Skip to main content
Top

12-01-2018 | Acute leukemia | Article

Comparable survival using a CMV-matched or a mismatched donor for CMV+ patients undergoing T-replete haplo-HSCT with PT-Cy for acute leukemia: a study of behalf of the infectious diseases and acute leukemia working parties of the EBMT

Journal: Bone Marrow Transplantation

Authors: Simone Cesaro, Roberto Crocchiolo, Gloria Tridello, Nina Knelange, Maria Teresa Van Lint, Yener Koc, Fabio Ciceri, Zafer Gülbas, Johanna Tischer, Boris Afanasyev, Benedetto Bruno, Luca Castagna, Didier Blaise, Mohamad Mohty, Giuseppe Irrera, J. L. Diez-Martin, Luca Pierelli, Pietro Pioltelli, Mutlu Arat, Mario Delia, Franca Fagioli, Gerhard Ehninger, Mahmoud Aljurf, Angelo Michele Carella, Hakan Ozdogu, Malgorzata Mikulska, Per Ljungman, Arnon Nagler, Jan Styczynski

Publisher: Nature Publishing Group UK

Abstract

The role of donor CMV serostatus in the setting of non T-cell depleted haplo-HSCT with post-transplant cyclophosphamide (PT-Cy) has not been specifically addressed so far. Here we analyzed the impact of the donor CMV serological status on the outcome of 983 CMV seropositive (CMV+), acute leukemia patients receiving a first, non T-cell depleted haplo-HSCT registered in the EBMT database. The 1-year NRM was 21.3% (95% CI: 18.4–24.8) and 18.8% (95% CI: 13.8–25.5) in the CMV D+/R+ and D−/R+ pairs, respectively (p = 0.40). Similarly, 1-year OS was 55.1% (95% CI: 50.1–58.0) and 55.7% (95% CI: 48.0–62.8) in the same groups (p = 0.50). The other main outcomes were comparable. No difference in NRM nor OS was observed after stratification for the intensity of conditioning and multivariate anaysis confirmed the lack of significant association with NRM or OS. In conclusion, the choice of a CMV-seronegative donor did not impair early survival of CMV-seropositive patients with acute leukemia after a first, non T-cell depleted haploidentical HSCT and PT-Cy among this series of 983 consecutive patients. Future research may focus on the assessment of the hierarchy of all the donor variables.
Literature
1.
Ljungman P, Brand R, Hoek J, de la Camara R, Cordonnier C, Heinsele H, et al. Infectious diseases working party of the European group for blood and marrow transplantation. Donor Cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation. Clin Infect Dis. 2014;59:473–81.CrossRef
2.
Sellar RS, Vargas FA, Henry JY, Verfuerth S, Charrot S, Beaton B, et al. CMV promotes recipient T-cell immunity following reduced-intensity T-cell-depleted HSCT, significantly modulating chimerism status. Blood. 2015;125:731–9.CrossRef
3.
Ugarte-Torres A, Hoegh-Petersen M, Liu Y, Zhou F, Williamson TS, Quinlan D, et al. Donor serostatus has an impact on Cytomegalovirus-specific immunity, cytomegaloviral disease incidence, and survival in seropositive hematopoietic cell transplant recipients. Biol Blood Marrow Transplant 2011;17:574–85.CrossRef
4.
Kröger N, Zabelina T, Krüger W, Renges H, Stute N, Schrum J, et al. Patient Cytomegalovirus seropositivity with or without reactivation is the most important prognostic factor for survival and treatment-related mortality in stem cell transplantation from unrelated donors using pretransplant in vivo T-cell depletion with anti-thymocyte globulin. Br J Haematol. 2001;113:1060–71.CrossRef
5.
Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Infect Dis Clin North Am. 2010;24:319–37.CrossRef
6.
Venton G, Crocchiolo R, Fürst S, Granata A, Oudin C, Faucher C, et al. Risk factors of Ganciclovir-related neutropenia after allogeneic stem cell transplantation: a retrospective monocentre study on 547 patients. Clin Microbiol Infect. 2014;20:160–6.CrossRef
7.
Härter G, Michel D. Antiviral treatment of Cytomegalovirus infection: an update. Expert Opin Pharmacother. 2012;13:623–7.CrossRef
8.
Apperley J, Niederwieser D, Huang XJ, Nagler A, Fuchs E, Szer J, et al. Haploidentical hematopoietic stem cell transplantation: a global overview comparing Asia, the European union, and the United States. Biol Blood Marrow Transplant. 2016;22:23–6.CrossRef
9.
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.CrossRef
10.
Raiola AM, Dominietto A, di Grazia C, Lamparelli T, Gualandi F, Ibatici A, et al. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transplant. 2014;20:1573–9.CrossRef
11.
Di Stasi A, Milton DR, Poon LM, Hamdi A, Rondon G, Chen J, et al. Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic syndrome patients with haploidentical versus 10/10 human leukocyte antigen-matched unrelated and related donors. Biol Blood Marrow Transplant. 2014;20:1975–81.CrossRef
12.
Cieri N, Greco R, Crucitti L, Morelli M, Giglio F, Levati G, et al. 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;21:1506–14.CrossRef
13.
Crocchiolo R, Bramanti S, Vai A, Sarina B, Mineri R, Casari E, et al. Infections after T-replete haploidentical transplantation and high-dose cyclophosphamide as graft-versus-host disease prophylaxis. Transpl Infect Dis. 2015;17:242–9.CrossRef
