Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in New-Onset Type 1 Diabetes: A Multicenter Analysis

• Published in: Diabetes (New York, N.Y.) Vol. 63; no. 9; pp. 3041 - 3046
• Main Authors: D’Addio, Francesca, Valderrama Vasquez, Alessandro, Ben Nasr, Moufida, Franek, Edward, Zhu, Dalong, Li, Lirong, Ning, Guang, Snarski, Emilian, Fiorina, Paolo
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.09.2014
• Subjects: Adolescent; Adult; Autoimmune diseases; Biological and medical sciences; C-Peptide - metabolism; Child; Children & youth; Cyclophosphamide - therapeutic use; Diabetes Mellitus, Type 1 - therapy; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Immune system; Immunosuppression; Immunotherapy; Insulin - therapeutic use; Male; Medical sciences; Peptides; Remission Induction; Stem cells; Transplantation, Autologous; Transplants & implants; Endocrinopathy; Immunopathology; Type 1 diabetes; Stem cell; Hematopoietic cell; Autoimmune disease; Transplantation
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db14-0295

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.