Journal
TRANSPLANTATION AND CELLULAR THERAPY
Volume 28, Issue 1, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtct.2021.09.015
Keywords
Non-CMV herpesvirus; Post-transplantation; cyclophosphamide; Haploidentical
Categories
Funding
- Public Health Service [U24CA076518]
- National Cancer Institute (NCI)
- National Heart, Lung and Blood Institute (NHLBI)
- National Institute of Allergy and Infectious Diseases (NIAID) [HHSH250201700006C]
- Health Resources and Services Administration (HRSA) [N00014-20-1-2705, N00014-20-1-2832]
- Office of Naval Research
- Match Foundation
- Medical College of Wisconsin
- Adaptive Biotechnologies Corporation
- Adienne SA
- Amgen, Inc.
- bluebird bio, inc.
- CareDx
- Fate Therapeutics
- Genentech Inc
- Incyte Corporation
- Jazz Pharmaceuticals, Inc.
- Karyopharm Therapeutics
- Kiadis Pharma
- Kite
- Gilead Company
- Kyowa Kirin
- Magenta Therapeutics
- Medac GmbH
- Merck Co.
- Takeda Oncology Co.
- Miltenyi Biotec, Inc.
- Novartis Pharmaceuticals Corporation
- Omeros Corporation
- Oncopeptides, Inc.
- Pharmacyclics, LLC
- Sanofi Genzyme
- Takeda Pharmaceuticals
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This study evaluates the incidence and outcomes of non-CMV herpesvirus infections in recipients of haploidentical and fully matched transplantations with post-transplantation cyclophosphamide (PTCy). The results indicate a higher risk of NCHV infections in the PTCy groups, particularly in the HaploCy group. The development of NCHV infection is associated with increased treatment-related mortality.
The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis in recipients of haploidentical and fully matched transplantations is on the increase. Published studies have reported an increased incidence of cytomegalovirus (CMV) infection with the use of PTCy. Limited data exist on the incidence and outcomes of infection with non-CMV herpesviruses (NCHV) in this setting. The aim of this study was to evaluate the cumulative incidence of NCHV infections and the association of NCHV infections with transplantation-specific outcomes in recipients of haploidentical transplantation with PTCy (HaploCy), matched sibling donor transplantation with PTCy (SibCy), and matched sibling donor transplantation with calcineurin inhibitor-based prophylaxis (SibCNI). We hypothesized that, like CMV infection, HaploCy recipients of also will have a higher risk of NCHV infections. Using the Center for International Blood and Marrow Transplantation Research database, we analyzed 2765 patients (HaploCy, n = 757; SibCNI, n = 1605; SibCy, n = 403) who had undergone their first hematopoietic stem cell transplantation (HCT) between 2012 and 2017 for acute myelogenous leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. The cumulative incidence of NCHV at 6 months post-NCT was 13.9% (99% confidence interval], 10.8% to 17.3%) in the HaploCy group, 10.7% (99% CI, 7.1% to 15%) in the SibCy group, and 5.7% (99% CI, 4.3% to 7.3%) in the Sib CNI group (P < .001). This was due primarily to a higher frequency of human herpesvirus 6 viremia reported in patients receiving PTCy. The incidence of Epstein-Barr viremia was low in all groups, and no cases of post-transplantation lymphoproliferative disorder were seen in either PTCy group. The incidence of NCHV organ disease was low in all 3 cohorts. The development of NCHV infection was associated with increased treatment-related mortality, particularly in the HaploCy group. There was no association with the development of GVHD, relapse, or disease-free survival. Patients in PTCy cohorts who did not develop NCHV infection had lower rates of cGVHD. This study demonstrates that the use of PTCy is associated with an increased risk of NCHV infection. The development of NCHV infection was associated with increased nonrelapse mortality, especially in the HaploCy group. Prospective trials should consider viral surveillance strategies in conjunction with assessment of immune reconstitution for a better understanding of the clinical relevance of viral reactivation in different HCT settings. (c) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.
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