Treatment Outcomes for Imatinib Mesylate and Allogeneic Stem Cell Transplantation in Patients with CML Based on RQ-PCR, and the Efficacy of Dose Escalation of Imatinib Mesylate in Patients with Cytogenetic or Hematologic Resistance.

This study examines the treatment outcome for imatinib mesylate (IM) and allogeneic stem cell transplantation (SCT) in patients with chronic myelogenous leukemia (CML) based on quantitative PCR data and the efficacy of a dose increment of IM in patients with cytogenetic or hematologic resistance.

A total of 60 Ph⁺ CML patients that received IM and 17 patients that received allogeneic SCT were enrolled in the current study. The cumulative incidence of a complete hematologic response (CHR) was estimated as 71% after 1 month and 93% after 3 months, while the cumulative incidence of a major molecular response (MMR) was estimated as 53% after 6 months and 73% after 1 year. Five (22.7%) out of 22 evaluable patients achieved MMR after 3 months of IM treatment. At 24 months, 10 patients (45.5%) achieved MMR, while 7 patients (31.8%) remained as non-responders. Thrirteen patients that exhibited a cytogenetic or hematologic resistance to the standard dose of IM were treated with an increased dose of IM. Four (80%) out of 5 patients who had low levels (10–55%) of Ph+ cells in their bone marrow at the time of cytogenetic resistance achieved a complete cytogenetic response (CCR) or MMR again with the increased dose of IM, while all the patients (n=8) who failed to respond cytogenetically or hmatologically to the increased dose of IM had 100% Ph+ cells in their bone marrow at the time of cytogenetic resistance. The Philadelphia positivity in the bone marrow indicated a cytogenetic or molecular response to an increased dose of IM (P=0.009). The overall survival rate at 3 years was 88% for the IM group at the median follow-up duration of 851 days (range, 13–3346 days) and 47% for the SCT group at the median follow-up duration of 456 days (range, 34–2455 days), respectively (P<0.001). Plus, the progression-free survival rate at 3 years was 61% for the IM and 47% for the SCT group, respectively (P=0.037). In conclusion, IM dose escalation can be regarded as an important treatment option in terms of reserving other treatment options, especially in patients with low levels (≤55%) of Ph+ cells in their marrow who are resistant cytogenetically or hematologically to the standard dose of IM.