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CD34+ -selected hematopoietic stem cell transplant conditioned with a myeloablative regimen in patients with advanced myelofibrosis

Bone Marrow Transplantation volume 57, pages 1101–1107 (2022)Cite this article

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Abstract

Allogeneic hematopoietic stem cell transplantation (Allo-HCT) remains the only curative treatment for myelofibrosis (MF). Transplantation in patients with MF is mostly done using a reduced intensity conditioning regimen with calcineurin inhibitors for graft versus host disease (GVHD) prophylaxis. Here we sought to evaluate outcomes of patients who underwent an ex vivo CD34+ -selected allo-HCT using myeloablative conditioning (MAC). Twenty-seven patients were included in this retrospective analysis. All patients were conditioned with busulfan, melphalan and fludarabine and antithymocyte globulin to prevent graft rejection. G-CSF mobilized peripheral blood stem cell grafts were depleted of T-cells using immunomagnetic CD34+ selection by CliniMACS device. Median follow-up among survivors was 50.6 months. The estimated 3-year overall survival, relapse free survival and the combined endpoint of GVHD/relapse free survival were 88% (95% CI, 75–100%), 80% (95% CI, 66–98%) and 74% (95% CI, 59–93%), respectively. The cumulative incidence of grade II-IV acute GVHD at day 100 was 33.3% (95% CI 16.4–51.3%), and two patients suffered chronic GVHD. There were no cases of primary graft failure. However, delayed graft failure occurred in two patients. We conclude that CD34+ selected allo-HCT with a MAC resulted in high survival rates in this cohort of patients with MF.

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Fig. 1: Overall Survival.
Fig. 2: Relapse Free Survival.
Fig. 3: Composite end point.
Fig. 4: Non-relapse mortality.
Fig. 5: Relapse.
Fig. 6: Graft versus Host Disease.

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Data availability

Raw data were generated at MSKCC. Derived data supporting the findings of this study are available from the corresponding author RT on request.

References

  1. Harrison CN, Schaap N, Vannucchi AM, Kiladjian JJ, Tiu RV, Zachee P, et al. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol. 2017;4:e317–24. https://doi.org/10.1016/S2352-3026(17)30088-1.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, et al. Safety and efficacy of fedratinib in patients with primary or secondary myelofibrosis. JAMA Oncol. 2015;1:643 https://doi.org/10.1001/jamaoncol.2015.1590.

    Article  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. Scott BL, Gooley TA, Sorror ML, Rezvani AR, Linenberger ML, Grim J, et al. The Dynamic International Prognostic Scoring System for myelofibrosis predicts outcomes after hematopoietic cell transplantation. Blood. 2012;119:2657–64. https://doi.org/10.1182/blood-2011-08-372904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. 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 Transpl. 2014;20:89–97. https://doi.org/10.1016/j.bbmt.2013.10.018.

    Article  Google Scholar 

  7. Gowin K, Ballen K, Ahn KW, Hu Z-H, Ali H, Arcasoy MO, et al. Survival following allogeneic transplant in patients with myelofibrosis. Blood Adv. 2020;4:1965–73. https://doi.org/10.1182/bloodadvances.2019001084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Devine SM, Carter S, Soiffer RJ, Pasquini MC, Hari PN, Stein A, et al. Low risk of chronic graft-versus-host disease and relapse associated with T cell–depleted peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission: results of the blood and marrow transplant clinical trials network prot. Biol Blood Marrow Transpl. 2011;17:1343–51. https://doi.org/10.1016/j.bbmt.2011.02.002.

    Article  Google Scholar 

  9. Luznik L, Pasquini MC, Logan B, Soiffer RJ, Wu J, Devine SM, et al. Randomized Phase III BMT CTN trial of calcineurin inhibitor-free chronic graft-versus-host disease interventions in myeloablative hematopoietic cell transplantation for hematologic malignancies. J Clin Oncol. 2022;40:356–68.

  10. Montoro J, Ceberio I, Hilden P, Maloy MA, Barker J, Castro-Malaspina H, et al. Ex vivo T cell-depleted hematopoietic stem cell transplantation for adult patients with acute myelogenous leukemia in first and second remission: long-term disease-free survival with a significantly reduced risk of graft-versus-host disease. Biol Blood Marrow Transpl. 2020;26:323–32. https://doi.org/10.1016/j.bbmt.2019.10.003.

