Improvement of Concurrent Autoimmune Diseases Following Reduced-Intensity Stem Cell Transplantation (RIST) for Hematological Disorders: Graft-Versus Autoimmunity (GVA) Effect.

[Introduction]

The effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) against autoimmune disease has been suggested by studies in animal models and patients who had undergone transplantation for hematological disorders. However, its significant treatment-related mortality (TRM) has limited its application to life-threatening cases. Reduced-intensity stem cell transplantation (RIST) is a rapidly expanding treatment strategy and diminishes TRM by decreasing conditioning regimen toxicity compared to conventional myeloablative transplants. The benefit of RIST for autoimmune disease still remains unclear.

[Purpose]

The purpose of this study is to analyze outcomes of patients with autoimmune diseases treated with RIST for coexisting hematological diseases.

[Patients and Methods]

Between April 2001 and March 2004, 19 patients (median age, 53 y; range, 20-70) underwent RIST from allogeneic donor. All of the patients were considered inappropriate for conventional allo-HSCT due to age > 50 years and/or organ dysfunction (generally attributable to autoimmune disease-related). Stem cell sources were unrelated CB (n=10), unmanipulated related PB (n=7) and unmanipulated unrelated BM (n=2). The preparative regimens were Flu/Mel-based (n=11), Flu/Bu-based (n=7), and Flu/CY (n=1). The primary disease were NHL (n=7), MDS (n=4), AML (n=3), HD (n=2), ATL (n=2), and SAA (n=1). Concurrent autoimmune diseases were ulcerative colitis (n=4), psoriasis (n=3), rheumatoid arthritis (n=2), interstitial pneumonitis (n=2), atopic dermatitis (n=1), ITP (n=1), CIDP (n=1), polychondritis (n=1), SLE (n=1), and MCTD (n=1). Eleven out of 19 patients were active in autoimmune disease, and seven needed immunosuppressive therapy.

[Results]

Median follow up period is 174 days (range, 33–987). All patients achieved neutrophile engraftment (median 22 days; range 12–42) and sustained 100% donor chimerism without DLI. 13 patients (68%) developed grade II-IV acute GVHD, and six (31%) developed chronic GVHD. Nine patients (47%) who were treated with steroid, died of transplant-related toxicity; sepsis (n=7), GI bleeding (n=1), and multiple organ failure (n=1). One patient died of leukemia relapse. As of August 2004, ten patients are alive at median follow-up of 402 days, and the actuarial overall survival rate is 51 % at 2 years. Regarding the clinical response for autoimmune disease, no patients experienced flares of the disease: complete remission is observed in seven patients (70%) and they become therapy-free. In the other three patients (30%), disease remains stable.

[Conclusion]

Our results suggest that a strategy that incorporates RIST for autoimmune disease may be worth considering for further intense evaluation. It may have a considerable graft-versus-autoimmunity (GVA) effect due to the recipient lymphoablation and reconstitution of donor T cells. Organ failure due to autoimmune disease, impaired immune response, and GVHD may contribute to high TRM. Management of regimen-related toxicity and the control of GVHD will be the focus of future investigation.