Accelerated Phase: 235 patients with accelerated phase disease were enrolled. These patients met one or more of the following criteria:≥15%-<30% blasts in PB or BM; ≥30% blasts + promyelocytes in PB or BM; ≥20% basophils in PB; and <100 x 109/L platelets. The first 77 patients were started at 400 mg, with the remaining 158 patients starting at 600 mg.

Effectiveness was eva luated primarily on the basis of the rate of hematologic response, reported as either complete hematologic response, no evidence of leukemia (i.e., clearance of blasts from the marrow and the blood, but without a full peripheral blood recovery as for complete responses), or return to chronic phase CML. Cytogenetic responses were also eva luated. Median duration of treatment was 18 months with 45% of patients treated for ≥24 months (maximum=35 months).Efficacy results are reported in Table 15. Response rates in accelerated phase CML were higher for the 600mg dose group than for the 400mg group:hematologic response (75% vs. 64%), confirmed and unconfirmed major cytogenetic response (31% vs. 19%).

Myeloid Blast Crisis: 260 patients with myeloid blast crisis were enrolled. These patients had ≥30% blasts in PB or BM and/or extramedullary involvement other than spleen or liver; 95 (37%) had received prior chemotherapy for treatment of either accelerated phase or blast crisis (“pretreated patients”) whereas 165 (63%) had not (“untreated patients”). The first 37 patients were started at 400 mg; the remaining 223 patients were started at 600 mg.

Effectiveness was eva luated primarily on the basis of rate of hematologic response, reported as either complete hematologic response, no evidence of leukemia, or return to chronic phase CML using the same criteria as for the study in accelerated phase. Cytogenetic responses were also assessed. Median duration of treatment was 4 months with 21% of patients treated for ≥12 months and 10% for ≥24 months (maximum=35 months).Efficacy results are reported in Table 15. The hematologic response rate was higher in untreated patients than in treated patients (36% vs. 22%, respectively) and in the group receiving an initial dose of 600 mg rather than 400 mg (33% vs. 16%). The confirmed and unconfirmed major cytogenetic response rate was also higher for the 600mg dose group than for the 400mg dose group (17% vs. 8%).

Table 15 Response in CML Studies  Chronic Phase IFN Failure
(n=532) Accelerated Phase
(n=235) Myeloid Blast Crisis
(n=260)
  600 mg n=158 600 mg n=223
 400 mg 400 mg n=77 400 mg n=37
 % of patients [CI 95%]
Hematologic Response1 95% [92.3−96.3] 71%[64.8-76.8] 31% [25.2−36.8]
Complete Hematologic
Response (CHR) 95% 38% 7%
No