Allogeneic Non Myeloablative Blood Stem Cell Transplantation for NHL in a Patient with Systemic Lupus Erythematosus: Clinical Outcome and Long Term Follow-Up.

Abstract

The severity and clinical course of systemic lupus erythematosus (SLE) varies widely. Overall mortality from SLE at 10 years is 30% (Ward et al., 1995), with a four fold increased risk of death compared to the general population (Moss et al., 2002). Non myeloblative allogeneic HSCT has been suggested as a way of improving disease free survival. We describe the successful treatment of a 47-year-old male with SLE who received a non-myeloablative sibling allogeneic blood stem cell transplant for high grade lymphoma.A 47-year-old man, presented with polyarthropathy and anti nuclear factor (ANA) IgG nuclear of 1:160. He was treated with prednisolone and azathioprine, but his SLE continued to pursue a relapsing aggressive course complicated by encephalitis in 1991 and biopsy confirmed membranous nephritis in 1993. He also developed steroid resistant immune thrombocytopaenia requiring splenectomy. In addition, he developed antiphospholipid syndrome with positive anti cardiolipin antibodies and dilute Russell viper venom test (DRVVT) complicated by pulmonary embolism requiring long term anticoagulation with warfarin.In 1999, he developed a high-grade plasmablastic lymphoma Stage IIIb associated with a serum IgG paraprotein. There was no infiltration of the bone marrow. He continued to have active SLE treated with prednisolone and azathioprine. Six courses of CHOP induction chemotherapy resulted in a partial response (indicated by a persistently elevated LDH, residual lymph nodes on CT and PET scanning). He subsequently received one course of DHAP chemotherapy but 3-months post-treatment he remained with residual lymphoma. Symptomatically, his SLE improved following chemotherapy, but his autoimmune markers remained positive (ANA IgG 1:40 positive nuclear pattern). Post-chemotherapy the patient had a large retroperitoneal bleed necessitating the withdrawal of warfarin. Because the patient had resistant disease and remained in partial remission, a decision was made to consolidate with stem cell transplantation from his histocompatibility (HLA)-matched brotherIn August 2000, transplant conditioning was given using Campath 1H (20mg D-7 to D-4), Fludarabine (30mg/m2 D-7 to D-3) and Melphalan (140mg/m2 on D-2). Cyclosporin was administered as graft versus host disease (GvHD) prophylaxis and LMWH given until the platelet count fell below 50000. The unmanipulated stem cell graft consisted of 5.51 X 106 CD34+ cells/kg body weight. There was no evidence of GvHD.Six months after the non-myeloablative transplant, he achieved CR from his lymphoma with full donor engraftment on chimeric studies. Both CT and PET scans were clear. His symptoms of SLE including the polyarthropathy had resolved and immunologically had become ANA negative with a normal complement level. His anti-cardiolipin antibody and DRVVT were negative and he had no further thrombotic problems. 27-months post-transplant, the patient continues to be in complete clinical and radiological remission from his lymphoma with 100% donor chimerism. Both serologically and clinically his SLE and antiphospholipid syndrome remain in complete remission. He is currently on no medication.We have demonstrated the efficacy and safety of non-myeloablative allogeneic transplantation for SLE. He is three years out from transplantation, he is alive and in clinical remission. We suggest that this approach needs further evaluation in a prospective study.