Phase I/II trial of autologous stem cell transplantation in systemic sclerosis

Procedure related mortality and impact on skin disease

M. Binks, J. R. Passweg, D. Furst, P. McSweeney, K. Sullivan, C. Besenthal, J. Finke, H. H. Peter, J. Van Laar, F. C. Breedveld, W. E. Fibbe, D. Farge, E. Gluckman, F. Locatelli, A. Martini, F. Van den Hoogen, L. Van de Putte, A. V N Schattenberg, R. Arnold, P. A. Bacon & 13 others P. Emery, I. Espigado, B. Hertenstein, F. Hiepe, A. Kashyap, I. Kötter, A. Marmont, A. Martinez, M. J. Pascual, A. Gratwohl, H. G. Prentice, C. Black, A. Tyndall

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Background - Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. Methods - Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being 25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. Conclusion - Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

Original languageEnglish
Pages (from-to)577-584
Number of pages8
JournalAnnals of the Rheumatic Diseases
Volume60
Issue number6
DOIs
Publication statusPublished - 2001

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Systemic Scleroderma
Stem Cell Transplantation
Stem cells
Skin Diseases
Skin
Mortality
Immunosuppression
Transplantation
Pulmonary diseases
Kidney
Lung
Vital Capacity
Kaplan-Meier Estimate
Censuses
Toxicity
Deterioration
Pulmonary Hypertension
Non-Hodgkin's Lymphoma
Lung Diseases
Autoimmune Diseases

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

Phase I/II trial of autologous stem cell transplantation in systemic sclerosis : Procedure related mortality and impact on skin disease. / Binks, M.; Passweg, J. R.; Furst, D.; McSweeney, P.; Sullivan, K.; Besenthal, C.; Finke, J.; Peter, H. H.; Van Laar, J.; Breedveld, F. C.; Fibbe, W. E.; Farge, D.; Gluckman, E.; Locatelli, F.; Martini, A.; Van den Hoogen, F.; Van de Putte, L.; Schattenberg, A. V N; Arnold, R.; Bacon, P. A.; Emery, P.; Espigado, I.; Hertenstein, B.; Hiepe, F.; Kashyap, A.; Kötter, I.; Marmont, A.; Martinez, A.; Pascual, M. J.; Gratwohl, A.; Prentice, H. G.; Black, C.; Tyndall, A.

In: Annals of the Rheumatic Diseases, Vol. 60, No. 6, 2001, p. 577-584.

Research output: Contribution to journalArticle

Binks, M, Passweg, JR, Furst, D, McSweeney, P, Sullivan, K, Besenthal, C, Finke, J, Peter, HH, Van Laar, J, Breedveld, FC, Fibbe, WE, Farge, D, Gluckman, E, Locatelli, F, Martini, A, Van den Hoogen, F, Van de Putte, L, Schattenberg, AVN, Arnold, R, Bacon, PA, Emery, P, Espigado, I, Hertenstein, B, Hiepe, F, Kashyap, A, Kötter, I, Marmont, A, Martinez, A, Pascual, MJ, Gratwohl, A, Prentice, HG, Black, C & Tyndall, A 2001, 'Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: Procedure related mortality and impact on skin disease', Annals of the Rheumatic Diseases, vol. 60, no. 6, pp. 577-584. https://doi.org/10.1136/ard.60.6.577
Binks, M. ; Passweg, J. R. ; Furst, D. ; McSweeney, P. ; Sullivan, K. ; Besenthal, C. ; Finke, J. ; Peter, H. H. ; Van Laar, J. ; Breedveld, F. C. ; Fibbe, W. E. ; Farge, D. ; Gluckman, E. ; Locatelli, F. ; Martini, A. ; Van den Hoogen, F. ; Van de Putte, L. ; Schattenberg, A. V N ; Arnold, R. ; Bacon, P. A. ; Emery, P. ; Espigado, I. ; Hertenstein, B. ; Hiepe, F. ; Kashyap, A. ; Kötter, I. ; Marmont, A. ; Martinez, A. ; Pascual, M. J. ; Gratwohl, A. ; Prentice, H. G. ; Black, C. ; Tyndall, A. / Phase I/II trial of autologous stem cell transplantation in systemic sclerosis : Procedure related mortality and impact on skin disease. In: Annals of the Rheumatic Diseases. 2001 ; Vol. 60, No. 6. pp. 577-584.
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title = "Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: Procedure related mortality and impact on skin disease",
abstract = "Background - Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. Methods - Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50{\%} of maximum in 20/33 (61{\%}) patients, with some lung disease attributable to SSc in 28/37 (76{\%}), the forced vital capacity being 25{\%} after transplantation occurred in 20/29 (69{\%}) evaluable patients, and deterioration in 2/29 (7{\%}). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19{\%}) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27{\%}) patients had died at census and seven (17{\%}) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73{\%} (95{\%} CI 58 to 88) by Kaplan-Meier analysis. Conclusion - Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10{\%}.",
author = "M. Binks and Passweg, {J. R.} and D. Furst and P. McSweeney and K. Sullivan and C. Besenthal and J. Finke and Peter, {H. H.} and {Van Laar}, J. and Breedveld, {F. C.} and Fibbe, {W. E.} and D. Farge and E. Gluckman and F. Locatelli and A. Martini and {Van den Hoogen}, F. and {Van de Putte}, L. and Schattenberg, {A. V N} and R. Arnold and Bacon, {P. A.} and P. Emery and I. Espigado and B. Hertenstein and F. Hiepe and A. Kashyap and I. K{\"o}tter and A. Marmont and A. Martinez and Pascual, {M. J.} and A. Gratwohl and Prentice, {H. G.} and C. Black and A. Tyndall",
year = "2001",
doi = "10.1136/ard.60.6.577",
language = "English",
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pages = "577--584",
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}

