Lack of persistent remission following initial recovery in patients with type 1 diabetes treated with autologous peripheral blood stem cell transplantation.

AIMS: To assess metabolic control in patients with newly diagnosed type 1 diabetes mellitus who underwent immunoablation followed by autologous peripheral blood stem cell transplantation (APBSCT) as a treatment of diabetes. METHODS: APBSCT was performed in 23 patients. Control group comprised 8 non-APBSCT patients in whom after diagnosis insulin therapy was initiated. Fasting plasma glucose, glycated hemoglobin, fasting and postprandial C-peptide were assessed in all subjects and continuous glucose monitoring was performed at 6th, 12th, 24th, 36th, 48th month after transplantation. The APBSCT group was observed for 72 months. RESULTS: Six months after the procedure, 22 of 23 transplant patients remained insulin-free, but after 6 years, there was only one APBSCT insulin-free patient. Good glycemic control was observed in all patients throughout the observation period, although fasting plasma glucose in control group was significantly higher in comparison with the both transplanted groups up to the 36th month. HbA1c values were significantly lower in the insulin-free group only at the 24th and 36th month. Fasting and postprandial C-peptide concentrations were higher in APBSCT group as compared with control group. The most serious adverse event was a fatal case of Pseudomonas aeruginosa sepsis. CONCLUSIONS: The effectiveness of APBSCT as a treatment for newly diagnosed DM1 seems to be limited in time. The metabolic control of APBSCT patients is similar to conventionally treated patients. The lower fasting plasma glucose and higher C-peptide achieved with APBSCT seem to not exceed the risks associated with the procedure.

Alleviation of exogenous insulin requirement in type 1 diabetes mellitus after immunoablation and transplantation of autologous hematopoietic stem cells.

An essential component of type 1 diabetes mellitus is autoaggression of the immune system against insulin-secreting pancreatic cells. It is thought that early destruction of the autoaggressive mechanism prior to the complete damage of beta cells should halt this process. In a 28-year-old male patient with a 4-week history of type 1 diabetes mellitus, three courses of plasmapheresis had been performed before cyclophosphamide, 2 g/m2 body surface area, was administered and hematopoietic cells were obtained. Six weeks after the diagnosis, 4 doses of cyclophosphamide 50 mg/kg body weight were again administered together with antithymocyte globulin, and autologous hematopoietic cells were transplanted. The procedure was associated with no significant side effects. Insulin requirement started to drop from the first course of plasmapheresis, and the patient has remained normoglycemic with no need of exogenous insulin or other hypoglycemic agents since the third week after the procedure, which has been 5 months until publication of this report. Independence from exogenous insulin is associated with the implemented therapy (a gradual decrease in insulin requirement has been observed after consecutive stages of the immunosuppressive treatment, with total discontinuation after bone marrow transplantation). The course of the disease and the type of treatment may suggest that such medical procedures could eliminate autoaggressive mechanism in diabetes and prevent further degeneration of insulin-producing cells, thus becoming a new therapeutic option for patients with type 1 diabetes mellitus.