COMPARISON OF INFECTIOUS COMPLICATIONS IN PATIENTS RECEIVING HIGH-DOSE CYCLOPHOSPHAMIDE AS GVHD AFTER TRANSPLANTATION FROM A 9/10 HLA-MATCHED UNRELATED DONOR WITH STANDARD GVHD PROPHYLAXIS AFTER TRANSPLANT FROM A FULL MATCHING DONOR Infection With PTCy Versus Standard GvHD Prophylaxis
Main Article Content
Keywords
Allogeneic hematopoietic cell transplantation, Cyclophosphamide, hemorrhagic cystitis, infection, invasive fungal infection, Post Cyclophosphamide GVHD Prophylaxis
Abstract
Background: The aim of this study was to evaluate whether cyclophosphamide administered after allogeneic stem cell transplantation (ASCT) from 9/10 HLA-Matched Unrelated Donors (MMUD) increases the rates of bloodstream infections (BSI) (fungal, viral (CMV, BK, hepatitis), bacterial), infectious complications (hemorrhagic cystitis(HC)) and infection-related mortality compared to allogeneic stem cell transplantation from matched related donors (MRD).
Metods: This is a retrospective multicenter study. 45 MMUD ASCT patients who received posttransplant cyclophosphamide + methotrexate + calcineurin inhibitor compared with 45 MRD ASCT patients who received methotrexate + calcineurin inhibitor.
Results: Although there was a statistically significant prolongation of neutrophil engraftment time in the PTCy arm, there was no statistically significant difference in bacterial BSI frequencies between the groups (PTCy; 9(20%), control;8 (17.8%), p=0.778). The distribution of CMV infection in the first 100 days was similar (p=0.827) but the distribution of CMV infection rate between the 100th and 365th days, was observed more frequently in the control group (p=0.005). HC rates and their grades were similar in both groups (PTCy; 4 (8.8%), control;6 (13.3%) p=0.502). The rates of VZV infection and invasive aspergillosis were similar in the PTCy and control groups (13.3% in the PTCy, and 17.8% in the control group p=0.561). IRM rate was statistically similar in both groups (13.3% in the PTCy arm and 17.8% in the control arm)
Conclusions: The addition of PTCy to standard GvHD prophylaxis in MMUD ASCT does not lead to an increase in CMV reactivation, bacterial BSI, invasive fungal infection, viral hemorrhagic cystitis or infection-related mortality.
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References
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2- Yoo JH, Lee DG, Choi SM, Choi JH, Park YH, Kim YJ, Kim HJ, Lee S, Kim DW, Lee JW, Min WS, Shin WS, Kim CC. Infectious complications and outcomes after allogeneic hematopoietic stem cell transplantation in Korea. Bone Marrow Transpl. 2004;34:497–504.
3- Irene GC, Albert E, Anna BV, Rahinatu A, Silvana N, Ana SSG. Patterns of infection and infectious-related mortality in patients receiving post-transplant high dose cyclophosphamide as graft-versus-host-disease prophylaxis: impact of HLA donor matching. Bone Marrow Transplantation. 2021;56:818–827.
4- Mitchell AE, Derrington P, Turner P, Hunt LP, Oakhill A, Marks DI. Gram-negative bacteremia (GNB) after 428 unrelated donor bone marrow transplants (UD-BMT): risk factors, prophylaxis, therapy and outcome. Bone Marrow Transpl. 2004;33:303–310.
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10- Shem-Tov N, Peczynski C, Labopin M, Itala-Remes M, Blaise D, Labussiera-Wallet, Socie G, Kröger N, Mielke S, Afanasyev B, Chevallier P, Tischer J, Helbig G, Jindra P, Peric Z, Giebel S, Mohty M, Nagler A. Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT. Leukemia.2020;34:283–292.
11- El Fakih R, Hashmi SK, Ciurea SO, Luznik L, Gale RP, Aljurf M. Post-transplant cyclophosphamide use in matched HLA donors: a review of literature and future application. Bone Marrow Transplant. 2020;55:40–47.
