Graft-versus-Host Disease Prophylaxis with Post- Transplantation Cyclophosphamide in Chronic Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation from an Unrelated or Mismatched Related Donor: A Comparative Study from the Chronic Malignancies Working Party of the EBMT (CMWP-EBMT).
Ortí, Guillermo; Gras, Luuk; Koster, Lindaet al.
2024 • In Transplantation and Cellular Therapy, 30, p. 93.e1 - 93.e12
[en] Outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) for chronic myeloid leukemia (CML) with post-transplantation cyclophosphamide (PTCy) using an unrelated donor (UD) or a mismatched related donor (MMRD) remain unknown. We report a retrospective comparison of PTCy-based allo-HCT from a UD, non-PTCy allo-HCT from a UD, and PTCy allo-HCT from an MMRD. Inclusion criteria were adult patients with CML undergoing first allo-HCT between 2012 and 2019 from a UD with either PTCy or non-PTCy graft-versus-host disease (GVHD) prophylaxis or from an MMRD using PTCy. The primary endpoint was GVHD-free/relapse-free survival (GRFS). A total of 1341 patients were included (82% in the non-PTCy UD cohort). With a median follow-up of 34.9 months, the 3-year GRFS was 43% in the non-PTCy cohort, 37% in the PTCy-UD cohort, and 39% PTCy-MMRD cohort (P = .15). Multivariable analyses revealed no significant differences among the 3 cohorts in terms of overall survival (OS), progression-free survival, RI, and nonrelapse mortality. Factors independently associated with worse OS in the overall cohort were Karnofsky Performance Status <90 (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.41 to 2.45; P < .001), older age (HR, 1.24, 95% CI, 1.11 to 1.38; P < .001), and disease stage (compared to chronic phase [CP] 1): blast phase (HR, 2.25; 95% CI, 1.60 to 3.16; P < .001), accelerated phase (HR, 1.63; 95% CI, 1.05 to 2.54; P = .03), and CP >2 (HR, 1.58; 95% CI, 1.15 to 2.17; P = .005). These results suggest that allo-HCT in patients with CML using either a UD or an MMRD with PTCy-based GVHD prophylaxis are feasible transplantation, platforms and that the disease stage at allo-HCT remains a major prognostic factor, highlighting the importance of closely monitoring CML patients and proposing transplantation when indicated when still in CP1.
Disciplines :
Hematology
Author, co-author :
Ortí, Guillermo ; Department of Hematology, Vall d`Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain. Electronic address: gorti@vhio.net
Gras, Luuk; EBMT Statistical Unit, Leiden, the Netherlands
Koster, Linda; EBMT Leiden Study Unit, Leiden, the Netherlands
Kulagin, Aleksander ; RM Gorbacheva Research Institute, Pavlov University, Petersburg, Russian Federation
Byrne, Jenny ; Nottingham University, Nottingham, United Kingdom
Apperley, Jane F; Imperial College, London, United Kingdom
Halaburda, Kazimierz ; Institute of Hematology and Transfusion Medicine, Warsaw, Poland
Blau, Igor Wolfgang; Charité-Universitätsmedizin Berlin, Berlin, Germany
Clark, Andrew; The Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
Kröger, Nicolaus ; University Hospital Eppendorf, Hamburg, Germany
Griskevicius, Laimonas; Vilnius University Hospital, Vilnius, Lithuania
Carlson, Kristina ; University Hospital, Uppsala, Sweden
Collin, Matthew; Northern Centre for Bone Marrow Transplantation, Newcastle Upon Tyne, United Kingdom
Bloor, Adrian; Christie NHS Trust Hospital, Manchester, United Kingdom
Raiola, Anna Maria; IRCCS Ospedale Policlinico San Martino, Genova, Italy
Blaise, Didier ; Programme de Transplantation & Therapie Cellulaire, Marseille, France
Aljurf, Mahmoud ; King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
Graft-versus-Host Disease Prophylaxis with Post- Transplantation Cyclophosphamide in Chronic Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation from an Unrelated or Mismatched Related Donor: A Comparative Study from the Chronic Malignancies Working Party of the EBMT (CMWP-EBMT).
Conflict of interest statement: G.O. has received consulting fees from BMS, Incyte, Norvartis and Pfizer; travel support from BMS, Incyte, Norvartis and Pfizer; institutional research grant from Incyte; and honoraria from BMS, Incyte, Jazz, Norvartis and Pfizer. Y.C. has received consulting fees for advisory board from MSD, Novartis, Incyte, BMS, Pfizer, Abbvie, Roche, Jazz, Gilead, Amgen, Astra-Zeneca, Servier; Travel support from MSD, Roche, Gilead, Amgen, Incyte, Abbvie, Janssen, Astra-Zeneca, Jazz, Sanofi all via the institution.
Hochhaus, A, Baccarani, M, Silver, RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 34 (2020), 966–984.
Deininger, MW, Shah, NP, Altman, JK, et al. Chronic myeloid leukemia, version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 18 (2020), 1385–1415.
Passweg, JR, Baldomero, H, Chabannon, C, et al. Hematopoietic cell transplantation and cellular therapy survey of the EBMT: monitoring of activities and trends over 30 years. Bone Marrow Transplant 56 (2021), 1651–1664.
Radich, J, Allogeneic transplant for chronic myeloid leukemia in 2010. Ther Adv Hematol 1 (2010), 5–13.
