Allogeneic hematopoietic cell transplantation with cord blood versus mismatched unrelated donor with post-transplant cyclophosphamide in acute myeloid leukemia

Springer Science and Business Media LLC - Tập 14 - Trang 1-11 - 2021
Bhagirathbhai Dholaria1, Myriam Labopin2, Jaime Sanz3, Annalisa Ruggeri4, Jan Cornelissen5, Hélène Labussière-Wallet6, Didier Blaise7, Edouard Forcade8, Patrice Chevallier9, Anna Grassi10, Ludmila Zubarovskaya11, Jürgen Kuball12, Patrice Ceballos13, Fabio Ciceri14, Frederic Baron15, Bipin N. Savani1, Arnon Nagler16,17, Mohamad Mohty2,18
1Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, USA
2EBMT ALWP Office, Hôpital Saint-Antoine, Paris, France
3Hematology Department, University Hospital La Fe, Valencia, Spain
4Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
5Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands
6Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France
7Programme de Transplantation and Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France
8Hôpital Haut-Leveque, CHU Bordeaux, Pessac, France
9Department of D’Hematologie, CHU Nantes, Nantes, France
10Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
11RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russian Federation
12Department of Haematology, University Medical Centre, Utrecht, The Netherlands
13Département d’Hématologie Clinique, CHU Lapeyronie, Montpellier, France
14Ospedale San Raffaele s.r.l., Haematology and BMT, Milan, Italy
15CHU and University of Liège, Liège, Belgium
16Chaim Sheba Medical Center, Tel Hashomer, Israel
17ALWP Office Hôpital Saint-Antoine, Paris, France
18Service d’Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, UMRs 938, AP-HP, Sorbonne University, and INSERM, Paris, France

Tóm tắt

Allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) and cord blood transplantation (CBT) are valid alternatives for patients without a fully human leukocyte antigen (HLA)-matched donor. Here, we compared the allo-HCT outcomes of CBT versus single-allele-mismatched MMUD allo-HCT with post-transplant cyclophosphamide (PTCy) in acute myeloid leukemia. Patients who underwent a first CBT without PTCy (N = 902) or allo-HCT from a (HLA 9/10) MMUD with PTCy (N = 280) were included in the study. A multivariate regression analysis was performed for the whole population. A matched-pair analysis was carried out by propensity score-based 1:1 matching of patients (177 pairs) with known cytogenetic risk. The incidence of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% (p = 0.07) and 15% versus 11% (p = 0.16) for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%, p < 0.01) and higher 2-year non-relapse mortality (NRM) (30% vs. 16%, p < 0.01) compared to MMUD. In the multivariate analysis, CBT was associated with a higher risk of, NRM (HR = 2.09, 95% CI 1.46–2.99, p < 0.0001), and relapse (HR = 1.35, 95% CI 1–1.83, p = 0.05), which resulted in worse leukemia-free survival (LFS) (HR = 1.68, 95% CI 1.34–2.12, p < 0.0001), overall survival (OS) (HR = 1.7, 95% CI 1.33–2.17, p < 0.0001), and GVHD-free, relapse-free survival (GRFS) (HR = 1.49, 95% CI 1.21–1.83, p < 0.0001) compared to MMUD. The risk of grade II–IV acute GVHD (p = 0.052) and chronic GVHD (p = 0.69) did not differ significantly between the cohorts. These results were confirmed in a matched-pair analysis. CBT was associated with lower LFS, OS, and GRFS due to higher NRM, compared to MMUD allo-HCT with PTCy. In the absence of a fully matched donor, 9/10 MMUD with PTCy may be preferred over CBT.