    Article  CAS  Google Scholar 

  11. Jakubowski AA, Small TN, Young JW, Kernan NA, Castro-Malaspina H, Hsu KC, et al. T cell–depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin. Blood. 2007;110:4552–9. https://doi.org/10.1182/blood-2007-06-093880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tamari R, Oran B, Hilden P, Maloy M, Kongtim P, Papadopoulos EB, et al. Allogeneic stem cell transplantation for advanced myelodysplastic syndrome: comparison of outcomes between CD34+ selected and unmodified hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2018;24:1079–87. https://doi.org/10.1016/j.bbmt.2018.01.001.

    Article  CAS  Google Scholar 

  13. Barba P, Hilden P, Devlin SM, Maloy M, Dierov D, Nieves J, et al. Ex vivo CD34 + -selected t cell–depleted peripheral blood stem cell grafts for allogeneic hematopoietic stem cell transplantation in acute leukemia and myelodysplastic syndrome is associated with low incidence of acute and chronic graft-versus-host diseas. Biol Blood Marrow Transpl. 2017;23:452–8. https://doi.org/10.1016/j.bbmt.2016.12.633.

    Article  Google Scholar 

  14. 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. https://doi.org/10.1182/blood-2005-05-2004.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Tefferi A, Cervantes F, Mesa R, Passamonti F, Verstovsek S, Vannucchi AM, et al. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013;122:1395–8. https://doi.org/10.1182/blood-2013-03-488098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Rowlings PA, Przepiorka D, Klein JP, Gale RP, Passweg JR, Jean Henslee‐Downey P, et al. IBMTR severity index for grading acute graft‐versus‐host disease: retrospective comparison with glucksberg grade. Br J Haematol. 1997;97:855–64. https://doi.org/10.1046/j.1365-2141.1997.1112925.x.

    Article  CAS  PubMed  Google Scholar 

  17. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transpl. 2015;21:389–401.e1. https://doi.org/10.1016/j.bbmt.2014.12.001.

    Article  Google Scholar 

  18. Dierov D, Webb N, Fatmi S, Nwanne C, Ciolino C, Mosesso K, et al. Establishing a standardized system for review and adjudication of chronic graft‐vs‐host disease data in accordance with the National Institutes Consensus criteria. Adv Cell Gene Ther. 2019;2. https://doi.org/10.1002/acg2.62.

  19. Copelan E, Casper JT, Carter SL, van Burik JAH, 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 Transpl. 2007;13:1469–76. https://doi.org/10.1016/j.bbmt.2007.08.047.

    Article  Google Scholar 

  20. Kucine N, Viny AD, Rampal R, Berger M, Socci N, Viale A, et al. Genetic analysis of five children with essential thrombocytosis identified mutations in cancer-associated genes with roles in transcriptional regulation. Haematologica. 2016;101:e237–9. https://doi.org/10.3324/haematol.2016.142935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Passamonti F, Mora B, Barraco D, Maffioli M. Post-ET and post-PV myelofibrosis: updates on a distinct prognosis from primary myelofibrosis. Curr Hematol Malig Rep. 2018;13:173–82. https://doi.org/10.1007/s11899-018-0453-y.

    Article  PubMed  Google Scholar 

  22. Gowin K, Coakley M, Kosiorek H, Mesa R. Discrepancies of applying primary myelofibrosis prognostic scores for patients with post polycythemia vera/essential thrombocytosis myelofibrosis. Haematologica. 2016;101:e405–6. https://doi.org/10.3324/haematol.2016.149013.

    Article  PubMed  PubMed Central  Google Scholar 

  23. O’Reilly RJ, Prockop S, Hasan A, Doubrovina E. Therapeutic advantages provided by banked virus-specific T-cells of defined HLA-restriction. Bone Marrow Transpl. 2019;54:759–64. https://doi.org/10.1038/s41409-019-0614-1.

    Article  CAS  Google Scholar 

  24. Goldberg JD, Zheng J, Ratan R, Small TN, Lai KC, Boulad F, et al. Early recovery of T-cell function predicts improved survival after T-cell depleted allogeneic transplant. Leuk Lymphoma. 2017;58:1859–71. https://doi.org/10.1080/10428194.2016.1265113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Phelan R, Arora M, Chen M. Current Uses and Outcomes of Hematopoietic Cell Transplantation (HCT): CIBMTR US Summary Slides. 2020. https://www.cibmtr.org.

  26. Nivison-Smith I, Dodds AJ, Butler J, Bradstock KF, Ma DDF, Simpson JM, et al. Allogeneic hematopoietic cell transplantation for chronic myelofibrosis in Australia and New Zealand: older recipients receiving myeloablative conditioning at increased mortality risk. Biol Blood Marrow Transpl. 2012;18:302–8. https://doi.org/10.1016/j.bbmt.2011.05.003.

