an accelerate-phase (AP) and the remaining 6 patients were treated with IM 800mg qd because of a blastic-phase (BP).

 De novoCP Late CP AP BC 
CHR(%) 32 (96) 28 (87) 4 (80) 3 (50) 
Time to CHR in months [median (range)] 1,8 (0,5–6) 1 (3–10) 2 (0,5-4) 3 (1–5) 
CCR(%) 30 (90) 22 (68) 3 (60) 1 (17) 
Tims to CCR in months [median (range)] 11 (6–63) 10 (6–36) 12 (7–18) — 
MMoIR(%) 20 (60) 15 (47) 1 (20) 1 (17) 
Time to MMoIR in months [median (range)] 18 (6–68) 22 (6–58) — — 
CMoIR(%) 
Time to CMoIR in months [median (range)] — — — — 
Relapses (%) 5 (15) 9 (28) 4 (80) 5 (87) 
Mutational analysis (n, %) 4 (80) 6 (66) 3 (75) 3 (50) 
    Positive 2 (50) 2 (33) 1 (33) 
    Negative 2 (50) 4 (67) 2 (67) 3 (100) 
Second-line treatment     
    Dasatinib 
    Allo-SCT 
    Others — — 
Follow-up from diagnosis 41 (11–90) 103 (34–215) 107 (37–185) 74 (13–158) 
Follow-up from beginning of IM 43 (11–97) 52 (6–87) 52 (13–83) 22 (1–88) 
    Alive 31(94) 22(69) 3(60) 2(33) 
    Death 2(6) 10(31) 2(40) 4(67) 
 De novoCP Late CP AP BC 
CHR(%) 32 (96) 28 (87) 4 (80) 3 (50) 
Time to CHR in months [median (range)] 1,8 (0,5–6) 1 (3–10) 2 (0,5-4) 3 (1–5) 
CCR(%) 30 (90) 22 (68) 3 (60) 1 (17) 
Tims to CCR in months [median (range)] 11 (6–63) 10 (6–36) 12 (7–18) — 
MMoIR(%) 20 (60) 15 (47) 1 (20) 1 (17) 
Time to MMoIR in months [median (range)] 18 (6–68) 22 (6–58) — — 
CMoIR(%) 
Time to CMoIR in months [median (range)] — — — — 
Relapses (%) 5 (15) 9 (28) 4 (80) 5 (87) 
Mutational analysis (n, %) 4 (80) 6 (66) 3 (75) 3 (50) 
    Positive 2 (50) 2 (33) 1 (33) 
    Negative 2 (50) 4 (67) 2 (67) 3 (100) 
Second-line treatment     
    Dasatinib 
    Allo-SCT 
    Others — — 
Follow-up from diagnosis 41 (11–90) 103 (34–215) 107 (37–185) 74 (13–158) 
Follow-up from beginning of IM 43 (11–97) 52 (6–87) 52 (13–83) 22 (1–88) 
    Alive 31(94) 22(69) 3(60) 2(33) 
    Death 2(6) 10(31) 2(40) 4(67) 

The results of our centre confirm the ones presented in prospective analysis. There is a small percentage of patients that relapse or progress under IM therapy, and this percentage is significantly higher in patients treated in advanced phases. Mutational analysis is relevant in up 50% of the patients studied, allowing changes in therapy according to the obtained results.

Disclosures: No relevant conflicts of interest to declare.

Author notes

Corresponding author