Recently, we demonstrated the feasibility of first-line imatinib interim therapy (400~600 mg/day for 4 weeks) prior to allogeneic stem cell transplantation (SCT) in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) (

Blood, 2003;102:3068
). Here, we report on the updated results of this strategy in 29 adult patients who completed induction chemotherapy and intended to undergo allogeneic SCT. In addition, we compared these results with those in 31 historic patients who proceeded to allogeneic SCT without imatinib therapy. There were no significant differences between the two groups with respect to presenting clinical and biologic characteristics. At the time of enrollment, 23 of the 29 patients (79.3%) had achieved a complete remission (CR) in the imatinib group, and the CR rate was not significantly different from the historic rate (26/31, 81.8%). In contrast, the relapse rate was significantly lower in the imatinib group during the post-remission treatment phase prior to SCT (3.5% vs 42.3%, p=0.002). Furthermore, 3 of the 6 refractory patients achieved a CR after the imatinib interim therapy. This study also found that the kinetics of the BCR-ABL transcript correlated well with the patients’ clinical course. Overall, the BCR-ABL/ABL ratios were decreased in 25 (86.2%) and increased in 4 (13.8%) patients after the imatinib interim therapy. A total of 57 patients (28 imatinib group, 29 historic group) underwent allogeneic SCT, and among them, 25 and 16 patients had sustained CR at the time of transplantation, respectively. The remaining 3 patients (1 imatinib group, 2 historic group) died of their disease progression before SCT. This has translated into lower relapse (4.8±4.7% vs 45.3±10.7%, p=0.004) and superior disease-free survival (75.8±12.9% vs 37.9±9.0%, p=0.001) for the imatinib group. Acute transplant-related toxicity and mortality were not different in the two groups. Considering the high frequency of relapse or refractoriness to chemotherapy-alone prior to SCT, imatinib interim therapy might provide a higher curative possibility for Ph+ ALL patients.

Topics:
imatinib mesylate, bcr-abl tyrosine kinase, transplantation, acute lymphocytic leukemia, allogeneic stem cell transplant, chemotherapy regimen, chemotherapy, neoadjuvant, complete remission, disease progression, disease remission

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2005, The American Society of Hematology
2004
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