Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 35-47 |
| Number of pages | 13 |
| Journal | New England Journal of Medicine |
| Volume | 378 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 4 2018 |
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ASJC Scopus subject areas
- Medicine(all)
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Myeloablative autologous stem-cell transplantation for severe scleroderma. / Sullivan, K. M.; Goldmuntz, E. A.; Keyes-Elstein, L.; McSweeney, P. A.; Pinckney, A.; Welch, B.; Mayes, M. D.; Nash, R. A.; Crofford, L. J.; Eggleston, B.; Castina, S.; Griffith, L. M.; Goldstein, J. S.; Wallace, D.; Craciunescu, O.; Khanna, D.; Folz, R. J.; Goldin, J.; Clair, E. W.; Seibold, J. R.; Phillips, K.; Mineishi, S.; Simms, R. W.; Ballen, K.; Wener, M. H.; Georges, G. E.; Heimfeld, S.; Hosing, C.; Forman, S.; Kafaja, S.; Silver, R. M.; Griffing, L.; Storek, J.; LeClercq, S.; Brasington, R.; Csuka, M. E.; Bredeson, C.; Keever-Taylor, C.; Domsic, R. T.; Kahaleh, M. B.; Medsger, T.; Furst, D. E.
In: New England Journal of Medicine, Vol. 378, No. 1, 04.01.2018, p. 35-47.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Myeloablative autologous stem-cell transplantation for severe scleroderma
AU - Sullivan, K. M.
AU - Goldmuntz, E. A.
AU - Keyes-Elstein, L.
AU - McSweeney, P. A.
AU - Pinckney, A.
AU - Welch, B.
AU - Mayes, M. D.
AU - Nash, R. A.
AU - Crofford, L. J.
AU - Eggleston, B.
AU - Castina, S.
AU - Griffith, L. M.
AU - Goldstein, J. S.
AU - Wallace, D.
AU - Craciunescu, O.
AU - Khanna, D.
AU - Folz, R. J.
AU - Goldin, J.
AU - Clair, E. W.
AU - Seibold, J. R.
AU - Phillips, K.
AU - Mineishi, S.
AU - Simms, R. W.
AU - Ballen, K.
AU - Wener, M. H.
AU - Georges, G. E.
AU - Heimfeld, S.
AU - Hosing, C.
AU - Forman, S.
AU - Kafaja, S.
AU - Silver, R. M.
AU - Griffing, L.
AU - Storek, J.
AU - LeClercq, S.
AU - Brasington, R.
AU - Csuka, M. E.
AU - Bredeson, C.
AU - Keever-Taylor, C.
AU - Domsic, R. T.
AU - Kahaleh, M. B.
AU - Medsger, T.
AU - Furst, D. E.
PY - 2018/1/4
Y1 - 2018/1/4
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85040338916&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1703327
DO - 10.1056/NEJMoa1703327
M3 - Article
C2 - 29298160
AN - SCOPUS:85040338916
VL - 378
SP - 35
EP - 47
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 1533-4406
IS - 1
ER -