Original Articles
Vol. 18 No. 1 (2026): Mediterranean Journal of Hematology and Infectious Diseases

POST-TRANSPLANT RELAPSE IN ACUTE LEUKEMIA: COMPARATIVE VALUE OF MRD AND CHIMERISM.

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Published: February 28, 2026
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Background: Relapse remains the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (AHSCT) in acute leukemia. Early molecular detection is critical for timely intervention. Measurable residual disease (MRD) and donor chimerism are routinely used for post-transplant monitoring, yet their comparative predictive value is uncertain.

Aims: To compare the prognostic utility of MRD and donor chimerism in predicting relapse after AHSCT in 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: Ninety-five patients relapsed (68 AML, 27 ALL). In AML, MRD positivity at month 3 (HR = 3.69, p < 0.001) and mixed chimerism (MC) (HR = 2.47, p = 0.029) were independent relapse predictors and correlated with inferior survival. MRD predicted relapse in 60% of AML cases versus 38% for MC. In ALL, only T-cell lineage independently predicted relapse (HR = 3.94, p = 0.016).

Conclusion: Post-transplant MRD monitoring at month 3 is a stronger independent predictor of relapse than chimerism in AML, while in ALL, the small cohort size limits statistical power; thus, the roles of MRD and chimerism should be interpreted cautiously.

 

