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Abstract

The use of intensive ‘pediatric’ protocols for the treatment of acute lymphoblastic leukemia in young adults has improved survival, raising the question of whether these approaches can be applied to older adults with appropriate modifications. In this report, Martell et al. describe the results of modifying the Dana Farber Cancer Institute (DFCI) pediatric protocol DFCI 91–01 in patients with newly diagnosed acute lymphoblastic leukemia aged 60–79 years. The main modifications to the original protocol were the inclusion of continuous imatinib (400 mg daily) in place of asparaginase in Philadelphia (Ph)-positive patients; the substitution of dexamethasone for prednisone; reduction of methotrexate from 4 g/m to 40 mg/m and asparaginase from 25,000 to 12,000 iu/m; removal of one vincristine dose; and no cranial radiation. The intensification phase was reduced to seven cycles. Maintenance phase methotrexate was switched to oral, and the dexamethasone dose was reduced to 6 mg. Fifty one patients (median age 65 years) were enrolled from January 2005 to October 2012. Complete response rates were impressive; 81 and 71% in Ph-positive and -negative patients, respectively. The estimated 5-year overall survival was 40.5% (95% CI: 20–60.2) in Ph-negative, and 47.3% (95% CI: 18.2–71.9) in Phpositive patients, with a median follow up of 33.7 months (range 5.5–95 months). Mortality during induction was 20%, with infections the most common toxicities, with 82% reporting infectious complication during induction The investigators conclude that the high dose of steroid, even with the reductions incorporated in the protocol modifications, significantly contributed to this and an induction death rate approximately double that of a comparable acute myeloid leukemia cohort. Reducing the rate of serious infectious should further improve the benefits of intensive treatment regimens for older patients with acute myeloid leukemia.