Low dose thymoglobulin versus basiliximab in cytomegalovirus positive kidney transplant recipients: Effectiveness of preemptive cytomegalovirus modified strategy / Timoglobulina en dosis bajas vs. basiliximab en receptores de trasplante renal positivos para citomegalovirus: efectividad de una estrategia preventiva modificada

Background: We performed a retrospective trial to determine asymptomatic CMV reactivation and CMV disease in kidney allograft recipients with positive CMV serostatus. Methods: Preemptive modified strategy under low dose thymoglobulin versus basiliximab induction was evaluated. Patients were monitored by CMV-polymerase chain reaction (PCR); if the viral load was >4000copies/μl, they received valganciclovir adjusted for their renal function. Results: 132 recipients were included in the study, 84 and 48 receiving basiliximab and thymoglobulin induction respectively, and followed up for 12 months. Asymptomatic CMV reactivation was significantly higher for thymoglobulin (77.1% vs. 16.7%, p<0.001). Treatment groups had similar rates of CMV disease (3.6% vs. 2.1%, p 0.538). The significant difference in asymptomatic CMV reactivation between two treatment groups did not have any impact on 1 year graft function (71±26ml/min vs. 74±19ml/min; p=0.475) and no histological differences in protocol biopsies were observed among patients with asymptomatic CMV reactivation vs those without CMV reactivation. Conclusions: Due to the high asymptomatic CMV reactivation incidence in patients who received thymoglobulin induction, our results suggest that valganciclovir prophylaxis may be advantageous in CMV seropositive renal transplant recipients after low dose thymoglobulin induction. A preemptive strategy appeared to significantly reduce the likelihood of CMV disease in both groups. Rejection risk and negative impact in renal function associated with asymptomatic CMV reactivation was not found in our series. (AU)

Antecedentes: Llevamos a cabo un estudio retrospectivo para determinar la reactivación y enfermedad por CMV en receptores de trasplante renal CMV seropositivos bajo diferentes esquemas de inducción. Métodos: Una estrategia preventiva modificada bajo inducción con basiliximab y timoglobulina en dosis bajas fue evaluada. Se llevó a cabo un seguimiento de la carga viral-reacción de cadena de la polimerasa-CMV; los valores mayores de 4000 copias/μl recibieron valganciclovir ajustado a la función renal. Resultados: Un total de 132 receptores de trasplante renal fueron incluidos; 84 y 48 recibieron inducción con basiliximab y timoglobulina respectivamente. Seguimiento hasta el mes 12 postrasplante. La reactivación asintomática de CMV fue significativamente mayor para timoglobulina (77,1% vs. 16,7%, p<0,001). La tasa de enfermedad por CMV fue similar en ambos grupos de tratamiento (3,6% vs. 2,1%, p=0,538). Ningún impacto en la función renal un año postrasplante fue encontrado entre los grupos a pesar de la diferencia significativa en reactivación asintomática de CMV (71±26ml/min vs. 74±19ml/min; p=0,475); igualmente, no encontramos diferencias en los hallazgos histológicos en biopsias por protocolo entre receptores con reactivación asintomática por CMV y aquellos sin reactivación. Conclusiones: La alta incidencia de reactivación asintomática por CMV en receptores seropositivos a pesar del uso de bajas dosis de timoglobulina sugiere que la profilaxis con valganciclovir es una estrategia apropiada en este grupo; sin embargo, una estrategia preventiva reduce significativamente la probabilidad de enfermedad por CMV en ambos grupos de tratamiento. El riesgo de rechazo y el impacto negativo en la función renal asociado a la reactivación asintomática por CMV no fue encontrado en nuestra experiencia.

Low dose thymoglobulin versus basiliximab in cytomegalovirus positive kidney transplant recipients: Effectiveness of preemptive cytomegalovirus modified strategy.