TY - JOUR

T1 - Phase I/II trial of autologous stem cell transplantation in systemic sclerosis

T2 - Procedure related mortality and impact on skin disease

AU - Binks, M.

AU - Passweg, J. R.

AU - Furst, D.

AU - McSweeney, P.

AU - Sullivan, K.

AU - Besenthal, C.

AU - Finke, J.

AU - Peter, H. H.

AU - Van Laar, J.

AU - Breedveld, F. C.

AU - Fibbe, W. E.

AU - Farge, D.

AU - Gluckman, E.

AU - Locatelli, F.

AU - Martini, A.

AU - Van den Hoogen, F.

AU - Van de Putte, L.

AU - Schattenberg, A. V N

AU - Arnold, R.

AU - Bacon, P. A.

AU - Emery, P.

AU - Espigado, I.

AU - Hertenstein, B.

AU - Hiepe, F.

AU - Kashyap, A.

AU - Kötter, I.

AU - Marmont, A.

AU - Martinez, A.

AU - Pascual, M. J.

AU - Gratwohl, A.

AU - Prentice, H. G.

AU - Black, C.

AU - Tyndall, A.

PY - 2001

Y1 - 2001

N2 - Background - Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. Methods - Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being 25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. Conclusion - Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

AB - Background - Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried. Recent developments in haemopoietic stem cell transplantation (HSCT) have allowed the application of profound immunosuppression followed by HSCT, or rescue, to autoimmune diseases such as SSc. Methods - Results for 41 patients included in continuing multicentre open phase I/II studies using HSCT in the treatment of poor prognosis SSc are reported. Thirty seven patients had a predominantly diffuse skin form of the disease and four the limited form, with some clinical overlap. Median age was 41 years with a 5:1 female to male ratio. The skin score was >50% of maximum in 20/33 (61%) patients, with some lung disease attributable to SSc in 28/37 (76%), the forced vital capacity being 25% after transplantation occurred in 20/29 (69%) evaluable patients, and deterioration in 2/29 (7%). Lung function did not change significantly after transplantation. One of five renal cases deteriorated but with no new occurrences of renal disease after HSCT, and the pulmonary hypertension did not progress in the evaluable cases. Disease progression was seen in 7/37 (19%) patients after HSCT with a median period of 67 (range 49-255) days. Eleven (27%) patients had died at census and seven (17%) deaths were considered to be related to the procedure (direct organ toxicity in four, haemorrhage in two, and infection/neutropenic fever in one). The cumulative probability of survival at one year was 73% (95% CI 58 to 88) by Kaplan-Meier analysis. Conclusion - Despite a higher procedure related mortality rate from HSCT in SSc compared with patients with breast cancer and non-Hodgkin's lymphoma, the marked impact on skin score, a surrogate marker of mortality, the trend towards stabilisation of lung involvement, and lack of other treatment alternatives justify further carefully designed studies. If future trials incorporate inclusion and exclusion criteria based on this preliminary experience, the predicted procedure related mortality should be around 10%.

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DO - 10.1136/ard.60.6.577

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