EXPERIENCE WITH ALEMTUZUMAB IN KIDNEY TRASPLANTATION Nestor Pedraza, Yenny Baez, Fernando Giron Transplant Surgeons Colombiana de Trasplantes Bogota, Colombia

INDUCTION THERAPY

INTRODUCTION Campath-1H is a humanized monoclonal antibody directed against CD52 glycoprotein expressed in approximately 95% of lymphocyte in peripheral blood; CD52 is not present in granulocytes, platelets, erythrocytes, or hematopoietic stem cells Its mechanism of action includes complement-mediated cytolysis, antibody-mediated cytotoxicity and apoptosis

MATERIALS AND METHODS Descriptive study of a prednisone-free immunosuppression protocol for kidney transplant recipients who received alemtuzumab as induction agent

p < 0,05 (yates corrected) STATISTICAL ANALYSES EPI INFO v 1.6 p < 0,05 (yates corrected)

GROUP 1

MATERIALS AND METHODS 100 patients received kidney transplant from living or cadaveric donor San Rafael Clinic and Marly Clinic Recipients > 14 y.o. Follow-up Time: 1 year Induction: Alemtuzumab 30 mg IV

IMMUNOSUPRESION AND MEDICAL THERAPEUTICS Pre-medication Clemastine 2 mg and acetaminophen 1 g Methylprednisolone 500mg, 250mg, 125mg Manteinance Anticalcineurinic Inhibitor. Target levels CSA C2 400-600 ng/ml TAC C0 5-7 ng/ml MMF (1500 mg/d) or Mycophenolic acid (MPA) (1080 mg/d)

PROPHYLAXIS Cephalosporin first or second generation Valganciclovir 450 mg qd for 3 months Nistatine 1 million U tid for 2 months Trimethoprim-sulfamethoxazole 480 mg 2x/week for 6 months

DEMOGRAPHICS CHARACTERISTICS Age M: 38.5 m: 36.5 38.54 +/- 23 years Range 15 – 68 years Gender (M:F) 56% : 44% Donor Source Cadaveric Living 94% 6% Pediatric recipients n: 100

* ACUTE REJECTION TIME (month) INCIDENCE CUMULATIVE RATE 1 0 % 3 4 % 6 5 % 9 % 12 8 % 17 % * All ACR were biopsy proven

REJECTION TYPE n = 17 Banff 1 a 9 (53%) Banff 1 b 6 (35%) Banff 2 a 1 (6%) Banff 2 b Banff 3 Humoral

INFECTIOUS COMPLICATIONS INFECTIONS 23% UTI 20% OTHERS INFECTIONS 3%

CONCLUSIONS Alemtuzumab may be given as a single dose, low cost, easy administration and allow to use prednisone-free immunosuppression Acute rejection for the first month was 0% A raise in acute rejection incidence after 3rd month Most acute rejections were mild

WHAT DID WE BELIEVE? Higher rate of later rejection ( 3-6 month) reflects inadequate maintenance immunosuppression exposure when lymphocyte repopulation would be anticipated

GROUP 2

MATERIALS AND METHODS 100 patients received kidney transplant from living or cadaveric donor San Rafael and Marly Clinic Recipients >14 y.o. Follow-up Time: 1 year Induction: Alemtuzumab 30 mg IV

IMMUNOSUPRESION AND MEDICAL THERAPEUTICS Pre-medication Clemastine 2 mg and acetaminofen 1 g Methylprednisolone 500mg, 250mg, 125mg Manteinance Anticalcineurinic Inhibitor. Target levels CSA C2 400-600 ng/ml TAC C0 5-7 ng/ml

MANTEINANCE IMMUNOSUPPRESSION Manteinance changes INCREASE MMF OR MPA: FULL DOSE 2 g or 1.4 g/day since 3rd month

PROPHYLAXIS Cephalosporin first or second generation Valganciclovir 450 mg qd for 3 months Nistatine 1 million U tid for 2 months Trimethoprim-sulfamethoxazole 480 mg 2x/week for 6 months

DEMOGRAPHICS CHARACTERISTICS Group 1 Group 2 * Age M: 38.5 m: 36.5 38.54 +/- 23 years M: 39.45 m: 40.5 39.45 +/- 25 years Range 15 – 68 years 14 – 63 years Gender (M:F) 56% : 44% 58% : 42% Donor Source Cadaveric Living 94% 6% 86% 14% Pediatric recipients 3% * p> 0,65

* ACUTE REJECTION TIME (month) INCIDENCE CUMULATIVE RATE 1 0 % 3 5 % 6 1 % 6 % 12 2 % 8 % * All ACR were biopsy proven

REJECTION TYPE n = 8 Banff 1 a 3 (37,5%) Banff 1 b Banff 2 a 1 (12,5%) Banff 3 Humoral

INFECTIOUS COMPLICATIONS INFECTIONS 11% UTI 9% OTHERS INFECTIONS 2%

CONCLUSIONS

ACUTE REJECTION INCIDENCE p< 0,04 o.r. 0,12 (0,01 – 0,94)

ACUTE REJECTION CUMULATIVE RATE % Incidence p< 0,05 o.r. 0,37 (0,13 – 0,95)

The increase in the maintenance immunosuppression regimen after third month is related with the reduction of acute rejection in kidney transplant