Umbilical Cord Blood Transplantation Provides an Alternative for Patients With Chronic Granulomatous Disease Lacking HLA-Matched Donors: A PIDTC Report

Authors

Danielle E. Arnold, National Cancer Institute, Bethesda, MD
Jennifer W. Leiding, Johns Hopkins University, Baltimore, MD
Brent Logan, Medical College of Wisconsin, Milwaukee, WI
Rebecca A. Marsh, University of Cincinnati, Cincinnati, OH
Linda M. Griffith, National Institutes of Health, Bethesda, MD
Eyal Grunebaum, Hospital for Sick Children, Toronto, Canada
Luis Murguía-Favela, Alberta Children's Hospital, Calgary, Canada
Kanwaldeep Mallhi, Fred Hutchinson Cancer Research Center, Seattle, WA
Deepakbabu Chellapandian, Johns Hopkins All Children's Hospital, St Petersburg, FL
Christin L. Deal, Children's Hospital of Pittsburgh, Pittsburgh, PA
Stephanie Si Lim, Kapi'olani Medical Center for Women & Children, Honolulu, HI
Vinod Prasad, Duke University, Durham, NC
Jennifer Heimall, Children's Hospital of Philadelphia, Philadephia, PA
Shanmuganathan Chandrakasan, Emory University, Atlanta, GA
Karin Chen, University of Washington, Seattle, WA
Lolie C. Yu, LSU Health Sciences Center - New OrleansFollow
Christine M. Seroogy, University of Wisconsin, Madison, WI
Alfred Gillio, Hackensack University Medical Center, Hackensack, NJ
Jeffrey J. Bednarski, Washington University, St. Louis, MI
Neena Kapoor, Children's Hospital, Los Angeles, CA
Theodore B. Moore, University of California, Los Angeles, CA
Geoffrey D. Cuvelier, Alberta Children's Hospital, Alberta, Canada
Fabien Touzot, University of Montreal, Montreal, Canada
Ahmad Rayes, University of Utah, Salt Lake City, UT
Christen L. Ebens, University of Minnesota, Minneapolis, MI
Edo Schaefer, Westchester Medical Center, Valhalla, NY
Andrea Bauchat, Duke University, Durham, NC
Ashley Chopek, University of Manitoba, Winnipeg, Canada
Lauri Burroughs, University of Washington, Seattle, WA
et al

Document Type

Article

Publication Date

10-2-2025

Publication Title

Transplantation and Cellular Therapy

Abstract

BACKGROUND: Allogeneic hematopoietic cell transplantation corrects the phagocytic defect in patients with chronic granulomatous disease (CGD) and resolve infection risk and immune dysregulation. Umbilical cord blood transplantation (UCBT) is an option for patients lacking suitable HLA-matched bone marrow or peripheral blood stem cell donors. However, information related to UCBT for CGD is limited to a few small case series and limited subsets of larger cohorts where detailed information is lacking. OBJECTIVES: To describe UCBT procedures and outcomes in patients with CGD. STUDY DESIGN: Thirty-nine patients with CGD who underwent UCBT at Primary Immune Deficiency Treatment Consortium (PIDTC) centers between 2001 and 2019 were included. RESULTS: All patients were male, and most (97%) had X-linked CGD due to pathogenic variants in CYBB. High infection burden (1.72/person years) and inflammatory disease (38%) were common in the year pre-UCBT. Median age at receipt of UCBT was 2.1 (range 0.3-14.0) years. Most (87%) patients received UCB from unrelated donors, and most (72%) patients received busulfan and cyclophosphamide-based conditioning. All but two (95%) patients received serotherapy with anti-thymocyte globulin or alemtuzumab. Neutrophil and platelet recovery occurred at a median of 18 (range 12-46) and 38 (range 21-186) days, respectively. Nine patients experienced early graft failure [donor myeloid chimerism < 10% or receipt of second hematopoietic cell transplantation (HCT) within 100 days] for a cumulative incidence of 23.1% (95% CI 11.3-37.3). There were no cases of late graft failure (after 100 days), and median whole blood and myeloid donor chimerism of engrafted patients were > 95% at all time points. One of the nine patients with early graft failure had autologous reconstitution. The remaining 8 patients underwent repeat HCT; six of the patients survived and achieved durable myeloid engraftment on long-term follow-up. Twenty-eight patients were alive at a median follow-up of 4.28 (IQR 2.66-6.08) years. Estimated 3-year overall and event-free survival were 73.7% (95% CI 56.5-84.9) and 56.2% (95% CI 39.3-70.1), respectively. No identifiable factors, including history of infection or inflammatory disease in the year prior to UCBT, year of UCBT, age at UCBT, conditioning regimen, cell dose, and recipient and donor HLA match, were associated with graft failure or survival. Infections decreased with time post-UCBT and pre-existing inflammatory disease resolved in all surviving patients CONCLUSIONS: UCBT for CGD is associated with high rates of early graft failure. Nevertheless, UCBT can provide an effective alternative for CGD patients when HLA-matched donors are not available with resolution of disease. Strategies to overcome high rates of early graft failure while optimizing conditioning regimens to minimize toxicity are needed.

PubMed ID

41046057

Comments

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Rights

Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.

Recommended Citation

Arnold, Danielle E.; Leiding, Jennifer W.; Logan, Brent; Marsh, Rebecca A.; Griffith, Linda M.; Grunebaum, Eyal; Murguía-Favela, Luis; Mallhi, Kanwaldeep; Chellapandian, Deepakbabu; Deal, Christin L.; Lim, Stephanie Si; Prasad, Vinod; Heimall, Jennifer; Chandrakasan, Shanmuganathan; Chen, Karin; Yu, Lolie C.; Seroogy, Christine M.; Gillio, Alfred; Bednarski, Jeffrey J.; Kapoor, Neena; Moore, Theodore B.; Cuvelier, Geoffrey D.; Touzot, Fabien; Rayes, Ahmad; Ebens, Christen L.; Schaefer, Edo; Bauchat, Andrea; Chopek, Ashley; Burroughs, Lauri; and al, et, "Umbilical Cord Blood Transplantation Provides an Alternative for Patients With Chronic Granulomatous Disease Lacking HLA-Matched Donors: A PIDTC Report" (2025). School of Medicine Faculty Publications. 4323.
https://digitalscholar.lsuhsc.edu/som_facpubs/4323
10.1016/j.jtct.2025.05.020