Safety and tolerability of the T-cell depletion protocol coupled with anakinra and etanercept for clinical islet cell transplantation.
BACKGROUND
Islet cell transplantation (ICT) is a promising approach to cure patients with type 1 diabetes. We have implemented a new immunosuppression protocol with antithymoglobulin plus anti-inflammatory agents of anakinra and eternacept for induction and tacrolimus plus mycophenolate mofetil for maintenance [T-cell depletion with anti-inflammatory (TCD-AI) protocol], resulting in successful single-donor ICT.


METHODS
Eight islet recipients with type 1 diabetes reported adverse events (AEs) monthly. AEs were compared between three groups: first infusion with the TCD-AI protocol (TCD-AI-1st) and first and second infusion with the Edmonton-type protocol (Edmonton-1st and Edmonton-2nd).


RESULTS
The incidence of symptomatic AEs within the initial three months in the TCD-AI-1st group was less than in the Edmonton-1st and Edmonton-2nd groups, with a marginally significant difference (mean ± SE: 5.5 ± 0.3, 7.5 ± 0.5, and 8.3 ± 1.3, respectively; p = 0.07). A significant reduction in liver enzyme elevation after ICT was found in the TCD-AI-1st group compared with the Edmonton-1st and Edmonton-2nd groups (p < 0.05). Because of AEs, all patients in the Edmonton protocol eventually converted to the TCD-AI protocol, whereas all patients tolerated the TCD-AI protocol.


CONCLUSIONS
TCD-AI protocol can be tolerated for successful ICT, although this study includes small cohort, and large population trial should be taken.
Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
Morihito
M
Takita
Shinichi
S
Matsumoto
Masayuki
M
Shimoda
Daisuke
D
Chujo
Takeshi
T
Itoh
Jeffrey A
JA
Sorelle
Kerri
K
Purcell
Nicholas
N
Onaca
Bashoo
B
Naziruddin
Marlon F
MF
Levy
D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation; D008212:Lymphocyte Depletion; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*
D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept