Myeloablative autologous stem-cell transplantation for severe scleroderma

K. M. Sullivan, E. A. Goldmuntz, L. Keyes-Elstein, P. A. McSweeney, A. Pinckney, B. Welch, M. D. Mayes, R. A. Nash, L. J. Crofford, B. Eggleston, S. Castina, L. M. Griffith, J. S. Goldstein, D. Wallace, O. Craciunescu, D. Khanna, R. J. Folz, J. Goldin, E. W. Clair, J. R. SeiboldK. Phillips, S. Mineishi, R. W. Simms, K. Ballen, M. H. Wener, G. E. Georges, S. Heimfeld, C. Hosing, S. Forman, S. Kafaja, R. M. Silver, L. Griffing, J. Storek, S. LeClercq, R. Brasington, M. E. Csuka, C. Bredeson, C. Keever-Taylor, R. T. Domsic, M. B. Kahaleh, T. Medsger, D. E. Furst

Research output: Contribution to journalArticle

80 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)35-47
Number of pages13
JournalNew England Journal of Medicine
Volume378
Issue number1
DOIs
StatePublished - Jan 4 2018

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Stem Cell Transplantation
Cyclophosphamide
Transplantation
Disease-Free Survival
Diffuse Scleroderma
Antirheumatic Agents
Survival
Systemic Scleroderma
Hematopoietic Stem Cell Transplantation
Vital Capacity
Kaplan-Meier Estimate
Respiratory Insufficiency
Immunosuppression
Population
Renal Insufficiency
Heart Failure
Transplants
Skin
Mortality
Health

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sullivan, K. M., Goldmuntz, E. A., Keyes-Elstein, L., McSweeney, P. A., Pinckney, A., Welch, B., ... Furst, D. E. (2018). Myeloablative autologous stem-cell transplantation for severe scleroderma. New England Journal of Medicine, 378(1), 35-47. https://doi.org/10.1056/NEJMoa1703327

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 journalArticle

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, 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 2018, 'Myeloablative autologous stem-cell transplantation for severe scleroderma', New England Journal of Medicine, vol. 378, no. 1, pp. 35-47. https://doi.org/10.1056/NEJMoa1703327
Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. New England Journal of Medicine. 2018 Jan 4;378(1):35-47. https://doi.org/10.1056/NEJMoa1703327
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. / Myeloablative autologous stem-cell transplantation for severe scleroderma. In: New England Journal of Medicine. 2018 ; Vol. 378, No. 1. pp. 35-47.
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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.",
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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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