Post-transplantation cyclophosphamide is associated with an increase in non-cytomegalovirus herpesvirus infections in patients with acute leukemia and myelodysplastic syndrome Journal Article


Authors: Singh, A.; Dandoy, C. E.; Chen, M.; Kim, S.; Mulroney, C. M.; Kharfan-Dabaja, M. A.; Ganguly, S.; Maziarz, R. T.; Kanakry, C. G.; Kanakry, J. A.; Patel, S. S.; Hill, J. A.; De Oliveir, S.; Taplitz, R.; Hematti, P.; Lazarus, H. M.; Abid, M. B.; Goldsmith, S. R.; Romee, R.; Komanduri, K. V.; Badawy, S. M.; Friend, B. D.; Beitinjaneh, A.; Politikos, I.; Perales, M. A.; Riches, M.
Article Title: Post-transplantation cyclophosphamide is associated with an increase in non-cytomegalovirus herpesvirus infections in patients with acute leukemia and myelodysplastic syndrome
Abstract: 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. © 2021
Keywords: leukemia, myeloid, acute; prospective study; prospective studies; cyclophosphamide; myelodysplastic syndrome; herpesviridae; cytomegalovirus infection; myelodysplastic syndromes; acute myeloid leukemia; cytomegalovirus infections; epstein-barr virus; hhv-6; humans; human; post-transplantation cyclophosphamide; haploidentical; non-cmv herpesvirus
Journal Title: Transplantation and Cellular Therapy
Volume: 28
Issue: 1
ISSN: 2666-6375
Publisher: Elsevier Inc.  
Date Published: 2022-01-01
Start Page: 48.e1
End Page: 48.e10
Language: English
DOI: 10.1016/j.jtct.2021.09.015
PUBMED: 34587551
PROVIDER: scopus
PMCID: PMC9717499
DOI/URL:
Notes: Article -- Export Date: 1 March 2022 -- Source: Scopus
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  1. Miguel-Angel Perales
    913 Perales
  2. Ioannis   Politikos
    103 Politikos