12- McCurdy SR, Kasamon YL, Kanakry CG, Meade JB, Tsai HL, Showel MM, Kanakry JA, Symons HJ, Gojo I, Smith BD, Bettinotti MP, Matsui WH, Dezern AE, Huff CA, Borrello I, Pratz KW, Gladstone DE, Swinnen LJ, Brodsky RA, Levis MJ, Ambinder RF, Fuchs EJ, Rosner GL, Jones RJ, Luznik L. Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide. Haematologica. 2017;102: 391–400.
13- Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen JJ, Elmaagacli A, Itala-Remes M, Blaise D, Meijer E, Koc Y, Milpied N, Schouten HC, Kroeger N, Mohty M, Nagler A. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol. 2018;11:40.
14- Fayard A, Daguenet E, Blaise D, Chevallier P, Labussière H, Berceanu A, Yakoub-Agha I, Socie G, Charbonnier A, Suarez F, Huynh A, Mercier M, Bulabois CE, Lioure B, Chantepie S, Beguin Y, Bourhis JH, Malfuson JV, Clement L, de la Tour RP, Cornillon J. Evaluation of infectious complications after haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide following reduced-intensity and myeloablative conditioning: a study on behalf of the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC). Bone Marrow Transplant. 2019 Oct;54(10):1586-1594.
15- Jorge AS, Suárez-Lledó M, Pereira A, Gutierrez G, Fernández-Avilés F, Rosiñol L, Llobet N, Solano T, Urbano-Ispizua A, Rovira M, Martinez C. Single Antigen–Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide Is a Suitable Alternative for Patients Lacking HLA-Matched Donors. Biol Blood Marrow Transplant. 2018;24:1196–1202.
16- Goldsmith SR, Abid MB, Auletta JJ, Bashey A, Beitinjaneh A, Castillo P, Chemaly RF, Chen M, Ciurea S, Dandoy CE, Diaz MA, Fuchs E, Ganguly S, Kanakry CG, Kanakry JA, Kim S, Komanduri KV, Krem MM, Lazarus HM, Liu H, Ljungman P, Masiarz R, Mulroney C, Nathan S, Nishihori T, Page KM, Perales MA, Taplitz R, Romee R, Riches M. Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis. Blood. 2021;137(23):3291–3305.
17- Crocchiolo R, Bramanti S, Vai A, Sarina B, Mineri R, Casari E, Tordato F, Mauro E, Timofeeva I, Lugli E, Mavilio D, Carlo-Stella C, Santoro A, Castagna L. Infections after T-replete haploidentical transplantation and high-dose cyclophosphamide as graft-versus-host disease prophylaxis. Transpl Infect Dis. 2015;17:242–249.
18- Cieri N, Greco R, Crucitti L, Morelli M, Giglio F, Levati G, Assanelli A, Carrabba MG, Bellio L, Milani R, Lorentino F, Stanghellini MTL, De Freitas T, Marktel S, Bernardi M, Corti C, Vago L, Bonini C, Ciceri F, Peccatori J. Post-transplantation cyclophosphamide and sirolimus after haploidentical hematopoietic stem cell transplantation using a treosulfan-based myeloablative conditioning and peripheral blood stem cells. Biol Blood Marrow Transplant. 2015;21:1506–1514.
19- Slade M, Goldsmith S, Romee R, DiPersio JF, Dubberke ER, Westervelt P, Uy GL, Lawrence SJ. Epidemiology of infections following haploidentical peripheral blood hematopoietic cell transplantation. Transpl Infect Dis. 2017;19: e12629 https://doi.org/10.1111/tid.12629. Epub 2016 Dec 28,
20- Mohty R, Brissot E, Battipaglia G, Ruggeri A, Dulery R, Bonnin A, Mediavilla C, Sestili S, Belhocine R, Vekhoff A, Ledraa T, Lapusan CS, Adaeva R, Isnard F, Legrand O, Mohty M, Malard F. Infectious complications after posttransplantation cyclophosphamide and anti-thymocyte globulin-based haploidentical stem cell transplantation. Br J Hematol. 2019;187:e64–e68
21- Oltolini C, Greco R, Galli L, Clerici D, Lorentino F, Xue E, Lupo Stanghellini MT, Giglio F, Uhr L, Ripa M, Scarpellini P, Bernardi M, Corti C, Peccatori J, Castagna A, Ciceri F. Infections after Allogenic Transplant with Post-Transplant Cyclophosphamide: Impact of Donor HLA Matching. Biol Blood Marrow Transplant. 2020;26:1179-1188.
