Allo-HCT Not Linked With Better OS vs Consolidation Chemotherapy in AML Patients in Complete Remission

While treatment with allogeneic hematopoietic cell transplantation (allo-HCT) showed improved disease-free survival compared with conventional consolidation chemotherapy, the findings suggest there may not be an overall survival (OS) benefit with allo-HCT for patients with intermediate-risk acute myeloid leukemia (AML) during first complete remission.

Findings of a randomized clinical trial published in JAMA Oncology suggest that primary allogeneic hematopoietic cell transplantation (HCT) may not improve overall survival (OS) compared with consolidation chemotherapy in patients with intermediate-risk acute myeloid leukemia (AML) during first complete remission (CR).

A significant proportion of patients with AML achieve CR, but the optimal treatment algorithm for intermediate-risk patients in this population is not clear, study authors noted. While consolidation chemotherapy based on high-dose cytarabine is known to benefit patients who are lower risk during first CR, allogeneic HCT (allo-HCT) is an option for high-risk patients when a donor can be found. Allo-HCT carries the lowest risk of relapse but a significant risk of transplant-related mortality, and some intermediate-risk patients can still respond to allo-HCT after AML relapse, the authors said.

In the randomized phase 3, open-label, 2-armed clinical trial (NCT01246752), patients with intermediate-risk AML at 16 hospitals in Germany received either allo-HCT or high-dose cytarabine for consolidation during first CR or CR with incomplete blood cell count recovery after standard induction therapy. In the cytarabine cohort, salvage HCT was only used in case of relapse.

The main end point was 2-year OS, and secondary end points included disease-free survival (DFS), cumulative incidence of relapse, treatment-related mortality, and quality of life.

A total of 143 patients aged 60 or younger (mean age, 48.2 years) were eligible for the study and were randomized 1 to 1 to either treatment. The allo-HCT group included 76 patients, and the consolidation chemotherapy group included 67 patients. In the allo-HCT cohort, 12 patients received 1 consolidation course of high-dose cytarabine to bridge until allo-HCT.

The probability of 2-year survival in the intention-to-treat analysis was 74% (95% CI, 62%-83%) after primary allogeneic HCT and 84% (95% CI, 73%-92%) after conventional consolidation chemotherapy (P = .22). DFS at 2 years was 69% (95% CI, 57%-80%) with allo-HCT compared with 40% (95% CI, 28%-53%) after consolidation chemotherapy (P = .001).

In the allo-HCT group, the cumulative incidence of relapse at 2 years was 20% (95% CI, 13%-31%), while the consolidation chemotherapy group had a cumulative incidence of relapse of 58% (95% CI, 47%-71%; P < .001) at 2 years. After primary allo-HCT, non-relapse mortality at 2 years was 9% (95% CI, 5%-19%), versus 2% (95% CI, 0%-11%) after consolidation chemotherapy (P = .005). Both cohorts had similar health-related quality of life.

Notably, all 41 patients in the consolidation chemotherapy group who relapsed in the study subsequently underwent allo-HCT either directly or after salvage therapy.

While patients treated with allo-HCT showed improved DFS compared with those given conventional consolidation chemotherapy, the findings suggest there may not be an OS benefit to opting for allo-HCT versus consolidation chemotherapy for intermediate-risk AML patients during first CR.

“The results of this randomized clinical trial support the notion that patients 60 years or younger with intermediate-risk AML, as defined by Medical Research Council cytogenetic criteria, despite an improved DFS, do not benefit from allo-HCT during first CR with regard to OS,” the authors concluded. “The early identification of a suitable donor allows timely rescuing of those patients with relapse after conventional consolidation chemotherapy.”

In future research, the authors note the importance of longitudinal monitoring of residual disease dynamics in this patient population to help determine the optimal timing for allo-HCT.


Bornhäuser M, Schliemann C, Schetelig J, et al. Allogeneic hematopoietic cell transplantation vs standard consolidation chemotherapy in patients with intermediate-risk acute myeloid leukemia. JAMA Oncol. Published online February 9, 2023. doi:10.1001/jamaoncol.2022.7605

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