Stem-cell transplants in scleroderma: ASTIS update

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Stem-cell transplants in scleroderma: ASTIS update

Rheumawire

June 30, 2004

Zosia Chustecka

Berlin, Germany - The first interim results to come out of an ongoing

international trial of stem-cell transplantation as a treatment option

for scleroderma (systemic sclerosis, SSc) are " encouraging, "

investigators told the recent EULAR 2004 meeting. They add to data

already collected from pilot studies that suggest that this approach can

improve skin symptoms and halt organ damage. " The signs are good, but by

no means do we claim that this will be a cure for all patients with

severe systemic sclerosis, " says Dr van Laar (Leiden University

Medical Center, the Netherlands). [1]

Autologous stem-cell transplantation has been explored as an option in

several autoimmune diseases, but because it's such a high-risk strategy,

it's been considered " a last-ditch attempt " to try when nothing else has

succeeded. In scleroderma, however, there are no other treatment

options, and severe forms of this disease are fatal. Hence the interest

in this approach, and the excitement that surrounded the early results

from open trials. When they were reported in 2001, an accompanying

editorial in the ls of Rheumatic Diseases [2] declared that

scleroderma " is probably rheumatology's most ominous disorder. Any

promising attempt to alter the fate of this disease or to improve our

understandings of its pathophysiology deserves full support by the

rheumatology community. "

The Autologous Stem Cell Transplantation International Scleroderma Trial

(ASTIS) began in March 2001 and has so far enrolled 30 patients. The

trial is comparing a regimen of high-dose immunosuppression

(cyclophosphamide and antithymocyte globulin) with standard chemotherapy

(pulse therapy cyclophosphamide). At the EULAR meeting, van Laar

discussed results from the first 20 patients. " It is too early to draw

definitive conclusions about the safety and effectiveness of the 2

different approaches, but the results so far are encouraging, " he said.

They have been promising enough to lead to a change in the

protocolinitially, the trial was open only to patients with severe

scleroderma but is now also recruiting patients with early diffuse

scleroderma. No treatment-related mortality has been observed as yet in

either arm.

It will be another 4 to 5 years before any recommendations can be made,

he added. The trial is ongoing, and multinational collaboration is

essential to accrue the large numbers of patients still needed to bring

the trial to a successful end. The original aim was for 100 patients to

be enrolled in each of the 2 arms of the study, with the primary end

point being event-free survival.

At the meeting, van Laar also gave an update on data that have accrued

on patients who received stem-cell transplants for scleroderma in

various pilot trials conducted throughout Europe and who have been

registered in the EMBT/EULAR database. He reviewed results in 57

patients with systemic sclerosis (median age 40 years, range 9-68; 47

females, 10 males) who had a median follow-up of 20 months (range

0.3-81.1 months).

An analysis of this EBMT/EULAR database shows durable responses in two

thirds of patients up to 3 years after stem-cell transplantation, van

Laar commented. Significant decreases in skin scores (p<0.005), defined

as greater than 25% change from baseline, were recorded in:

26/37 patients (70.2%) at 6 months.

20/30 patients (66.7%) at 12 months.

15/19 patients (78.9%) at 24 months.

6/10 (60%) of patients at 36 months.

No significant changes were observed in pulmonary or renal function.

Disease outcome was categorized as a partial response in 32/50 patients

(64%), a complete response in 14/50 patients (28%), and as a nonresponse

in 4/50 patients (8%). Relapses occurred in 16/46 patients (35%) who

initially had a partial or complete response at a median of 10 months

(2.2-48 months) after the stem-cell transplant. Disease progression was

documented in 19/50 patients (38%), and 13 of the 57 patients (22.7%)

died during follow-up. In 5 of these cases, the death was thought to be

treatment related, while in the other 8 cases it was due to disease

progression.

At 5 years, the probability of disease progression was 48% (95%CI 28-68)

and the projected survival was 72% (95% CI 59-75) in this group of

patients treated with stem-cell transplantation, van Laar told the

meeting.

A previous report [3] notes that severe forms of the disease, and

rapidly progressive diffuse SSc in particular, are associated with a

significant mortality secondary to pulmonary, cardiac, renal, and

gastrointestinal disease. It estimates an overall 5-year mortality of

30%, with subgroup differences of up to 58%, depending on the clinical

features at presentation.

Sources

Van Laar JM, Farge D, Tyndall A. Autologous stem cell

transplantation for severe systemic sclerosis: a retrospective registry

analysis and update on the ASTIS trial. Presented at: EULAR 2004;

Berlin, Germany; June 9-12, 2004.

Machold KP, Smolen JS. Stem cell transplantation:

limits and hopes. Ann Rheum Dis 2001 Jun; 60(6):548-549.

C, Knight C, Black CM, Silman AJ. Prediction of

five-year survival following presentation with scleroderma--development

of a simple model using three disease factors at first visit. Arthritis

Rheum 1999; 42:2660-2665.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org