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Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma
#MMPMID29298160
Sullivan KM
; Goldmuntz EA
; Keyes-Elstein L
; McSweeney PA
; Pinckney A
; Welch B
; Mayes MD
; Nash RA
; Crofford LJ
; Eggleston B
; Castina S
; Griffith LM
; Goldstein JS
; Wallace D
; Craciunescu O
; Khanna D
; Folz RJ
; Goldin J
; St Clair EW
; Seibold JR
; Phillips K
; Mineishi S
; Simms RW
; Ballen K
; Wener MH
; Georges GE
; Heimfeld S
; Hosing C
; Forman S
; Kafaja S
; Silver RM
; Griffing L
; Storek J
; LeClercq S
; Brasington R
; Csuka ME
; Bredeson C
; Keever-Taylor C
; Domsic RT
; Kahaleh MB
; Medsger T
; Furst DE
N Engl J Med
2018[Jan]; 378
(1
): 35-47
PMID29298160
show ga
BACKGROUND: Despite current therapies, diffuse cutaneous systemic sclerosis
(scleroderma) often has a devastating outcome. We compared myeloablative CD34+
selected autologous hematopoietic stem-cell transplantation with
immunosuppression by means of 12 monthly infusions of cyclophosphamide in
patients with scleroderma. METHODS: We randomly assigned adults (18 to 69 years
of age) with severe scleroderma to undergo myeloablative autologous stem-cell
transplantation (36 participants) or to receive cyclophosphamide (39
participants). The primary end point was a global rank composite score comparing
participants with each other on the basis of a hierarchy of disease features
assessed at 54 months: death, event-free survival (survival without respiratory,
renal, or cardiac failure), forced vital capacity, the score on the Disability
Index of the Health Assessment Questionnaire, and the modified Rodnan skin score.
RESULTS: In the intention-to-treat population, global rank composite scores at 54
months showed the superiority of transplantation (67% of 1404 pairwise
comparisons favored transplantation and 33% favored cyclophosphamide, P=0.01). In
the per-protocol population (participants who received a transplant or completed
?9 doses of cyclophosphamide), the rate of event-free survival at 54 months was
79% in the transplantation group and 50% in the cyclophosphamide group (P=0.02).
At 72 months, Kaplan-Meier estimates of event-free survival (74% vs. 47%) and
overall survival (86% vs. 51%) also favored transplantation (P=0.03 and 0.02,
respectively). A total of 9% of the participants in the transplantation group had
initiated disease-modifying antirheumatic drugs (DMARDs) by 54 months, as
compared with 44% of those in the cyclophosphamide group (P=0.001).
Treatment-related mortality in the transplantation group was 3% at 54 months and
6% at 72 months, as compared with 0% in the cyclophosphamide group. CONCLUSIONS:
Myeloablative autologous hematopoietic stem-cell transplantation achieved
long-term benefits in patients with scleroderma, including improved event-free
and overall survival, at a cost of increased expected toxicity. Rates of
treatment-related death and post-transplantation use of DMARDs were lower than
those in previous reports of nonmyeloablative transplantation. (Funded by the
National Institute of Allergy and Infectious Diseases and the National Institutes
of Health; ClinicalTrials.gov number, NCT00114530 .).
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