Tài liệu tham khảo

Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371(4):339–48. Zheng CC, Zhu XY, Tang BL, Zhang XH, Zhang L, Geng LQ, et al. Clinical separation of cGvHD and GvL and better GvHD-free/relapse-free survival (GRFS) after unrelated cord blood transplantation for AML. Bone Marrow Transplant. 2017;52(1):88–94. Weisdorf D, Eapen M, Ruggeri A, Zhang MJ, Zhong X, Brunstein C, et al. Alternative donor transplantation for older patients with acute myeloid leukemia in first complete remission: a center for international blood and marrow transplant research-eurocord analysis. Biol Blood Marrow Transplant. 2014;20(6):816–22. Fuchs EJ, O’Donnell PV, Eapen M, Logan B, Antin JH, Dawson P, et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021;137(3):420–8. Sanz J, Sanz MA, Saavedra S, Lorenzo I, Montesinos P, Senent L, et al. Cord blood transplantation from unrelated donors in adults with high-risk acute myeloid leukemia. Biol Blood Marrow Transplant. 2010;16(1):86–94. Keating AK, Langenhorst J, Wagner JE, Page KM, Veys P, Wynn RF, et al. The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia. Blood Adv. 2019;3(7):1118–28. Eapen M, Rubinstein P, Zhang M-J, Stevens C, Kurtzberg J, Scaradavou A, et al. Outcomes of transplantation of unrelated donor umbilical cord blood and bone marrow in children with acute leukaemia: a comparison study. Lancet. 2007;369(9577):1947–54. Atsuta Y, Suzuki R, Nagamura-Inoue T, Taniguchi S, Takahashi S, Kai S, et al. Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia. Blood. 2009;113(8):1631–8. Majhail NS, Brunstein CG, Shanley R, Sandhu K, McClune B, Oran B, et al. Reduced-intensity hematopoietic cell transplantation in older patients with AML/MDS: umbilical cord blood is a feasible option for patients without HLA-matched sibling donors. Bone Marrow Transplant. 2012;47(4):494–8. Brunstein CG, Eapen M, Ahn KW, Appelbaum FR, Ballen KK, Champlin RE, et al. Reduced-intensity conditioning transplantation in acute leukemia: the effect of source of unrelated donor stem cells on outcomes. Blood. 2012;119(23):5591–8. Macmillan ML, Weisdorf DJ, Brunstein CG, Cao Q, Defor TE, Verneris MR, et al. Acute graft-versus-host disease after unrelated donor umbilical cord blood transplantation: analysis of risk factors. Blood. 2009;113(11):2410–5. O’Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377–86. Cytryn S, Abdul-Hay M. Haploidentical hematopoietic stem cell transplantation followed by ‘post-cyclophosphamide’: the future of allogeneic stem cell transplant. Clin Hematol Int. 2020;2(2):49–58. Wachsmuth LP, Patterson MT, Eckhaus MA, Venzon DJ, Gress RE, Kanakry CG. Post-transplantation cyclophosphamide prevents graft-versus-host disease by inducing alloreactive T cell dysfunction and suppression. J Clin Invest. 2019;129(6):2357–73. 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(1):40–7. McCurdy SR, Kasamon YL, Kanakry CG, Bolanos-Meade J, Tsai HL, Showel MM, et al. Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide. Haematologica. 2017;102(2):391–400. Shem-Tov N, Peczynski C, Labopin M, Itala-Remes M, Blaise D, Labussiere-Wallet H, et al. 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(1):283–92. Battipaglia G, Labopin M, Kroger N, Vitek A, Afanasyev B, Hilgendorf I, et al. Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. Blood. 2019;134(11):892–9. Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen JJ, Elmaagacli A, et al. 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(1):40. Lorentino F, Labopin M, Ciceri F, Vago L, Fleischhauer K, Afanasyev B, et al. Post-transplantation cyclophosphamide GvHD prophylaxis after hematopoietic stem cell transplantation from 9/10 or 10/10 HLA-matched unrelated donors for acute leukemia. Leukemia. 2021;35(2):585–94. Tegla C, Choi J, Abdul-Hay M, Cirrone F, Cole K, Al-Homsi AS. Current status and future directions in graft-versus-host disease prevention following allogeneic blood and marrow transplantation in adults. Clin Hematol Int. 2020;2(1):5–12. Al Malki MM, Tsai N-C, Palmer J, Mokhtari S, Cao T, Ali H, et al. Efficacy of post-transplant cyclophosphamide as graft-versus-host disease prophylaxis after peripheral blood stem cell HLA-mismatched unrelated donor hematopoietic cell transplantation; A Prospective Pilot Trial. Blood. 2020;136(Supplement 1):49–50. 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(2):541–53. Shaw BE, Jimenez-Jimenez A, Burns LJ, Logan B, Khimani F, Shaffer BC, et al. Bridging the gap in access to transplant for underserved minority patients using mismatched unrelated donors and post-transplant cyclophosphamide: a national marrow donor program/be the match (NMDP/BTM) initiative. Blood. 2020;136(Supplement 1):48–9. 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(12):1628–33. Ruggeri A, Labopin M, Battipaglia G, Chiusolo P, Tischer J, Diez-Martin JL, et al. Timing of post-transplantation cyclophosphamide administration in haploidentical transplantation: a comparative study on behalf of the acute leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2020;26(10):1915–22. