MRD positivity was the poor prognostic factor for adverse-risk AML patients with allogeneic hematopoietic stem cell transplantation: a multicenter TROPHY study

Acute myeloid leukemia (AML) is a highly heterogeneous disease distinguished by different cytogenetic and genetic characteristics [1,2].Currently, the risk classification based on the cytogenetics and molecular markers (e.g., the European LeukemiaNet [ELN] risk stratification) is the mainstay criterion that direct the treatments of adult AML patients, and those with adverse-risk AML are recommended to receive allogeneic hematopoietic stem cell transplantation (allo-HSCT) in their first complete remission (CR1) [1,3].Several studies have reported that the efficacy of allo-HSCT is superior to that of those receiving consolidation chemotherapy alone in adverse-risk AML patients and the benefit of allo-HSCT is observed across ages and donor type [4].Measurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) is the commonly used approach to predict post-transplant relapse in AML [5][6][7][8][9].Many studies reported that the risk of post-transplant relapse significantly increased in patients who were MFC positivity before allo-HSCT [10-12]; however, some authors suggested that pre-transplant MFC MRD was less important in predicting relapse than variables reflecting the biology of the disease (e.g., cytogenetics) [13].Thus far, the prognostic value of pre-HSCT MFC MRD positivity is still controversial in AML patients.In addition, no study had compared the clinical outcomes between patients who were MRD positivity and MRD negativity in the adverse-risk AML group.In the present study, we aimed to identify the prognostic value of pre-HSCT MFC MRD positivity in patients with adverse-risk AML, which may further optimize the timing of allo-HSCT.This multicenter, retrospective study based on the transplant database of Wuhan Tongji Hospital, Shanghai Ruijin Hospital, and Peking University Institute of Hematology (PUIH) (i.e., TROPHY group).Consecutive AML patients receiving allo-HSCT from January 2017 to June 2022 were screened, and the eligibility criteria were as follows: (1) aged ≥ 16 years; (2) adverse-risk AML based on ELN 2022 criteria; (3) achieving CR1 before allo-HSCT.The last follow-up was June 30, 2023.The study was approved by the institutional review board of each participated hospital and was conducted in accordance with the Declaration of Helsinki.The protocols for preconditioning regimen, graft-versus-host disease prophylaxis, and infection prophylaxis were reported previously [14,15].MRD status was monitored after consolidation chemotherapy, before allo-HSCT and at 1, 2, 3, 4, 5, 6, 9, and 12 months after allo-HSCT and at 6-month intervals thereafter.