Efficacy of basiliximab in the treatment of 87 cases of steroid-refractory or steroid-dependent acute graft-versus-host disease / 中华血液学杂志

Objective: To evaluate the efficacy and prognosis of basiliximab in the treatment of steroid-refractory or steroid-dependent acute graft-versus-host disease (SR/SD-aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Clinical data of 87 patients with SR/SD-aGVHD in the skin, intestine, and liver after allo-HSCT at the Institute of Hematology & Blood Diseases Hospital Transplantation Center from January 2015 to December 2018 were retrospectively analyzed. The administration plan of basiliximab was as follows: 20 mg for adults and children weighing ≥35 kg and 10 mg for children weighing<35 kg. The drug was administered once on the 1st, 4th, and 8th days, respectively, and then once weekly. The efficacy was evaluated on the 7th, 14th, 21st, and 28th days after basiliximab treatment. Results: ①There were 51 males (58.6%) and 36 females (41.4%) , with a median (range) age of 34 (4-63) years. There were 54 cases of classic aGVHD, 33 of late aGVHD, 49 of steroid-refractory aGVHD, and 38 of steroid-dependent aGVHD. ②Thirty-five patients (40.2%) achieved complete remission (CR) , 23 (26.4%) achieved partial remission (PR) , and 29 had no remission (NR) . The total effective rate[overall response rate (ORR) ] was 66.7% (58/87) . ③The ORR of the classic and late aGVHD groups was 77.8% (42/54) and 48.5% (16/33) , respectively. ④The median (range) follow-up time was 154 (4-1813) days, the 6-month overall survival (OS) rate of the 87 patients was 44.8% (95% CI 39.5%-50.1%) and the 1-year OS was 39.4% (95%CI 34.2%-44.3%) . ⑤After treatment with basiliximab, the 6-month OS in the CR (35 cases) , PR (23 cases) , and NR (29 cases) groups was 80.0% (95%CI 73.2%-86.8%) , 39.1% (95%CI 28.9%-49.3%) , and 6.9% (95%CI 2.2%-11.6%) , respectively (χ(2)=34.679, P<0.001) , and the 1-year OS was 74.3% (95%CI 66.9%-81.7%) , 30.4% (95%CI 20.8%-40.0%) , and 3.4% (95%CI 0%-6.8%) , respectively (χ(2)=43.339, P<0.001) . The OS of the classic and late aGVHD groups was 57.4% (95%CI 50.7%-64.1%) and 24.2% (95%CI 16.7%-31.7%) , respectively (χ(2)=9.109, P=0.004) , and the 1-year OS was 51.9% (95%CI 45.1%-58.7%) and 18.2% (95%CI 11.5%-24.9%) , respectively (χ(2)=9.753, P=0.003) . ⑥Univariate and multivariate analyses showed that late aGVHD (OR=3.121, 95%CI 1.770-5.503, P<0.001) , Minnesota score high-risk group before medication (OR=3.591, 95%CI 1.931-6.679, P<0.001) , active infection before medication (OR=1.881, 95%CI 1.029-3.438, P=0.040) , and impairment of important organ function caused by non-GVHD (OR=3.100, 95%CI 1.570-6.121, P=0.001) were independent risk factors affecting the efficacy of basiliximab. Conclusion: Basiliximab has good efficacy and safety for SR/SD-aGVHD, but not in patients with late aGVHD, high-risk group of Minnesota score, and infection or impaired function of important organs.

