Ph+ ALL accounts for approximately one third of ALL cases in patients aged 55 years or older. The median survival of older Ph+ ALL patients is one year, with practically no long-term survivor (

Blood, 98, Supp1 p319a, 2001
). Imatinib has demonstrated remarkable, although transient, activity in relapsed and refractory Ph+ ALL, which prompted the GRAALL to implement a treatment protocol associating imatinib and chemotherapy in previously untreated elderly patients: ALL patients aged 55 years or older are treated with steroids during one week and Ph+ve cases are then offered a specific therapy including an induction treatment with steroids, cyclophosphamide, daunorubicin and vincristine, followed, irrespective of response to induction chemotherapy, by imatinib, 600 mg daily, combined with intermittent steroids during 2 months. Patients in complete response are then given 10 blocks of alternating chemotherapy, including 2 additional two-month blocks of imatinib, for a total treatment duration of 2 years. Therapy of occult central nervous system leukemia includes 5 intrathecal injections of methotrexate and cranial irradiation. The study is intended to include 30 patients and its main objective is to improve overall one-year survival to 70%. Results are compared with those obtained in 21 Ph+ ALL elderly patients treated according to our previous protocol. Since January 2003, 21 patients aged 58 to 78 years (median: 64.7 years) were included in the AFR09 protocol. Their median follow-up is 3 months. 15/19 patients are in complete response after induction chemotherapy vs 6/21 in the historical controls given similar induction regimen but with no steroids before chemotherapy (p=0.002). The projected overall survival is 95% at 9 months vs 62% in the control group (p=0.08, log-rank test). The 9-month projected event-free survival is 83% vs 10% (p<0.0001) and the projected 6-month relapse-free survival is 79% vs 22% (p=0.006, log-rank test). In conclusion, although preliminary, this interim analysis suggests that the use of imatinib in elderly patients with Ph+-ALL is very likely to dramatically improve prognosis. Of note, an unexpected high proportion of patients accrued in this study achieved a CR after induction chemotherapy possibly denoting a beneficial impact of steroids given before starting chemotherapy.

Topics:
acute lymphocytic leukemia, chemotherapy regimen, imatinib mesylate, interim analysis, older adult, steroids, chemotherapy, neoadjuvant, complete remission, central nervous system leukemia, cranial irradiation

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2005, The American Society of Hematology
2004
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