BACKGROUND: We performed a retrospective trial to determine asymptomatic CMV reactivation and CMV disease in kidney allograft recipients with positive CMV serostatus. METHODS: Preemptive modified strategy under low dose thymoglobulin versus basiliximab induction was evaluated. Patients were monitored by CMV-polymerase chain reaction (PCR); if the viral load was >4000copies/µl, they received valganciclovir adjusted for their renal function. RESULTS: 132 recipients were included in the study, 84 and 48 receiving basiliximab and thymoglobulin induction respectively, and followed up for 12 months. Asymptomatic CMV reactivation was significantly higher for thymoglobulin (77.1% vs. 16.7%, p<0.001). Treatment groups had similar rates of CMV disease (3.6% vs. 2.1%, p 0.538). The significant difference in asymptomatic CMV reactivation between two treatment groups did not have any impact on 1 year graft function (71±26ml/min vs. 74±19ml/min; p=0.475) and no histological differences in protocol biopsies were observed among patients with asymptomatic CMV reactivation vs those without CMV reactivation. CONCLUSIONS: Due to the high asymptomatic CMV reactivation incidence in patients who received thymoglobulin induction, our results suggest that valganciclovir prophylaxis may be advantageous in CMV seropositive renal transplant recipients after low dose thymoglobulin induction. A preemptive strategy appeared to significantly reduce the likelihood of CMV disease in both groups. Rejection risk and negative impact in renal function associated with asymptomatic CMV reactivation was not found in our series.

Inducción con timoglobulina: ¿incrementa el riesgo hemorrágico en receptores renales sensibilizados? / Could thymoglobulin increase hemorrhagic risk in the perioperative transplantation period of sensitized kidney recipients?

Objetivo: Se ha descrito que la timoglobulina podría aumentar el riesgo de infecciones y neoplasias, en comparación con basiliximab. La leucocitopenia y la trombocitopenia también son más frecuentes en los primeros días tras el trasplante en los pacientes tratados con timoglobulina.Nuestro objetivo fue analizar las complicaciones hemorrágicas en este subconjunto de pacientes.Material y métodos: Se evaluaron las complicaciones hemorrágicas en 515 trasplantes renales realizados en nuestra institución entre 2012 y 2018. Se comparó a los pacientes tratados con timoglobulina (grupo 1, N=91) con los tratados con basiliximab (grupo 2, N=424).Resultados: Encontramos diferencias en cuanto al descenso plaquetario: 95.142,2 (55.339,6) en el grupo 1 y 52.364,3 (69.116,6) en el grupo 2 (p=0,001), número de pacientes con trombocitopenia grave (< 7.5000/mm3) (20,8% vs. 3,7%, p=0,001), número de concentrados de hematíes transfundidos (3,25 [0,572] vs. 2,2 [0,191], p=0,028) y porcentaje de pacientes que requirieron reintervención por sangrado (18,2% vs. 7,7%, p=0,046). En un análisis multivariable de regresión lineal múltiple (la variable dependiente fue el número de concentrado de hematíes transfundidos), solo la edad (OR 0,037, IC del 95%, 0,003-0,070) y el tipo de inmunosupresión (OR 1,592, IC del 95%, 1,38-2,84) tuvieron significación estadística.Conclusiones: El uso de timoglobulina en el período perioperatorio del trasplante podría aumentar las complicaciones hemorrágicas. En nuestra serie, la trombocitopenia grave y el sangrado activo que requirió reintervención, fueron 6 y 2,5 veces más frecuente, respectivamente, en el grupo de pacientes con timoglobulina. En lugar de suspender el uso de este agente inmunosupresor, se podría ajustar la dosis para continuar con el tratamiento.Se debe evaluar el uso de timoglobulina en el postoperatorio de estos pacientes (AU)

