Allogeneic hematopoietic stem cell transplantation with fludarabine, busulfan, and thiotepa conditioning is associated with favorable outcomes in myelofibrosis.
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
05
07
2019
accepted:
09
08
2019
revised:
06
08
2019
pubmed:
30
8
2019
medline:
22
6
2021
entrez:
30
8
2019
Statut:
ppublish
Résumé
Allogeneic stem cell transplantation is a curative therapy for myelofibrosis. The optimal conditioning regimen has not been well defined. We retrospectively compared transplantation outcomes in patients with myelofibrosis (n = 67) conditioned with myeloablative (MAC, 36%) and reduced-intensity (RIC, 46%) regimens, and more recently with the combination of thiotepa, busulfan, and fludarabine (TBF, 18%). Patients were transplanted from HLA-matched sibling (n = 26) or unrelated donors (n = 41) between the years 2003 and 2018. The median follow-up was 2.9 years for all patients but shorter in the TBF group (1.1 years). The probability of 3-year progression-free survival (PFS) was 43%. At 1 year, the rate of PFS was 80%, 54%, and 45% with TBF, MAC, and RIC, respectively (p = 0.031). In a multivariable model, there was a greater risk for death with MAC (hazard ratio [HR] 12.26, p = 0.026) and lower PFS with both MAC (hazard ratio [HR] 7.78, p = 0.017) and RIC (HR 5.43, p = 0.027) compared with TBF. Relapse was higher with RIC (HR 8.20, p = 0.043) while nonrelapse mortality was increased with MAC (HR 9.63 p = 0.049). Our results indicate that TBF is a promising preparative regimen in myelofibrosis patients transplanted from matched sibling or unrelated donors, and should be further explored.
Identifiants
pubmed: 31462682
doi: 10.1038/s41409-019-0653-7
pii: 10.1038/s41409-019-0653-7
doi:
Substances chimiques
Thiotepa
905Z5W3GKH
Vidarabine
FA2DM6879K
Busulfan
G1LN9045DK
fludarabine
P2K93U8740
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
147-156Références
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405. https://doi.org/10.1182/blood-2016-03-643544
doi: 10.1182/blood-2016-03-643544
Tefferi A. Myelofibrosis with myeloid metaplasia. New Engl J Med. 2000;342:1255–65.
doi: 10.1056/NEJM200004273421706
Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799–807. https://doi.org/10.1056/NEJMoa1110557
doi: 10.1056/NEJMoa1110557
pubmed: 22375971
pmcid: 22375971
Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366:787–98. https://doi.org/10.1056/NEJMoa1110556
doi: 10.1056/NEJMoa1110556
pubmed: 22375970
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. https://doi.org/10.1038/leu.2015.233
doi: 10.1038/leu.2015.233
pubmed: 26293647
pmcid: 26293647
Kroger N, Giorgino T, Scott BL, Ditschkowski M, Alchalby H, Cervantes F, et al. Impact of allogeneic stem cell transplantation on survival of patients less than 65 years of age with primary myelofibrosis. Blood. 2015;125:3347–50. https://doi.org/10.1182/blood-2014-10-608315 .
doi: 10.1182/blood-2014-10-608315
pubmed: 25784679
pmcid: 4440886
Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115:1703–8. https://doi.org/10.1182/blood-2009-09-245837
doi: 10.1182/blood-2009-09-245837
pubmed: 20008785
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. https://doi.org/10.1200/JCO.2010.32.2446
doi: 10.1200/JCO.2010.32.2446
pubmed: 21149668
Tefferi A, Guglielmelli P, Lasho TL, Gangat N, Ketterling RP, Pardanani A, et al. MIPSS70+ version 2.0: Mutation and Karyotype-Enhanced International Prognostic Scoring System for primary myelofibrosis. J Clin Oncol. 2018;36:1769–70. https://doi.org/10.1200/JCO.2018.78.9867
doi: 10.1200/JCO.2018.78.9867
pubmed: 29708808
Guardiola P, Anderson JE, Bandini G, Cervantes F, Runde V, Arcese W, et al. Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European Group for Blood and Marrow Transplantation, Societe Francaise de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood. 1999;93:2831–8.