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15(6):825–8. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69(2):204–17. Ruggeri A, Labopin M, Ciceri F, Mohty M, Nagler A. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP–EBMT analysis on patients with AML in remission. Bone Marrow Transplant. 2016;51(4):610–1. Kanate AS, Nagler A, International BSJCH. Summary of scientific and statistical methods, study endpoints and definitions for observational and registry-based studies in hematopoietic cell transplantation. Clin Hematol Int. 2019;2(1):2–4. Andersen PK, Klein JP, Zhang MJ. Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med. 1999;18(12):1489–500. 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(6):1485–93. Deteix C, Mesnil F, Furst S, Milpied N, Yakoub-Agha I, Fegueux N, et al. Influence of alternative donor type on early survival after hematopoietic stem cell transplantation for acute myeloid leukemia lacking a sibling donor. Bone Marrow Transplant. 2020;55(4):749–57. Jorge AS, Suarez-Lledo M, Pereira A, Gutierrez G, Fernandez-Aviles F, Rosinol 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(6):1196–202. Retière C, Willem C, Guillaume T, Vié H, Gautreau-Rolland L, Scotet E, et al. Impact on early outcomes and immune reconstitution of high-dose post-transplant cyclophosphamide vs anti-thymocyte globulin after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation. Oncotarget. 2018;9(14):11451–64. D'Souza A ZX. CIBMTR Summary Slides - HCT Trends and Survival Data 2017. https://www.cibmtr.org/ReferenceCenter/SlidesReports/SummarySlides/Pages/index.aspx#CiteSummarySlides. Accessed 1 Mar 2021. Fuchs EJ, O'Donnell PV, Eapen M, Logan BR, Antin JH, Dawson P, et al. Double unrelated umbilical cord blood versus HLA-haploidentical bone marrow transplantation (BMT CTN 1101). Blood. 2020. Kasamon YL, Fuchs EJ, Zahurak M, Rosner GL, Symons HJ, Gladstone DE, et al. Shortened-duration tacrolimus after nonmyeloablative, HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant. 2018;24(5):1022–8. Admiraal R, van Kesteren C, Jol-van der Zijde CM, Lankester AC, Bierings MB, Egberts TC, et al. Association between anti-thymocyte globulin exposure and CD4+ immune reconstitution in paediatric haemopoietic cell transplantation: a multicentre, retrospective pharmacodynamic cohort analysis. Lancet Haematol. 2015;2(5):e194-203. Chiesa R, Gilmour K, Qasim W, Adams S, Worth AJJ, Zhan H, et al. Omission of in vivo T-cell depletion promotes rapid expansion of naïve CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant. Br J Haematol. 2012;156(5):656–66. Admiraal R, Lindemans CA, Van Kesteren C, Bierings MB, Versluijs AB, Nierkens S, et al. Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation. Blood. 2016;128(23):2734–41. Rambaldi B, Kim HT, Reynolds C, Chamling Rai S, Arihara Y, Kubo T, et al. Impaired T- and NK-cell reconstitution after haploidentical HCT with posttransplant cyclophosphamide. Blood Adv. 2021;5(2):352–64. Willem C, Guillaume T, Makanga DR, Legrand N, Cesbron A, Gagne K, et al. Ptcy + ATG Vs Ptcy alone as Gvhd prophylaxis for peripheral blood stem cells haplo-transplants: comparison of NK and T cell effector reconstitution. Blood. 2019;134(Supplement_1):1999. Wang Y, Wu DP, Liu QF, Xu LP, Liu KY, Zhang XH, et al. Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients. J Hematol Oncol. 2019;12:88. https://doi.org/10.1186/s13045-019-0781-y. Viswabandya A, Mattsson J, Lipton JH, Kumar R, Thyagu S, Michelis FV, et al. Safety and efficacy of haploidentical peripheral blood stem cell transplantation for myeloid malignancies using post-transplantation cyclophosphamide and anti-thymocyte globulin as graft-versus-host disease prophylaxis. Clin Hematol Int. 2019;1(2):105–13. Salas MQ, Prem S, Atenafu EG, Datt Law A, Lam W, Al-Shaibani Z, et al. Dual T-cell depletion with ATG and PTCy for peripheral blood reduced intensity conditioning allo-HSCT results in very low rates of GVHD. Bone Marrow Transplant. 2020;55(9):1773–83. Horwitz ME, Wease S, Blackwell B, Valcarcel D, Frassoni F, Boelens JJ, et al. Phase I/II study of stem-cell transplantation using a single cord blood unit expanded ex vivo with nicotinamide. J Clin Oncol. 2019;37(5):367–74. De Lima M, Mcniece I, Robinson SN, Munsell M, Eapen M, Horowitz M, et al. Cord-blood engraftment with ex vivo mesenchymal-cell coculture. N Engl J Med. 2012;367(24):2305–15. Emiloju OE, Potdar RR, Jorge V, Gupta S, Varadi G. Clinical advancement and challenges of ex vivo expansion of human cord blood cells. Clin Hematol Int. 2019;2(1):18–26. van Besien K, Artz A, Champlin RE, Guarneri D, Bishop MR, Chen J, et al. Haploidentical vs haplo-cord transplant in adults under 60 years receiving fludarabine and melphalan conditioning. Blood Adv. 2019;32019:1858–67. Milano F, Gooley T, Wood B, Woolfrey A, Flowers ME, Doney K, et al. Cord-blood transplantation in patients with minimal residual disease. N Engl J Med. 2016;375(10):944–53.
Thông tin
Thông tin xuất bản

Springer Science and Business Media LLC

Tập 14

1-11

Thông tin tác giả