Autologous Hematopoietic Stem Cell Transplantation for Autoimmune Diseases

Abstract

Ten years have passed since the first published consensus statement on the use of hematopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease (AD) appeared. During that time, around 700 patients suffering from severe AD have undergone HSCT in the frame of phase I/II clinical trials from over 20 countries including the US. The majority have received an autologous HSCT using one of a limited number of regimens, consistent with the original consensus statement. Long-term drug-free remissions, remission then relapse, no response and treatment-related mortality (TRM) were seen in all the subgroups of AD. An overall TRM of 7% was observed, with marked variation between ADs, i.e. 11% in systemic lupus erythematosus (SLE) and only 1 patient in rheumatoid arthritis (RA). Phase III prospective, comparative randomized trials are running or being planned in multiple sclerosis (MS), systemic sclerosis (SSc), SLE and RA. Basic science programs are also being undertaken to study the immunological mechanisms underlying the clinical events observed.

Reversal of autoimmune disease in lupus-prone New Zealand black/New Zealand white mice by nonmyeloablative transplantation of purified allogeneic hematopoietic stem cells

“…In these patients, treatment-related mortality is significant, approaching 11%. 14 To improve safety, less toxic nonmyeloablative conditioning regimens that use lower doses of chemoablation combined with polyclonal antibodies that eliminate lymphocytes are currently being investigated. These protocols target selfreactive lymphocytes with limited myeloablation.…”

An analysis of the optimal timing of peripheral blood stem cell harvesting following priming with cyclophosphamide and G-CSF

“…Autologous transplantation is now considered the treatment of choice for initial therapy of multiple myeloma and for relapsed high-grade non-Hodgkin's and Hodgkin's lymphoma, in addition to experimental procedures in non-malignant disorders such as autoimmune disease. 3 Intravenous cyclophosphamide supported by haematopoietic growth factors for example, G-CSF, is a commonly used priming regimen for patients with myeloma and lymphoma. Although high doses of cyclophosphamide (4-7 g/m 2 ) are effective, 4,5 lower doses (1.2-2 g/m 2 ) are as effective but with less toxicity.…”

Autologous Peripheral Blood Purified Stem Cells Transplantation for Treatment of Systemic Lupus Erythematosus

“…Because of the transplanted organ damage associated with SLE patients, most scholars do not advocate the use of intense myeloablative program, but the lymphatic clearance program. The current use of cyclophosphamide (200mg/kg) + anti-thymocyte globulin (ATG, 90mg/kg) is more common, while some individual case reports cyclophosphamide (120 ~ 150mg/kg) + systemic lymph node irradiation (400 ~ 600cGy, lung shielding to 400cGy) or cyclophosphamide (120mg/kg) + busulfan (16 mg / kg) and the BEAM program (BCNU 300mg / m 2 , VP16 400 ~ 800mg / m 2 , cytarabine 800 ~ 1600mg / m 2 , melphalan 140mg / m 2 ) [10,15,18]. The whole body and lymph node irradiation can induce more tumor-related complications, should be taken seriously enough [15].…”

“…We applied plenty of ATG in vivo to remove the residual T lymphocytes and memory cells to enhance the success rate and reduce the relapse rate. The exact mechanism of autologous peripheral blood stem cell transplantation for autoimmune diseases is not fully clear, what can be certain is that the original autoimmune cell clones were completely destroyed while re-established a normal immune system [7][8][9][10]. By high dose systemic immunosuppressants or radiation, we eliminate its own mature immune cells, while stem cells, due to a large quantity of aldehyde dehydrogenase, can resist to cyclophosphamide.…”

“…Van lear have found that 45 SLE patients undergoing transplantation, 27 of which have significantly improved, 14 recurred after the initial alleviation, 7 deaths, for 5 have relation with the transplantation and the overall transplant-related mortality rate is 11% [20]. Traynor et al from North America [10] found 15 patients with SLE completing the study of autologous transplantation were alive, but 2 died after mobilization. In more than 1 year's follow-up, 12 patients, 8 cases completely withdrawaled, 2 have small doses of hormones to maintain, 2 had disease activity requiring the addition of immunosuppressive agents.…”