Autologous nonmyeloablative hematopoietic stem cell transplantation in new-onset type 1 diabetes: a multicenter analysis

Diabetes. 2014 Sep;63(9):3041-6. doi: 10.2337/db14-0295. Epub 2014 Jun 19.

Abstract

Type 1 diabetes (T1D) is one of the major autoimmune diseases affecting children and young adults worldwide. To date, the different immunotherapies tested have achieved insulin independence in <5% of treated individuals. Recently, a novel hematopoietic stem cell (HSC)-based strategy has been tested in individuals with new-onset T1D. The aim of this study was to determine the effects of autologous nonmyeloablative HSC transplantation in 65 individuals with new-onset T1D who were enrolled in two Chinese centers and one Polish center, pooled, and followed up for 48 months. A total of 59% of individuals with T1D achieved insulin independence within the first 6 months after receiving conditioning immunosuppression therapy (with antithymocyte globulin and cyclophosphamide) and a single infusion of autologous HSCs, and 32% remained insulin independent at the last time point of their follow-up. All treated subjects showed a decrease in HbA1c levels and an increase in C-peptide levels compared with pretreatment. Despite a complete immune system recovery (i.e., leukocyte count) after treatment, 52% of treated individuals experienced adverse effects. Our study suggests the following: 1) that remission of T1D is possible by combining HSC transplantation and immunosuppression; 2) that autologous nonmyeloablative HSC transplantation represents an effective treatment for selected individuals with T1D; and 3) that safer HSC-based therapeutic options are required.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • C-Peptide / metabolism
  • Child
  • Cyclophosphamide / therapeutic use
  • Diabetes Mellitus, Type 1 / therapy*
  • Female
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Immunosuppression Therapy
  • Insulin / therapeutic use
  • Male
  • Remission Induction
  • Transplantation, Autologous

Substances

  • C-Peptide
  • Insulin
  • Cyclophosphamide