High-dose immunosuppression with autologous stem cell transplantation in severe refractory systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an immune-mediated disease that is responsive to suppression or modulation of the immune system. Patients with SLE who experience persistent multiorgan dysfunction, despite standard doses of intravenous cyclophosphamide (Cy), represent a subset of patients at high risk of early death. We investigated the efficacy and toxicity of high-dose immunosuppression and autologous hematopoietic stem cell transplantation (SCT) to treat such patients. Six patients (all female, age 15-29 years) with severe refractory SLE were enrolled in the clinic of our institution from 1998 to 2003. All patients were seriously ill, with SLE disease activity indices (SLEDAI) of 6-30, including two cases with central nervous system lupus, one case with lung vasculitis, and three cases with nephritis and nephrotic syndrome. All patients were registered in the European Group for Blood and Marrow Transplantation (EBMT)/European League Against Rheumatism (EULAR) database. Previous immunosuppression included pulse Cy intravenous, prednisolone (standard doses and pulse therapy), oral Cy and azathioprine, with little or no effect on disease progression. Autologous hemopoietic stem cells were collected from bone marrow (n = 4) or mobilized from peripheral blood with Cy and granulocyte colony-stimulating factor (G-CSF) (n = 2). Pre-transplant conditioning regimens included BEAM +/- ATG (n = 2), melphalan 140 mg/m2 + etoposid 1600 mg/m2 (n = 2) and Cy 200 mg/kg +/- ATG (n = 2). Median time to an absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L and platelet count greater than 50 x 10(9)/L was 13 and 15 days, respectively. Three patients died on days 11, 22 and 63 due to transplant-related complications. The follow-up is now 60 and six months for two patients (complete remission), and 42 months for one other patient (partial response). All patients had experienced multiple and severe episodes of infections pre-SCT and long-term history of corticosteroid therapy (3-14 years). We conclude that achievement of prolonged, corticosteroid-free remissions is a reality. Judicious selection of patients earlier in disease or in remission, but with a high risk of relapse or further progression, will diminish transplantation-related mortality.

Vasculitis treatment – new therapeutic approaches

“…A number of reports have appeared in the literature showing that this technique has potential benefit in severe autoimmune disease [70], in PAN [85] and in SLE [59,68]. Such a step is not going to be taken lightly but none-the-less may have a role when there is no alternative approach available.…”

The use of stem cells for the treatment of autoimmune diseases

“…Transplantation is able to change the behavior of severe diseases, making them more benign and responsive to therapy. It has been suggested that the reported higher rates of mortality in Brazil and other countries (25) can be controlled by appropriate patient selection, the choice of a less aggressive conditioning regime and the acquisition of more experience in managing specific complications associated with the procedure (21).…”

Transplante de células-tronco hematopoéticas em doenças reumáticas parte 1: experiência internacional

“…Por outro lado, o grupo de Zhengzhou transplantou 18 pacientes, observando-se 12 remissões completas, três parciais, três falhas terapêuticas e duas recaídas, mas nenhum óbito (33) e o grupo de Shangai relatou TCTH bem sucedido em duas crianças (de cinco e sete anos) portadoras de LES (34) . Na experiência russa, dentre seis pacientes com LES condicionados com BEAM+ATG, ocorreram três óbitos por complicações do transplante, duas remissões completas e uma remissão parcial (35) .…”