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.

An economic analysis of autologous hematopoietic stem cell transplantation (AHSCT) in the treatment of new onset type 1 diabetes.

AIMS: Autologous hematopoietic stem cell transplantation (AHSCT) is an emerging treatment option in new onset type 1 diabetes (T1DM), leading to a remission of the T1DM for a longer time period in up to 50 % of patients. The aim of the study was to analyze the cost-effectiveness of this treatment option compared with standard insulin therapy. METHODS: The medical records of patients who had undergone immunoablation with AHSCT for new onset T1DM were analyzed for the cost-effectiveness of the treatment using the IMS CORE Diabetes Model. RESULTS: The expected survival of patients with T1DM treated solely with insulin (without transplantation) was estimated to be 34.4 years, and their quality-adjusted survival was 13.8 QALY, whereas the expected survival of the patients treated with AHSCT was 34.9 years when the HbA1c benefit over standard treated patients lasted for 2, 35.4 years with 8-year benefit and even up to 40.3 years with the lifelong benefit scenario. Values under the threshold of ICER were reached after 8 years of sustained benefit in terms of HbA1c concentration. If discounting was not applied, the threshold values were reached after 3 years of HbA1c benefit over the standard group, independent of insulin use after transplantation. CONCLUSIONS: The results of our study show that hematopoietic stem cell transplantation could be cost-effective in treating new onset T1DM, providing that the benefits of the transplantation lasted over 3-8 years, depending on application of discounting.

Preoperative glucose abnormalities in patients with pancreatic tumours.

INTRODUCTION: Pancreatic cancer is a neoplasm characterised by poor prognosis. The only effective, possible treatment is radical surgery, but most patients do not qualify for surgery because of delayed diagnosis. AIM: To determine if assessment of endocrine pancreatic function could serve as a means of screening for pancreatic cancer. MATERIAL AND METHODS: This prospective study was conducted on a group of 50 patients diagnosed with pancreatic tumour, who were qualified for surgery. RESULTS: From 1.07.2010 to 4.07.2011 a further 50 patients were added to the study group. They had been admitted to the hospital with pancreatic tumours. During the preoperative period, nine of these people had been treated for diabetes, 14 were newly diagnosed with diabetes and 15 had been diagnosed with impaired glucose tolerance, but only 12 had a normal glucose profile. Afterwards, patients underwent the surgical treatment. Histopathological examination revealed that out of the 50 operated patients, 36 suffered from malignant disease, and of these only four had no impaired glucose tolerance before treatment. CONCLUSIONS: In most cases, patients with pancreatic tumours have impaired glucose tolerance. Screening patients over 50 years of age could speed up diagnosis and surgical treatment.

Potential role of immunoablation and hematopoietic cell transplantation in the treatment of early diabetes type 1.

Immunoablation with autologous hematopoietic cell transplantation has shown some effectiveness in the treatment of autoimmune diseases as diverse as aplastic anemia, systemic lupus erythematosus, multiple sclerosis and Crohn's disease. It has been recently shown that this treatment might prevent or delay development of diabetes type 1. The majority of more than 30 patients with early diabetes type 1 who underwent immunoablation and hematopoietic cell transplantation in various centers in the world achieved durable remission of diabetes and independence of exogenous insulin. This review summarizes advantages and risks of this treatment of early diabetes type 1.

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.