Abstract
The aim of this study is to compare clinical outcomes of patients who underwent allogeneic stem cell transplantation (HCT) for myelofibrosis with reduced intensity conditioning (RIC) using either Busulfan Fludarabine (BuFlu), Fludarabine Bis-chlorethyl-nitroso-urea/ carmustine Melphalan (FBM) or Fludarabine Melphalan (FluMel) regimens. Sixty-one patients were identified who underwent HCT with one of these RIC regimens. Overall survival (OS) was not different in the 3 groups. However, 100% donor chimerism was seen in more frequently at day +30 and day +100 in patients who received FBM or FluMel than BuFlu, in both CD3 and CD33 fractions. For instance, 100% donor chimerism in CD33 fraction was present in 100% patients in FBM cohort, 90% in FluMel cohort while 44% in BuFlu cohort at day +100. Acute graft-versus host disease, grade 2–4 and grade 3–4, was not statistically different in the 3 groups (BuFlu 47 and 35%, FBM 68 and 27%, FluMel 68 and 46%; p = 0.31 and 0.45). Relapses and non-relapse mortality was also not statistically significantly different. Our study shows similar OS with these 3 RIC regimens in myelofibrosis; although donor chimerism at day +30 and day +100 was better in patients who received FBM and FluMel.
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References
Ballen KK, Shrestha S, Sobocinski KA, Zhang MJ, Bashey A, Bolwell BJ, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2010;16:358–67.
Kroger NM, Deeg JH, Olavarria E, Niederwieser D, Bacigalupo A, Barbui T, et al. Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group. Leukemia. 2015;29:2126–33.
Kroger N, Panagiota V, Badbaran A, Zabelina T, Triviai I, Araujo Cruz MM, et al. Impact of molecular genetics on outcome in myelofibrosis patients after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2017;23:1095–101.
Palmer J,Mesa R, Transplantation in myelofibrosis reaches the molecular age. Biol Blood Marrow Transplant. 2017;23:1043–4.
Mesa R, Jamieson C, Bhatia R, Deininger MW, Gerds AT, Gojo I, et al. Myeloproliferative neoplasms, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2016;14:1572–611.
Mesa RA, Silverstein MN, Jacobsen SJ, Wollan PC, Tefferi A. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976–95. Am J Hematol. 1999;61:10–5.
Tefferi A,Lasho TL,Jimma T,Finke CM,Gangat N,Vaidya R, et al. One thousand patients with primary myelofibrosis: the mayo clinic experience. Mayo Clin Proc. 2012;87:25–33.
Gupta V, Malone AK, Hari PN, Ahn KW, Hu Z-H, Gale RP, et al. Reduced-intensity hematopoietic cell transplantation for patients with primary myelofibrosis: a cohort analysis from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2014;20:89–97.
Kroger N, Holler E, Kobbe G, Bornhauser M, Schwerdtfeger R, Baurmann H, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2009;114:5264–70.
Kroger N, Zabelina T, Schieder H, Panse J, Ayuk F, Stute N, et al. Pilot study of reduced-intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosis. Br J Haematol. 2005;128:690–7.
Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998;91:756–63.
Giralt S, Thall PF, Khouri I, Wang X, Braunschweig I, Ippolitti C, et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood. 2001;97:631–7.
Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A, et al. Reduced-toxicity conditioning with fludarabine, BCNU, and melphalan in allogeneic hematopoietic cell transplantation: particular activity against advanced hematologic malignancies. Blood. 2008;112:415–25.
Shimoni A, Hardan I, Shem-Tov N, Rand A, Herscovici C, Yerushalmi R, et al. Comparison between two fludarabine-based reduced-intensity conditioning regimens before allogeneic hematopoietic stem-cell transplantation: fludarabine/melphalan is associated with higher incidence of acute graft-versus-host disease and non-relapse mortality and lower incidence of relapse than fludarabine/busulfan. Leukemia. 2007;21:2109–16.
