Early Immune Intervention is Key to Managing Posttransplant Relapse in AML

Timely donor lymphocyte infusion (DLI) following the detection of impending molecular relapse may significantly improve outcomes for patients with acute myeloid leukemia (AML) who undergo allogeneic hematopoietic stem cell transplantation (alloHSCT) with active disease, according to a retrospective study published in Leukemia Research.¹

The single-center study analyzed 67 patients who experienced relapse after receiving their first alloHSCT for active AML between 2014 and 2024. Investigators categorized patients into 2 cohorts: those with impending molecular relapse (n=42) and those with overt hematologic relapse (n=25). Impending relapse was defined by the persistence or recurrence of genetic aberrations or a drop in CD34-positive (CD34+) donor chimerism to less than 95%.

Key Findings: CD34+ Chimerism as a Sentinel Marker

A key finding of the analysis was the sensitivity of CD34+ donor chimerism in predicting relapse. Among patients in the impending relapse group, 88% exhibited a decrease in CD34+ chimerism, with a median level of 78%. Only 12% of patients in this cohort harbored molecular evidence of relapse without a concomitant drop in chimerism.

Clinical outcomes differed sharply based on the stage at which relapse was identified and treated. Patients diagnosed during the impending molecular phase achieved a 2-year overall survival (OS) of 45% (95% CI, 31%-64%), with 57% achieving measurable residual disease (MRD)-negative remissions after DLI. In contrast, those who presented with overt hematologic relapse faced a dismal prognosis, with a 1-year OS of only 24% (95% CI, 12%-48%).

“Interestingly, we detected a novel FLT3-ITD mutation in a patient experiencing impending relapse, which indicates clonal evolution,” noted authors Ronnacker et al in the discussion section.¹ “This underscores the importance of repeated molecular profiling, even in cases of impending relapse, as it may lead to opportunities for targeted therapies such as gilteritinib [Xospata].”

Importantly, receipt of DLI was associated with improved relapse-free survival (RFS), with RFS being significantly shorter in patients with impending relapse who did not receive DLI compared with those receiving DLI-based therapies (HR, 3.23; 95% CI, 1.22-8.33; P =.02).

Clinical Implications

Treatment for overt relapse remains a significant challenge. In the study, patients who progressed to overt relapse received a variety of treatments, including intensive salvage chemotherapy, hypomethylating agents, or targeted therapies. Despite these interventions, the 1-year OS remained low, and only 5 patients were able to proceed to a second alloHSCT.

The data suggest that proactive immune-based interventions guided by CD34+ donor chimerism monitoring can induce durable remissions and may be an effective tool for preventing progression to overt leukemia. The authors recommend frequent assessment of CD34+ donor chimerism as a primary surveillance tool, noting that it often precedes hematologic relapse by several weeks or months.

“Our data align with previous reports, underscoring the importance of close and standardized follow-up after transplantation, especially in high-risk AML,” the authors concluded.¹ “If relapse is imminent, early immune intervention should be initiated whenever feasible. Continued improvements in posttransplant monitoring, coupled with the increasing availability of targeted therapies, are essential to further improve the survival of high-risk patients [with AML].”

REFERENCES

1. Ronnacker J, Urbahn MA, Reicherts C, et al. Relapse after allogeneic hematopoietic stem cell transplantation in patients with active acute myeloid leukemia. Leukemia Res. 2025;160:108153-108153. doi:10.1016/j.leukres.2025.108153