Abstract
We aimed to evaluate the determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) and to describe factors predicting the main post-HCT complications. This retrospective study by the European Society for Blood and Marrow Transplantation included 2916 myelofibrosis patients who underwent first allo-HCT from an HLA-identical sibling or unrelated donor between 2000 and 2016. After a median follow-up of 4.7 years from transplant, projected median survival of the series was 5.3 years. Factors independently associated with increased mortality were age ≥ 60 years and Karnofsky Performance Status <90% at transplant, and occurrence of graft failure, grades III–IV acute graft-vs.-host disease (aGVHD), and disease progression/relapse during follow-up. The opposing effects of chronic graft-vs.-host disease (GVHD) on non-relapse mortality and relapse incidence resulted in a neutral influence on survival. Graft failure increased in unrelated donor recipients and decreased with myeloablative conditioning (MAC) and negative donor/recipient cytomegalovirus serostatus. Risk of grades III–IV aGVHD was higher with unrelated donors and decreased with MAC. Relapse incidence tended to be higher in patients with intermediate-2/high-risk DIPSS categories and to decrease in CALR-mutated patients. Acute and chronic GVHD reduced the subsequent risk of relapse. This information has potential implications for patient counseling and clinical decision-making.
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References
Cervantes F, Dupriez B, Passamonti F, Vannucchi AM, Morra E, Reilly JT, et al. Improving survival trends in primary myelofibrosis: an international study. J Clin Oncol. 2012;30:2981–7.
Devlin R, Gupta V. Myelofibrosis: to transplant or not to transplant? Hematol Am Soc Hematol Educ Program. 2016;2016:543–51.
Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S, Dreger P, et al. Impact of drug development on the use of stem cell transplantation: a report by the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2017;52:191–6.
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.
Patriarca F, Bacigalupo A, Sperotto A, Isola M, Soldano F, Bruno B, et al. Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica. 2008;93:1514–22.
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.
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.
Ditschkowski M, Elmaagacli AH, Trenschel R, Gromke T, Steckel NK, Koldehoff M, et al. Dynamic International Prognostic Scoring System scores, pre-transplant therapy and chronic graft-versus-host disease determine outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis. Haematologica. 2012;97:1574–81.
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.
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.
Samuelson Bannow BT, Salit RB, Storer BE, Stevens EA, Wu D, Yeung C, et al. Hematopoietic cell transplantation for myelofibrosis: the dynamic International Prognostic Scoring System Plus Risk predicts post-transplant outcomes. Biol Blood Marrow Transplant. 2018;24:386–92.
Gagelmann N, Ditschkowski M, Bogdanov R, Bredin S, Robin M, Cassinat B, et al. Comprehensive clinical-molecular transplant scoring system for myelofibrosis undergoing stem cell transplantation. Blood. 2019;133:2233–42.
McLornan D, Szydlo R, Koster L, Chalandon Y, Robin M, Wolschke C, et al. Myeloablative and reduced-intensity conditioned allogeneic hematopoietic stem cell transplantation in myelofibrosis: a retrospective study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2019;25:2167–71.
Robin M, Tabrizi R, Mohty M, Furst S, Michallet M, Bay JO, et al. Allogeneic haematopoietic stem cell transplantation for myelofibrosis: a report of the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC). Br J Haematol. 2011;152:331–9.
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.
Robin M, de Wreede LC, Wolschke C, Schetelig J, Eikema DJ, Van Lint MT, et al. Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis. Haematologica. 2019;104:1782–8.
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.
Alchalby H, Yunus DR, Zabelina T, Ayuk F, Kroger N. Incidence and risk factors of poor graft function after allogeneic stem cell transplantation for myelofibrosis. Bone Marrow Transplant. 2016;51:1223–7.
McLornan DP, Szydlo R, Robin M, van Biezen A, Koster L, Blok HJP, et al. Outcome of patients with myelofibrosis relapsing after allogeneic stem cell transplant: a retrospective study by the Chronic Malignancies Working Party of EBMT. Br J Haematol. 2018;182:418–22.
Caulier A, Drumez E, Gauthier J, Robin M, Blaise D, Beguin Y, et al. Scoring system based on post-transplant complications in patients after allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: a study from the SFGM-TC. Curr Res Transl Med. 2019;67:8–15.
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. 2019;25:522–8.
Olsson RF, Logan BR, Chaudhury S, Zhu X, Akpek G, Bolwell BJ, et al. Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies. Leukemia. 2015;29:1754–62.
Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.
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;69:204–17.
