Combined Pancreatic Islet–Lung Transplantation: A Novel Approach to the Treatment of End‐Stage Cystic Fibrosis

Abstract

Patients with end-stage cystic fibrosis (CF) and severe CF-related diabetes (CFRD) may benefit from combined lung-pancreatic islet transplantation. In the present study, we report the long-term follow-up of four end-stage CF patients treated with combined bilateral lung and pancreatic islet transplantation from the same donor. All patients were C-peptide negative (<0.5 lg/L) and inadequately controlled despite intensive insulin treatment. One patient was transplanted with 4 019 ± 490 islet equivalent/kg injected into the transverse colic vein using a surgical approach. In the remaining three patients, islets were cultured for 3-6 days and transplanted by percutaneous transhepatic catheterization of the portal vein. In all patients, islet allograft recovery was recognized by elevation in the plasma level of C-peptide (>0.5 lg/L). At 6 months after transplantation, one patient showed multiple episodes of acute lung transplant rejection and a progressive decline in pancreatic islet cell function. Three out of four patients experienced an improved control of glucose levels with a HbA1c of 5.2%, 7% and 6% respectively at 1.5, 2 and 15 years follow-up. Compared with the pretransplant period, there was a 50% reduction in mean daily insulin needs. Pulmonary function remained satisfactory in all patients. In conclusion, our cases series shows that combined bilateral lung and pancreatic islet transplantation may be a viable therapeutic option for patients with end-stage CF and CFRD.

Anti-Donor HLA Antibody Response After Pancreatic Islet Grafting: Characteristics, Risk Factors, and Impact on Graft Function

“…Before grafting, HBA 1c was 8.4 ± 0.3% and average insulin requirement was 0.54 ± 0.03 UI/kg. About a third of recipients had already undergone organ transplantation before pancreatic islet grafting (Table , left column), including 2 (4.8%) lung recipients . Of the 42 islet‐grafting procedures analyzed, 7 (16.7%) were considered as primary failures (Figure ).…”

Optic Disc Swelling and Vision Loss in a Patient with Cystic Fibrosis and Diabetes

“…Interestingly, our patient's c-peptide became undetectable 4 years after her initial diagnosis, which is more consistent with type 1 diabetes as are her rapid progression from normal glucose tolerance to mild DKA in absence of CF exacerbation and initially normal pancreatic exocrine function. However, Kessler and colleagues have reported that baseline c-peptide levels in CFRD patients may be undetectable even in patients with negative GAD antibodies [6]. In addition, CF patients have been shown to have a blunted response to hyperglycemia based on their c-peptide in Moran et al's paper [7].…”

Autologous and Allogenous Antibodies in Lung and Islet Cell Transplantation

“…The SIK/IAK rate in North America is 10% were as that in European centers are >35%. A small number of islets after LTx have been successfully performed at the GRAGIL (Groupe Rhin-Rhône-Alpes-Genève pour la Transplantation d’Ilots de Langerhans) consortium (1). This combined transplantation was particularly beneficial for patients with end-stage cystic fibrosis and severe cystic fibrosis-related diabetes.…”

“…As of 2012, approximately 1,400 islet cell transplantations have been recorded (Collaborative Islet Transplant Registry, 2 accessed on July 25, 2016). Additionally, combined transplantation of lungs and pancreatic islets is an effective treatment option to restore respiratory and pancreatic insufficiency in terminal cystic fibrosis (1). The global need for organ transplantation is rising steadily with more prospective transplant recipients added to active waitlists (both first-time transplantation and re-transplantation due to graft failure).…”