Allogeneic hematopoietic cell transplantation in patients with CALR-mutated myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT.
Journal
Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
25
06
2023
accepted:
17
08
2023
revised:
03
08
2023
medline:
4
12
2023
pubmed:
8
9
2023
entrez:
7
9
2023
Statut:
ppublish
Résumé
Allogeneic hematopoietic cell transplantation (allo-HCT) is curative for myelofibrosis (MF) but assessing risk-benefit in individual patients is challenging. This complexity is amplified in CALR-mutated MF patients, as they live longer with conventional treatments compared to other molecular subtypes. We analyzed outcomes of 346 CALR-mutated MF patients who underwent allo-HCT in 123 EBMT centers between 2005 and 2019. After a median follow-up of 40 months, the estimated overall survival (OS) rates at 1, 3, and 5 years were 81%, 71%, and 63%, respectively. Patients receiving busulfan-containing regimens achieved a 5-year OS rate of 71%. Non-relapse mortality (NRM) at 1, 3, and 5 years was 16%, 22%, and 26%, respectively, while the incidence of relapse/progression was 11%, 15%, and 17%, respectively. Multivariate analysis showed that older age correlated with worse OS, while primary MF and HLA mismatched transplants had a near-to-significant trend to decreased OS. Comparative analysis between CALR- and JAK2-mutated MF patients adjusting for confounding factors revealed better OS, lower NRM, lower relapse, and improved graft-versus-host disease-free and relapse-free survival (GRFS) in CALR-mutated patients. These findings confirm the improved prognosis associated with CALR mutation in allo-HCT and support molecular profiling in prognostic scoring systems to predict OS after transplantation in MF.
Identifiants
pubmed: 37679647
doi: 10.1038/s41409-023-02094-1
pii: 10.1038/s41409-023-02094-1
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1357-1367Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Tefferi A. Primary myelofibrosis: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98:801–21.
doi: 10.1002/ajh.26857
pubmed: 36680511
Bewersdorf JP, Sheth AH, Vetsa S, Grimshaw A, Giri S, Podoltsev NA, et al. Outcomes of allogeneic hematopoietic cell transplantation in patients with myelofibrosis—a systematic review and meta-analysis. Transpl Cell Ther. 2021;27:873.e1–e13.
doi: 10.1016/j.jtct.2021.05.016
McLornan D, Eikema DJ, Czerw T, Kroger N, Koster L, Reinhardt HC, et al. Trends in allogeneic haematopoietic cell transplantation for myelofibrosis in Europe between 1995 and 2018: a CMWP of EBMT retrospective analysis. Bone Marrow Transpl. 2021;56:2160–72.
doi: 10.1038/s41409-021-01305-x
Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martinez-Trillos A, Casetti I, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014;124:1062–9.
doi: 10.1182/blood-2014-05-578435
pubmed: 24986690
pmcid: 4133481
Passamonti F, Mora B, Giorgino T, Guglielmelli P, Cazzola M, Maffioli M, et al. Driver mutations’ effect in secondary myelofibrosis: an international multicenter study based on 781 patients. Leukemia. 2017;31:970–3.
doi: 10.1038/leu.2016.351
pubmed: 27885272
Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113:2895–901.
doi: 10.1182/blood-2008-07-170449
pubmed: 18988864
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.
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.
doi: 10.1200/JCO.2010.32.2446
pubmed: 21149668
Mosquera-Orgueira A, Perez-Encinas M, Hernandez-Sanchez A, Gonzalez-Martinez T, Arellano-Rodrigo E, Martinez-Elicegui J, et al. Machine learning improves risk stratification in myelofibrosis: an analysis of the Spanish registry of myelofibrosis. Hemasphere. 2023;7:e818.
doi: 10.1097/HS9.0000000000000818
pubmed: 36570691
Guglielmelli P, Lasho TL, Rotunno G, Mudireddy M, Mannarelli C, Nicolosi M, et al. MIPSS70: mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis. J Clin Oncol. 2018;36:310–8.
doi: 10.1200/JCO.2017.76.4886
pubmed: 29226763
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.
doi: 10.1200/JCO.2018.78.9867
pubmed: 29708808
Passamonti F, Giorgino T, Mora B, Guglielmelli P, Rumi E, Maffioli M, et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017;31:2726–31.
doi: 10.1038/leu.2017.169
pubmed: 28561069
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.
doi: 10.1038/leu.2015.233
pubmed: 26293647
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.
doi: 10.1182/blood-2018-12-890889
pubmed: 30760453
Tamari R, McLornan DP, Ahn KW, Estrada-Merly N, Hernandez-Boluda JC, Giralt SA, et al. A simple prognostic system in myelofibrosis patients undergoing allogeneic stem cell transplant: a CIBMTR/EBMT analysis. Blood Adv. 2023;7:3993–4002.
