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Failure to Prevent Severe Graft-Versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide in Chronic Granulomatous Disease

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Abstract

Purpose

Haploidentical related donor (HRD) transplantation was performed in 7 recipients with chronic granulomatous disease (CGD) who had no matched-related or unrelated donor.

Methods

Peripheral blood cell (PBC) products were used with a conditioning regimen consisting of low-dose cyclophosphamide, fludarabine, total body irradiation, and busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of high-dose post-transplant cyclophosphamide and sirolimus. Recipients were ages 14–26 years, and 3 had severe infections active at transplant.

Results

All 7 recipients achieved full engraftment with complete donor chimerism early in the post-transplant period. Acute GVHD occurred in all cases and was grade 3 or steroid refractory in 3. Two patients with steroid-refractory GVHD died. Three patients with severe infectious complications active at transplant, 1 Nocardia pneumonia and 2 extensive invasive fungal infections), survived and were cured of their infection at last follow-up. Bacterial disease occurred post-transplant in all recipients, and viral infections/reactivation were common, including 4 cases of BK virus–associated hemorrhagic cystitis.

Conclusions

Seven patients with CGD achieved rapid and full-donor engraftment from HRDs utilizing PBCs and a conditioning regimen with PTCy and sirolimus GVHD prophylaxis. However, the incidence of grade 3 and steroid-refractory GVHD was high and led to 2 deaths. Patients with active infections at transplant had successful transplant courses and were cured of their disease. Although there was an initial success with this regimen, the cumulative experience does not support its use in CGD due to an unacceptable rate of severe GVHD.

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Funding

This project has been funded in whole or in part with federal funds from the following components of the National Institutes of Health (NIH): National Cancer Institute, NIH, under Contract No. HHSN261200800001E; and the National Institute of Allergy and Infectious Disease under Intramural Project #1-ZAI-AI000989. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; and (in part) by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.

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Authors and Affiliations

  1. Clinical Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA

    Mark Parta

  2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Dr., Rm. 6-3754, MSC 1763, Bethesda, MD, 20892-1456, USA

    Dianne Hilligoss, Corin Kelly, Nana Kwatemaa, Narda Theobald, Christa S. Zerbe, Steven M. Holland, Harry L. Malech & Elizabeth M. Kang

Authors
  1. Mark Parta
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  2. Dianne Hilligoss
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  3. Corin Kelly
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  4. Nana Kwatemaa
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  5. Narda Theobald
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  6. Christa S. Zerbe
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  7. Steven M. Holland
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  8. Harry L. Malech
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  9. Elizabeth M. Kang
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Corresponding author

Correspondence to Mark Parta.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent was obtained from all individual participants included in the study under IRB-approved NIH Protocol #s 94-I-0073, 05-I-0213 and/or 15-I-0007.

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The authors declare that they have no conflict of interest.

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Parta, M., Hilligoss, D., Kelly, C. et al. Failure to Prevent Severe Graft-Versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide in Chronic Granulomatous Disease. J Clin Immunol 40, 619–624 (2020). https://doi.org/10.1007/s10875-020-00772-z

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  • DOI: https://doi.org/10.1007/s10875-020-00772-z

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