Abstract
Prior studies suggest increased cytomegalovirus (CMV) infection after haploidentical donor transplantation with posttransplant cyclophosphamide (HaploCy). The role of allograft source and posttransplant cyclophosphamide (PTCy) in CMV infection is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection, and effects of serostatus and CMV infection on transplant outcomes. We examined patients reported to the Center for International Blood and Marrow Transplantation Research between 2012 and 2017 who had received HaploCy (n = 757), matched related (Sib) with PTCy (SibCy, n = 403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n = 1605). Cumulative incidences of CMV infection by day 180 were 42%, 37%, and 23%, respectively (P < .001). CMV disease was statistically comparable. CMV infection risk was highest for CMV-seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor (HaploCy [n = 545]: hazard ratio [HR], 50.3; SibCy [n = 279]: HR, 47.7; SibCNI [n = 1065]: HR, 24.4; P < .001). D+/R− patients also had increased risk for CMV infection. Among R+ or those developing CMV infection, HaploCy had worse overall survival and nonrelapse mortality. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic graft-versus-host disease (GVHD) overall, but CMV infection in PTCy recipients was associated with higher chronic GVHD (P = .006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally, CMV infection may negate the chronic GVHD protection of PTCy. This study supports aggressive prevention strategies in all receiving PTCy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3291-3305 |
| Number of pages | 15 |
| Journal | Blood |
| Volume | 137 |
| Issue number | 23 |
| DOIs | |
| State | Published - Jun 10 2021 |
Keywords
- CIMBTR
- CMV
- MARROW AND STEM CELL TRANSPLANTATION
- haploidentical
- organ specific toxicity: infectious
- outcomes
- posttransplant cyclophosphamide
ASJC Scopus subject areas
- Biochemistry
- Immunology
- Hematology
- Cell Biology
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Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection : a CIBMTR analysis. / CIBMTR Infection and Immune Reconstitution Working Committee.
In: Blood, Vol. 137, No. 23, 10.06.2021, p. 3291-3305.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection
T2 - a CIBMTR analysis
AU - CIBMTR Infection and Immune Reconstitution Working Committee
AU - Goldsmith, Scott R.
AU - Abid, Muhammad Bilal
AU - Auletta, Jeffery J.
AU - Bashey, Asad
AU - Beitinjaneh, Amer
AU - Castillo, Paul
AU - Chemaly, Roy F.
AU - Chen, Min
AU - Ciurea, Stefan
AU - Dandoy, Christopher E.
AU - Díaz, Miguel Ángel
AU - Fuchs, Ephraim
AU - Ganguly, Siddhartha
AU - Kanakry, Christopher G.
AU - Kanakry, Jennifer A.
AU - Kim, Soyoung
AU - Komanduri, Krishna V.
AU - Krem, Maxwell M.
AU - Lazarus, Hillard M.
AU - Liu, Hongtao
AU - Ljungman, Per
AU - Masiarz, Richard
AU - Mulroney, Carolyn
AU - Nathan, Sunita
AU - Nishihori, Taiga
AU - Page, Kristin M.
AU - Perales, Miguel Angel
AU - Taplitz, Randy
AU - Romee, Rizwan
AU - Riches, Marcie
N1 - Funding Information: S.G. acknowledges the Washington University School of Medicine R25 STRENGTH Program (R25CA190190; principal investigator: Ramaswamy Govindan) for protected research time, and the Mentors in Medicine Program at Washington University School of Medicine. The Center for International Blood and Marrow Transplantation Research (CIBMTR) is supported primarily by Public Health Service grant U24CA076518 from the National Institutes of Health (NIH)/National Cancer Institute (NCI), the NIH/National Heart, Lung, and Blood Institute (NHLBI), and the NIH/National Institute of Allergy and Infectious Diseases, as well as NIH/NHLBI/NCI grant U24HL138660, NIH/NHLBI grant U01HL128568, NIH/Health Resources and Services Administration (HRSA) grants HHSH250201700006C and HHSH250201700007C, and US Office of Naval Research grants N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705. Additional federal support is provided by NIH grants P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and the Biomedical Advanced Research and Development Authority (BARDA). Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St Baldrick's Foundation, Stanford University, the Medical College of Wisconsin the National Marrow Donor Program, and from the following commercial entities: AbbVie, Actinium Pharmaceuticals, Inc, Adaptive Biotechnologies, Adienne SA, Allovir, Inc, Amgen Inc, Angiocrine Bioscience, Astellas Pharma US, AstraZeneca, Atara Biotherapeutics, Inc, bluebird bio, Inc, Bristol Myers Squibb Co, Celgene Corp, CSL Behring, CytoSen Therapeutics, Inc, Daiichi Sankyo Co, Ltd, Gamida-Cell, Ltd, Genentech Inc, HistoGenetics, Inc, Incyte Corporation, Janssen Biotech, Inc, Jazz Pharmaceuticals, Inc, Johnson & Johnson, Kiadis Pharma, Kite, a Gilead Company, Kyowa Kirin, Legend Biotech, Magenta Therapeutics, Mallinckrodt LLC, Merck & Company, Inc, Merck Sharp & Dohme Corp, Millennium, the Takeda Oncology Co, Miltenyi Biotec, Inc, Novartis Pharmaceuticals Corporation, Omeros Corporation, Oncoimmune, Inc, Orca Biosystems, Inc, Pfizer, Inc, Pharmacyclics, LLC, Sanofi Genzyme, Shire, Sobi, Inc, Stemcyte, Takeda Pharma, Terumo BCT, Viracor Eurofins, Vor Bio Pharma, and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, HRSA, or any other agency of the US Government. Funding Information: S.G. acknowledges the Washington University School of Medicine R25 STRENGTH Program (R25CA190190; principal investigator: Ramaswamy Govindan) for protected research time, and the Mentors in Medicine Program at Washington University School of Medicine. The Center for International Blood and Marrow Transplantation Research (CIBMTR) is supported primarily by Public Health Service grant U24CA076518 from the National Institutes of Health (NIH)/National Cancer Institute (NCI), the NIH/National Heart, Lung, and Blood Institute (NHLBI), and the NIH/National Institute of Allergy and Infectious Diseases, as well as NIH/NHLBI/NCI grant U24HL138660, NIH/NHLBI grant U01HL128568, NIH/Health Resources and Services Administration (HRSA) grants HHSH250201700006C and HHSH250201700007C, and US Office of Naval Research grants N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705. Additional federal support is provided by NIH grants P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and the Biomedical Advanced Research and Development Authority (BARDA). Support is also provided by Be the Match Foundation, Boston Children's Hospital, Dana Farber, St Baldrick's Foundation, Stanford University, the Medical College of Wisconsin the National Marrow Donor Program, and from the following commercial entities: AbbVie, Actinium Pharmaceuticals, Inc, Adaptive Biotechnologies, Adienne SA, Allovir, Inc, Amgen Inc, Angiocrine Bioscience, Astellas Pharma US, AstraZeneca, Atara Biotherapeutics, Inc, bluebird bio, Inc, Bristol Myers Squibb Co, Celgene Corp, CSL Behring, CytoSen Therapeutics, Inc, Daiichi Sankyo Co, Ltd, Gamida-Cell, Ltd, Genentech Inc, HistoGenetics, Inc, Incyte Corporation, Janssen Biotech, Inc, Jazz Pharmaceuticals, Inc, Johnson & Johnson, Kiadis Pharma, Kite, a Gilead Company, Kyowa Kirin, Legend Biotech, Magenta Therapeutics, Mallinckrodt LLC, Merck & Company, Inc, Merck Sharp & Dohme Corp, Millennium, the Takeda Oncology Co, Miltenyi Biotec, Inc, Novartis Pharmaceuticals Corporation, Omeros Corporation, Oncoimmune, Inc, Orca Biosystems, Inc, Pfizer, Inc, Pharmacyclics, LLC, Sanofi Genzyme, Shire, Sobi, Inc, Stemcyte, Takeda Pharma, Terumo BCT, Viracor Eurofins, Vor Bio Pharma, and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the NIH, the Department of the Navy, the Department of Defense, HRSA, or any other agency of the US Government. Funding Information: Conflict-of-interest disclosure: S.R.G. has consulted for Wugen Inc. R.M has consulted for, sat on the advisory board, and received funding from Celgene/Juno; has consulted for, sat on the advisory board, received honorary and sat on the scientific steering committee for Novartis; has consulted for, sat on the advisory board for, and received honoraria from Kite Therapeutics; has consulted for and received honoraria from Juno Therapeutics and Incyte Corporation; and is a patent holder and receives royalties from Athersys, Inc. R.R. received research funding from Kleo Pharma; sat on the advisory board for Glycostem; and has consulted for Kiadis Pharma. R.F.C. received research grants paid to the institution from Merck, Chimerix, Shire/Takeda, Gilead, Ansun Pharmaceuticals, Viracor, Karius, Pulmotec, and Janssen; and was a paid consultant for Merck, Chimerix, Ansun Pharmaceuticals, Kyorin, ReViral, Clinigen, Oxford Immunotec, Janssen, Shire/Takeda, Genentech, Paratek, and Shinogei. K.V.K. has consulted for and sat on the advisory board for Kiadis, Atara, Novartis, Incyte, and Kiadis; sat on the advisory board and received honoraria from Celgene/Juno; consulted for Helocyte; has consulted for, sat on the advisory board, and received research funding from Kite/Gilead; consulted for, sat on the advisory board, and received honoraria from Kadmon; consulted for Takeda and Celgene; and sat on the advisory board for and received research funding from Kite/Gilead. M.