Baron F, Labopin M, Peniket A, Jindra P, Afanasyev B, Sanz MA, et al. Reduced-intensity conditioning with fludarabine and busulfan versus fludarabine and melphalan for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Cancer. 2015;121:1048–55.
Damlaj M, Alkhateeb HB, Hefazi M, Partain DK, Hashmi S, Gastineau DA, et al. Fludarabine-busulfan reduced-intensity conditioning in comparison with fludarabine-melphalan is associated with increased relapse risk in spite of pharmacokinetic dosing. Biol Blood Marrow Transplant. 2016;22:1431–9.
Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.
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.
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;15:825–8.
Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Henslee-Downey PJ, et al. IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol. 1997;97:855–64.
Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011;29:392–7.
Uno H, Claggett B, Tian L, Inoue E, Gallo P, Miyata T, et al. Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis. J Clin Oncol. 2014;32:2380–5.
Kawamura K, Kako S, Mizuta S, Ishiyama K, Aoki J, Yano S, et al. Comparison of conditioning with fludarabine/busulfan and fludarabine/melphalan in allogeneic transplantation recipients 50 years or older. Biol Blood Marrow Transplant. 2017;23:2079–87.
Robin M, Porcher R, Wolschke C, Sicre de Fontbrune F, Alchalby H, Christopeit M, et al. Outcome after transplantation according to reduced-intensity conditioning regimen in patients undergoing transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2016;22:1206–11.
Slack JL, Dueck AC, Fauble VD, Sproat LO, Reeder CB, Noel P, et al. Reduced toxicity conditioning and allogeneic stem cell transplantation in adults using fludarabine, carmustine, melphalan, and antithymocyte globulin: outcomes depend on disease risk index but not age, comorbidity score, donor type, or human leukocyte antigen mismatch. Biol Blood Marrow Transplant. 2013;19:1167–74.
Martino R, de Wreede L, Fiocco M, van Biezen A, von dem Borne PA, Hamladji RM, et al. Comparison of conditioning regimens of various intensities for allogeneic hematopoietic SCT using HLA-identical sibling donors in AML and MDS with 10% BM blasts: a report from EBMT. Bone Marrow Transplant. 2013;48:761–70.
Jain T,Temkit H,Partain DK,Patnaik MM,Slack JL,Khera N, et al. Day + 30 and day + 100 CD33 chimerisms predict survival after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. Blood. 2016;128:4653
Valcarcel D, Martino R, Caballero D, Mateos MV, Perez-Simon JA, Canals C, et al. Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant. 2003;31:387–92.
Molina AMP,Maloney DG,Sandmaier B,Wagner JL,Nash RA,Chauncey T,Bryant E,Storb R, Degree of early donor T-cell chimerism predicts GVHD and graft rejection in patients with non-myeloablative hematopoietic stem cell allografts. Blood. 1999;94:1745
Perez-Simon JA, Caballero D, Diez-Campelo M, Lopez-Perez R, Mateos G, Canizo C, et al. Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation. Leukemia. 2002;16:1423–31.
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Author contribution:
TJ: Conceptualization, data acquisition, interpretation of results, writing—drafting the manuscript, reviewing and editing of manuscript and approved the final version. KLK and MT: Formal analysis, editing and reviewing of manuscript. DKP: Data acquisition. MSP, JLS, NK, WJH, VR, PN, JFL, LZS, VF, RAM: Writing—reviewing and editing of manuscript and approved the final version. JP: conceptualization, supervision, interpretation of results, reviewing and editing of manuscript and approved the final version.
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RAM—Consultant: Novartis, Ariad, Galena; Research Support: Incyte, Gilead, CTI, Promedior, Celgene; The remaining authors declare that they have no conflict of interest.
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Jain, T., Kunze, K.L., Temkit, M. et al. Comparison of reduced intensity conditioning regimens used in patients undergoing hematopoietic stem cell transplantation for myelofibrosis. Bone Marrow Transplant 54, 204–211 (2019). https://doi.org/10.1038/s41409-018-0226-1
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DOI: https://doi.org/10.1038/s41409-018-0226-1
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