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Biol Blood Marrow Transplant. 2019 Jul 5. pii: S1083-8791(19)30418-5. doi: 10.1016/j.bbmt.2019.06.034. [Epub ahead of print]

Myeloablative and Reduced-intensity conditioned Allogeneic Haematopoietic Stem Cell Transplantation in Myelofibrosis: A Retrospective Study by the Chronic Malignancies Working Party of EBMT.

Author information

1
Guy's and St. Thomas' NHS Foundation Trust, London, UK. Electronic address: donal.mclornan@nhs.net.
2
Department of Clinical Sciences, Imperial College, London, UK.
3
EBMT Data Office, Leiden, The Netherlands.
4
Geneva University Hospitals, Division of Hematology, Geneva, Switzerland, 1211.
5
Hôpital Saint-Louis, Service d'Hématologie-Greffe, Assistance Publique Hôpitaux de Paris, Paris, France.
6
Division of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany.
7
Division of Haematology, University Hospital, Essen, Germany.
8
Universitaetsklinikum Dresden, Dresden, Germany.
9
Ospedale San Martino, Genova, Italy.
10
University Hospital Leipzig, Leipzig, Germany.
11
Charité Universitätsmedizin Berlin, Berlin, Germany.
12
University of Freiburg, Freiburg, Germany.
13
Institute of Hematology and Blood Transfusion, Prague, Czech Republic.
14
HUCH Comprehensive Cancer Center, Helsinki, Finland.
15
Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.
16
Universität Tübingen, Tübingen, Germany.
17
Department of Haematology, King's College Hospital, London, UK.
18
CHU Nantes, Nantes, France.
19
University of Münster, Münster, Germany.
20
University Medical Centre, Utrecht, The Netherlands.
21
Department of Stem Cell Transplantation, University Hospitals, Bristol, UK.
22
Cliniques Universitaires St. Luc, Brussels, Belgium.
23
Hospital Clínico Universitario de Valencia, Valencia, Spain.
24
Maria Sklodowska-Curie Memorial Cencer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
25
Department of Haematology, St.James Hospital, Dublin, Ireland.
26
CHU de Lille, LIRIC, INSERM U995, Universite de Lille, 59000 LILLE, France.

Abstract

This retrospective study by the EBMT analysed the outcome of 2224 Myelofibrosis patients who underwent allogeneic stem cell transplantation (allo-SCT) between 2000-2014; 781 (35%) underwent myeloablative conditioning (MAC) and 1443 (65%) reduced intensity conditioning (RIC). Median patient age was 52.9 years (r, 18-74) and 57.5 years (range(r), 21-76) in the MAC and RIC cohorts respectively. Donor type was similar: matched sibling donors (MAC- 317 (41%)) and RIC- 552 (38%) and unrelated donors (UD; 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-IV acute (a) GVHD were 28% (MAC) and 31% (RIC; (p=ns). Cumulative cGVHD rates (limited/ extensive) were 22%/27% (MAC) and 19%/ 31% (RIC; p=0.10). Cumulative incidences of Non-relapse 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). There was a trend towards a higher relapse rate with RIC regimens compared to MAC (p=0.08); 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 5yr probabilities of overall survival (OS) was noted: MAC 53.0% (95% confidence intervals (CI) 49.1-56.9) and RIC 51.0% (95% CI: 48.3-53.7); p=0.78. 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: 29.0-36.1) in the MAC group and 26.1% (95% CI: 23.9-28.2) in the RIC group (p=0.001). In the MAC cohort, multivariable analysis confirmed worse OS and NRM with older age (>50 yrs), using an unrelated donor and a Karnofsky Performance Status (KPS) of 80 or less. For the RIC cohort, worse OS and NRM was associated with age 60- 70 years when compared to 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 towards 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 optimisation to reduce significant relapse and NRM rates are required.

KEYWORDS:

Myeloablative; Myeloproliferative; Reduced Intensity; Stem Cell Transplantation

PMID:
31284069
DOI:
10.1016/j.bbmt.2019.06.034

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