RESUMO
BACKGROUND: Studies show that alemtuzumab, a potent lymphocyte-depleting agent, is well tolerated in pediatric renal transplantation. We report on the use of alemtuzumab induction in highly HLA sensitized (HS) pediatric kidney transplant patients. METHODS: Fifty pediatric renal transplants were performed from 1/2009-12/2014. 15 HS patients received IVIG (2 g/kg ×2 doses)/rituximab (375 mg/m ×1) for desensitization with alemtuzumab induction (15-30 mg, 1 dose, subcutaneous), whereas 35 nonsensitized patients received anti-IL-2R. Graft survival and infections were compared between 2 groups. RESULTS: All HS patients had received a prior transplant and were older with lower risk for viral infections due to serostatus. Patient survival was 100%, and graft outcomes were similar with mean 1-year creatinine of 1.03 ± 0.45 versus 0.99 ± 0.6 (P = 0.48). Although a higher incidence of acute cellular rejection was seen in HS patients receiving alemtuzumab (P = 0.001), there was a nonsignificant difference in antibody-mediated rejection. White blood cell and absolute lymphocyte count were significantly lower in alemtuzumab group at 30 days (P < 0.0001) and at 1 year (P = 0.026 and P = 0.001), respectively. There was no significant difference in bacterial, viral, or fungal infections after transplant. CONCLUSIONS: Alemtuzumab induction with desensitization led to nearly equivalent graft survival and functional outcomes in HS pediatric patients as nonsensitized patients receiving anti-IL-2R induction. With this small sample size, we observed significant reduction of white blood cell and absolute lymphocyte count up to 1 year posttransplant. The risk of infection was comparable between the 2 groups; however, patients who received alemtuzumab were older and at lower risk of viral infection due to serostatus.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Antígenos HLA/imunologia , Histocompatibilidade , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Depleção Linfocítica/métodos , Adolescente , Fatores Etários , Alemtuzumab , Anticorpos Monoclonais Humanizados/efeitos adversos , Biomarcadores/sangue , Criança , Dessensibilização Imunológica/efeitos adversos , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Humanos , Hospedeiro Imunocomprometido , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/efeitos adversos , Isoanticorpos/sangue , Estimativa de Kaplan-Meier , Transplante de Rim/mortalidade , Contagem de Linfócitos , Depleção Linfocítica/efeitos adversos , Masculino , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Estudos Retrospectivos , Fatores de Risco , Rituximab/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Viral infections represent significant morbidity and mortality factors in kidney transplant recipients, with CMV, EBV, and BKV infections being most common. Desensitization (DES) with IVIg and rituximab with/without plasma exchange followed by kidney transplantation with alemtuzumab induction increased successful transplant rates in HLA-sensitized patients but may represent an increased risk for viral infections due to severe lymphocyte depletion. Here, we report on the posttransplant viral infection status in 372 DES versus 538 non-DES patients. CMV and EBV viremia were significantly lower in DES patients, while BKV viremia was similar. This trend was observed primarily in CMV sero(-), EBV sero(+), and sero(-) patients. No patient developed PTLD. The incidence of BKAN, allograft, and patient survival was similar in both groups. These viral infections were not associated with subsequent allograft rejection which occurred within 6 months after the infection. Conclusions. The IVIg + rituximab desensitization combined with alemtuzumab induction with triple immunosuppression maintenance does not increase the risk for CMV, EBV, and BKV infections. Possible factors include, in addition to posttransplant antiviral prophylaxis and PCR monitoring, presence of memory T cells and antibodies specific to CMV and likely EBV, NK cell-mediated ADCC despite lymphocyte depletion, elimination of EBV and CMV reservoirs by rituximab and alemtuzumab, and use of IVIg with antiviral properties.
Assuntos
Infecções por Citomegalovirus , Dessensibilização Imunológica , Infecções por Vírus Epstein-Barr , Antígenos HLA , Transplante de Rim , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alemtuzumab , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Vírus BK , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/prevenção & controle , Infecções por Vírus Epstein-Barr/virologia , Antígenos HLA/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Rim/imunologia , Depleção Linfocítica , Infecções por Polyomavirus/tratamento farmacológico , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Rituximab/uso terapêutico , Transplantados , Transplante Homólogo , Viremia/tratamento farmacológico , Viremia/imunologia , Viremia/prevenção & controleRESUMO
BACKGROUND: Global immunosuppression can be measured by assessing adenosine triphospate (ATP) levels in mitogen-stimulated CD4+ T cells. METHODS: We investigated the effect of storage time on ATP levels in 234 blood samples from 18 healthy individuals and 152 transplant patients. The difference between day 0 (<13 hours post-blood draw) and day 1 (24-37 hours) measurements was analyzed and compared with various factors; a subset of samples was also analyzed in 6-hour intervals. RESULTS: The ATP levels were significantly lower on day 1 compared with that on day 0 in healthy individuals (279±159 vs 414±159 ng/mL, P<0.001) and patients (356±209 vs 455±221 ng/mL, P<0.0001). Of the 18 healthy individuals, 17 showed ATP reduction, whereas 192 (89%) of 216 patients did so on day 1 (24.8±24.1%). In the time course analysis, ATP levels decreased with the blood storage time in healthy and patient samples, and the reduction began as early as 7 hours post-blood draw. The reduction rate was significantly higher in patient samples with low day 0 ATP levels compared with samples with moderate or high levels (44.7±31.3% vs 23.2±23.6% or 18.7±15.7%; P<0.001). The reduction rate in patients treated with alemtuzumab induction was slightly higher than that in daclizumab-treated patients (28.8±24.6% vs 21.3±21.3%, P=0.09). CD4+ cell number did not change within 24 hours post-blood draw, but CD4 expression decreased 2.0±2.8% (P<0.05). CONCLUSIONS: The ATP levels are significantly lower in 1-day-old blood compared with fresh blood, suggesting that fresh blood should be used for assessing the T cell immune function to obtain the most accurate results.