    Article  Google Scholar 

  27. Abelsson J, Merup M, Birgegård G, WeisBjerrum O, Brinch L, Brune M, et al. The outcome of allo-HSCT for 92 patients with myelofibrosis in the Nordic countries. Bone Marrow Transpl. 2012;47:380–6. https://doi.org/10.1038/bmt.2011.91.

    Article  CAS  Google Scholar 

  28. 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 Transpl. 2019;25:1142–51. https://doi.org/10.1016/j.bbmt.2019.01.002.

    Article  CAS  Google Scholar 

  29. Hernández-Boluda JC, Pereira A, Kröger N, Beelen D, Robin M, Bornhäuser M, et al. Determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation. Leukemia. 2021;35:215–24. https://doi.org/10.1038/s41375-020-0815-z.

    Article  PubMed  Google Scholar 

  30. 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 Transpl. 2016;22:432–40. https://doi.org/10.1016/j.bbmt.2015.10.005.

    Article  CAS  Google Scholar 

  31. Kröger N, Shahnaz Syed Abd Kadir S, Zabelina T, Badbaran A, Christopeit M, Ayuk F, et al. Peritransplantation ruxolitinib prevents acute graft-versus-host disease in patients with myelofibrosis undergoing allogenic stem cell transplantation. Biol Blood Marrow Transpl. 2018;24:2152–6. https://doi.org/10.1016/j.bbmt.2018.05.023.

    Article  CAS  Google Scholar 

  32. Shahnaz Syed Abd Kadir S, Christopeit M, Wulf G, Wagner E, Bornhauser M, Schroeder T, et al. Impact of ruxolitinib pretreatment on outcomes after allogeneic stem cell transplantation in patients with myelofibrosis. Eur J Haematol. 2018;101:305–17. https://doi.org/10.1111/ejh.13099.

    Article  CAS  PubMed  Google Scholar 

  33. Shah GL, Lin A, Kamrowski A, Carino CA. Successful personalization of propylene glycol free melphalan (PGF-MEL) for multiple myeloma (MM) and AL amyloidosis (AL) patients undergoing autologous hematopoietic stem cell transplant (AHCT) using pharmacokinetic (PK)-directed dosing. Transpl Cell Ther. 2020;26:S154–5.

    Google Scholar 

  34. Scordo M, Bhatt V, Hilden P, Smith M, Thoren K, Cho C, et al. Standard antithymocyte globulin dosing results in poorer outcomes in overexposed patients after ex vivo CD34+ selected allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2019;25:1526–35. https://doi.org/10.1016/j.bbmt.2019.02.021.

    Article  CAS  Google Scholar 

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Funding

This research was supported in part by National Institutes of Health award numbers P01 CA23766 and NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Author notes

  1. These authors contributed equally: Mariam T. Nawas, Jeong-Ok Lee.

Authors and Affiliations

  1. Hematopoietic Cellular Therapy Program, Department of Medicine, University of Chicago Medicine, Chicago, IL, USA

    Mariam T. Nawas

  2. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea

    Jeong-Ok Lee

  3. Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Jessica Flynn & Sean Devlin

  4. Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Molly Maloy, Ann A. Jakubowski, Esperanza B. Papadopoulos, Christina Cho, Doris M. Ponce, Craig S. Sauter, Miguel-Angel Perales, Sergio A. Giralt, Hugo R. Castro-Malaspina & Roni Tamari

  5. Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    Ann A. Jakubowski, Esperanza B. Papadopoulos, Christina Cho, Doris M. Ponce, Craig S. Sauter, Miguel-Angel Perales, Sergio A. Giralt, Hugo R. Castro-Malaspina & Roni Tamari

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Contributions

MN and JL were responsible for extracting and analyzing data, interpreting results and creating summary tables they were responsible for writing the report, JF and SD conducted the analyses and interpreted results as well as provided feedback on the report, MM was responsible for screening potentially eligible studies. She contributed to extracting and analyzing data, AJ, EP, CC, DP, CS, MAP, SG, HCM provided feedback on the report, RT was responsible for designing the review protocol, writing the protocol and report, conducting the search, screening potentially eligible studies, extracting and analyzing data, interpreting results, updating reference lists and creating summary tables.

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Correspondence to Roni Tamari.

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Nawas, M.T., Lee, JO., Flynn, J. et al. CD34+ -selected hematopoietic stem cell transplant conditioned with a myeloablative regimen in patients with advanced myelofibrosis. Bone Marrow Transplant 57, 1101–1107 (2022). https://doi.org/10.1038/s41409-022-01684-9

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