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Adult Acute Myeloid Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Adult Acute Myeloid Leukemia in Remission

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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%.[14] 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.[15][Level of evidence: 3iiiA]

Autologous BMT yielded DFS rates between 35% and 50% in patients with AML in first remission. Autologous BMT has also cured a smaller proportion of patients in second remission.[17,18,19,20,21,22,23] Treatment-related mortality rates of patients who have had autologous peripheral blood or marrow transplantation range from 10% to 20%. Ongoing controversies include the optimum timing of autologous stem cell transplantation, whether it should be preceded by postremission chemotherapy, and the role of ex vivo treatment of the graft with chemotherapy, such as 4-hydroperoxycyclophosphamide (4-HC) [21] or mafosphamide,[22] or monoclonal antibodies, such as anti-CD33.[23] Purged marrows have demonstrated delayed hematopoietic recovery; however, most studies that use unpurged marrow grafts have included several cycles of postremission chemotherapy and may have included patients who were already cured of their leukemia.

In a prospective trial of patients with AML in first remission, City of Hope investigators treated patients with one course of high-dose cytarabine postremission therapy, followed by unpurged autologous BMT following preparative therapy of total-body radiation therapy, etoposide, and cyclophosphamide. In an intent-to-treat analysis, actuarial DFS was approximately 50%, which is comparable to other reports of high-dose postremission therapy or purged autologous transplantation.[24][Level of evidence: 3iiDii]

A randomized trial by ECOG and the Southwest Oncology Group (SWOG) compared autologous BMT using 4-HC-purged bone marrow with high-dose cytarabine postremission therapy.[25] No difference in DFS was found between patients treated with high-dose cytarabine, autologous BMT, or allogeneic BMT; however, OS was superior for patients treated with cytarabine compared with those who received BMT.[25][Level of evidence: 1iiA]

A randomized trial has compared the use of autologous BMT in first CR with postremission chemotherapy, with the latter group eligible for autologous BMT in second CR. The two arms of the study had equivalent survival.[26] Two randomized trials in pediatric AML have shown no advantage of autologous transplantation following busulfan/cyclophosphamide preparative therapy and 4HC-purged graft when compared with postremission chemotherapy, including high-dose cytarabine.[27,28] An additional randomized Groupe Ouest Est d'etude des Leucemies et Autres Maladies du Sang trial (NCT01074086) of autologous BMT versus intensive postremission chemotherapy in adult AML, using unpurged bone marrow, showed no advantage to receiving autologous BMT in first remission.[29] Certain subsets of AML may specifically benefit from autologous BMT in first remission. In a retrospective analysis of 999 patients with de novo AML treated with allogeneic or autologous BMT in first remission in whom cytogenetic analysis at diagnosis was available, patients with poor-risk cytogenetics (abnormalities of chromosomes 5, 7, 11q, or hypodiploidy) had less favorable outcomes following allogeneic BMT than patients with normal karyotypes or other cytogenetic abnormalities. Leukemia-free survival for the patients in the poor-risk groups was approximately 20%.[30][Level of evidence: 3iiiDii]

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