Post-Transplant Relapse in Acute Leukemia: Comparative Value of MRD and Chimerism

Mediterr J Hematol Infect Dis. 2026 Mar 1;18(1):e2026028. doi: 10.4084/MJHID.2026.028. eCollection 2026.

Abstract

Background: Relapse remains the principal cause of treatment failure after allogeneic hematopoietic stem cell transplantation (AHSCT) in acute leukemia. Post-transplant surveillance commonly relies on measurable residual disease (MRD) and donor chimerism monitoring; however, their relative predictive value and optimal timing remain uncertain.

Aims: To compare the prognostic performance of MRD and donor chimerism in predicting relapse after AHSCT in adult patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Methods: This retrospective cohort included 264 adults (186 AML, 78 ALL) who underwent AHSCT. MRD was assessed by multiparametric flow cytometry on day 28 and at months 3 and 12, and chimerism by short tandem repeat PCR. Cox regression identified independent relapse predictors.

Results: Relapse occurred in 95 patients (68 AML, 27 ALL). In AML, MRD positivity at month 3 (HR 3.69, p<0.001) and mixed total chimerism at month 3 (HR 2.47, p=0.029) independently predicted relapse and were associated with inferior overall and disease-free survival. MRD detected relapse earlier and with greater sensitivity than chimerism. In ALL, total mixed chimerism at month 3 was associated with relapse in univariate analysis, whereas MRD showed limited statistical power due to small sample size.

Conclusion: Post-transplant MRD monitoring at month 3 provides superior risk stratification compared with chimerism in AML. In ALL, both approaches appear complementary, but conclusions are limited by cohort size. Disease-specific, risk-adapted surveillance strategies are warranted.

Keywords: Acute leukemias; Allogeneic hematopoietic stem cell transplantation; Chimerism; Measurable residual disease; Multiparametric flow cytometry.