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

Bris, Yannick Le; Costes, Domitille; Bourgade, Raphaël; Guillaume, Thierry; Péterlin, Pierre; Garnier, Alice; Bourgeois, Amandine Le; Chevallier, Patrice; Béné, Marie‐Christine

doi:10.1038/s41409-022-01747-x

Cited by 2 publications

(1 citation statement)

References 15 publications

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“…In this context, a degree of disease-specific donor chimerism can still be sufficient to relieve the clinical phenotype but deserves close follow-up and specific therapeutic interventions. To this aim, it has been established that lineage-specific chimerism assessment is more predictive than total chimerism both in the context of malignant and nonmalignant diseases and is therefore recommended for clinical management of patients [5][6][7][8]. However, chimerism on specific fractions can only be performed after FACS-sorting or magnetic beads sorting of subsets of interest.…”

Section: Introductionmentioning

confidence: 99%

A novel flow-cytometric based method to assess post-HSCT donor chimerism exploiting RNA hybridization

Nucera,

Sindoni,

Bugarin

et al. 2023

Bone Marrow Transplant

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Analysis of donor-recipient chimerism after hematopoietic stem cell transplantation (HSCT) is of pivotal importance for patient’s clinical management, especially in the context of mixed chimerism. Patients are routinely monitored for chimerism in sorted subsets of peripheral blood cells. However, measurement of chimerism in sorted immune cell subsets is technically challenging and time consuming. We here propose a novel, flow cytometry-based approach to detect donor cell chimerism in sex-mismatched HSCT. We exploit RNA PrimeFlow™ system, based on RNA hybridization, to detect mRNA from a lysine demethylase encoded by Y chromosome, KDM5D. This approach allows to distinguish male and female derived cells with around 1% sensitivity. The procedure can be coupled with multiparametric immunophenotyping to assess chimerism in specific immune cell subsets without the need for prior FACS-sorting. We apply this method to a cohort of HSCT patients (n = 10) and we show that it is consistent with standard PCR-based method. We also show that different T lymphocyte subsets display variable degrees of donor chimerism, especially in CD8+ T cell compartment where we observe an enrichment for recipient chimerism in central memory T cells. This method can be exploited to advance current knowledge on immune reconstitution focusing on specific subsets avoiding prior FACS-sorting.

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Section: Introductionmentioning

confidence: 99%

A novel flow-cytometric based method to assess post-HSCT donor chimerism exploiting RNA hybridization

Nucera,

Sindoni,

Bugarin

et al. 2023

Bone Marrow Transplant

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Bone marrow CD34+ molecular chimerism as an early predictor of relapse after allogeneic stem cell transplantation in patients with acute myeloid leukemia

Malagola

Polverelli²,

Beghin³

et al. 2023

Front. Oncol.

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BackgroundMinimal residual disease (MRD) monitoring is an important tool to optimally address post-transplant management of acute myeloid leukemia (AML) patients.MethodsWe retrospectively analyzed the impact of bone marrow CD34+ molecular chimerism and WT1 on the outcome of a consecutive series of 168 AML patients submitted to allogeneic stem cell transplantation.ResultsThe cumulative incidence of relapse (CIR) was significantly lower in patients with donor chimerism on CD34+ cells ≥ 97.5% and WT1 < 213 copies/ABL x 10^4 both at 1st month (p=0.008 and p<0.001) and at 3rd month (p<0.001 for both). By combining chimerism and WT1 at 3rd month, 13 patients with chimerism < 97.5% or WT1 > 213 showed intermediate prognosis. 12 of these patients fell in this category because of molecular chimerism < 97.5% at a time-point in which WT1 was < 213.ConclusionsOur results confirm that lineage-specific molecular chimerism and WT1 after allo-SCT (1st and 3rd month) are useful MRD markers. When considered together at 3rd month, CD34+ molecular chimerism could represent an earlier predictor of relapse compared to WT1. Further studies are necessary to confirm this preliminary observation.

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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

Cited by 2 publications

References 15 publications

A novel flow-cytometric based method to assess post-HSCT donor chimerism exploiting RNA hybridization

A novel flow-cytometric based method to assess post-HSCT donor chimerism exploiting RNA hybridization

Bone marrow CD34+ molecular chimerism as an early predictor of relapse after allogeneic stem cell transplantation in patients with acute myeloid leukemia

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