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Better outcome with haploidentical over HLA-matched related donors in patients with Hodgkin’s lymphoma undergoing allogeneic haematopoietic cell transplantation—a study by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy

Abstract

The question of the best donor type between haploidentical (HAPLO) and matched-related donors (MRD) for patients with advanced HL receiving an allogeneic hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of data comparing these two types of donor in the setting of non-myeloablative (NMA) or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective study using graft-vs.-host disease-free relapse-free survival (GRFS) as our primary endpoint. We analysed the data of 151 consecutive HL patients who underwent NMA or RIC allo-HCT from a HAPLO (N  =  61) or MRD (N  =  90) between January 2011 and January 2016. GRFS was defined as the probability of being alive without evidence of relapse, grade 3–4 acute GVHD or chronic GVHD. In multivariable analysis, MRD donors were independently associated with lower GRFS compared to HAPLO donors (HR  =  2.95, P   < 0.001). Disease status at transplant other than CR was also associated with lower GRFS in multivariable analysis (HR  =  1.74, P  =  0.01). In addition, the administration of ATG was independently linked to higher GRFS (HR  =  0.52, P  =  0.009). In summary, we observed significantly higher GRFS in HL patients receiving an allo-HCT using the HAPLO PT-Cy platform compared to MRD.

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References

  1. Sarina B, Castagna L, Farina L, Patriarca F, Benedetti F, Carella AM, et al. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood. 2010;115:3671–7.

    Article  CAS  Google Scholar 

  2. Raiola A, Dominietto A, Varaldo R, Ghiso A, Galaverna F, Bramanti S, et al. Unmanipulated haploidentical BMT following non-myeloablative conditioning and post-transplantation CY for advanced Hodgkin’s lymphoma. Bone Marrow Transplant. 2014;49:190–4.

    Article  CAS  Google Scholar 

  3. Gayoso Balsalobre, Pascual Castilla-Llorente, López-Corral Kwon, et al. Busulfan-based reduced intensity conditioning regimens for haploidentical transplantation in relapsed/refractory Hodgkin lymphoma: Spanish multicenter experience. Bone Marrow Transplant. 2016;51:1307–12.

    Article  CAS  Google Scholar 

  4. Castagna Bramanti, Devillier Sarina, Crocchiolo Furst, et al. Haploidentical transplantation with post-infusion cyclophosphamide in advanced Hodgkin lymphoma. Bone Marrow Transplant. 2017;52:683–88.

    Article  CAS  Google Scholar 

  5. 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.

    Article  CAS  Google Scholar 

  6. Burroughs LM, O’Donnell PV, Sandmaier BM, Storer BE, Luznik L, Symons HJ, et al. Comparison of outcomes of HLA-matched related, unrelated, or HLA-haploidentical related hematopoietic cell transplantation following nonmyeloablative conditioning for relapsed or refractory Hodgkin lymphoma. Biol Blood Marrow Transplant. 2008;14:1279–87.

    Article  Google Scholar 

  7. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, et al. Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17:1244.

    Article  CAS  Google Scholar 

  8. Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25:579–86.

    Article  Google Scholar 

  9. Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.

    Article  Google Scholar 

  10. Blaise D, Nguyen S, Bay JO, Chevallier P, Contentin N, Dhedin N, et al. [Allogeneic stem cell transplantation from an HLA-haploidentical related donor: SFGM-TC recommendations (Part 1)]. Pathol Biol. 2014;62:180–4.

    Article  CAS  Google Scholar 

  11. Nguyen S, Chalandon Y, Lemarie C, Simon S, Masson D, Dhedin N, et al. [Haploidentical hematopoietic stem cell transplantation: guidelines from the Francophone society of marrow transplantation and cellular therapy (SFGM-TC)]. Bull Cancer. 2016;103:S229–42.

    Article  Google Scholar 

  12. Nguyen S, Blaise D, Bay JO, Chevallier P, Contentin N, Dhedin N, et al. [Allogeneic stem cell transplantation from an HLA-haploidentical related donor: SFGM-TC recommendations (part 2)]. Pathol Biol. 2014;62:185–9.

