Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
From 2002 to 2007, 103 patients with primary myelofibrosis or postessential thrombocythemia and polycythemia vera myelofibrosis and a median age of 55 years (range, 32-68 years) were included in a prospective multicenter phase 2 trial to determine efficacy of a busulfan (10 mg/kg)/fludarabine (180 mg/m(2))-based reduced-intensity conditioning regimen followed by allogeneic stem cell transplantation from related (n = 33) or unrelated donors (n = 70). All but 2 patients (2%) showed leukocyte and platelet engraftment after a median of 18 and 22 days, respectively. Acute graft-versus-host disease grade 2 to 4 occurred in 27% and chronic graft-versus-host disease in 43% of the patients. Cumulative incidence of nonrelapse mortality at 1 year was 16% (95% confidence interval, 9%-23%) and significantly lower for patients with a completely matched donor (12% vs 38%; P = .003). The cumulative incidence of relapse at 3 years was 22% (95% confidence interval, 13%-31%) and was influenced by Lille risk profile (low, 14%; intermediate, 22%; and high, 34%; P = .02). The estimated 5-year event-free and overall survival was 51% and 67%, respectively. In a multivariate analysis, age older than 55 years (hazard ratio = 2.70; P = .02) and human leukocyte antigen-mismatched donor (hazard ratio = 3.04; P = .006) remained significant factors for survival. The study was registered at www.clinicaltrials.gov as #NCT 00599547.
Kröger
Nicolaus
N
Center for Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. nkroeger@uke.uni-hamburg.de
Holler
Ernst
E
Kobbe
Guido
G
Bornhäuser
Martin
M
Schwerdtfeger
Rainer
R
Baurmann
Herrad
H
Nagler
Arnon
A
Bethge
Wolfgang
W
Stelljes
Matthias
M
Uharek
Lutz
L
Wandt
Hannes
H
Burchert
Andreas
A
Corradini
Paolo
P
Schubert
Jörg
J
Kaufmann
Martin
M
Dreger
Peter
P
Wulf
Gerald G
GG
Einsele
Hermann
H
Zabelina
Tatjana
T
Kvasnicka
Hans Michael
HM
Thiele
Jürgen
J
Brand
Ronald
R
Zander
Axel R
AR
Niederwieser
Dietger
D
de Witte
Theo M
TM
D000328:Adult; D000368:Aged; D002066:Busulfan / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D055728:Primary Myelofibrosis / Q000401:mortality / Q000601:surgery*; D012008:Recurrence; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
D019653:Myeloablative Agonists; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine