Alemtuzumab induction in kidney transplantation: clinical results and impact on T-regulatory cells.
Alemtuzumab (ALT), a humanized monoclonal anti-CD52 antibody, was introduced in solid organ transplantation as an induction agent. ALT associated with anticalcineurins has provided a low incidence of acute rejection episodes (ARE) and potential tolerogenic properties. We analyzed the clinical outcomes and effects on peripheral Treg of renal transplant recipients treated with ALT. Six-month data on kidney alone or kidney combined with pancreas or liver patients treated with ALT and tacrolimus (TAC) in standard doses were compared with those on renal transplant recipients of similar demography who were not treated with ALT. We evaluated patient and graft survivals, ARE incidence, hematological parameters, renal function, adverse events, and CD4+CD25+FoxP3+ T cells in peripheral blood. Demographics of recipients, donors, and transplants were similar in both groups. Mean HLA mismatch was slightly greater among ALT-treated patients (3.5 vs 2.5). No combined transplantation was performed in the ALT-untreated group. Patient and graft survivals were 100% without rejection or serious infections in both groups. ALT-treated recipients showed anemia and leukopenia in 3 patients as well as severe lymphopenia in 5 recipients, who partially recovered on day 90. Final mean plasma creatinine was 1.4 mg/dL, while calculated creatinine clearance was approximately 65 mL/min in both groups. Mean Treg cell percentage was higher among ALT-treated recipients than the comparative group or healthy controls (P < .05). In conclusion, renal transplantation results obtained using ALT with rigorous immunosuppressive therapy were excellent; serious adverse events and acute rejection were absent. The effect of the increased proportion of Treg cells must be evaluated with longer observation.
Morales
J
J
Centro de Trasplante, Clínica Las Condes, Laboratoric de Inmunologia, Facutad de Ciencìas, Universidad Andrés Bello and Fundación Ciencìa para la Vida, Santiago, Santiago, Chile. jmorales@clc.cl
Bono
M R
MR
Fierro
A
A
Iñiguez
R
R
Zehnder
C
C
Rosemblatt
M
M
Calabran
L
L
Herzog
C
C
Benavente
D
D
Aguiló
J
J
Pefaur
J
J
Alba
A
A
Ferrario
M
M
Simon
W
W
Contreras
L
L
Buckel
E
E
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D018791:CD4 Lymphocyte Count; D000074301:CD52 Antigen; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007674:Kidney Diseases / Q000145:classification / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D016559:Tacrolimus