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. 2004 Aug;63(8):974–981. doi: 10.1136/ard.2003.011205

Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry

D Farge 1, J Passweg 1, J M van Laar 1, Z Marjanovic 1, C Besenthal 1, J Finke 1, H Peter 1, F Breedveld 1, W Fibbe 1, C Black 1, C Denton 1, I Koetter 1, F Locatelli 1, A Martini 1, A Schattenberg 1, F van den Hoogen 1, L van de Putte 1, F Lanza 1, R Arnold 1, P Bacon 1, S Bingham 1, F Ciceri 1, B Didier 1, J Diez-Martin 1, P Emery 1, W Feremans 1, B Hertenstein 1, F Hiepe 1, R Luosujarvi 1, L Leon 1, A Marmont 1, A Martinez 1, C Pascual 1, C Bocelli-Tyndall 1, E Gluckman 1, A Gratwohl 1, A Tyndall 1
PMCID: PMC1755096  PMID: 15249325

Abstract

Objective: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases.

Methods: Only patients with SSc, treated by HSCT in European phase I–II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier).

Results: Given as median (range). Among 57 patients aged 40 (9.1–68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5–81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2–48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75).

Conclusion: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.

Full Text

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Figure 4.

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 Cumulative probability of survival was 72+13% at 5 years according to Kaplan-Meier plot calculation.

Figure 1.

Figure 1

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 Evaluation of skin score in patients with severe systemic sclerosis before inclusion (n = 47) and then at 6 (n = 37), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT. The proportional change from baseline measurement was calculated for each patient at each available point using the Wilcoxon signed rank test, (p<0.001).

Figure 2.

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 Evaluation of vital capacity (VC) in patients with severe systemic sclerosis before inclusion (n = 47) and then at 6 (n = 26), 12 (n = 27), 24 (n = 18), and 36 (n = 10) months after HSCT. There was no significant deterioration for each patient when calculated at the available point compared with the baseline measurement using the Wilcoxon signed rank test (NS).

Figure 3.

Figure 3

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 Evaluation of TLCO in patients with severe SSc before inclusion (n = 47) and then at 6 (n = 25), 12 (n = 26), 24 (n = 18), and 36 (n = 10) months after HSCT. The proportional change from baseline measurement was calculated for each patient at each available point using the Wilcoxon signed rank test (NS).

Figure 5.

Figure 5

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 Cumulative probability of disease progression in 57 patients with severe SSc, as reported by local investigators, was estimated at 48+20% at 5 years according to the Kaplan-Meier method calculation. Disease progression was defined by an increase in skin score >25% compared with baseline values, the onset of a decrease in VC or in TLCO >15% compared with baseline, and/or progressive vital organ failure.

Selected References

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