Objective: It has been described that thymoglobulin could increase the risk of infections and malignancies, in comparison to basiliximab. Leukopenia and thrombocytopenia are also more common within the first days after transplantation among thymoglobulin patients. Our objective was to analyze bleeding complications in this subset of patients.Material and methods: Bleeding complications were evaluated among 515 renal transplants carried out at our institution between 2012 and 2018. We compared patients treated with thymoglobulin (Group 1, N=91) with those treated with basiliximab (Group 2, N=424).Results: We found differences in platelet decrease:95142.2 (55,339.6) in Group 1 and 52,364.3 (69,116.6) in Group 2 (P=.001), number of patients with severe thrombocytopenia (<75,000/mm3) (20.8% vs. 3.7%, P=.001), number of blood units transfused (3.25 (0.572) vs. 2.2 (0.191, P=.028) and percentage of patients that required surgery due to bleeding (18.2% vs. 7.7%, P=.046). In a multiple lineal regression multivariable analysis (dependent variable was number of blood units transfused), only age [OR 0.037, 95% CI (0.003-0.070)] and type of immunosuppression [OR 1.592, 95% CI (1.38-2.84)] showed statistical significance.Conclusions: The use of thymoglobulin in the perioperative transplantation period could increase bleeding complications. In our series, in the group of patients with thymoglobulin, severe thrombocytopenia was 6 times more frequent, and active bleeding that required surgery was also 2.5 times more frequent. One way to continue with the use of this immunosuppression agent, might be to adjust the dose instead of discontinuing it. The use of thymoglobulin should be a factor to consider in the postoperative period of these patients (AU)

Could thymoglobulin increase hemorrhagic risk in the perioperative transplantation period of sensitized kidney recipients?

OBJECTIVE: It has been described that thymoglobulin could increase the risk of infections and malignancies, in comparison to basiliximab. Leukopenia and thrombocytopenia are also more common within the first days after transplantation among thymoglobulin patients. Our objective was to analyze bleeding complications in this subset of patients. MATERIAL AND METHODS: Bleeding complications were evaluated among 515 renal transplants carried out at our institution between 2012 and 2018. We compared patients treated with thymoglobulin (Group 1, N=91) with those treated with basiliximab (Group 2, N=424). RESULTS: We found differences in platelet decrease: 95,142.2 (55,339.6) in Group 1 and 52,364.3 (69,116.6) in Group 2 (P=0.001), number of patients with severe thrombocytopenia (<75,000/mm3) (20.8% vs. 3.7%, P=0.001), number of blood units transfused (3.25 (0.572) vs. 2.2 (0.191, P=0.028) and percentage of patients that required surgery due to bleeding (18.2% vs. 7.7%, P=0.046). In a multiple lineal regression multivariable analysis (dependent variable was number of blood units transfused), only age [OR 0.037, 95% CI (0.003-0.070)] and type of immunosuppression [OR 1.592, 95% CI (1.38-2.84)] showed statistical significance. CONCLUSIONS: The use of thymoglobulin in the perioperative transplantation period could increase bleeding complications. In our series, in the group of patients with thymoglobulin, severe thrombocytopenia was 6 times more frequent, and active bleeding that required surgery was also 2.5 times more frequent. One way to continue with the use of this immunosuppression agent, might be to adjust the dose instead of discontinuing it. The use of thymoglobulin should be a factor to consider in the postoperative period of these patients.

Desenlace de los pacientes pediátricos con falla medular tratados en un centro de alta complejidad / Outcomes in pediatrics patients diagnosed with bone marrow failure disorders treated in a tertiary care center

