Adult Acute Myeloid Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Adult Acute Myeloid Leukemia in Remission
Although individual patients have been reported to have long disease-free survival (DFS) or cure with a single cycle of chemotherapy, postremission therapy is always indicated in therapy that is planned with curative intent. In a small randomized study conducted by the Eastern Cooperative Oncology Group (ECOG), all patients who did not receive postremission therapy experienced a relapse after a short median complete remission duration. Current approaches to postremission therapy include short-term, relatively intensive chemotherapy with cytarabine-based regimens similar to standard induction clinical trials (postremission chemotherapy), postremission chemotherapy with more dose-intensive cytarabine-based treatment, high-dose chemotherapy or chemoradiation therapy with autologous bone marrow rescue, and high-dose marrow-ablative therapy with allogeneic bone marrow rescue. While older studies have included longer-term therapy at lower doses (maintenance), no convincing evidence is available with acute myeloid leukemia (AML) that maintenance therapy provides prolonged disease-free survival (DFS) beyond shorter-term, more dose-intensive approaches, and few current treatment clinical trials include maintenance therapy.
Nontransplant postremission therapy using cytarabine-containing regimens has treatment-related death rates that are usually less than 10% to 20% and have yielded reported long-term DFS rates from 20% to 50%.[3,4,5,6] A large randomized trial that compared three different cytarabine-containing postremission therapy regimens showed a clear benefit in survival to patients younger than 60 years who received high-dose cytarabine. Intensification of cytarabine dose or duration of postremission chemotherapy with conventionally dosed cytarabine did not improve disease-free or OS in patients aged 60 years or older, as evidenced in the Medical Research Council (MRC-LEUK-AML11) trial.[7,8] The duration of postremission therapy has ranged from one cycle [4,6] to four or more cycles.[3,5] The optimal doses, schedules, and duration of postremission chemotherapy have not been determined. Therefore, to address these issues, patients with AML should be included in clinical trials at institutions that treat large numbers of such patients.
Dose-intensive cytarabine-based chemotherapy can be complicated by severe neurologic  and/or pulmonary toxic effects  and should be administered by physicians experienced in these regimens at centers that are equipped to deal with potential complications. In a retrospective analysis of 256 patients who received high-dose bolus cytarabine at a single institution, the most powerful predictor of cytarabine neurotoxicity was renal insufficiency. The incidence of neurotoxicity was significantly greater in patients treated with twice daily doses of 3 g/m2 /dose when compared with 2 g/m2 /dose.
Allogeneic bone marrow transplantation (BMT) results in the lowest incidence of leukemic relapse, even when compared with BMT from an identical twin (syngeneic BMT). This has led to the concept of an immunologic graft-versus-leukemia effect, similar to (and related to) graft-versus-host disease. The improvement in freedom from relapse using allogeneic BMT as the primary postremission therapy is offset, at least in part, by the increased morbidity and mortality caused by graft-versus-host disease, veno-occlusive disease of the liver, and interstitial pneumonitis. The DFS rates using allogeneic transplantation in first complete remission have ranged from 45% to 60%.[11,12,13] The use of allogeneic BMT as primary postremission therapy is limited by the need for a human leukocyte antigen (HLA)-matched sibling donor and the increased mortality from allogeneic BMT of patients who are older than 50 years. The mortality from allogeneic BMT that uses an HLA-matched sibling donor ranges from 20% to 40%, depending on the series. The use of matched, unrelated donors for allogeneic BMT is being evaluated at many centers but has a very substantial rate of treatment-related mortality, with DFS rates less than 35%. Retrospective analysis of data from the International Bone Marrow Transplant Registry suggests that postremission chemotherapy does not lead to an improvement in DFS or OS for patients in first remission undergoing allogeneic BMT from an HLA-identical sibling.[Level of evidence: 3iiiA]