-A.P. received honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda; serve on Data and Safety Monitoring Boards for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune; received research support for clinical trials from Incyte, Kite/Gilead, and Miltenyi Biotec; serves in a volunteer capacity as a member of the Board of Directors of American Society for Transplantation and Cellular Therapy and Be The Match (National Marrow Donor Program; has consulted for Merck, Novartis, and Incyte; and has received research support for clinical trials to the institution from Kite, Incyte, and Miltenyi. M.R. received compensation from DSMC and Gamida Cell. T.N. has research funding from Karyopharm and Novartis. S.G. received personal fees from Seattle Genetics, Kite Pharma, and Kadmon. H.L. received research funding from BMS and Karyopharm and personal fees from Agios. S.C. has sat on the advisory board for Kiadis, CareDx, Spectrum, Cellularity, and MollMed; has consulted for Hansa; has received research funding from Milteny and Kiadis; and has received equity from Kiadis. P.L. received research funding from Merck, Oxford Immunotec and received personal fees from Shire/Takeda and AiCuris. The remaining authors declare no competing financial interests. Publisher Copyright: © 2021 American Society of Hematology
PY - 2021/6/10
Y1 - 2021/6/10
N2 - Prior studies suggest increased cytomegalovirus (CMV) infection after haploidentical donor transplantation with posttransplant cyclophosphamide (HaploCy). The role of allograft source and posttransplant cyclophosphamide (PTCy) in CMV infection is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection, and effects of serostatus and CMV infection on transplant outcomes. We examined patients reported to the Center for International Blood and Marrow Transplantation Research between 2012 and 2017 who had received HaploCy (n = 757), matched related (Sib) with PTCy (SibCy, n = 403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n = 1605). Cumulative incidences of CMV infection by day 180 were 42%, 37%, and 23%, respectively (P < .001). CMV disease was statistically comparable. CMV infection risk was highest for CMV-seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor (HaploCy [n = 545]: hazard ratio [HR], 50.3; SibCy [n = 279]: HR, 47.7; SibCNI [n = 1065]: HR, 24.4; P < .001). D+/R− patients also had increased risk for CMV infection. Among R+ or those developing CMV infection, HaploCy had worse overall survival and nonrelapse mortality. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic graft-versus-host disease (GVHD) overall, but CMV infection in PTCy recipients was associated with higher chronic GVHD (P = .006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally, CMV infection may negate the chronic GVHD protection of PTCy. This study supports aggressive prevention strategies in all receiving PTCy.
AB - Prior studies suggest increased cytomegalovirus (CMV) infection after haploidentical donor transplantation with posttransplant cyclophosphamide (HaploCy). The role of allograft source and posttransplant cyclophosphamide (PTCy) in CMV infection is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection, and effects of serostatus and CMV infection on transplant outcomes. We examined patients reported to the Center for International Blood and Marrow Transplantation Research between 2012 and 2017 who had received HaploCy (n = 757), matched related (Sib) with PTCy (SibCy, n = 403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n = 1605). Cumulative incidences of CMV infection by day 180 were 42%, 37%, and 23%, respectively (P < .001). CMV disease was statistically comparable. CMV infection risk was highest for CMV-seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor (HaploCy [n = 545]: hazard ratio [HR], 50.3; SibCy [n = 279]: HR, 47.7; SibCNI [n = 1065]: HR, 24.4; P < .001). D+/R− patients also had increased risk for CMV infection. Among R+ or those developing CMV infection, HaploCy had worse overall survival and nonrelapse mortality. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic graft-versus-host disease (GVHD) overall, but CMV infection in PTCy recipients was associated with higher chronic GVHD (P = .006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally, CMV infection may negate the chronic GVHD protection of PTCy. This study supports aggressive prevention strategies in all receiving PTCy.
KW - CIMBTR
KW - CMV
KW - MARROW AND STEM CELL TRANSPLANTATION
KW - haploidentical
KW - organ specific toxicity: infectious
KW - outcomes
KW - posttransplant cyclophosphamide
UR - http://www.scopus.com/inward/record.url?scp=85105959173&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85105959173&partnerID=8YFLogxK
U2 - 10.1182/blood.2020009362
DO - 10.1182/blood.2020009362
M3 - Article
C2 - 33657221
AN - SCOPUS:85105959173
VL - 137
SP - 3291
EP - 3305
JO - Blood
JF - Blood
SN - 0006-4971
IS - 23
ER -