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Keywords:

  • acute lymphoblastic leukemia;
  • Philadelphia chromosome;
  • BCR/ABL;
  • minimal residual disease;
  • randomized trial

Abstract

BACKGROUND

Elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete remission (CR) rate, high induction mortality, and short remission duration. Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known.

METHODS

Patients with de novo Ph+ALL were randomly assigned to induction therapy with either imatinib (IndIM) or multiagent, age-adapted chemotherapy (Indchemo). Imatinib was subsequently coadministered with consolidation chemotherapy.

RESULTS

In all, 55 patients (median age, 68 years) were enrolled. The overall CR rate was 96.3% in patients randomly assigned to IndIM and 50% in patients allocated to Indchemo (P = .0001). Nine patients (34.6%) were refractory and 2 patients died during Indchemo; none failed imatinib induction. Severe adverse events were significantly more frequent during Indchemo (90% vs 39%; P = .005). The estimated overall survival (OS) of all patients was 42% ± 8% at 24 months, with no significant difference between the 2 cohorts. Median disease-free survival was significantly longer in the 43% of patients (21 of 49 evaluable) in whom BCR-ABL transcripts became undetectable (18.3 months vs 7.2 months; P = .002).

CONCLUSIONS

In elderly patients with de novo Ph+ALL, imatinib induction results in a significantly higher CR rate and lower toxicity than induction chemotherapy. With subsequent combined imatinib and chemotherapy consolidation, this initial benefit does not translate into improved survival compared with chemotherapy induction. Cancer 2007. © 2007 American Cancer Society.