Copelan E, Casper JT, Carter SL, van Burik JA, Hurd D, Mendizabal AM, et al. A scheme for defining cause of death and its application in the T cell depletion trial. Biol Blood Marrow Transplant. 2007;13:1469–76.
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.
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106:2912–9.
Grambsch PM, Therneau T. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika. 1994;81:515–6.
Jann B. Splitting time–span records with categorical time–varying covariates. Stata J. 2004;4:221–2.
Lambert PC. The estimation and modelling of cause-specific cumulative incidence functions using time-dependent weights. Stata J. 2017;17:181–207.
Alchalby H, Yunus DR, Zabelina T, Kobbe G, Holler E, Bornhauser M, et al. Risk models predicting survival after reduced-intensity transplantation for myelofibrosis. Br J Haematol. 2012;157:75–85.
Tamari R, Rapaport F, Zhang N, McNamara C, Kuykendall A, Sallman DA, et al. Impact of high-molecular-risk mutations on transplantation outcomes in patients with myelofibrosis. Biol Blood Marrow Transplant. 2019;25:1142–51.
Gagelmann N, Eikema DJ, de Wreede LC, Koster L, Wolschke C, Arnold R, et al. Comparison of Dynamic International Prognostic Scoring System and MYelofibrosis SECondary to PV and ET prognostic model for prediction of outcome in polycythemia vera and essential thrombocythemia myelofibrosis after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25:e204–8.
Samuelson S, Sandmaier BM, Heslop HE, Popat U, Carrum G, Champlin RE, et al. Allogeneic haematopoietic cell transplantation for myelofibrosis in 30 patients 60-78 years of age. Br J Haematol. 2011;153:76–82.
Daghia G, Zabelina T, Zeck G, von Pein UM, Christopeit M, Wolschke C, et al. Allogeneic stem cell transplantation for myelofibrosis patients aged >/=65 years. Eur J Haematol. 2019;103:370–8.
Shanavas M, Popat U, Michaelis LC, Fauble V, McLornan D, Klisovic R, et al. Outcomes of allogeneic hematopoietic cell transplantation in patients with myelofibrosis with prior exposure to Janus Kinase 1/2 inhibitors. Biol Blood Marrow Transplant. 2016;22:432–40.
Olsson R, Remberger M, Schaffer M, Berggren DM, Svahn BM, Mattsson J, et al. Graft failure in the modern era of allogeneic hematopoietic SCT. Bone Marrow Transplant. 2013;48:537–43.
Slot S, Smits K, van de Donk NW, Witte BI, Raymakers R, Janssen JJ, et al. Effect of conditioning regimens on graft failure in myelofibrosis: a retrospective analysis. Bone Marrow Transplant. 2015;50:1424–31.
Nakamae H, Storer B, Sandmaier BM, Maloney DG, Davis C, Corey L, et al. Cytopenias after day 28 in allogeneic hematopoietic cell transplantation: impact of recipient/donor factors, transplant conditions and myelotoxic drugs. Haematologica. 2011;96:1838–45.
Dominietto A, Raiola AM, van Lint MT, Lamparelli T, Gualandi F, Berisso G, et al. Factors influencing haematological recovery after allogeneic haemopoietic stem cell transplants: graft-versus-host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol. 2001;112:219–27.
Hart C, Klatt S, Barop J, Muller G, Schelker R, Holler E, et al. Splenic pooling and loss of VCAM-1 causes an engraftment defect in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation. Haematologica. 2016;101:1407–16.
Boyiadzis M, Arora M, Klein JP, Hassebroek A, Hemmer M, Urbano-Ispizua A, et al. Impact of chronic graft-versus-host disease on late relapse and survival on 7,489 patients after myeloablative allogeneic hematopoietic cell transplantation for leukemia. Clin Cancer Res. 2015;21:2020–8.
Gratwohl A, Brand R, Apperley J, Biezen Av A, Bandini G, Devergie A, et al. Graft-versus-host disease and outcome in HLA-identical sibling transplantations for chronic myeloid leukemia. Blood. 2002;100:3877–86.
Ali H, Aldoss I, Yang D, Mokhtari S, Khaled S, Aribi A, et al. MIPSS70+ v2.0 predicts long-term survival in myelofibrosis after allogeneic HCT with the Flu/Mel conditioning regimen. Blood Adv. 2019;3:83–95.
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.
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We are indebted to all centers participating to the EBMT database.
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Hernández-Boluda, J.C., Pereira, A., Kröger, N. et al. Determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation. Leukemia 35, 215–224 (2021). https://doi.org/10.1038/s41375-020-0815-z
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DOI: https://doi.org/10.1038/s41375-020-0815-z
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