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

Author notes

Corresponding author

2005, The American Society of Hematology
2005
Sign in via your Institution