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 survivors (

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 alternating chemotherapy and imatinib in previously untreated elderly patients: ALL patients aged 55 years or older were treated with steroids during one week and Ph+ cases were 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 (CR) were 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 included 5 intrathecal injections of methotrexate and cranial irradiation. Results are compared with those obtained in 21 Ph+ ALL elderly patients treated according to our previous protocol. From January 2003 to November 2004, 30 patients aged 58 to 78 years (median: 65.8 years) were included in the present study. The median follow-up of surviving patients is 15 months. 20/29 assessable patients were in complete response after induction chemotherapy vs 6/21 in the historical controls given similar induction regimen but with no steroids before chemotherapy (p=0.009). Two patients died during induction treatment vs none in the control group. Out of 6 patients alive with disease at completion of induction, 5 were in CR after salvage with imatinib. The projected overall survival is 71% at 1 year vs 43% in the control group (p=0.008, log-rank test). The 1 year projected relapse-free survival is 58% vs 11% (p=0.003) and the projected 1 year event-free survival (defined as failure to obtain a CR, death or relapse) is 57% vs 5% (p<0.0001). In conclusion, the use of imatinib in elderly patients with Ph+ALL is very likely to dramatically improve prognosis, including overall survival. Compared to our previous study, 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, older adult, steroids, chemotherapy, neoadjuvant, complete remission, central nervous system leukemia, cranial irradiation, cyclophosphamide

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2005, The American Society of Hematology
2005
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