Graft-versus-host-disease prophylaxis with ATG or PTCY in patients with lymphoproliferative disorders undergoing reduced intensity conditioning regimen HCT from one antigen mismatched unrelated donor.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8702459 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5365 (Electronic) Linking ISSN: 02683369 NLM ISO Abbreviation: Bone Marrow Transplant Subsets: MEDLINE

Publication: <2003->: London : Nature Publishing Group
Original Publication: Basingstoke, Hampshire : Scientific & Medical Division, Macmillan Press, c1986-

Transplantation Conditioning*/methods ; Graft vs Host Disease*/prevention & control ; Hematopoietic Stem Cell Transplantation*/methods ; Cyclophosphamide*/therapeutic use ; Lymphoproliferative Disorders*/therapy ; Lymphoproliferative Disorders*/mortality ; Unrelated Donors*; Humans ; Female ; Male ; Middle Aged ; Adult ; Antilymphocyte Serum/therapeutic use ; Aged

Post-transplant cyclophosphamide (PTCY) has been introduced as graft-versus-host disease (GvHD) prophylaxis in mismatched and matched unrelated hematopoietic cell transplant (HCT). However, data comparing outcomes of PTCY or ATG in patients undergoing a 1 antigen mismatched HCT for lymphoproliferative disease are limited. We compared PTCY versus ATG in adult patients with lymphoproliferative disease undergoing a first 9/10 MMUD HCT with a reduced intensity conditioning regimen from 2010 to 2021. Patients receiving PTCY were matched to patients receiving ATG according to: age, disease status at transplant, female to male matching, stem cell source and CMV serology. Grade II-IV acute GvHD at 100 day was 26% and 41% for the ATG and PTCY group, respectively (p = 0.08). Grade III-IV acute GvHD was not significantly different between the two groups. No differences were observed in relapse incidence, non-relapse mortality, progression-free survival, overall survival and GvHD-relapse-free survival at 1 year. The cumulative incidence of 1-year extensive chronic GvHD was 18% in the ATG and 5% in the PTCY group, respectively (p = 0.06). In patients with lymphoproliferative diseases undergoing 9/10 MMUD HCT, PTCY might be a safe option providing similar results to ATG prophylaxis. Due to the limited number of patients, prospective randomized trials are needed.
(© 2024. The Author(s).)

Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–50. (PMID: 10.1016/j.bbmt.2008.03.005184899892633246)
Luznik L, Bolaños-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, et al. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010;115:3224–30. (PMID: 10.1182/blood-2009-11-251595201245112858487)
Kasamon YL, Ambinder RF, Fuchs EJ, Zahurak M, Rosner GL, Bolaños-Meade J, et al. Prospective study of nonmyeloablative, HLA-mismatched unrelated BMT with high-dose posttransplantation cyclophosphamide. Blood Adv. 2017;1:288–92. (PMID: 10.1182/bloodadvances.2016002766292428525726600)
Mielcarek M, Furlong T, O’Donnell PV, Storer BE, McCune JS, Storb R, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127:1502–8. (PMID: 10.1182/blood-2015-10-672071267643564797026)
Carnevale-Schianca F, Caravelli D, Gallo S, Coha V, D’Ambrosio L, Vassallo E, et al. Post-transplant cyclophosphamide and tacrolimus-mycophenolate mofetil combination prevents graft-versus-host disease in allogeneic peripheral blood hematopoietic cell transplantation from HLA-matched donors. Biol Blood Marrow Transplant. 2017;23:459–66. (PMID: 10.1016/j.bbmt.2016.12.63628039079)
Jorge AS, Suárez-Lledó M, Pereira A, Gutierrez G, Fernández-Avilés F, Rosiñol L, et al. 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;24:1196–202. (PMID: 10.1016/j.bbmt.2018.01.02129410343)
Broers AEC, de Jong CN, Bakunina K, Hazenberg MD, van Marwijk Kooy M, de Groot MR, et al. Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial. Blood Adv. 2022;6:3378–85. (PMID: 10.1182/bloodadvances.2021005847351436449198908)
Penack O, Marchetti M, Ruutu T, Aljurf M, Bacigalupo A, Bonifazi F, et al. Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol. 2020;7:e157–67. (PMID: 10.1016/S2352-3026(19)30256-X32004485)
Metheny L, de Lima M. Hematopoietic stem cell transplant with HLA-mismatched grafts: impact of donor, source, conditioning, and graft versus host disease prophylaxis. Expert Rev Hematol. 2019;12:47–60. (PMID: 10.1080/17474086.2019.156233130582393)
Kim HJ, Min WS, Cho BS, Eom KS, Kim YJ, Min CK, et al. Successful prevention of acute graft-versus-host disease using low-dose antithymocyte globulin after mismatched, unrelated, hematopoietic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant. 2009;15:704–17. (PMID: 10.1016/j.bbmt.2009.02.01019450755)
Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007;110:4576–83. (PMID: 10.1182/blood-2007-06-09738617785583)
Lee SJ, Logan B, Westervelt P, Cutler C, Woolfrey A, Khan SP, et al. Comparison of patient-reported outcomes in 5-year survivors who received bone marrow vs peripheral blood unrelated donor transplantation: long-term follow-up of a randomized clinical trial. JAMA Oncol. 2016;2:1583–9. (PMID: 10.1001/jamaoncol.2016.2520275325085145732)
Mushtaq MU, Shahzad M, Tariq E, Iqbal Q, Chaudhary SG, Zafar MU, et al. Outcomes with mismatched unrelated donor allogeneic hematopoietic stem cell transplantation in adults: a systematic review and meta-analysis. Front Oncol. 2022;12:1005042. (PMID: 10.3389/fonc.2022.1005042362760849583270)
Battipaglia G, Labopin M, Kröger N, Vitek A, Afanasyev B, Hilgendorf I, et al. Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. Blood. 2019;134:892–9. (PMID: 10.1182/blood.201900048731270102)
Mehta RS, Saliba RM, Chen J, Rondon G, Hammerstrom AE, Alousi A, et al. Post-transplantation cyclophosphamide versus conventional graft-versus-host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation. Br J Haematol. 2016;173:444–55. (PMID: 10.1111/bjh.13977269477695459488)
Soltermann Y, Heim D, Medinger M, Baldomero H, Halter JP, Gerull S, et al. Reduced dose of post-transplantation cyclophosphamide compared to ATG for graft-versus-host disease prophylaxis in recipients of mismatched unrelated donor hematopoietic cell transplantation: a single-center study. Ann Hematol. 2019;98:1485–93. (PMID: 10.1007/s00277-019-03673-330915500)
Bailén R, Kwon M, Pascual-Cascón MJ, Ferrà C, Sanz J, Gallardo-Morillo A, et al. Post-transplant cyclophosphamide for GVHD prophylaxis compared to ATG-based prophylaxis in unrelated donor transplantation. Ann Hematol. 2021;100:541–53. (PMID: 10.1007/s00277-020-04317-733140137)
Jethava YS, Sica S, Savani B, Socola F, Jagasia M, Mohty M, et al. Conditioning regimens for allogeneic hematopoietic stem cell transplants in acute myeloid leukemia. Bone Marrow Transplant. 2017;52:1504–11. (PMID: 10.1038/bmt.2017.8328504666)
Przepiorka D, Chan KW, Champlin RE, Culbert SJ, Petropoulos D, Ippoliti C, et al. Prevention of graft-versus-host disease with anti-CD5 ricin A chain immunotoxin after CD3-depleted HLA-nonidentical marrow transplantation in pediatric leukemia patients. Bone Marrow Transplant. 1995;16:737–41. (PMID: 8750262)
Lee SJ. Classification systems for chronic graft-versus-host disease. Blood. 2017;129:30–7. (PMID: 10.1182/blood-2016-07-686642278215035216262)
Shaw BE, Jimenez-Jimenez AM, Burns LJ, Logan BR, Khimani F, Shaffer BC, et al. National marrow donor program-sponsored multicenter, phase II trial of HLA-mismatched unrelated donor bone marrow transplantation using post-transplant cyclophosphamide. J Clin Oncol. 2021;39:1971–82. (PMID: 10.1200/JCO.20.03502339052648260905)
Flomenberg N, Baxter-Lowe LA, Confer D, Fernandez-Vina M, Filipovich A, Horowitz M, et al. Impact of HLA class I and class II high-resolution matching on outcomes of unrelated donor bone marrow transplantation: HLA-C mismatching is associated with a strong adverse effect on transplantation outcome. Blood. 2004;104:1923–30. (PMID: 10.1182/blood-2004-03-080315191952)
Kanda J, Ichinohe T, Fuji S, Maeda Y, Ohashi K, Fukuda T, et al. Impact of HLA mismatch direction on the outcome of unrelated bone marrow transplantation: a retrospective analysis from the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2015;21:305–11. (PMID: 10.1016/j.bbmt.2014.10.01525464119)
Modi D, Kondrat K, Kim S, Deol A, Ayash L, Ratanatharathorn V, et al. Post-transplant cyclophosphamide versus thymoglobulin in HLA-mismatched unrelated donor transplant for acute myelogenous leukemia and myelodysplastic syndrome. Transplant Cell Ther. 2021;27:760–7. (PMID: 10.1016/j.jtct.2021.06.01834174469)
Kröger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M, et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. N Engl J Med. 2016;374:43–53. (PMID: 10.1056/NEJMoa150600226735993)
Kawamura K. Effect of antithymocyte globulin on HLA-mismatched unrelated transplantation. Int J Hematol. 2019;110:22–9. (PMID: 10.1007/s12185-019-02597-y30680666)
Finke J, Bethge WA, Schmoor C, Ottinger HD, Stelljes M, Zander AR, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10:855–64. (PMID: 10.1016/S1470-2045(09)70225-619695955)

8N3DW7272P (Cyclophosphamide)
0 (Antilymphocyte Serum)

Date Created: 20240208 Date Completed: 20240506 Latest Revision: 20240729

20240730

PMC11073988

10.1038/s41409-024-02225-2

38331980