NEWS - Stem-cell transplants might bring RA cure closer

[Guest guest]

Stem-cell transplants might bring RA cure closer

Rheumawire

April 7, 2006

Janis

Tasmania, Australia - Two women with severe rheumatoid arthritis (RA) who

received allogeneic bone-marrow transplants 19 and 21 years ago for

therapy-induced aplastic anemia became and remain free of signs and symptoms

of active RA. Dr Ray M Lowenthal (Royal Hobart Hospital, Tasmania,

Australia) and colleagues report 20-year follow-up data for the two cases in

the April 2006 Journal of Rheumatology [1].

An editorial by Dr Alan Tyndall (University of Basel, Switzerland) suggests

that although the jury is still out on allogeneic hematopoietic stem-cell

transplantation (HSCT) for autoimmune diseases such as RA, the Lowenthal

data show that " the 'holy grail' of tolerance induction without long-term

immunosuppression is in our sights " [2].

Tyndall told rheumawire that this development is likely to add to the

impetus for early, aggressive treatment.

" As with all the autoimmune diseases, we need to 'bite the bullet' and

employ such potential tolerance-inducing treatment strategies early, before

an irrevocable chronic inflammatory course is set, " he said.

Controlled studies needed of HSCT vs other approaches

Tyndall emphasizes the importance of prospective controlled studies

currently under way. European researchers are conducting the Autologous Stem

Cell International Scleroderma (ASTIS) trial as well as studies of stem-cell

transplants for multiple sclerosis (MS) and for Crohn's disease. Safety data

for the ASTIS trial have already been reported, and Tyndall predicted that

efficacy data will be available in about 18 months. North American

researchers are working on the Scleroderma Cyclophosphamide or

Transplantation (SCOT) trial and on studies in patients with MS and with

systemic lupus erythematosus (SLE).

Tyndall says that a well-designed, prospective, randomized controlled trial

of HSCT is urgently needed in RA. " Eligibility criteria might include

patients who have failed best-available therapy (including rituximab), have

a poor prognosis, have early destructive disease but not totally destroyed

joints and clinically active disease, and are seropositive for rheumatoid

factor and cyclic-citrullinated-peptide antibody, " he said.

The first of the two cases reported by Lowenthal et al is of a 49-year old

woman who had an allogeneic, HLA-identical, mixed lymphocyte culture (MLC)

nonreactive sibling bone-marrow transplant for gold-induced severe aplastic

anemia in 1984, at age 27. She was in remission at the time aplastic anemia

developed, although she had bilateral elbow nodules and damaged wrists

requiring splints. She had been treated by gold injections for five years

and had had RA for six years. Transplant was done following conditioning

with cyclophosphamide alone, and she had both acute and mild chronic

graft-vs-host disease (GVHD) following transplant, which was successfully

treated with corticosteroids and methotrexate. At 21 years of follow-up she

has no evidence of active RA, takes no regular analgesia, and has normal or

negative measures on all RA laboratory tests.

The second case underwent allogeneic bone-marrow transplant at age 30 for

penicillamine-induced aplastic anemia. " At that time she had had severe

nodular RA for a total of nine years and could barely walk 250 meters, "

Lowenthal writes. Transplant condition was with cyclophosphamide alone, and

she suffered a series of posttransplant infections and GVHD but within two

years was off all RA medications, including corticosteroids. At 19 years of

follow-up she remains well, continues to work full time, regularly walks 3.5

km, and takes no medications.

Lowenthal notes that although most early transplants in RA were allogeneic

HSCT, more recent reports have been of autologous or nonmyeloablative

allogeneic transplants. " Responses, although common, are generally

short-lived: that is, of the order of six to 12 months. This contrasts with

the prolonged response in our cases, which followed allogeneic HSCT with

full myeloablative conditioning, " he writes.

" We need to know more about the mechanism of tolerance induction, " Tyndall

agrees. " Why do some autologous HSCTs do well 10 years later and others

relapse? That may then guide the choice of allo vs autotransplant, rather

than theoretical, unproven reasoning, as is the case at the moment. "

Sources

1. Lowenthal RM, Francis H, Gill DS. Twenty-year remission of

rheumatoid arthritis in 2 patients after allogeneic bone marrow transplant.

J Rheumatol 2006; 33:812-813.

2. Tyndall A. Allogeneic bone marrow transplantation for

autoimmune disease-the jury is still out. J Rheumatol 2006; 33:644-646.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org