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MRD Status and Remission Number Impact HSCT Outcomes in AML

• A retrospective study of 580 AML patients undergoing allo-HSCT revealed the impact of pre-transplant MRD status on outcomes. • Patients in second complete remission (CR) had distinct characteristics, including higher rates of FLT3-ITD mutations and normal karyotype. • MRD assessment before HSCT is crucial for refining risk stratification and predicting outcomes in AML patients. • The study highlights the importance of considering both genetic risk and MRD status when evaluating AML patients for HSCT.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a curative option for acute myeloid leukemia (AML). A recent study published in Blood Advances investigated the impact of measurable residual disease (MRD) status and the number of remissions on HSCT outcomes in AML patients.
The retrospective study, led by Jentzsch et al., evaluated 580 AML patients who underwent their first allo-HSCT between January 1999 and November 2020. The study aimed to assess the predictive value of genetic risk stratification models and MRD status on patient outcomes following HSCT in first or second remission.

Study Design and Patient Characteristics

The study included patients with cytogenetic analysis at diagnosis, including mutation status of CEBPA, NRM1, and internal tandem duplication (ITD) in FLT3 (FLT3-ITD). MRD assessment was performed up to 28 days before HSCT using remission samples. The median follow-up time was 3.9 years. The median age at HSCT was 59.6 years, with 72% of patients receiving nonmyeloablative or reduced-intensity conditioning and 28% myeloablative conditioning.

Key Findings

Patients undergoing HSCT in the second CR or CR with incomplete peripheral cell count recovery (CRi) period (n = 120) compared to those transplanted in first CR/CRi (n = 460) showed an increased likelihood of de novo AML (p = 0.002), NPM1 mutation (p = 0.03), normal karyotype (p < 0.001), and FLT3-ITD mutation (p < 0.001). Patients in second CR/CRi also had elevated levels of hemoglobin (p = 0.01), white blood cell counts (p = 0.006), and bone marrow blasts (p = 0.03) when compared with baseline levels. This group had a lower likelihood of having a monosomal or complex karyotype and received fewer cycles of chemotherapy prior to HSCT. They also more often received grafts from human leukocyte antigen (HLA)-mismatched donors compared with patients in their first CR/CRi receiving other types of grafts.

Clinical Implications

The study underscores the importance of MRD assessment prior to HSCT in AML patients. Considering both genetic risk and MRD status can refine risk stratification and improve outcome prediction. The distinct characteristics of patients undergoing HSCT in second remission highlight the need for tailored treatment strategies in this population.
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Reference News

[1]
Impact of MRD status and number of remissions on HSCT outcomes - AML Hub
aml-hub.com · Nov 7, 2022

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for AML patients, especially in firs...

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