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Defining a lineage-specific chimerism threshold for the use of donor lymphocyte infusions in treating myeloid malignancies

Bone Marrow Transplantation volume 60, pages 535–537 (2025)Cite this article

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Although allogeneic stem cell transplantation (aSCT) is potentially curative for myeloid neoplasms (MN), outcomes are frequently compromised by relapse [1,2,3]. Lineage-specific chimerism (LSC) may have utility in predicting post-aSCT outcomes and guiding decision-making on the initiation of donor lymphocyte infusions (DLI) to stave off incident relapse [4,5,6]. No widely accepted LSC threshold currently exists that can identify patients most likely to benefit from DLI.

This retrospective study was conducted in accordance with the Yale IRB, and examined peripheral blood from 94 MN patients between 2016-2023 with ≥1 LSC study after aSCT. Each LSC panel included data for unsorted, myeloid (MC), and T-cell (TC) chimerism. As a significant number of patients (N = 44, 46.8%) had no follow-up LSC data, the most recent LSC panel was used for patients with no evidence of relapse. Relapse and graft failure were determined based on established guidelines, and in these cases, the closest LSC panel to this event was used [7, 8]. The panel immediately prior to DLI infusion was used for those treated with DLI (N = 21). The most common indications for LSC testing were declining unsorted chimerism values and recurrent disease-specific molecular or cytogenetic alterations.

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Fig. 1: Kaplan-Meier Curves for DLI and LSC Threshold Values.

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Data from this manuscript will be made available upon reasonable request of the authors.

References

  1. Döhner H, Wei AH, Appelbaum FR, Craddock C, DiNardo CD, Dombret H, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022;140:1345–77.

    Article  PubMed  Google Scholar 

  2. Abou Dalle I, Atoui A, Bazarbachi A. The Elephant in The Room: AML Relapse Post Allogeneic Hematopoietic Cell Transplantation. Front Oncol 2021;11:793274.

    Article  PubMed  Google Scholar 

  3. Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, et al. Myeloablative Versus Reduced-Intensity Hematopoietic Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndromes. J Clin Oncol 2017;35:1154–61.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Koreth J, Kim HT, Nikiforow S, Milford EL, Armand P, Cutler C, et al. Donor chimerism early after reduced-intensity conditioning hematopoietic stem cell transplantation predicts relapse and survival. Biol Blood Marrow Transplant 2014;20:1516–21.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lee HC, Saliba RM, Rondon G, Chen J, Charafeddine Y, Medeiros LJ, 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;21:1948–54.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Saito B, Fukuda T, Yokoyama H, Kurosawa S, Takahashi T, Fuji S, et al. Impact of T cell chimerism on clinical outcome in 117 patients who underwent allogeneic stem cell transplantation with a busulfan-containing reduced-intensity conditioning regimen. Biol Blood Marrow Transplant 2008;14:1148–55.

    Article  CAS  PubMed  Google Scholar 

  7. Cheson BD, Bennett JM, Kopecky KJ, Büchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003;21:4642–9.

    Article  PubMed  Google Scholar 

  8. Valcárcel D, Sureda A Graft Failure. In: Carreras E, Dufour C, Mohty M, Kröger N, editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. Cham (CH): Springer Copyright 2019, EBMT and the Author(s). 2019;307-13.

  9. Bendjelloul M, Usureau C, Etancelin P, Saidak Z, Lebon D, Garçon L, et al. Utility of assessing CD3(+) cell chimerism within the first months after allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia. Hla 2022;100:18–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hoffmann JC, Stabla K, Burchert A, Volkmann T, Bornhäuser M, Thiede C, et al. Monitoring of acute myeloid leukemia patients after allogeneic stem cell transplantation employing semi-automated CD34+ donor cell chimerism analysis. Ann Hematol 2014;93:279–85.

    Article  CAS  PubMed  Google Scholar 

  11. Azam F, Latif MF, Farooq A, Tirmazy SH, AlShahrani S, Bashir S, et al. Performance Status Assessment by Using ECOG (Eastern Cooperative Oncology Group) Score for Cancer Patients by Oncology Healthcare Professionals. Case Rep. Oncol 2019;12:728–36.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

The authors (CJP, SS, HR, CAT, AJS) have no relevant funding to disclose.

Author information

Authors and Affiliations

  1. Yale School of Medicine, New Haven, CT, USA

    Christian J. Puzo

  2. Department of Hematology, Yale School of Medicine, New Haven, CT, USA

    Stuart Seropian

  3. Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA

    Henry Rinder, Christopher A. Tormey & Alexa J. Siddon

  4. Department of Pathology, Yale School of Medicine, New Haven, CT, USA

    Alexa J. Siddon

Authors
  1. Christian J. Puzo
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  2. Stuart Seropian
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  3. Henry Rinder
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  4. Christopher A. Tormey
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  5. Alexa J. Siddon
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Contributions

AJS was responsible for generating the initial research question, overseeing data collection, and contributing to the final manuscript. CJP collected and analyzed the data and wrote the manuscript. SS, HR, and CAT contributed critical edits to the final manuscript.

Corresponding author

Correspondence to Alexa J. Siddon.

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The authors declare no competing interests.

Ethics statement

This retrospective study was conducted in accordance with the Declaration of Helsinki and in accordance with the IRB of Yale School of Medicine (ID 2000034785).

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Puzo, C.J., Seropian, S., Rinder, H. et al. Defining a lineage-specific chimerism threshold for the use of donor lymphocyte infusions in treating myeloid malignancies. Bone Marrow Transplant 60, 535–537 (2025). https://doi.org/10.1038/s41409-025-02510-8

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