Lost in Transplantation? Unexpected shift from multipotent to late lymphomyeloid hematopoietic stem and progenitor cells in patients 1 year after hematopoietic stem cell transplantation

Görgens, André; Murke, Florian; Kordelas, Lambros; Giebel, Bernd

doi:10.1038/bmt.2016.146

Cited by 2 publications

(2 citation statements)

References 18 publications

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“…We recently published data on the distribution of CD34 subsets between various stem cell sources and showed that early CD45RA − CD133 + CD38 low subpopulations are significantly more frequent in PBSC than in BM of healthy donors, and very low in the BM of patients 1 year after allogeneic transplantation . In the present study we focused on differences between PBSC mobilized either with GP or CGP.…”

Section: Discussionmentioning

confidence: 82%

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure

Worel

Fritsch

Agis

et al. 2016

J of Clinical Apheresis

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Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 10 CD34 cells/kg for a single or ≥5 × 10 CD34 cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34 cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34 cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 10 CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19 and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.

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Section: Discussionmentioning

confidence: 82%

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure

Worel

Fritsch

Agis

et al. 2016

J of Clinical Apheresis

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“…To better estimate correlations with MLPs after cryopreservation, the flow panel might be expanded to include B lymphocyte-specific antibodies. To mimic the in vivo situation, placing the cells into a niche-like model after thawing might be an option, and this has already been realized by some groups using mesenchymal stromal cells [34][35][36][37].…”

Section: Subpopulations After Cryopreservationmentioning

confidence: 99%

Flow Cytometric Characterization of Hematopoietic Stem and Progenitor Cell Subpopulations in Autologous Peripheral Blood Stem Cell Preparations after Cryopreservation

Heuer,

Löwhagen,

Uhlig

et al. 2023

Transfus Med Hemother

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Introduction: Autologous stem cell transplantation is a successful routine procedure with only a small number of non-engraftment cases, although the time to hematopoietic recovery may vary considerably across patients. While CD34 has been the decisive marker for enumerating hematopoietic stem and progenitor cells (HSPCs) for more than 30 years, the impact of CD34-positive cellular subpopulations in autologous HSPC grafts on hematopoietic reconstitution remains unclear. Methods: The two-color ISHAGE protocol represents the current gold standard for CD34+ cell enumeration but includes only the number of viable CD45+/CD34+ cells relative to the body weight of the recipient. We adapted a multicolor flow cytometry marker panel for advanced characterization of CD34 subpopulations in retained samples of autologous peripheral blood stem cell products (n = 49), which had been cryostored for a wide range from 4 to 15 years. The flow cytometric analysis included CD10, CD34, CD38, CD45, CD45RA, CD133, and viability staining with 7AAD. The findings were correlated with clinical engraftment data, including reconstitution of leukocytes, neutrophils, and platelets after transplantation (TPL). Results: We demonstrated that the identification of autologous HSPC subpopulations by flow cytometry after cryopreservation is feasible. Regarding the distribution of HSPC subpopulations, a markedly different pattern was observed in comparison to previously published data obtained using fresh autologous material. Our data revealed the largest ratio of lympho-myeloid progenitors (LMPPs) after freezing and thawing, followed by multipotent progenitors and erythroid-myeloid progenitors. A high ratio of LMPPs, representing an immature stage of differentiation, correlated significantly with early neutrophilic granulocyte and leukocyte engraftment (p = 0.025 and p = 0.003). Conversely, a large ratio of differentiated cells correlated with late engraftment of neutrophilic granulocytes (p = 0.024). Overall, successful engraftment was documented for all patients. Conclusion: We established an advanced flow cytometry panel to assess the differentiation ability of cryostored autologous peripheral blood stem cell grafts and correlated it with timely hematopoietic reconstitution. This approach represents a novel and comprehensive way to identify hematopoietic stem and progenitor subpopulations. It is a feasible way to indicate the engraftment capacity of stem cell products.

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Lost in Transplantation? Unexpected shift from multipotent to late lymphomyeloid hematopoietic stem and progenitor cells in patients 1 year after hematopoietic stem cell transplantation

Cited by 2 publications

References 18 publications

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure

Flow Cytometric Characterization of Hematopoietic Stem and Progenitor Cell Subpopulations in Autologous Peripheral Blood Stem Cell Preparations after Cryopreservation

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