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 Transpl. 2017;23:1095–101.
doi: 10.1016/j.bbmt.2017.03.034
Gagelmann N, Salit RB, Schroeder T, Badbaran A, Rautenberg C, Panagiota V, et al. High molecular and cytogenetic risk in myelofibrosis does not benefit from higher intensity conditioning before hematopoietic cell transplantation: an international collaborative. Anal Hemasphere. 2022;6:e784.
doi: 10.1097/HS9.0000000000000784
Panagiota V, Thol F, Markus B, Fehse B, Alchalby H, Badbaran A, et al. Prognostic effect of calreticulin mutations in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation. Leukemia. 2014;28:1552–5.
doi: 10.1038/leu.2014.66
pubmed: 24504025
Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8.
doi: 10.1182/blood-2014-10-609032
pubmed: 25593335
pmcid: 4335084
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 Transpl. 2007;13:1469–76.
doi: 10.1016/j.bbmt.2007.08.047
Hernandez-Boluda JC, Pereira A, Kroger N, Beelen D, Robin M, Bornhauser M, et al. Determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation. Leukemia. 2021;35:215–24.
doi: 10.1038/s41375-020-0815-z
pubmed: 32286544
Hernandez-Boluda JC, Pereira A, Kroger N, Cornelissen JJ, Finke J, Beelen D, et al. Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: a study of the chronic malignancies working party of EBMT and the Spanish Myelofibrosis Registry. Am J Hematol. 2021;96:1186–94.
doi: 10.1002/ajh.26279
pubmed: 34152630
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.
doi: 10.1182/bloodadvances.2018026658
pubmed: 30622146
pmcid: 6325305
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.
doi: 10.1016/j.bbmt.2019.01.002
Murthy GSG, Kim S, Estrada-Merly N, Abid MB, Aljurf M, Assal A, et al. Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis. Haematologica. 2023;108:1900–8.
Holmstrom MO, Riley CH, Svane IM, Hasselbalch HC, Andersen MH. The CALR exon 9 mutations are shared neoantigens in patients with CALR mutant chronic myeloproliferative neoplasms. Leukemia. 2016;30:2413–6.
doi: 10.1038/leu.2016.233
pubmed: 27560107
Tvorogov D, Thompson-Peach CAL, Fosselteder J, Dottore M, Stomski F, Onnesha SA, et al. Targeting human CALR-mutated MPN progenitors with a neoepitope-directed monoclonal antibody. EMBO Rep. 2022;23:e52904.
doi: 10.15252/embr.202152904
pubmed: 35156745
pmcid: 8982588
Handlos Grauslund J, Holmstrom MO, Jorgensen NG, Klausen U, Weis-Banke SE, El Fassi D, et al. Therapeutic cancer vaccination with a peptide derived from the calreticulin exon 9 mutations induces strong cellular immune responses in patients with CALR-mutant chronic myeloproliferative neoplasms. Front Oncol. 2021;11:637420.
doi: 10.3389/fonc.2021.637420
pubmed: 33718228
pmcid: 7952976
Gigoux M, Holmstrom MO, Zappasodi R, Park JJ, Pourpe S, Bozkus CC, et al. Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine. Sci Transl Med. 2022;14:eaba4380.
doi: 10.1126/scitranslmed.aba4380
pubmed: 35704596
Plo I, Nakatake M, Malivert L, de Villartay JP, Giraudier S, Villeval JL, et al. JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders. Blood. 2008;112:1402–12.
doi: 10.1182/blood-2008-01-134114
pubmed: 18515659
Marty C, Lacout C, Droin N, Le Couedic JP, Ribrag V, Solary E, et al. A role for reactive oxygen species in JAK2 V617F myeloproliferative neoplasm progression. Leukemia. 2013;27:2187–95.
doi: 10.1038/leu.2013.102
pubmed: 23558526
Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH, et al. CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28:1472–7.
doi: 10.1038/leu.2014.3
pubmed: 24402162
Christopeit M, Badbaran A, Zabelina T, Zeck G, Fehse B, Ayuk F, et al. Similar outcome of calreticulin type I and calreticulin type II mutations following RIC allogeneic haematopoietic stem cell transplantation for myelofibrosis. Bone Marrow Transpl. 2016;51:1391–3.
doi: 10.1038/bmt.2016.128