Long-Term Insulin Independence in Type 1 Diabetes Mellitus Using a Simplified Autologous Stem Cell Transplant

J Clin Endocrinol Metab. 2016 May;101(5):2141-8. doi: 10.1210/jc.2015-2776. Epub 2016 Feb 9.

Abstract

Context: Efforts to find a cure for type 1 diabetes have focused on the removal of the autoimmune pathophysiologic substrate, with the use of immunosuppressive regimens including autologous hematopoietic stem cell transplantation (AHSCT).

Objective: The main objective of determining long-term insulin independence as well as changes in glycated hemoglobin (HbA1c). Secondary outcomes were procedure morbidity and the need for hospital management.

Design: We enrolled patients with type 1 diabetes between 2012 and 2014. Median follow-up was 34 months (range, 25-56 mo).

Setting: Ambulatory care.

Interventions: We decided to carry out an AHSCT protocol using a less toxic and affordable simplified method based on fludarabine in an outpatient setting.

Patients: Patients were of both sexes, age 8-25 years, with positive levels of anti-GAD antibodies, a C-peptide level >1.0 ng/mL, and <3 months since diagnosis.

Main outcome measure(s): Insulin independence.

Results: Sixteen patients were included. Overall response was 81% with seven patients achieving insulin independence (44%); six were partial responders (37%) whereas three were nonresponders (19%). The HbA1c level showed a mean decrease of -2.3% at 6 months in the Insulin Independence group. Median age was 12 years old (range, 8-17 years old). A mean of 11.5 × 10(6) CD34+ cells (SD ± 8.2) was obtained. Related mortality at 100 days was 0% as well as during follow-up. Outpatient setting was 100%.

Conclusions: Simplified AHSCT in an outpatient setting is a feasible, safe and potentially therapeutic intervention for early-onset type 1 diabetes.

Trial registration: ClinicalTrials.gov NCT01121029.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / metabolism*
  • Child
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / therapy*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Transplantation, Autologous
  • Treatment Outcome
  • Young Adult

Substances

  • Blood Glucose
  • Immunosuppressive Agents

Associated data

  • ClinicalTrials.gov/NCT01121029