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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

D. McLornan, R. Szydlo, L. Koster, Y. Chalandon, M. Robin, C. Wolschke, D. Beelen, G. Socié, M. Bornhäuser, E. Angelucci, D. Niederwieser, A. Gerbitz, J. Finke, A. Vitek, M. Itälä-Remes, A. Radujkovic, L. Kanz, V. Potter, P. Chevallier, M....

. 2019 ; 25 (11) : 2167-2171. [pub] 20190705

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, multicentrická studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc20025523

This retrospective study by the European Society for Blood and Marrow Transplantation analyzed the outcome of 2224 patients with myelofibrosis (MF) who underwent allogeneic stem cell transplantation (allo-SCT) between 2000 and 2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced-intensity conditioning (RIC). Median patient age was 52.9 years (range, 18 to 74 years) and 57.5 years (range, 21 to 76 years) in the MAC and RIC cohorts, respectively. Donor type was similar: matched sibling donors (MAC, 317 [41%]; RIC, 552 [38%]) and unrelated donors (MAC, 464 [59%]; RIC, 891 [62%]). Median time to both neutrophil and platelet (>20 × 109/L) engraftment did not differ between cohorts. Rates of grade II to IV acute GVHD were 28% (MAC) and 31% (RIC; P = NS). Cumulative chronic GVHD rates (limited/extensive) were 22%/27% (MAC) and 19%/31% (RIC; P = .10). Cumulative incidences of nonrelapse mortality (NRM) at 1, 3, and 5 years were 25.5%, 32.2%, and 34.6% (MAC) and 26.3%, 32.8%, and 34.4% (RIC), respectively. There was a trend toward a higher relapse rate with RIC regimens compared with MAC (P = .08); rates at 1, 3, and 5 years were 10.9%, 17.2%, and 20.1% (MAC) and 14%, 19.7%, and 23.2% (RIC), respectively. No significant difference in 5-year probabilities of overall survival (OS) was noted: MAC (53.0%; 95% confidence interval [CI], 49.1% to 56.9%) and RIC (51.0%; 95% CI, 48.3% to 53.7%); P = .78. Regarding the composite end point of GVHD-free/relapse-free survival (GRFS), the unadjusted Kaplan-Meier estimate of 5-year GRFS was 32.4% (95% CI, 29.0% to 36.1%) in the MAC group and 26.1% (95% CI, 23.9% to 28.2%) in the RIC group (P = .001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 years), using an unrelated donor and a Karnofsky Performance Status of 80 or less. For the RIC cohort, worse OS and NRM were associated with age 60 to 70 years compared with younger recipients, use of a mismatched donor, and poor performance status. In conclusion, although similar OS rates existed for both cohorts overall, this study suggests that MAC should still be used for younger individuals suitable for such an approach due to a trend toward less relapse and an overall suggested advantage of improved GRFS, albeit this should be examined in a more homogeneous cohort. RIC allo-SCT still offers significant survival advantage in the older, fitter MF allograft patient, and optimization to reduce significant relapse and NRM rates is required.

Department of Clinical Sciences Imperial College London United Kingdom

Department of Haematology Charité Universitätsmedizin Berlin Berlin Germany

Department of Haematology CHU de Lille LIRIC INSERM U995 Universite de Lille Lille France

Department of Haematology CHU Nantes Nantes France

Department of Haematology Cliniques Universitaires St Luc Brussels Belgium

Department of Haematology EBMT Data Office Leiden The Netherlands

Department of Haematology Guy's and St Thomas' NHS Foundation Trust London United Kingdom

Department of Haematology Hospital Clínico Universitario de Valencia Valencia Spain

Department of Haematology HUCH Comprehensive Cancer Center Helsinki Finland

Department of Haematology Institute of Hematology and Blood Transfusion Prague Czech Republic

Department of Haematology King's College Hospital London United Kingdom

Department of Haematology Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology Gliwice Branch Gliwice Poland

Department of Haematology Ospedale San Martino Genova Italy

Department of Haematology Service d'Hématologie Greffe Assistance Publique Hôpitaux de Paris Hôpital Saint Louis Paris France

