Presentation: Evolution of Fibrosing Alveolitis Associated with Systemic Sclerosis after Autologous Bone Marrow Transplantation (2007)

31 Evolution of Fibrosing Alveolitis Associated with Systemic Sclerosis after Autologous Bone Marrow Transplantation

Purpose : Fibrosing alveolitis (FA) is the most frequent cause of death after cardiac involvement and pulmonary hypertension in systemic sclerosis (SSc). Cyclophosphamide (CY) was demonstrated in a randomised, placebo-controlled prospective study, to have significant, albeit modest, effect on FA-SSc and lung function. Since 1996, the use of high doses of CY followed by autologous hematopoietic stem cell transplantation (ASCT) allowed impressive clinical responses in severe diffuse SSc in phase I-II studies. Data on the evolution of FA associated SSc and especially chest high-resolution CT scan (HRCT) patterns are lacking. The aim of our study is to describe the evolution of FA-SSc after ASCT with a special focus on serial HRCT changes.
Methods : 9 diffuse SSc patients (6F/3M), diagnosed according to the ACR criteria, median age 41 (17-61) yrs, who had been treated for severe disease and early visceral involvement with CD34+-selected ASCT in the ISAMAIR phase I-II trial according to previously published criteria (Farge D. Br J Haematol 2002;119:726-39) were evaluated just before (T0) and then at 6 (M6) and 12 mths (M12) after ASCT for FA-SSc. Two independent observers reviewed all the HRCT to measure the extent and severity of FA-SSc according to the Wells score (Desai SR. Radiology 2004;232:560-7), blindly to clinical results. Results (median, range) were analysed in light of the evolution of the modified Rodnan skin score (mRSS) and pulmonary function tests measured within the same week as HRCT evaluation using the non parametric paired Wilcoxon test to compare patients individual values.
Results :
T0 before ASCTM6 after ASCTM12 after ASCT
Disease extent, median (range) %10 (0-45)4* (0-36)6 (0-39)NS
Ground-glass attenuation, mediane (range) %50 (12-90)30.5(0-90)NS42 (0-67)NS
Improvement/stability/worsening on serial HRCT, n-5/4/03/2/4
Vital Capacity (VC) %72 (37-108)74(32-114)NS76(36-113)NS
Total Lung Capacity %82 (42-114)81(43-100)NS73(53-109)NS
Forced Expiratory Volume (FEV) 1 %69 (47-112)83(38-122)NS82(37-128)NS
FEV1/VC %104 (92-123)110(99-118)*106(98-113)µ
Carbon Dioxyde Diffusion Lung Capacity (TLCO) %46 (21-61)51 (12-76) NS43 (36-53)NS
TLCO/VA %67 (36-86)57 (16-80)NS48 (32-74)NS
Modified Rodnan Skin Score36 (9-51)24 (4-37)*25 (4-44)*
*p<0.05; µ p=0.05, NS: non significant as compared to baseline
Conclusions : This study first reports improvement or stabilisation of FA-SSc in 9 SSc patients treated by ASCT, with significant regression of its extent at 6 months on serial HRCT evaluation. HRCT improvement was predominantly associated with attenuation of some ground-glass areas, meanwhile significant regression of the mRSS was found at 6 and 12 months after ASCT as previously reported. New increase in FA-SSc 1 year after ASCT raised the question of potential relapse after immune reconstitution in some patients (Farge D. Arthritis Rheum 2005;52:1555-63).

 D. Launay, None.