Safety and Clinical Outcomes of Using Low-Molecular-Weight Dextran During Islet Autotransplantation in Children.

OBJECTIVES: The objective of this study was to evaluate potential safety and clinical benefit of low-molecular-weight dextran (dextran) use in patients undergoing total pancreatectomy with islet auto transplantation (TPIAT). METHODS: We evaluated 124 children undergoing TPIAT at a single institution, either with (n = 72) or without (n = 52) perioperative dextran infusion. Data on islet graft function and postoperative complications were collected through electronic medical records and patient-reported outcomes from research questionnaires. RESULTS: Islet graft failure was less likely at 1 year (odds ratio, 0.186; 95% confidence interval, 0.04-0.65) and 2 years (odds ratio, 0.063; 95% confidence interval, 0.003-0.35) post-TPIAT in the dextran group. This finding remained significant at 2 years in multivariate logistic regression modeling adjusting for islet mass, body surface area, and sex. Likewise, in multivariate regression, the odds of partial islet graft function were higher at 1 and 2 years in the dextran group. Dextran use was overall safe, although it did lead to a higher incidence of postoperative bleeding requiring blood transfusions (P < 0.001). CONCLUSIONS: These findings suggest that dextran use may increase the likelihood for sustained post-TPIAT islet graft function, potentially mitigating severity of postoperative diabetes for these children.

Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation.

BACKGROUND: Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity. METHODS: Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis. RESULTS: Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72). CONCLUSIONS: Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.