Failure to Prevent Severe Graft-Versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation with Post-Trans
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ORIGINAL ARTICLE
Failure to Prevent Severe Graft-Versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide in Chronic Granulomatous Disease Mark Parta 1 & Dianne Hilligoss 2 & Corin Kelly 2 & Nana Kwatemaa 2 & Narda Theobald 2 & Christa S. Zerbe 2 & Steven M. Holland 2 & Harry L. Malech 2 & Elizabeth M. Kang 2 Received: 17 December 2019 / Accepted: 20 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 posttransplant 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. Keywords Chronic granulomatous disease . haploidentical . graft-versus-host disease . post-transplant cyclophosphamide
Chronic granulomatous disease (CGD) is a phenotypically complex primary immunodeficiency. Immunologically first characterized by neutrophil dysfunction mediated by genetic changes in the phox reactive oxygen intermediate generating
* Mark Parta [email protected] 1
Clinical Research Directorate, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA
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
system, CGD is associated with an increased risk of infection but also non-infectious inflammatory disease, often involving the gastrointestinal tract; hematopoietic cell transplanta
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