pubmed: 10216077
Kerbauy DM, Gooley TA, Sale GE, Flowers ME, Doney KC, Georges GE, et al. Hematopoietic cell transplantation as curative therapy for idiopathic myelofibrosis, advanced polycythemia vera, and essential thrombocythemia. Biol Blood Marrow Transplant. 2007;13:355–65. https://doi.org/10.1016/j.bbmt.2006.11.004
doi: 10.1016/j.bbmt.2006.11.004
pubmed: 17317589
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, 1976-1995. Am J Hematol. 1999;61:10–15.
doi: 10.1002/(SICI)1096-8652(199905)61:1<10::AID-AJH3>3.0.CO;2-I
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. https://doi.org/10.1182/blood-2009-07-234880
doi: 10.1182/blood-2009-07-234880
pubmed: 19812383
Rondelli D, Goldberg JD, Isola L, Price LS, Shore TB, Boyer M, et al. MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. Blood. 2014;124:1183–91. https://doi.org/10.1182/blood-2014-04-572545
doi: 10.1182/blood-2014-04-572545
pubmed: 24963042
pmcid: 4133490
Gupta V, Malone AK, Hari PN, Ahn KW, Hu ZH, 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. https://doi.org/10.1016/j.bbmt.2013.10.018
doi: 10.1016/j.bbmt.2013.10.018
pubmed: 24161923
Jain T, Kunze KL, Temkit M, Partain DK, Patnaik MS, Slack JL, et al. Comparison of reduced intensity conditioning regimens used in patients undergoing hematopoietic stem cell transplantation for myelofibrosis. Bone Marrow Transplant. 2019;54:204–11. https://doi.org/10.1038/s41409-018-0226-1
doi: 10.1038/s41409-018-0226-1
pubmed: 29795431
Sanz J, Boluda JC, Martin C, Gonzalez M, Ferra C, Serrano D, et al. Single-unit umbilical cord blood transplantation from unrelated donors in patients with hematological malignancy using busulfan, thiotepa, fludarabine and ATG as myeloablative conditioning regimen. Bone Marrow Transplant. 2012;47:1287–93. https://doi.org/10.1038/bmt.2012.13
doi: 10.1038/bmt.2012.13
pubmed: 22327127
Ruggeri A, Sanz G, Bittencourt H, Sanz J, Rambaldi A, Volt F, et al. Comparison of outcomes after single or double cord blood transplantation in adults with acute leukemia using different types of myeloablative conditioning regimen, a retrospective study on behalf of Eurocord and the Acute Leukemia Working Party of EBMT. Leukemia. 2014;28:779–86. https://doi.org/10.1038/leu.2013.259
doi: 10.1038/leu.2013.259
pubmed: 24005245
Giannotti F, Labopin M, Shouval R, Sanz J, Arcese W, Angelucci E, et al. Haploidentical transplantation is associated with better overall survival when compared to single cord blood transplantation: an EBMT-Eurocord study of acute leukemia patients conditioned with thiotepa, busulfan, and fludarabine. J Hematol Oncol. 2018;11:110. https://doi.org/10.1186/s13045-018-0655-8
doi: 10.1186/s13045-018-0655-8
pubmed: 30165887
pmcid: 6117895
Di Bartolomeo P, Santarone S, De Angelis G, Picardi A, Cudillo L, Cerretti R, et al. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013;121:849–57. https://doi.org/10.1182/blood-2012-08-453399
doi: 10.1182/blood-2012-08-453399
pubmed: 23165479
pmcid: 23165479
Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant. 2013;19:117–22. https://doi.org/10.1016/j.bbmt.2012.08.014
doi: 10.1016/j.bbmt.2012.08.014
Saraceni F, Labopin M, Hamladji RM, Mufti G, Socie G, Shimoni A, et al. Thiotepa-busulfan-fludarabine compared to busulfan-fludarabine for sibling and unrelated donor transplant in acute myeloid leukemia in first remission. Oncotarget. 2018;9:3379–93. https://doi.org/10.18632/oncotarget.23273
doi: 10.18632/oncotarget.23273
pubmed: 29423053
pmcid: 29423053
Saraceni F, Beohou E, Labopin M, Arcese W, Bonifazi F, Stepensky P, et al. Thiotepa, busulfan and fludarabine compared to busulfan and cyclophosphamide as conditioning regimen for allogeneic stem cell transplant from matched siblings and unrelated donors for acute myeloid leukemia. Am J Hematol. 2018;93:1211–9. https://doi.org/10.1002/ajh.25225
doi: 10.1002/ajh.25225
pubmed: 30033639
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. https://doi.org/10.1016/j.bbmt.2009.07.004
doi: 10.1016/j.bbmt.2009.07.004
pubmed: 19896087
pmcid: 2861656
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.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945–56. https://doi.org/10.1016/j.bbmt.2005.09.004
doi: 10.1016/j.bbmt.2005.09.004
pubmed: 16338616
pmcid: 16338616
Carreras E, Dufour C, Mohty M, Kröger N, ediotrs. The EBMT handbook: hematopoietic stem cell Transplantation and Cellular Therapies. Springer; 2019.
