title: Autologous nonmyeloablative hematopoietic stem cell transplantation in new-onset type 1 diabetes: a multicenter analysis.
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.
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA Transplant Medicine, IRCCS San Raffaele Hospital, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: D'Addio
authors.affiliation: Transplant Medicine, IRCCS San Raffaele Hospital, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valderrama Vasquez
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Moufida
authors.initials: M
authors.lastname: Ben Nasr
authors.affiliation: Department of Internal Diseases, Diabetology and Endocrinology, Central Hospital, Ministry of Interior Affairs and Administration, Warsaw, Poland Department of Endocrinology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Edward
authors.initials: E
authors.lastname: Franek
authors.affiliation: Division of Endocrinology, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Division of Endocrinology, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Lirong
authors.initials: L
authors.lastname: Li
authors.affiliation: Shangai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.affiliation: Department of Hematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Emilian
authors.initials: E
authors.lastname: Snarski
authors.affiliation: Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA Transplant Medicine, IRCCS San Raffaele Hospital, Milan, Italy paolo.fiorina@childrens.harvard.edu.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorina
mesh_terms: D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000378:metabolism; D002648:Child; D003520:Cyclophosphamide / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007165:Immunosuppression Therapy; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D012074:Remission Induction; D014182:Transplantation, Autologous
chemical_list: D002096:C-Peptide; D007328:Insulin; D003520:Cyclophosphamide