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Favorable outcomes following CD34-selected stem cell boost for poor graft function after allogeneic hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 59, pages 134–137 (2024)Cite this article

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for several hematologic disorders [1]. Poor graft function (PGF) is a life-threatening complication after allo-HSCT occurring in 5–27% of allo-HSCT recipients and increased risk has been observed with older age, CMV infection, ABO incompatibility, and severe GVHD [2, 3]. PGF is characterized by multilineage cytopenia in two or more cell lineages, i.e., absolute neutrophil count (ANC) ≤ 1 K/uL, platelets (PLT) ≤ 30 K/uL, and hemoglobin (HGB) ≤ 8 g/dL with transfusion and growth factor dependence for 2 weeks beyond day 14 post-allo-HSCT in the presence of full (>95%) donor chimerism and absence of relapse, severe graft-versus-host disease (GVHD), cytomegalovirus (CMV) reactivation, or drug-related myelosuppression [4, 5]. Primary PGF is defined as the lack of initial engraftment of donor cells without an ANC ≥ 500/μL by day +30. In contrast, secondary PGF is the development of cytopenias following initial engraftment. The etiology of PGF is not entirely understood; however, recent reports suggest the underlying pathogenesis involves dysregulation of T cell responses against donor stem cells and impaired bone marrow microenvironment [6]. Recent studies have shown CD34 + -selected stem cell boost (CD34 + -SCB) to be a potentially safe and effective strategy to improve graft function and survival outcomes [4, 5]. We aimed to investigate outcomes following CD34 + -SCB for PGF after allo-HSCT.

We conducted a single-center study including all (n = 51) patients aged 18 and older who received a CD34 + -SCB for PGF after HSCT at the Kansas University Medical Center from May 2009 to August 2022. This study was approved by the institutional review board. CD34+ selection was performed with the Miltenyi CliniMACS System. Data were collected through a retrospective review of electronic medical records and worksheets. Complete hematologic response (CHR) was defined as achieving a response in all lineages, i.e., ANC > 1 K/uL, PLT > 30 K/uL, and HGB > 8 g/dL without transfusion/growth factor for 2 weeks (eltrombopag allowed), while partial response (PR) was defined as achieving a response in at two lineages and no response represents failure to achieve response in at least two lineages. Data were analyzed using SPSS version 28. Bivariate analyses, using the chi-square and ANOVA, were performed. Kaplan-Meier analyses were conducted. Odds ratios with 95% confidence intervals (CI) were obtained. Statistical significance was considered at p < 0.05.

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The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

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Author notes

  1. These authors contributed equally: Joe S. Al-Ramahi, Moazzam Shahzad.

Authors and Affiliations

  1. Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA

    Joe S. Al-Ramahi, Moazzam Shahzad, Andrea Nguyen, Kevin Li, Muhammad Kashif Amin, Nausheen Ahmed, Forat Lutfi, Shaun DeJarnette, Sibgha Gull Chaudhary, Rajat Bansal, Haitham Abdelhakim, Leyla Shune, Al-Ola Abdallah, Anurag K. Singh, Sunil H. Abhyankar, Joseph P. McGuirk & Muhammad Umair Mushtaq

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Contributions

All authors contributed to the manuscript and fulfilled the criteria per the uniform requirements set forth by the International Committee of Medical Journal Editors (ICJME) guidelines. All authors have reviewed and approved the final version of the manuscript.

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Correspondence to Muhammad Umair Mushtaq.

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Competing interests

SHA has speaking, consulting, and advisory roles, and research funding from Incyte and Therakos. JPM has speaking, consulting, and advisory role in Kite, Juno Therapeutics, Allovir, Magenta Therapeutics, EcoR1 Capital, and has research funding from Novartis, Fresenius Biotech, Astellas Pharma, Bellicum Pharmaceuticals, Gamida Cell, Pluristem Therapeutics, Kite and AlloVir. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Al-Ramahi, J.S., Shahzad, M., Nguyen, A. et al. Favorable outcomes following CD34-selected stem cell boost for poor graft function after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 59, 134–137 (2024). https://doi.org/10.1038/s41409-023-02125-x

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