Allogeneic hematopoietic cell transplantation in patients with CALR-mutated myelofibrosis: a study of the Chronic Malignancies Working Party of EBMT.
Juan Carlos Hernández-Boluda
(1)
,
Diderik-Jan Eikema
(2)
,
Linda Koster
(3)
,
Nicolaus Kröger
(2)
,
M. Robin
(4)
,
Moniek de Witte
(5)
,
Jürgen Finke
(6)
,
Maria Chiara Finazzi
(7)
,
Annoek Broers
(8)
,
Ludek Raida
,
Nicolaas Schaap
(9)
,
Patrizia Chiusolo
(10)
,
Mareike Verbeek
(11)
,
Carin L. E. Hazenberg
(12)
,
Kazimierz Halaburda
(13)
,
Aleksandr Kulagin
(14)
,
Hélène Labussière-Wallet
(15)
,
Tobias Gedde-Dahl
(16)
,
Werner Rabitsch
(17)
,
Kavita Raj
(18)
,
Joanna Drozd-Sokolowska
(19)
,
Giorgia Battipaglia
(20)
,
Nicola Polverelli
(21)
,
Tomasz Czerw
(22)
,
Ibrahim Yakoub-Agha
(23)
,
Donal P. Mclornan
(24)
1
UPV -
Universitat Politècnica de València = Universitad Politecnica de Valencia = Polytechnic University of Valencia
2 Universiteit Leiden = Leiden University
3 LUMC - Leiden University Medical Center
4 AP-HP - Hopital Saint-Louis [AP-HP]
5 UMCU - University Medical Center [Utrecht]
6 University of Freiburg [Freiburg]
7 UNIMI - Università degli Studi di Milano = University of Milan
8 Erasmus MC - Erasmus University Medical Center [Rotterdam]
9 Radboud University Medical Center [Nijmegen]
10 Fondazione Policlinico Universitario Agostino Gemelli IRCCS
11 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
12 University of Groningen [Groningen]
13 Warsaw University of Technology [Warsaw]
14 Pavlov First Saint Petersburg State Medical University [St. Petersburg]
15 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
16 Oslo University Hospital [Oslo]
17 Medizinische Universität Wien = Medical University of Vienna
18 KCH - King's College Hospital
19 Medical University of Warsaw - Poland
20 University of Naples Federico II = Università degli studi di Napoli Federico II
21 UniBs - Università degli Studi di Brescia = University of Brescia
22 MCMCC - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
23 LIRIC - Lille Inflammation Research International Center - U 995
24 UCLH - University College London Hospitals NHS Foundation Trust [London, UK]
2 Universiteit Leiden = Leiden University
3 LUMC - Leiden University Medical Center
4 AP-HP - Hopital Saint-Louis [AP-HP]
5 UMCU - University Medical Center [Utrecht]
6 University of Freiburg [Freiburg]
7 UNIMI - Università degli Studi di Milano = University of Milan
8 Erasmus MC - Erasmus University Medical Center [Rotterdam]
9 Radboud University Medical Center [Nijmegen]
10 Fondazione Policlinico Universitario Agostino Gemelli IRCCS
11 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
12 University of Groningen [Groningen]
13 Warsaw University of Technology [Warsaw]
14 Pavlov First Saint Petersburg State Medical University [St. Petersburg]
15 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
16 Oslo University Hospital [Oslo]
17 Medizinische Universität Wien = Medical University of Vienna
18 KCH - King's College Hospital
19 Medical University of Warsaw - Poland
20 University of Naples Federico II = Università degli studi di Napoli Federico II
21 UniBs - Università degli Studi di Brescia = University of Brescia
22 MCMCC - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
23 LIRIC - Lille Inflammation Research International Center - U 995
24 UCLH - University College London Hospitals NHS Foundation Trust [London, UK]
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.