Cancer Treatment Today

Lay Summary: Role of allogeneic transplantation in AML depends of underlying risk of recurrence.

Allogeneic bone marrow transplantation results in the lowest incidence of leukemic relapse, even when compared with bone marrow transplantation from an identical twin (syngeneic bone marrow transplantation). 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 bone marrow transplantation 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. Disease-free survival rates using allogeneic transplantation in first complete remission have ranged from 45% to 60%. The use of allogeneic bone marrow transplantation as primary postremission therapy is limited by the need for a human leukocyte antigen (HLA)-matched sibling donor and the increased mortality from allogeneic bone marrow transplantation of patients who are older than 50 years. The mortality from allogeneic bone marrow transplantation that uses an HLA-matched sibling donor ranges from 20% to 40%, depending on the series. The use of matched, unrelated donors for allogeneic bone marrow transplantation is being evaluated at many centers but has a very substantial rate of treatment-related mortality, with disease-free survival rates less than 35%.
Because bone marrow transplantation can cure about 30% of patients who experience relapse following chemotherapy, some investigators suggested that allogeneic bone marrow transplantation can be reserved for early first relapse or second complete remission without compromising the number of patients who are ultimately cured; however, clinical and cytogenetic information can define certain subsets of patients with predictable better or worse prognoses using consolidation chemotherapy. Good-risk factors include t(8;21), inv(16) associated with M4 AML with eosinophilia, and t(15;17) associated with M3 AML. Poor-risk factors include deletion of 5q and 7q, trisomy 8, t(6;9), t(9;22), and a history of myelodysplasia or antecedent hematologic disorder. FLT status is now generally agreed to denote poor prognosis and warrant a consolidative transplant. Patients in the good-risk group have a reasonable chance of cure with intensive consolidation, and it may be reasonable to defer transplantation in that group until early first relapse. The poor-risk group is unlikely to be cured with consolidation chemotherapy, and allogeneic bone marrow transplantation in first complete remission is a reasonable option for patients with an HLA-identical sibling donor. However, even with allogeneic stem cell transplantation, the outcome for patients with high-risk AML is poor (5-year disease-free survival of 8% to 30% for patients with treatment-related leukemia or myelodysplasia). The efficacy of autologous stem cell transplantation in the poor-risk group has not been reported to date but is the subject of active clinical trials. Patients with normal cytogenetics are in an intermediate-risk group, and postremission management should be individualized or, ideally, managed according to a clinical trial.

In regard to MUD allogeneic transplant, a recent guideline says: “In the absence of an HLA-identical family donor, it seems reasonable to offer allogeneic SCT from a matched unrelated donor (MUD) to patients with poor-risk disease, either for biological features or for late achievement of CR. With the use of MUD transplantation, a long-term OS comparable to that obtained with a sibling donor, and far exceeding that observed with autotransplant, has been observed by some authors in this high-risk cohort However, the evidence supporting an advantage with MUD-SCT in high-risk patients without a sibling donor is weak.”

2016 NCCN generally recommends consolidation with Cytarabine or reduced intensity transplant but says in a footnote that says that patients who are good candidates and have an appropriate donor should be transplanted in first remission (AML-13).

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Allogeneic stem cell transplant in adult patients with acute myelogenous leukemia: a systematic analysis of international guidelines and recommendations.Leuk Lymphoma. 2011 Mar;52(3):444-57.

Yanfeng Liu et al,Prognostic significance of NPM1 mutations in acute myeloid leukemia: A meta-analysis. Oncology.
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NCCN, AML 2022

M.A. Sekeres et al, American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. Blood Adv (2020) 4 (15): 3528–3549.

Rautenberg C, Germing U, Haas R, Kobbe G, Schroeder T. Relapse of Acute Myeloid Leukemia after Allogeneic Stem Cell Transplantation: Prevention, Detection, and Treatment. Int J Mol Sci. 2019;20(1):228. Published 2019 Jan 8. doi:10.3390/ijms20010228