Kolb, HJ, Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood 112 (2008), 4371–4383.
Jabbour, E, Cortes, J, Kantarjian, HM, et al. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib failure. Blood 108 (2006), 1421–1423.
Gratwohl, A, Hermans, J, Goldman, JM, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet 352 (1998), 1087–1092.
Arora, M, Weisdorf, DJ, Spellman, SR, et al. HLA-identical sibling compared with 8/8 matched and mismatched unrelated donor bone marrow transplant for chronic phase chronic myeloid leukemia. J Clin Oncol 27 (2009), 1644–1652.
Lee, SJ, Klein, J, Haagenson, M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 110 (2007), 4576–4583.
Pearce, KF, Lee, SJ, Haagenson, M, et al. Analysis of non-HLA genomic risk factors in HLA-matched unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia. Haematologica 97 (2012), 1014–1019.
Craddock, C, Szydlo, RM, Dazzi, F, et al. Cytomegalovirus seropositivity adversely influences outcome after T-depleted unrelated donor transplant in patients with chronic myeloid leukaemia: the case for tailored graft-versus-host disease prophylaxis. Br J Haematol 112 (2001), 228–236.
Sehn, LH, Alyea, EP, Weller, E, et al. Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion. J Clin Oncol 17 (1999), 561–568.
McGlave, PB, Shu, XO, Wen, W, et al. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the national marrow donor program. Blood 95 (2000), 2219–2225.
Luznik, L, O'Donnell, PV, Symons, HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 14 (2008), 641–650.
Kanakry, JA, Kasamon, YL, Gocke, CD, et al. Outcomes of related donor HLA-identical or HLA-haploidentical allogeneic blood or marrow transplantation for peripheral T cell lymphoma. Biol Blood Marrow Transplant 19 (2013), 602–606.
Burroughs, LM, O'Donnell, PV, Sandmaier, BM, 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 14 (2008), 1279–1287.
Sanz, J, Galimard, JE, Labopin, M, et al. Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT. J Hematol Oncol, 13, 2020, 46.
Sahebi, F, Eikema, DJ, Koster, L, et al. Post-transplantation cyclophosphamide for graft-versus- host disease prophylaxis in multiple myeloma patients who underwent allogeneic hematopoietic cell transplantation: first comparison by donor type. A study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation. Transplant Cell Ther 27 (2021), 999.e1–999.e10.
Sanz, J, Galimard, JE, Labopin, M, et al. Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT. J Hematol Oncol, 14, 2021, 84.
Baccarani, M, Cortes, J, Pane, F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 27 (2009), 6041–6051.
Baccarani, M, Deininger, MW, Rosti, G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122 (2013), 872–884.
Vardiman, JW, Thiele, J, Arber, DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114 (2009), 937–951.
Arber, DA, Orazi, A, Hasserjian, R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127 (2016), 2391–2405.
Weisdorf, DJ, Hurd, D, Carter, S, et al. Prospective grading of graft-versushost disease after unrelated donor marrow transplantation: a grading algorithm versus blinded expert panel review. Biol Blood Marrow Transplant 9 (2003), 512–518.
Harris, AC, Young, R, Devine, S, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant 22 (2016), 4–10.
Pavletic, SZ, Martin, P, Lee, SJ, et al. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant 12 (2006), 252–266.
Lee, SJ, Wolff, D, Kitko, C, et al. Measuring therapeutic response in chronic graft-versus-host disease. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: IV. The 2014 Response Criteria Working Group report. Biol Blood Marrow Transplant 21 (2015), 984–999.
R Core Team. R: A language and environment for statistical computing. 2022, R Foundation for Statistical Computing, Vienna, Austria https://www.R-project.org/.
Chalandon, Y, Sbianchi, G, Gras, L, et al. Allogeneic hematopoietic cell transplantation in patients with chronic phase chronic myeloid leukemia in the era of third generation tyrosine kinase inhibitors: a retrospective study by the chronic malignancies working party of the EBMT. Am J Hematol 98 (2023), 112–121.
Wang, W, Cortes, JE, Tang, G, et al. Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood 127 (2016), 2742–2750.
Branford, S, Kim, DDH, Apperley, JF, et al. Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia. Leukemia 33 (2019), 1835–1850.
Soverini, S, Bavaro, L, De Benedittis, C, et al. Prospective assessment of NGS-detectable mutations in CML patients with nonoptimal response: the NEXT-in-CML study. Blood 135 (2020), 534–541.
Ciurea, SO, Zhang, MJ, Bacigalupo, AA, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood 126 (2015), 1033–1040.
Al Malki, MM, Yang, D, Labopin, M, et al. Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation. Blood Adv 4 (2020), 2073–2083.
Sorror, M, Storer, B, Sandmaier, BM, et al. Hematopoietic cell transplantation-comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation. Cancer 112 (2008), 1992–2001.
Chhabra, S, Ahn, KW, Hu, ZH, et al. Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia. Blood Adv 2 (2018), 2922–2936.
Rea, D, Etienne, G, Nicolini, F, et al. First-line imatinib mesylate in patients with newly diagnosed accelerated phase-chronic myeloid leukemia. Leukemia 26 (2012), 2254–2259.
Khoury, JD, Solary, E, Abla, O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 36 (2022), 1703–1719.
