Alemtuzumab induction in pediatric kidney transplantation

Abstract

Recipient parenchymal lymphatic cells are crucial for direct and indirect pathways of allorecognition. We proposed that alemtuzumab, being infused several weeks pretransplant could eradicate peripheral lymphatic cells and promote donor-specific tolerance. We present here a single center, retrospective review of 101 consecutive living-donor kidney transplantations to pediatric patients aged from seven month to 18 yr, performed between September 2006 and April 2010. Immunosupression protocol included two 30 mg doses of alemtuzumab: first given 12-29 d prior to transplantation and second at the time of transplantation. Maintenance immunosupression was based on combination of low dose and wide range CNI and mycophenolate. Patients were followed for 3.8 ± 1.4 yr and protocol biopsies were taken one month, one, and three yr post transplant. The Kaplan-Meier graft and patient survival was 96% and 97% for one yr, 89% and 93% for three yr. Biopsy proven acute rejection developed in 26% patients at one yr and in 35% at two yr, no rejections occurred beyond two yr. We conclude that alemtuzumab pretreatment prior to living related donor kidney transplantation allows to reach satisfactory middle-term results in pediatric patients with wide range and low CNI concentrations.

Fig. 1

Evolution of maintenance immunosuppression.

Fig. 2

(a) Acute rejection in 101 alemtuzumab treated patients; (b) patients stratified by time of transplantation. Incidence of clinical rejection depicted by dotted lines. (c) Mean Banff scores for chronic interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, chronic fibrointimal thickening, and chronic glomerulopathy.

Fig. 3

(a) Positive nucleic acid tests regardless of viral bodies concentrations. (b) BK viruria more than 10⁷ copies/mL and CMV of 10³ or more copies/mL – generally accepted as “dangerous” viral loads – considered as positve.

Fig. 4

(a) Tacrolimus treated patients at the time of sampling. Positive nucleic acid tests regardless of viral load, as a function of time on tacrolimus. (b) Tacrolimus treated patients at the time of sampling. BK viruria more than 10⁷ copies/mL and CMV of 10³ or more copies/mL – generally accepted as “dangerous” viral loads – considered as positve.

Fig. 5

(a) Cyclosporine treated patients at the time of sampling. Positive nucleic acid tests regardless of viral load, as a function of time on cyclosporine. (b) Cyclosporine treated patients at the time of sampling. BK viruria more than 10⁷ copies/mL and CMV of 10³ or more copies/mL – generally accepted as “dangerous” viral loads – considered as positve.

Fig. 6

(a) CNI-free patients at the time of sampling. Positive nucleic acid tests regardless of viral load, as a function of time without CNI. (b) CNI-free patients at the time of sampling. BK viruria more than 10⁷ copies/mL and CMV of 10³ or more copies/mL – generally accepted as “dangerous” viral loads – considered as positve.