Dataset Information

Fetal hemoglobin and F-cell variance in mobilized CD34⁺ cell-transplanted rhesus monkeys.

ABSTRACT: Elevated fetal hemoglobin (HbF) is associated with reduced severity of sickle cell disease. Therefore, γ-globin protein levels and F-cell (HbF-positive red blood cell) percentages are used for estimation of clinical benefit. Here, we monitored transplantation-related changes in HbF and F-cell percentages for rhesus macaques (Macaca mulatta) following total body irradiation or busulfan conditioning prior to CD34⁺ cell transplantation. HbF protein expression peaked in the first 4-9 weeks posttransplant (0.99%-2.53%), and F-cells increased in the first 6-17 weeks posttransplant (8.7%-45.3%). HbF and F-cell ratios gradually decreased and stabilized to levels similar to those of control animals (1.96 ± 1.97% for F cells and 0.49 ± 0.19% γ-globin expression) 4-7 months post-transplant. These findings confirm and expand on previous reports of transient induction in HbF and F-cell percentages in rhesus macaques following CD34⁺ cell transplantation, an observation that must be taken into consideration when evaluating therapeutic strategies that aim to specifically elevate HbF expression, which are currently in clinical development.

SUBMITTER: Demirci S

PROVIDER: S-EPMC8459570 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Fetal hemoglobin and F-cell variance in mobilized CD34<sup>+</sup> cell-transplanted rhesus monkeys.

Demirci Selami S Mora Juan J Haro JJH Yapundich Morgan M Drysdale Claire C Gamer Jackson J Nassehi Tina T Bonifacino Aylin C AC Krouse Allen E AE Linde Nathaniel S NS Donahue Robert E RE Tisdale John F JF Uchida Naoya N

Experimental hematology 20190605

Elevated fetal hemoglobin (HbF) is associated with reduced severity of sickle cell disease. Therefore, γ-globin protein levels and F-cell (HbF-positive red blood cell) percentages are used for estimation of clinical benefit. Here, we monitored transplantation-related changes in HbF and F-cell percentages for rhesus macaques (Macaca mulatta) following total body irradiation or busulfan conditioning prior to CD34<sup>+</sup> cell transplantation. HbF protein expression peaked in the first 4-9 week ...[more]

PMID: 31173819

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Project description:CD34+-selected stem cell boost (SCB) without conditioning has recently been utilized for poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation with promising results. Unfortunately, many patients have been unable to receive the boost infusion as their donors were unwilling or unable to undergo an additional stem cell collection. Therefore, we conducted this study utilizing either fresh or cryopreserved peripheral blood stem cell products to create CD34+-selected boost infusions for the treatment of PGF. Additionally, to explore relationship of CD34+ dose and response, we included a cohort of donors mobilized with plerixafor in addition to the standard granulocyte colony-stimulating factor (G-CSF). Twenty-six patients with PGF were included in this study. Seventeen donor-recipient pairs were enrolled onto the prospective study; an additional 9 patients treated off protocol were reviewed retrospectively. Three different donor products were used for CD34+ selection: (1) fresh mobilized product using G-CSF only, (2) fresh mobilized products using G-CSF and plerixafor, and (3) cryopreserved cells mobilized with G-CSF. CD34+ cell selection was performed using a CliniMACS. The infusion was not preceded by administration of any chemotherapy or conditioning regimen. The primary objective was hematologic response rate and secondary objectives included CD34+ yields, incidence and severity of acute and chronic graft-versus-host disease (GVHD), overall survival (OS), and relapse-free survival (RFS). The median post-selection CD34+ counts per kilogram of recipient weight were 3.1 × 106, 10.9 × 106, and 1 × 106 for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. The median CD34+ yields (defined as the number of CD34+ cells after selection/CD34+ cells before CD34+ selection) were 69%, 66%, and 28% for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. After SCB, 16 of the 26 recipients (62%) had a complete response, including 5 of 8 (63%) who received cryopreserved products. Five had a partial response (19%), resulting in an overall response rate of 81%. One-year RFS and OS were 50% and 65%, respectively. There was no treatment-related toxicity reported other than GVHD: 6 (23%) developed acute GVHD (2 grade I and 4 grade II) and 8 (31%) developed chronic GVHD (2 limited and 6 extensive). Cryopreserved products are viable alternatives to create SCB for the treatment of PGF. When collecting fresh products is an option, the addition of plerixafor increases CD34+ yield over G-CSF alone; however, it is currently unclear if the CD34+ cell dose impacts the efficacy of the SCB.

Dataset Information

Fetal hemoglobin and F-cell variance in mobilized CD34⁺ cell-transplanted rhesus monkeys.

Publications

Fetal hemoglobin and F-cell variance in mobilized CD34<sup>+</sup> cell-transplanted rhesus monkeys.

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Dataset Information

Fetal hemoglobin and F-cell variance in mobilized CD34+ cell-transplanted rhesus monkeys.

Publications

Fetal hemoglobin and F-cell variance in mobilized CD34<sup>+</sup> cell-transplanted rhesus monkeys.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Fetal hemoglobin and F-cell variance in mobilized CD34⁺ cell-transplanted rhesus monkeys.