Incomplete response to induction in acute myelogenous leukemia and salvage approaches

Standard Therapy of acute myelogenous leukemia (excluding acute promyelocytic leukemia) begins with induction chemotherapy and is followed by consolidation and sometimes by maintenance phases of treatment. Various acceptable induction regimens are available. The most common approach is called ”3 and 7,” which consists of 3 days of a 15- to 30-minute infusion of an anthracycline (idarubicin or daunorubicin) or anthracenedione (mitoxantrone), combined with 100 mg/m2 of arabinosylcytosine (araC) as a 24-hour infusion daily for 7 days. Idarubicin is given at a dose of 12 mg/m2/d for 3 days, daunorubicin at 45-60 mg/m2/d for 3 days, or mitoxantrone at 12 mg/m2/d for 3 days. Using these regimens, approximately 50% of patients achieve remission with one course. Another 10-15% enter remission following a second course of therapy. Prognosis does not change based on whether one or two inductions were required to achieve a remission. A retrospective analysis of six Eastern Cooperative Oncology Group (ECOG) studies that included both younger and older adults demonstrated that 26% of patients achieving complete remission (CR) following anthracycline and cytarabine-based induction therapy required a second cycle of identical induction therapy to do so [Rowe et al. 2010].

Occasionally, a patient largely responds to two induction chemotherapies but is found to have persistent leukemia cells in the marrow. It is known that without farther intervention, such a patient is destined to relapse within a few months. Studies in 1980s and 1990s demonstrate that effective salvage regimens for relapsed or refractory AML include Ara-C and anthracycline-like compounds as the backbone of the regimens. Combinations that included flu-darabine and/or combinations of both Ara-C and anthracycline-like compounds also demonstrated efficacy and three drug salvage regimens are being studied. Also being explored are targeted agents, and allogeneic SCT, alone of in combinaitons. Prognostic significance of cytogenetic and other markers that can guide this choice is also being explored.

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