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Impact on outcomes of mixed chimerism of bone marrow CD34+ sorted cells after matched or haploidentical allogeneic stem cell transplantation for myeloid malignancies

Abstract

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT), proposed to patients with high-risk myeloid malignancies, may ultimately fail because of disease relapse. Bone marrow (BM) CD34+ cells in Allo-HSCT recipients can be either re-emerging recipient malignant cells or donor cells attesting of hematopoietic reconstitution. In this context, investigating donor/recipient chimerism in the population of BM CD34+ sorted cells (BM-CD34+SC) was performed in 261 Allo-HSCT recipients (matched n = 145, haploidentical n = 65, matched unrelated n = 51) with myeloid malignancies. BM-CD34+SC chimerism was compared to that of whole peripheral blood (PB) cells as well as other Allo-HSCT-related parameters, and impact on relapse and survival was assessed. Thresholds of 98% donor cells for PB and 90% for BM-CD34+SC were found to allow relapse prediction. This was completed by the application of machine learning tools to explore the predictive value of these parameters in multidimensional models with repeated iterations. BM-CD34+SC mixed chimerism stood out with all these methods as the most robust predictor of relapse with a significant impact on disease-free and overall survivals even after haploidentical Allo-HSCT and/or PTCY administration. This marker therefore appears to be of great interest for the decision of preemptive treatment to avoid post-transplant relapse.

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Fig. 1: Impact of BM CD34+SC chemotherapy on patient survivals.
Fig. 2: Features importance in predicting relapse with a Random Forest classifier, based on 100 iterations.

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All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.

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Acknowledgements

The authors are grateful to the technical staff in the molecular hematology laboratory of Nantes Hematology Biology department for their involvement in the study.

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YLB designed the study, analyzed the data, performed statistics and wrote the manuscript. DC collected clinical information and AlloHSCT outcomes from the patient files. RB designed and performed machine learning analyzes. TG, PP and AG managed the patients and supervised sampling. PC designed the study, provided samples, contributed to data analysis and wrote the manuscript. MCB performed analyzes and wrote the manuscript.

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Correspondence to Yannick Le Bris.

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Le Bris, Y., Costes, D., Bourgade, R. et al. Impact on outcomes of mixed chimerism of bone marrow CD34+ sorted cells after matched or haploidentical allogeneic stem cell transplantation for myeloid malignancies. Bone Marrow Transplant (2022). https://doi.org/10.1038/s41409-022-01747-x

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