14.
Crocchiolo R, Castagna L, Fürst S, Devillier R, Sarina B, Bramanti S, et al. The patient’s CMV serological status affects clinical outcome after T-cell replete haplo-HSCT and post-transplant cyclophosphamide. Bone Marrow Transplant. 2016;51:1134–6.CrossRef
15.
Ljungman P, Brandan R. Factors influencing Cytomegalovirus seropositivity in stem cell transplant patients and donors. Haematologica. 2007;92:1139–42.CrossRef
16.
Bate SL, Dollard SC, Cannon MJ. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. Clin Infect Dis. 2010;50:1439–47.CrossRef
17.
Passweg JR, Baldomero H, Bader P, Bonini C, Duarte RF, Dufour C, et al. Use of haploidentical stem cell transplantation continues to increase: the 2015 European society for blood and marrow transplant activity survey report. Bone Marrow Transplant. 2017;52:811–7.CrossRef
18.
Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE, et al. Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation. Blood. 2015;125:2855–64.CrossRef
19.
Kalra A, Williamson T, Daly A, Savoie ML, Stewart DA, Khan F, et al. Impact of donor and recipient Cytomegalovirus serostatus on outcomes of antithymocyte globulin-conditioned hematopoietic cell tansplantation. Biol Blood Marrow Transplant. 2016;22:1654–63.CrossRef
20.
Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, et al. Haploidentical transplant with posttransplant cyclophosphamide vs. matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126:1033–40.CrossRef
21.
Blaise D, Fürst S, Crocchiolo R, El-Cheikh J, Granata A, Harbi S, et al. Haploidentical T Cell-Replete transplantation with post-transplantation cyclophosphamide for patients in or above the sixth decade of age compared with allogeneic hematopoietic stem cell transplantation from an Hhman leukocyte antigen-matched related or unrelated donor. Biol Blood Marrow Transplant. 2016;22:119–24.CrossRef
22.
Ruggeri A, Sun Y, Labopin M, Bacigalupo A, Lorentino F, Arcese W, et al. Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant. Haematologica. 2017;102:401–10.CrossRef
23.
Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101.CrossRef
24.
Luznik L, Bolanos-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.CrossRef
25.
Kanakry CG, O’Donnell PV, Furlong T, de Lima MJ, Wei W, Medeot M, et al. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014;32:3497–505.CrossRef
26.
Alousi AM, Brammer JE, Saliba RM, Andersson B, Popat U, Hosing C, et al. Phase II trial of graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide after reduced-intensity busulfan/fludarabine conditioning for hematological malignancies. Biol Blood Marrow Transplant. 2015;21:906–12.CrossRef
27.
Lindner S, Berg T, Riemann J, Ajib S, Jedlickova Z, Gueller S, et al. Mismatched unrelated hematopoietic stem cell transplantation with post-transplant cyclophosphamide for high-risk acute myeloid leukemia. Ann Hematol. 2016;95:1023–5.CrossRef
28.
Rashidi A, Slade M, DiPersio JF, Westervelt P, Vij R, Romee R. Post-transplant high-dose cyclophosphamide after HLA-matched vs haploidentical hematopoietic cell transplantation for AML. Bone Marrow Transplant. 2016;51:1561–4.CrossRef
29.
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.CrossRef
30.
Kimura F, Sato K, Kobayashi S, Ikeda T, Sao H, Okamoto S, et al. Impact of AB0-blood group incompatibility on the outcome of recipients of bone marrow transplants from unrelated donors in the Japan marrow donor program. Haematologica. 2008;93:1686–93.CrossRef
31.
Canaani J, Savani BN, Labopin M, Huang XJ, Ciceri F, Arcese W, et al. Impact of ABO incompatibility on patient outcome in haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia - a report from the acute leukemia working party of the EBMT. Haematologica. 2017;102:1066–74.CrossRef
32.
Rimondo A, Bramanti S, Crocchiolo R, Giordano L, Sarina B, Morabito L, et al. Bone marrow donor-related variables associated with harvest outcome in HLA-haploidentical transplantation with postinfusion cyclophosphamide. Vox Sang. 2016;111:93–100.CrossRef
33.
Tu W, Rao S. Mechanisms underlying T cell immunosenescence: aging and Cytomegalovirus infection. Front Microbiol. 2016;7:2111.CrossRef
34.
Bachegowda LS, Saliba RM, Ramlal R, Kongtim P, Chen J, Rondon G, et al. Predictive model for survival in patients with AML/MDS receiving haploidentical stem cell transplantation. Blood. 2017;129:3031–3.CrossRef
35.
McCurdy SR, Kanakry JA, Showel MM, Tsai HL, Bolaños-Meade J, Rosner GL, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. 2015;125:3024–31.CrossRef
36.
Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S, Dreger P, et al Hematopoietic stem cell transplantation in Europe 2014: more than 40,000 transplants annually. Bone Marrow Transplant. 2016;51:786–92.CrossRef