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Alizadeh M, Bernard M, Danic B, Dauriac C, Birebent B, Lapart C, Lamy T, Le Prisé PY, Beauplet A, Bories D et al: Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood 2002, 99(12):4618–4625.
Contreras Yametti GP, Ostrow TH, Jasinski S, Raetz EA, Carroll WL, Evensen NA: Minimal Residual Disease in Acute Lymphoblastic Leukemia: Current Practice and Future Directions. Cancers (Basel) 2021, 13(8).
Walter RB, Ofran Y, Wierzbowska A, Ravandi F, Hourigan CS, Ngai LL, Venditti A, Buccisano F, Ossenkoppele GJ, Roboz GJ: Measurable residual disease as a biomarker in acute myeloid leukemia: theoretical and practical considerations. Leukemia 2021, 35(6):1529–1538.
Clark JR, Scott SD, Jack AL, Lee H, Mason J, Carter GI, Pearce L, Jackson T, Clouston H, Sproul A et al: Monitoring of chimerism following allogeneic haematopoietic stem cell transplantation (HSCT): technical recommendations for the use of short tandem repeat (STR) based techniques, on behalf of the United Kingdom National External Quality Assessment Service for Leucocyte Immunophenotyping Chimerism Working Group. Br J Haematol 2015, 168(1):26–37.
Lee HC, Saliba RM, Rondon G, Chen J, Charafeddine Y, Medeiros LJ, Alatrash G, Andersson BS, Popat U, Kebriaei P et al: Mixed T Lymphocyte Chimerism after Allogeneic Hematopoietic Transplantation Is Predictive for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes. Biol Blood Marrow Transplant 2015, 21(11):1948–1954.
Kruse A, Abdel-Azim N, Kim HN, Ruan Y, Phan V, Ogana H, Wang W, Lee R, Gang EJ, Khazal S et al: Minimal Residual Disease Detection in Acute Lymphoblastic Leukemia. Int J Mol Sci 2020, 21(3).
Short NJ, Zhou S, Fu C, Berry DA, Walter RB, Freeman SD, Hourigan CS, Huang X, Nogueras Gonzalez G, Hwang H et al: Association of Measurable Residual Disease With Survival Outcomes in Patients With Acute Myeloid Leukemia: A Systematic Review and Meta-analysis. JAMA Oncol 2020, 6(12):1890–1899.
Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA et al: Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017, 129(4):424–447.
Brown PA, Shah B, Advani A, Aoun P, Boyer MW, Burke PW, DeAngelo DJ, Dinner S, Fathi AT, Gauthier J et al: Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021, 19(9):1079–1109.
Pollyea DA, Bixby D, Perl A, Bhatt VR, Altman JK, Appelbaum FR, de Lima M, Fathi AT, Foran JM, Gojo I et al: NCCN Guidelines Insights: Acute Myeloid Leukemia, Version 2.2021. J Natl Compr Canc Netw 2021, 19(1):16–27.
Bader P, Kreyenberg H, Hoelle W, Dueckers G, Handgretinger R, Lang P, Kremens B, Dilloo D, Sykora KW, Schrappe M et al: Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation: possible role for pre-emptive immunotherapy? J Clin Oncol 2004, 22(9):1696–1705.
Broglie L, Helenowski I, Jennings LJ, Schafernak K, Duerst R, Schneiderman J, Tse W, Kletzel M, Chaudhury S: Early mixed T-cell chimerism is predictive of pediatric AML or MDS relapse after hematopoietic stem cell transplant. Pediatr Blood Cancer 2017, 64(9).
Ossenkoppele GJ, Schuurhuis GJ: MRD in AML: it is time to change the definition of remission. Best Pract Res Clin Haematol 2014, 27(3-4):265–271.
Ribera JM, Oriol A, Morgades M, Montesinos P, Sarrà J, González-Campos J, Brunet S, Tormo M, Fernández-Abellán P, Guàrdia R et al: Treatment of high-risk Philadelphia chromosome-negative acute lymphoblastic leukemia in adolescents and adults according to early cytologic response and minimal residual disease after consolidation assessed by flow cytometry: final results of the PETHEMA ALL-AR-03 trial. J Clin Oncol 2014, 32(15):1595–1604.
Berry DA, Zhou S, Higley H, Mukundan L, Fu S, Reaman GH, Wood BL, Kelloff GJ, Jessup JM, Radich JP: Association of Minimal Residual Disease With Clinical Outcome in Pediatric and Adult Acute Lymphoblastic Leukemia: A Meta-analysis. JAMA Oncol 2017, 3(7):e170580.
Appelbaum FR: Measurement of minimal residual disease before and after myeloablative hematopoietic cell transplantation for acute leukemia. Best Pract Res Clin Haematol 2013, 26(3):279–284.
Bastos-Oreiro M, Perez-Corral A, Martínez-Laperche C, Bento L, Pascual C, Kwon M, Balsalobre P, Muñoz C, Buces E, Serrano D et al: Prognostic impact of minimal residual disease analysis by flow cytometry in patients with acute myeloid leukemia before and after allogeneic hemopoietic stem cell transplantation. Eur J Haematol 2014, 93(3):239–246.
Shah MV, Jorgensen JL, Saliba RM, Wang SA, Alousi AM, Andersson BS, Bashir Q, Ciurea SO, Kebriaei P, Marin D et al: Early Post-Transplant Minimal Residual Disease Assessment Improves Risk Stratification in Acute Myeloid Leukemia. Biol Blood Marrow Transplant 2018, 24(7):1514–1520.
Klyuchnikov E, Badbaran A, Massoud R, Fritsche-Friedland U, Janson D, Ayuk F, Christopeit M, Wolschke C, Bacher U, Kröger N: Post-Transplantation Multicolored Flow Cytometry-Minimal Residual Disease Status on Day 100 Predicts Outcomes for Patients With Refractory Acute Myeloid Leukemia. Transplant Cell Ther 2022, 28(5):267.e261–267.e267.
Lamba R, Abella E, Kukuruga D, Klein J, Savasan S, Abidi MH, Mohamed A, Peres E: Mixed hematopoietic chimerism at day 90 following allogenic myeloablative stem cell transplantation is a predictor of relapse and survival. Leukemia 2004, 18(10):1681–1686.
Scheffold C, Kroeger M, Zuehlsdorf M, Tchinda J, Silling G, Bisping G, Stelljes M, Buechner T, Berdel WE, Kienast J: Prediction of relapse of acute myeloid leukemia in allogeneic transplant recipients by marrow CD34+ donor cell chimerism analysis. Leukemia 2004, 18(12):2048–2050.
Bernal T, Diez-Campelo M, Godoy V, Rojas S, Colado E, Alcoceba M, González M, Vidriales B, Sánchez-Guijo FM, López-Corral L et al: Role of minimal residual disease and chimerism after reduced-intensity and myeloablative allo-transplantation in acute myeloid leukemia and high-risk myelodysplastic syndrome. Leuk Res 2014, 38(5):551–556.
Loke J, McCarthy N, Jackson A, Siddique S, Hodgkinson A, Mason J, Crawley C, Gilleece M, Peniket A, Protheroe R et al: Posttransplant MRD and T-cell chimerism status predict outcomes in patients who received allografts for AML/MDS. Blood Adv 2023, 7(14):3666–3676.
Georgi JA, Stasik S, Bornhäuser M, Platzbecker U, Thiede C: Analysis of Subset Chimerism for MRD-Detection and Pre-Emptive Treatment in AML. Front Oncol 2022, 12:841608.
Pincez T, Santiago R, Bittencourt H, Louis I, Bilodeau M, Rouette A, Jouan L, Landry JR, Couture F, Richer J et al: Intensive monitoring of minimal residual disease and chimerism after allogeneic hematopoietic stem cell transplantation for acute leukemia in children. Bone Marrow Transplant 2021, 56(12):2981–2989.
Andreani G, Cilloni D: Strategies for minimal residual disease detection: current perspectives. Blood Lymphat Cancer 2019, 9:1–8.
Della Starza I, Chiaretti S, De Propris MS, Elia L, Cavalli M, De Novi LA, Soscia R, Messina M, Vitale A, Guarini A et al: Minimal Residual Disease in Acute Lymphoblastic Leukemia: Technical and Clinical Advances. Front Oncol 2019, 9:726.
Ladetto M, Böttcher S, Kröger N, Pulsipher MA, Bader P: Methods and role of minimal residual disease after stem cell transplantation. Bone Marrow Transplant 2019, 54(5):681–690.
Terwey TH, Hemmati PG, Nagy M, Pfeifer H, Gökbuget N, Brüggemann M, Le Duc TM, le Coutre P, Dörken B, Arnold R: Comparison of chimerism and minimal residual disease monitoring for relapse prediction after allogeneic stem cell transplantation for adult acute lymphoblastic leukemia. Biol Blood Marrow Transplant 2014, 20(10):1522–1529.
Tsirigotis P, Byrne M, Schmid C, Baron F, Ciceri F, Esteve J, Gorin NC, Giebel S, Mohty M, Savani BN et al: Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT. Bone Marrow Transplant 2016, 51(11):1431–1438.
Shen Z, Gu X, Mao W, Yin L, Yang L, Zhang Z, Liu K, Wang L, Huang Y: Influence of pre-transplant minimal residual disease on prognosis after Allo-SCT for patients with acute lymphoblastic leukemia: systematic review and meta-analysis. BMC Cancer 2018, 18(1):755.
Greil C, Engelhardt M, Ihorst G, Duque-Afonso J, Shoumariyeh K, Bertz H, Marks R, Zeiser R, Duyster J, Finke J et al: Prognostic factors for survival after allogeneic transplantation in acute lymphoblastic leukemia. Bone Marrow Transplant 2021, 56(4):841–852.

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How to Cite



“POST-TRANSPLANT RELAPSE IN ACUTE LEUKEMIA: COMPARATIVE VALUE OF MRD AND CHIMERISM”. (2026) Mediterranean Journal of Hematology and Infectious Diseases, 18(1). doi:10.4084/MJHID.2026.028.