Hallazgos histológicos en biopsia por protocolo asociados con reducción en función renal 12 meses postrasplante, en receptores de trasplante renal con bajo riesgo inmunológico, recibiendo inducción con basiliximab / Histological findings in protocol biopsy associated with reduction in renal function 12 months post transplant in renal transplant recipients with low immunological risk

Resumen Introducción: identificar los factores asociados con pérdida de la función del injerto puede ser un paso importante hacia la prolongación de la sobrevida del injerto renal. Objetivo: determinar la asociación entre los cambios histológicos presentes en las biopsias por protocolo, en el primer año postrasplante en receptores de bajo riesgo inmunológico, recibiendo inducción con basiliximab y pérdida en la función del injerto 12 meses postrasplante. Métodos: se incluyeron pacientes receptores de riñones de donante cadavérico (95 %) o donante vivo (5 %) trasplantados entre agosto de 2007 y julio de 2012. El desenlace primario fue pérdida en la tasa de filtración glomerular calculada (Cockroft & Gault) mayor a 5ml/min 12 meses postrasplante, en comparación con la función renal previa a la biopsia por protocolo. Resultados: la cohorte de estudio estuvo conformada por 114 pacientes, de los cuales 25 presentaron el desenlace principal. Los hallazgos asociados con pérdida de función fueron glomerulitis (p=0,024), inflamación intersticial (p=0,001), tubulitis (p=0,001), capilaritis (p=0,001), glomerulitis + capilaritis (p=0,001), nefropatía por polioma virus (p=0,04) y la presencia de rechazo subclínico (p=0,015). Por análisis de regresión logística la presencia de inflamación intersticial (OR = 2,11; IC 95 %: 1,13-3,95) y capilaritis (0R=7,12; IC 95 %:1,57-32,27) fueron las variables asociadas con pérdida de función del injerto renal 12 meses postrasplante renal. Conclusión: la inflamación intersticial y capilaritis son variables histológicas asociadas con pérdida de función del injerto renal, 12 meses postrasplante, independiente de otras variables.

Abstract Introduction: Identifying factors that are associated of allograft function loss might be an important step toward prolonging kidney allograft survival. Purpose: In this study we found to determine the association between histologic changes on 1-year surveillance biopsies and changes in graft function. Methods: Recipients of kidneys from deceased donors (95%) or living donors (5%) trasplanted between 2007 and 2012. The primary end point was reduction in calculated glomerular filtration rate (Cockroft anf Gault) higher 5ml/min 12 months post transplant vs calculated glomerular filtration rate previous surveillance biopsie. Results: This analysis included 114 adults, recipients of kidneys with low immunological risk receiving basiliximab induction from deceased donors (95%) or living donors (5%), transplanted between august 2007 and july 2012. The primary end point was reduction in calculated glomerular filtration rate (Cockroft & Gault) higher 5ml/min 12 months post trasplant. 25 of 114 patientes showing reduction; The histologic changes associated with renal function reduction were glomerulitis (p=0,024), interstitial inflamation (p=0,001), tubulitis (p=0,001), capilaritis (p=0,001), glomerulitis + capilaritis (p=0,001), polyoma virus nephropathy (p=0,04) and subclinical rejection (p=0,015). By regression analyses, interstitial inflamation (OR = 2,11; IC 95%: 1,13-3,95) and capilaritis (0R=7,12; IC 95%: 1,57-32,27) were associated with renal function reduction 12 month post-transplant. Conclusion: inflammation and capilaritis in protocol biopsies in first year post-transplant predict loss of graft function and independently of other variables.

Effect of cyclosporine and simulect mono and combination therapy on cardiac allo-transplantation in rats / 中南大学学报(医学版)

OBJECTIVE@#To observe the effect of cyclosporine and simulect mono or combination therapy on cardiac allo-transplantation in rats.@*METHODS@#Recipients with allografts were treated with different doses of cyclosporine and/or simulect after cardiac allo-transplantation. Graft survival time was observed; the histopathological examination of graft tissues was performed; and levels of serum IL-2 and IL-4 were determined.@*RESULTS@#Mono or combination therapy with cyclosporine and/or simulect increased the survival of cardiac allografts. With the prolongation of survival time of the grafts, the rejection of grafts was moderated. The serum IL-2 level increased in acute rejected grafts; the serum IL-4 level increased evidently in long survival grafts.@*CONCLUSION@#Cyclosporine and simulect have an effect in the prolongation of cardiac allograft survival in rats, and the combination therapy shows an evident synergistic effect.