Autologous umbilical cord blood transfusion in very young children with type 1 diabetes

Michael J Haller, Clive H Wasserfall, Kieran M McGrail, Miriam Cintron, Todd M Brusko, John R Wingard, Susan S Kelly, Jonathan J Shuster, Mark A Atkinson, Desmond A Schatz, Michael J Haller, Clive H Wasserfall, Kieran M McGrail, Miriam Cintron, Todd M Brusko, John R Wingard, Susan S Kelly, Jonathan J Shuster, Mark A Atkinson, Desmond A Schatz

Abstract

Objective: Interest continues to grow regarding the therapeutic potential for umbilical cord blood therapies to modulate autoimmune disease. We conducted an open-label phase I study using autologous umbilical cord blood infusion to ameliorate type 1 diabetes.

Research design and methods: Fifteen patients diagnosed with type 1 diabetes and for whom autologous umbilical cord blood was stored underwent a single intravenous infusion of autologous cells and completed 1 year of postinfusion follow-up. Intensive insulin regimens were used to optimize glycemic control. Metabolic and immunologic assessments were performed before infusion and at established time periods thereafter.

Results: Median (interquartile range [IQR]) age at infusion was 5.25 (3.1-7.3) years, with a median postdiagnosis time to infusion of 17.7 (10.9-26.5) weeks. No infusion-related adverse events were observed. Metabolic indexes 1 year postinfusion were peak C-peptide median 0.50 ng/ml (IQR 0.26-1.30), P = 0.002; A1C 7.0% (IQR 6.5-7.7), P = 0.97; and insulin dose 0.67 units * kg(-1) * day(-1) (IQR 0.55-0.77), P = 0.009. One year postinfusion, no changes were observed in autoantibody titers, regulatory T-cell numbers, CD4-to-CD8 ratio, or other T-cell phenotypes.

Conclusions: Autologous umbilical cord blood transfusion in children with type 1 diabetes is safe but has yet to demonstrate efficacy in preserving C-peptide. Larger randomized studies as well as 2-year postinfusion follow-up of this cohort are needed to determine whether autologous cord blood-based approaches can be used to slow the decline of endogenous insulin production in children with type 1 diabetes.

Trial registration: ClinicalTrials.gov NCT00305344.

Figures

Figure 1
Figure 1
Autologous cord blood infusion in type 1 diabetes: study timeline. Our study was designed as a 2-year observational study of the effects of autologous cord blood infusion in children with type 1 diabetes. Each child was followed every 3 months during the first year postinfusion and every 6 months during the second year postinfusion. Blood was obtained for metabolic and immunologic studies at each visit. Mean time from type 1 diabetes diagnosis to umbilical cord blood infusion was 6 months. Herein, we report 1 year postinfusion data on the first 15 umbilical cord blood recipients to reach 1 year of post–cord blood infusion follow-up. T1D, type 1 diabetes; UCB, umbilical cord blood; q, every.
Figure 2
Figure 2
Insulin use (A) and A1C (B) in umbilical cord blood recipients and historical control subjects over 1 year. Data are medians with error bars showing IQRs and are presented for the sake of comparison with clinical expectations. Because the average time from diagnosis to umbilical cord blood infusion was 6 months, comparisons correlate with 6, 12, and 18 months post–type 1 diabetes diagnosis in both umbilical cord blood recipients and historical control subjects. Whereas the absolute value of A1C and insulin requirement in umbilical cord blood recipients was lower than that in control subjects at baseline, 6 months, and 12 months, the relevant statistical comparison of percent change was no different over time (Table 2).

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Source: PubMed

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