    Article  CAS  Google Scholar 

  13. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8.

    Article  CAS  Google Scholar 

  14. Prentice RL, Kalbfleisch JD, Peterson JA, Flournoy N, Farewell VT, Breslow NE. The analysis of failure times in the presence of competing risks. Biometrics. 1978;34:541–54.

    Article  CAS  Google Scholar 

  15. Ghosh N, Karmali R, Rocha V, Ahn KW, DiGilio A, Hari PN, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors versus hla-matched sibling donors: a center for international blood and marrow transplant research analysis. J Clin Oncol. 2016;34:3141–9. https://doi.org/10.1200/JCO.2015.66.3476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Garciaz S, Castagna L, Bouabdallah R, Furst S, Bramanti S, Coso D, et al. Familial haploidentical challenging unrelated donor Allo-SCT in advanced non-Hodgkin lymphomas when matched related donor is not available. Bone Marrow Transplant. 2015;50:880.

    Article  CAS  Google Scholar 

  17. Kanakry C, Coffey D, Towlerton A, Vulic A, Storer B, Chou J, et al. Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide. Jci Insight. 2016;1: e86252.

    Article  Google Scholar 

  18. Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med. 2002;196:389–99.

    Article  CAS  Google Scholar 

  19. Robb RJ, Lineburg KE, Kuns RD, Wilson YA, Raffelt NC, Olver SD, et al. Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation. Blood. 2012;119:5898–908.

    Article  CAS  Google Scholar 

  20. Zheng J, Liu Y, Liu Y, Liu M, Xiang Z, Lam KT, et al. Human CD8+regulatory T cells inhibit GVHD and preserve general immunity in humanized mice. Sci Transl Med. 2013;5:168ra9.

    PubMed  Google Scholar 

  21. Ganguly S, Ross D, Panoskaltsis-Mortari A, Kanakry C, Blazar B, Levy R, et al. Donor CD4+Foxp3+regulatory T cells are necessary for posttransplantation cyclophosphamide-mediated protection against GVHD in mice. Blood. 2014;124:2131–41.

    Article  CAS  Google Scholar 

  22. McCurdy S, Kasamon Y, Kanakry C, Bolaños-Meade J, Tsai H-L, Showel M, et al. Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide. Haematologica. 2016;102:391–400.

    Article  Google Scholar 

  23. Mielcarek M, Furlong T, O’Donnell P, Storer B, McCune J, Storb R, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127:1502–08.

    Article  CAS  Google Scholar 

  24. 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;51:1561–64.

    Article  CAS  Google Scholar 

  25. Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino P, Bartolomeo Pdi, et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood. 2001;98:2942–47.

    Article  CAS  Google Scholar 

  26. Socié G, Schmoor C, Bethge W, Ottinger H, Stelljes M, Zander A, et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti–T-cell globulin ATG-Fresenius. Blood. 2011;117:6375–82.

    Article  Google Scholar 

  27. Kröger N, Solano C, Wolschke C, Bandini G, Patriarca F, Pini M, et al. Antilymphocyte globulin for prevention of chronic graft-versus-host disease. New Engl J Med. 2016;374:43–53.

    Article  Google Scholar 

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Acknowledgements

We wish to thank all participating centers as well as our data manager Nicole Raus and Rachel Tipton, the SFGM-TC secretary. IYA wishes to thank the “Association Capucine”.

Author contributions

JG and IYA designed the study. JG wrote the manuscript and performed all statistical analyses. All authors reviewed and approved the manuscript.

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Correspondence to Ibrahim Yakoub-Agha.

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Gauthier, J., Poiré, X., Gac, AC. et al. Better outcome with haploidentical over HLA-matched related donors in patients with Hodgkin’s lymphoma undergoing allogeneic haematopoietic cell transplantation—a study by the Francophone Society of Bone Marrow Transplantation and Cellular Therapy. Bone Marrow Transplant 53, 400–409 (2018). https://doi.org/10.1038/s41409-017-0018-z

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