Complete Remission of Refractory Systemic Lupus Erythematosus

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Complete Remission of Refractory Systemic Lupus Erythematosus With High-Dose

Chemotherapy and Stem Cell Transplantation

S. Fauci, MD, Chief, Laboratory of Immunoregulation; Director, National

Institute of Allergy and Infectious Diseases, National Institutes of Health,

Bethesda, MD

[Copyright © 1998, 1999, 2000 by The McGraw-Hill Companies, Inc. Reproduced with

permission of The McGraw-Hill Companies.]

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Dysregulation of both cellular and humoral limbs of the immune system are

characteristic of systemic lupus erythematosus (SLE). Although autoantibodies

play an important role in mediating immunopathogenic tissue damage, T cell

defects likely play an important role in initiating and propagating the

autoimmune process. One therapeutic approach in this setting would be to use

chemotherapy and immunosuppression to allow subsequent maturation and outgrowth

of transplanted lymphocyte progenitors that would not likely be capable of

reacting against self antigens. Traynor and colleagues (2000) thus undertook a

study of high-dose chemotherapy combined with autologous hematopoietic stem cell

transplantation for the treatment of severe, refractory SLE.

Eligible patients were required to have severe lupus nephritis that was

unresponsive to at least 6 cycles of intravenous cyclophosphamide; lupus

cerebritis or transverse myelitis that was unresponsive to at least 6 cycles of

intravenous cyclophosphamide; lupus vasculitis involving the heart or lung that

was unresponsive to at least 6 cycles of intravenous cyclophosphamide;

lupus-associated life-threatening cytopenias that were unresponsive to standard

doses of cyclophosphamide; or catastrophic antiphospholipid syndrome. Patients

underwent leukapheresis for CD34 cell (i.e., stem cell) collection. Intravenous

cyclophosphamide was given at a dose of 50 mg/kg per day on day-6 to -3 before

transplantation. Antithymocyte globulin was given at a dose of 30 mg/kg per day

on day-5 to -3; each dose was preceeded by 1 g of methylprednisolone,

administered intravenously. Neutropenic precautions and prophylaxis against

bacterial, herpesvirus, and fungal infections followed standard guidelines.

Nine patients were enrolled in the study. The median duration of steroid

dependence was 4 years; the median daily prednisone dose was 50 mg. One patient

developed CMV viremia after stem cell harvest; one patient died of disseminated

mucormycosis. Despite very severe disease prior to transplantation, all seven

successfully transplanted patients achieved a complete clinical remission of

their SLE through a median follow-up period of 25 months. Antinuclear and

antidouble stranded DNA antibody titers declined to normal in all patients;

transient increases thereafter were not associated with disease flares. Serum

complement levels also normalized in all patients after transplantation. The

function of organs affected by SLE improved significantly in most patients.

Glucocorticoids were successfully discontinued in three patients and tapered to

a dose of 5 mg/day in three other patients; no patients received any other

adjunct therapy for SLE. Measures of immunologic function also normalized after

transplantation. Interestingly, the T cell receptor repertoire, which was skewed

in the three patients analyzed before transplantation, normalized as well.

These exciting results not only provide hope for a durable remission in cases of

severe, life-threatening SLE, but also hint at immunopathogenic mechanisms that

might be operative in SLE. Importantly, the patients' own stem cells were

capable of reconstituting an essentially normal immune system following

high-dose chemotherapy.

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References

1.. Traynor AE et al: Treatment of severe systemic lupus erythematosus with

high-dose chemotherapy and haematopoietic stem-cell transplantation: A phase I

study. Lancet 356:701, 2000 [PMID 11085688]

http://rheumatology.medscape.com/HOL/articles/2000/12/hol71/hol71.html