Department of Haematology St James Hospital Dublin Ireland

Department of Haematology Universitaetsklinikum Dresden Dresden Germany

Department of Haematology Universität Tübingen Tübingen Germany

Department of Haematology University Hospital Leipzig Leipzig Germany

Department of Haematology University Medical Centre Utrecht The Netherlands

Department of Haematology University of Freiburg Freiburg Germany

Department of Haematology University of Münster Münster Germany

Department of Internal Medicine 5 University of Heidelberg Heidelberg Germany

Department of Stem Cell Transplantation University Hospitals Bristol United Kingdom

Division of Hematology Geneva University Hospitals Geneva Switzerland

Division of Hematology University Hospital Essen Germany

Division of Stem Cell Transplantation University Hospital Eppendorf Hamburg Germany

Citace poskytuje Crossref.org

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$a 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 / $c D. McLornan, R. Szydlo, L. Koster, Y. Chalandon, M. Robin, C. Wolschke, D. Beelen, G. Socié, M. Bornhäuser, E. Angelucci, D. Niederwieser, A. Gerbitz, J. Finke, A. Vitek, M. Itälä-Remes, A. Radujkovic, L. Kanz, V. Potter, P. Chevallier, M. Stelljes, E. Petersen, S. Robinson, X. Poiré, E. Klyuchnikov, JC. Hernández-Boluda, T. Czerw, P. Hayden, N. Kröger, I. Yakoub-Agha,
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$a This retrospective study by the European Society for Blood and Marrow Transplantation analyzed the outcome of 2224 patients with myelofibrosis (MF) who underwent allogeneic stem cell transplantation (allo-SCT) between 2000 and 2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced-intensity conditioning (RIC). Median patient age was 52.9 years (range, 18 to 74 years) and 57.5 years (range, 21 to 76 years) in the MAC and RIC cohorts, respectively. Donor type was similar: matched sibling donors (MAC, 317 [41%]; RIC, 552 [38%]) and unrelated donors (MAC, 464 [59%]; RIC, 891 [62%]). Median time to both neutrophil and platelet (>20 × 109/L) engraftment did not differ between cohorts. Rates of grade II to IV acute GVHD were 28% (MAC) and 31% (RIC; P = NS). Cumulative chronic GVHD rates (limited/extensive) were 22%/27% (MAC) and 19%/31% (RIC; P = .10). Cumulative incidences of nonrelapse mortality (NRM) at 1, 3, and 5 years were 25.5%, 32.2%, and 34.6% (MAC) and 26.3%, 32.8%, and 34.4% (RIC), respectively. There was a trend toward a higher relapse rate with RIC regimens compared with MAC (P = .08); rates at 1, 3, and 5 years were 10.9%, 17.2%, and 20.1% (MAC) and 14%, 19.7%, and 23.2% (RIC), respectively. No significant difference in 5-year probabilities of overall survival (OS) was noted: MAC (53.0%; 95% confidence interval [CI], 49.1% to 56.9%) and RIC (51.0%; 95% CI, 48.3% to 53.7%); P = .78. Regarding the composite end point of GVHD-free/relapse-free survival (GRFS), the unadjusted Kaplan-Meier estimate of 5-year GRFS was 32.4% (95% CI, 29.0% to 36.1%) in the MAC group and 26.1% (95% CI, 23.9% to 28.2%) in the RIC group (P = .001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 years), using an unrelated donor and a Karnofsky Performance Status of 80 or less. For the RIC cohort, worse OS and NRM were associated with age 60 to 70 years compared with younger recipients, use of a mismatched donor, and poor performance status. In conclusion, although similar OS rates existed for both cohorts overall, this study suggests that MAC should still be used for younger individuals suitable for such an approach due to a trend toward less relapse and an overall suggested advantage of improved GRFS, albeit this should be examined in a more homogeneous cohort. RIC allo-SCT still offers significant survival advantage in the older, fitter MF allograft patient, and optimization to reduce significant relapse and NRM rates is required.
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