Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus
Abstract
Context Type 1 diabetes mellitus (DM) results from a cell-mediated autoimmune attack against pancreatic beta cells. Previous animal and clinical studies suggest that moderate immunosuppression in newly diagnosed type 1 DM can prevent further loss of insulin production and can reduce insulin needs. Objective To determine the safety and metabolic effects of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) in newly diagnosed type 1 DM. Design, setting, and participants A prospective phase 1/2 study of 15 patients with type 1 DM (aged 14-31 years) diagnosed within the previous 6 weeks by clinical findings and hyperglycemia and confirmed with positive antibodies against glutamic acid decarboxylase. Enrollment was November 2003-July 2006 with observation until February 2007 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirão Preto, Ribeirão Preto, Brazil. Patients with previous diabetic ketoacidosis were excluded after the first patient with diabetic ketoacidosis failed to benefit from AHST. Hematopoietic stem cells were mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (10 microg/kg per day) and then collected from peripheral blood by leukapheresis and cryopreserved. The cells were injected intravenously after conditioning with cyclophosphamide (200 mg/kg) and rabbit antithymocyte globulin (4.5 mg/kg). Main outcome measures Morbidity and mortality from tra…
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A 2007 trial of autologous haematopoietic stem-cell transplantation combined with high-dose immunosuppression (ie, cytoxan and thymoglobulin) reported increased C-peptide production and insulin independence in most patients who received treatment at disease onset.
“A 2007 trial of autologous haematopoietic stem-cell transplantation combined with high-dose immunosuppression (ie, cytoxan and thymoglobulin) reported increased C-peptide production and insulin independence in most patients who received treatment at disease onset.144”
From Type 1 diabetes (2014) · cites this paper as [144]
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- Authors
- Voltarelli, J. C., Couri, C. E. B., Stracieri, A. B. P. L., Oliveira, M. C., Moraes, D. A., Pieroni, F., Coutinho, M., Malmegrim, K. C. R., Foss-Freitas, M. C., Simões, B. P., Foss, M. C., Squiers, E., & Burt, R. K.
- Affiliations
- Universidade de São Paulo (BR)
- Y'S Therapeutics Co., Ltd. (Japan) (JP)
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2007-04-11
- Volume
- 297
- Issue
- 14
- Pages
- 1568
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2167304816
- Cited by
- 573
- References
- 28
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 14 · 2023: 14 · 2022: 27 · 2021: 19 · 2020: 14 · 2019: 22 · 2018: 28 · 2017: 31 · 2016: 27 · 2015: 35 · 2014: 35 · 2013: 36 · 2012: 56
- FWCI
- 29.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 1 diabetes, autologous stem cell transplantation, nonmyeloablative conditioning, immunosuppression, newly diagnosed diabetes, glutamic acid decarboxylase antibodies, insulin requirement, C-peptide, beta-cell function, antithymocyte globulin, cyclophosphamide, leukapheresis, safety and toxicity
- MeSH terms
- Adolescent, Adult, Autoantibodies, C-Peptide, Diabetes Mellitus, Type 1, Female, Glutamate Decarboxylase, Glycated Hemoglobin, Hemoglobins, Humans, Immunosuppression Therapy, Insulin, Male, Prospective Studies, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning, Hematopoietic Stem Cell Mobilization
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