Standard Induction Followed by Attenuated Consolidation Therapy in Elderly Patients with Acute Myeloid Leukemia.

Compared to younger patients with acute myeloid leukemia (AML), elderly patients are associated with poorer prognosis and only a few survive long-term. Although several randomized trials demonstrate that elderly patients benefit from full-dose application of cytarabine plus anthracyclines rather than less intensive chemotherapy for induction therapy, optimal post-remission therapy remains to be determined. We performed a prospective phase II multicenter trial of standard induction therapy (7+3 of cytarabine plus daunorubicin) followed by 2 cycles of attenuated consolidation therapy (5+1 of cytarabine plus daunorubicin) for elderly AML patients excluding M3. This study was designed to reduce fatal complications by intensive post-remission therapy, benefits of which have not been evidenced in elderly patients. Induction therapy consisted of cytarabine (200 mg/m²/d x 7) and daunorubicin (45 mg/m²/d x 3). If interim bone marrow examination, which was done at 14 days after the start of induction therapy, showed persistent leukemia, the second attempt of induction therapy was tried with the same doses of cytarabine for 5 days and daunorubicin for 2 days. The patients who attained complete remission (CR) by induction therapy received 2 cycles of attenuated dose consolidation therapy (cytarabine 200 mg/m²/d x 5 plus daunorubicin 45 mg/m²/d x 1). Forty-one patients, 25 males and 16 females, were enrolled into the study between Jan 2002 and Dec 2004. Median age was 66 years (range, 60–78 years). Thirty-seven patients received the planned dose of induction therapy and 4 did not complete it due to intolerance in 3 or tumor lysis syndrome in 1. CR was attained in 16 patients after a first attempt of induction therapy. A second attempt of induction therapy was administered to 16 patients, 8 of whom attained CR. Overall, 24 (58.5%; 95% CI, 43.5–73.6%) of 41 enrolled patients achieved CR at a median of 34 days (range, 21–86 days). In the 17 patients who did not achieve CR, the cause of treatment failure was resistant leukemia in 15, complications of aplasia in 1, and indeterminate in 1. Of 24 CR patients, 17 completed all 2 cycles of consolidation therapy, 3 received 1 cycle, and 4 did not receive consolidation therapy. During induction therapy, most common non-hematologic toxicities (≥ grade 3) were febrile neutropenia (83%) and metabolic abnormalities (44%). During consolidation therapy, non-hematologic toxicities (≥ grade 3) were infrequent except febrile neutropenia (45% for the first consolidation and 41% for the second consolidation). There were no fatal complications during consolidation therapy. After a median follow-up duration of 566 days (range, 63–1190 days) among surviving patients, 27 died and actuarial 3-year overall survival was 17.0%. No patient died in remission. Fifteen of 24 CR patients relapsed and actuarial 3-year disease-free survival was 22.5%. Our study suggests that attenuated consolidation does not compromise the outcomes of elderly AML patients, compared to the results from previous reports using more intensive consolidation therapy.