Dulery R, Bastos J, Paviglianiti A, Malard F, Brissot E, Battipaglia G, et al. Thiotepa, busulfan, and fludarabine conditioning regimen in T cell-replete HLA-haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25:1407–15. https://doi.org/10.1016/j.bbmt.2019.02.025
doi: 10.1016/j.bbmt.2019.02.025
pubmed: 30871978
Patriarca F, Masciulli A, Bacigalupo A, Bregante S, Pavoni C, Finazzi MC, et al. Busulfan- or thiotepa-based conditioning in myelofibrosis: a phase ii multicenter randomized study from the GITMO Group. Biol Blood Marrow Transplant. 2018. https://doi.org/10.1016/j.bbmt.2018.12.064
doi: 10.1016/j.bbmt.2018.12.064
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. https://doi.org/10.1016/j.bbmt.2009.10.025
doi: 10.1016/j.bbmt.2009.10.025
pubmed: 19879949
Bregante S, Dominietto A, Ghiso A, Raiola AM, Gualandi F, Varaldo R, et al. Improved outcome of alternative donor transplantations in patients with myelofibrosis: from unrelated to haploidentical family donors. Biol Blood Marrow Transplant. 2016;22:324–9. https://doi.org/10.1016/j.bbmt.2015.09.028
doi: 10.1016/j.bbmt.2015.09.028
pubmed: 26456259
Raj K, Eikema DJ, McLornan DP, Olavarria E, Blok HJ, Bregante S, et al. Family mismatched allogeneic stem cell transplantation for myelofibrosis: report from the chronic malignancies working party of European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2018. https://doi.org/10.1016/j.bbmt.2018.10.017
doi: 10.1016/j.bbmt.2018.10.017
McClune BL, Weisdorf DJ, Pedersen TL, Tunes da Silva G, Tallman MS, Sierra J, et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol. 2010;28:1878–87. https://doi.org/10.1200/JCO.2009.25.4821
doi: 10.1200/JCO.2009.25.4821
pubmed: 20212255
pmcid: 20212255
Blaise D, Devillier R, Lecoroller-Sorriano AG, Boher JM, Boyer-Chammard A, Tabrizi R, et al. Low non-relapse mortality and long-term preserved quality of life in older patients undergoing matched related donor allogeneic stem cell transplantation: a prospective multicenter phase II trial. Haematologica. 2015;100:269–74. https://doi.org/10.3324/haematol.2014.113571
doi: 10.3324/haematol.2014.113571
pubmed: 25425691
pmcid: 4803127
Versluis J, Labopin M, Niederwieser D, Socie G, Schlenk RF, Milpied N, et al. Prediction of non-relapse mortality in recipients of reduced intensity conditioning allogeneic stem cell transplantation with AML in first complete remission. Leukemia. 2015;29:51–57. https://doi.org/10.1038/leu.2014.164
doi: 10.1038/leu.2014.164
pubmed: 24913728
Cornelissen JJ, Blaise D. Hematopoietic stem cell transplantation for patients with AML in first complete remission. Blood. 2016;127:62–70. https://doi.org/10.1182/blood-2015-07-604546
doi: 10.1182/blood-2015-07-604546
pubmed: 26660427