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

• Published in: The journal of clinical endocrinology and metabolism Vol. 101; no. 5; pp. 2141 - 2148
• Main Authors: Cantú-Rodríguez, Olga Graciela, Lavalle-González, Fernando, Herrera-Rojas, Miguel Ángel, Jaime-Pérez, José Carlos, Hawing-Zárate, José Ángel, Gutiérrez-Aguirre, César Homero, Mancias-Guerra, Consuelo, González-Llano, Oscar, Zapata-Garrido, Alfonso, Villarreal-Pérez, Jesús Zacarias, Gómez-Almaguer, David
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.05.2016; Copyright by The Endocrine Society
• Subjects: 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
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2015-2776

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 × 106 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. We carried out an AHSCT (autologous hematopoietic stem cell transplantation) protocol using a less toxic and affordable simplified method based on fludarabine in an outpatient setting with the main objective of determining long-term insulin independence as well as changes in glycated hemoglobin (HbA1c). Simplified AHSCT in an outpatient setting is a feasible, safe and potentially therapeutic intervention for early-onset type 1 diabetes.