22- Gooptu M, Romee R, St Martin A, Arora M, Al Malk M, Antin JH, Bredeson CN, Brunstein CG, Chhabra S, Fuchs EJ, Ghosh N, Grunwald MR, Kanakry CG, Kekre N, McGuirk JP, McNiece IK, Mehta RS, Mielcarek M, Milano F, Modi D, Reshef R, Solomon SR, Schroeder MA, Waller EK, Inamoto Y, Soiffer RJ, Eapen M. HLA-haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide based prophylaxis. Blood. 2021;138:273–282.
23- Battipaglia G, Galimard JE, Labopin M, Raiola AM, Blaise D, Ruggeri A, Koc Y, Gülbas Z, Vitek A, Sica S, Diez-Martin JL, Castagna L, Bruno B, Rovira M, Moiseev I, Martino M, Grillo G, Araujo MC, Bulabois CE, Nguyen S, Socie G, Arat M, Pavlu J, Tischer J, Martin H, Corral LL, Choi G, Forcade E, McDonald A, Pane F, Bazarbachi A, Ciceri F, Nagler A, Mohty M. Post-transplant cyclophosphamide in one-antigen mismatched unrelated donor transplantation versus haploidentical transplantation in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplantation.2022;57:562 – 571.
24- Reploeg MD, Storch GA, Clifford DB. Bk virus: a clinical review. Clin Infect Dis. 2001;33:191-202,
25- Rorije NM, Shea MM, Satyanarayana G, Hammond SP, Ho VT, Baden LR, Antin JH, Soiffer RJ, Marty FM. BK Virus Disease after Allogeneic Stem Cell Transplantation: A Cohort Analysis. Biol Blood Marrow Transplant. 2014;20:564-570.
26- Bedi A, Miller CB, Hanson JL, Goodman S, Ambinder RF, Charache P, Arthur RR, Jones RJ. Association of BK virus with failure of prophylaxis against hemorrhagic cystitis following bone marrow transplantation. J Clin Oncol. 1995;13:1103-1109.
27- Copelan OR, Sanikommu SR, Trivedi JS, Butler C, Ai J, Ragon BK, Jacobs R, Knight TG, Usmani SZ, Grunwald MR, Ghosh N, Symanowski JT, Shahid Z, Clark PE, He J. Higher incidence of hemorrhagic cystitis following haploidentical related donor transplantation compared with matched related donor transplantation. Biol Blood Marrow Transplant. 2019;25:785–790.
28- Ngo D, Samuels D, Chen J, Koller JB, Al Malki MM. A Clinical Review of the Different Strategies to Minimize Hemorrhagic Cystitis Associated with the Use of Post-Transplantation Cyclophosphamide in an Allogeneic Transplant. Transplantation and Cellular Therapy. 2022;28:349-354.
29- Mukherjee A, Milton D, Ledesma C, Olson A, Alatrash G, Anderlini P, Alousi AM, Bashir Q, Ciurea SO, Kebriaei P, Marin D, Molldrem JJ, Oran B, Popat UR, Qazilbash MH, Rondon G, Champlin RE, Gulbis AM, Khouri IF. Influence of the Intensity of the allogeneic conditioning regimen on the risk of hemorrhagic cystitis (HC) in patients receiving post-transplant cyclophosphamide (PT-Cy) as GVHD prophylaxis. Biol Blood Marrow Transplant. 2019;25:147–148.
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Feb 29, 2024
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SAYIN, S. (2024) “COMPARISON OF INFECTIOUS COMPLICATIONS IN PATIENTS RECEIVING HIGH-DOSE CYCLOPHOSPHAMIDE AS GVHD AFTER TRANSPLANTATION FROM A 9/10 HLA-MATCHED UNRELATED DONOR WITH STANDARD GVHD PROPHYLAXIS AFTER TRANSPLANT FROM A FULL MATCHING DONOR: Infection With PTCy Versus Standard GvHD Prophylaxis”, Mediterranean Journal of Hematology and Infectious Diseases, 16(1), p. e2024016. doi: 10.4084/MJHID.2024.016.
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