INTRODUCCIÓN: Los síndromes de falla medular (SFM) son trastornos infrecuentes, con una incidencia anual de 2-4 casos por millón. Las opciones de tratamiento incluyen terapia de inmunosupresión (TIS) y restaura ción de la hematopoyesis con trasplante de progenitores hematopoyéticas (TPH). OBJETIVO: Analizar los desenlaces de pacientes pediátricos diagnosticados con SFM tratados en una institución de alta complejidad. PACIENTES Y MÉTODO: Estudio retrospectivo de pacientes pediátricos con diagnóstico de SFM que consultaron a la Fundación Valle del Lili, Cali. Se realizo análisis estadístico descriptivo según SFM adquirida (SFMA) y SFM congénita (SFMC). Los desenlaces incluyeron: tratamiento, complicaciones, supervivencia global (SG) en los trasplantados, calculada con el método Kaplan Meier. RESULTADOS: Se incluyeron 24 pacientes con SFM, edad 6,5 ± 4 años, 50% mujeres. El 58% fue ron SFMC, 9 con anemia de Fanconi, 2 disqueratosis congénita, 2 trombocitopenia amegacariocítica congénita, uno anemia Diamond-Blackfan. Doce pacientes con TPH tuvieron SG a 5 años de 83%. SFMA correspondió al 42%, 6 recibieron TIS-TPH, 3 TIS y 1 TPH, la SG del grupo con TIS-TPH fue 86%. Seis pacientes fallecieron, 4/6 relacionadas con infección. CONCLUSIONES: En esta serie fue mayor el número de casos con SFMC. La SG de los pacientes llevados a TPH es comparable con la reportada en estudios recientes. La causa de muerte predominante fue infecciosa que también se ha reportado previamente. El tratamiento instaurado en los pacientes de esta serie mostró resultados favorables en un centro de alta complejidad en un país latinoamericano.

INTRODUCTION: Bone marrow failure (BMF) syndromes are rare disorders with an annual incidence of 2-4 cases per million. Treatment options include immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT). OBJECTIVE: To analyze the outcomes of pediatric patients diagnosed with BMF treated in a tertiary care center. PATIENTS AND METHODP: Retrospective study of pediatric patients diagnosed with BMF who consulted at Fundación Valle de Lili, Cali. Descriptive statistical analysis was performed according to Acquired BMF (ABMF) and Inherited BMF (IBMF). The outcomes include treatment, complications, overall survival (OS) in transplant patients, calculated using the Kaplan Meier method. RESULTS: We included 24 patients with BMF, average age 6.5 ± 4 years, and 50% were women. 58% presented IBMF, 9 with Fanconi anemia (FA), 2 dyskeratosis congenita, 2 congenital amegakaryocytic thrombocytopenia, and 1 presented Diamond-Blackfan anemia. 12 patients treated with HSCT had a 5-year OS of 83%. ABMF represented 42%. 6 patients received IST-HSCT, 3 received IST, and 1 received HSCT. The OS of the IST-HSCT group was 86%. Six patients died, four of them related to infection. CONCLUSIONS: In this series, there was a higher number of cases with IBMF. The OS of patients treated with HSCT is similar to that reported in recent studies. The most frequent cause of death was of infectious origin which has also been previously reported. The treatment esta blished in the patients showed favorable results in a Latin American tertiary care center.

Lymphocyte-depleting induction and steroid minimization after kidney transplantation: A review.

Steroid minimization after kidney transplantation has become more widely practiced as transplant clinicians seek the potential benefits such as reduced cardiovascular risk factors, improved growth in pediatric patients, and improved compliance with the immunosuppression regimen. Steroid avoidance (i.e. no steroids after the first week) is generally favored compared to later withdrawal. Induction therapy is routine in this setting, frequently rabbit antithymocyte globulin (rATG, Thymoglobulin®) or off-license use of alemtuzumab. Direct comparisons of steroid minimization regimens versus standard steroid regimens are rare. However, the available data show that the risk of acute rejection is low when rATG or alemtuzumab induction is given to support steroid-avoidance regimens after kidney transplantation. Steroid avoidance may be inadvisable in patients at high immunological risk or at risk of recurrent glomerular disease. Steroid withdrawal after day 8 may be possible without additional risk of rejection in patients given rATG induction, but while encouraging, the data are too sparse for firm conclusions. In summary, steroid avoidance may be beneficial for patients after renal transplantation, with the potential to avoid or reduce steroid-related comorbidities. Whilst depleting induction therapy could be the treatment of choice, results of prospective randomized, controlled studies are eagerly awaited.