Clinical Features of Acute Kidney Injury in the Early Post-Transplantation Period Following Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative therapy for patients with hematologic malignancies but is associated with acute kidney injury (AKI). To date, few studies have examined risk factors for AKI at engraftment, or the relationship between AKI and clinical outcomes. This study examined the incidence and risk factors for periengraftment AKI, as well as the association between AKI and overall survival (OS) and nonrelapse mortality (NRM). We conducted a retrospective analysis of adult patients undergoing reduced-intensity conditioning (RIC) allogeneic HCT at the Dana-Farber Cancer Institute between 2012 and 2019. Periengraftment (day 0 to day 30) AKI incidence and severity were defined using modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Factors associated with periengraftment AKI risk were examined using Cox regression analysis. The impact of periengraftment AKI on OS and NRM (defined as death without recurrent disease after HCT), was evaluated using Cox regression and the Fine and Gray competing risks model, respectively. Kidney recovery, defined as a return of serum creatinine (SCr) to within 25% of baseline or liberation from kidney replacement therapy (KRT), was examined at day 90 post-HCT. Periengraftment AKI occurred in 330 of 987 patients (33.4%) at a median of 13 days (interquartile range, 4 to 30 days) post-transplantation. Factors associated with a higher multivariable-adjusted risk of AKI were supratherapeutic rapamycin (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.20 to 2.03; P < .001), fludarabine/melphalan conditioning (HR, 1.35, 95% CI, 1.01 to 1.81; P = .05, compared to fludarabine/busulfan and fludarabine, cyclophosphamide, and total body irradiation), HCT Comorbidity Index ≥4 (HR, 1.43; 95% CI, 1.14 to 1.79; P = .002), albumin <3.4 g/dL (HR, 2.04; 95% CI, 1.33 to 3.12; P = .001), hemoglobin ≤12 (HR, 1.96; 95% CI, 1.38 to 2.78; P < .001), supratherapeutic tacrolimus (HR, 1.45; 95% CI, 1.07 to 1.95; P = .02), and baseline SCr >1.1 mg/dL (HR, 1.87; 95% CI, 1.48 to 2.35; P < .001). Periengraftment AKI was associated with worse OS (HR, 1.40; 95% CI, 1.16 to 1.71; P < .001) and NRM (subdistribution HR, 2.10; 95% CI, 1.52 to 2.89; P < .001). Kidney recovery occurred in 18%, 15%, and 30% of patients with stage 1, stage 2, and stage 3 AKI without KRT, respectively, and 4 of 16 patients (25%) were liberated from KRT. Periengraftment AKI is common among RIC allogeneic HCT recipients. We identified several important risk factors for periengraftment AKI. Its association with worse OS and NRM underscores the importance of timely recognition and management.

Expansion, persistence, and efficacy of donor memory-like NK cells infused for posttransplant relapse.

BackgroundResponses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell-based therapy is a promising modality to treat post-HCT relapse.MethodsWe initiated this ongoing phase I trial of adoptively transferred cytokine-induced memory-like (CIML) NK cells in patients with myeloid malignancies who relapsed after haploidentical HCT. All patients received a donor-derived NK cell dose of 5 to 10 million cells/kg after lymphodepleting chemotherapy, followed by systemic IL-2 for 7 doses. High-resolution profiling with mass cytometry and single-cell RNA sequencing characterized the expanding and persistent NK cell subpopulations in a longitudinal manner after infusion.ResultsIn the first 6 enrolled patients on the trial, infusion of CIML NK cells led to a rapid 10- to 50-fold in vivo expansion that was sustained over months. The infusion was well tolerated, with fever and pancytopenia as the most common adverse events. Expansion of NK cells was distinct from IL-2 effects on endogenous post-HCT NK cells, and not dependent on CMV viremia. Immunophenotypic and transcriptional profiling revealed a dynamic evolution of the activated CIML NK cell phenotype, superimposed on the natural variation in donor NK cell repertoires.ConclusionGiven their rapid expansion and long-term persistence in an immune-compatible environment, CIML NK cells serve as a promising platform for the treatment of posttransplant relapse of myeloid disease. Further characterization of their unique in vivo biology and interaction with both T cells and tumor targets will lead to improvements in cell-based immunotherapies.Trial RegistrationClinicalTrials.gov NCT04024761.FundingDunkin' Donuts, NIH/National Cancer Institute, and the Leukemia and Lymphoma Society.

Experiencia de embolización de la arteria renal previa a nefrectomía / Experience of Renal Artery Embolization Prior to Nephrectomy

Resumen Objetivo: Describir la evolución perioperatoria de pacientes sometidos a nefrectomía con y sin embolización de la arteria renal (EAR) prequirúrgica, en un hospital de alta complejidad de Medellín, Colombia. Materiales y Métodos: Observacional descriptivo retrospectivo; se incluyeron pacientes de 18-90 años con diagnóstico de tumor renal, sometidos a nefrectomía con y sin EAR prequirúrgica. Las variables cualitativas se expresaron por medio de frecuencias y proporciones, y las cuantitativas mediante medidas de tendencia central y dispersión. Resultados: Se incluyeron 71 pacientes con una media de edad de 58,1 (DE: 10,6) años, 41 eran mujeres y el 69% tenía diagnóstico de carcinoma de células claras. La media del volumen de sangrado intraoperatorio fue de 540,8 cc, y 19,7% requirió transfusión. El tiempo quirúrgico promedio fue de 2,6 horas y el 38% presentó alguna complicación, con una mortalidad total del 4,2%. Al observar comparativamente los pacientes con EAR (15 pacientes) versus aquellos sin ella (56 pacientes), se identificó un mayor volumen de sangrado intraoperatorio y la necesidad de transfusión en los primeros. Conclusión: Los pacientes sometidos a EAR presentaron un mayor volumen de sangrado, mayor frecuencia de transfusión y complicaciones postoperatorias, siendo necesario un consenso sobre su real pertinencia terapéutica.

Abstract Aim: To describe the perioperative outcomes of patients undergoing nephrectomy with and without preoperative Renal Artery Embolization (RAE) in a high-complexity hospital in Medellín, Colombia. Materials and Methods: Retrospective, descriptive and observational study; 18-90 years old patients with renal tumor diagnosis, submitted to nephrectomy with and without preoperative RAE were included. Qualitative variables were expressed by measures of frequencies and proportions, and quantitative variables were expressed by measures of central tendency and dispersion. Results: 71 patients with a media age of 58,1 (SD: 10,6) years were included, 41 were women and 69% were diagnosed with clear cell carcinoma. The blood loss volume media was 540.8 cc, and 19.7% required transfusion. The operative time media was 2.6 hours and 38% had any complication, with a total mortality of 4.2%. Comparatively observing patients with RAE (15 patients) versus patients without RAE (56 patients), a higher intraoperative blood loss and transfusion requirements were identified in the first ones. Conclusion: Patients submitted to RAE presented greater volume of bleeding, greater frequency of transfusion and post-operative complications, requiring a consensus on its real therapeutic relevance.

Síndrome de Budd-Chiari: etiología, manejo y resultados en una cohorte de 35 pacientes del Hospital Pablo Tobón Uribe / Budd-Chiari Syndrome: Etiology, management, and outcomes in a study of 35 patients at the Hospital Pablo Tobón Uribe

Resumen El síndrome de Budd-Chiari (Budd-Chiari syndrome, BCS) es una entidad rara, definida por la obstrucción del flujo venoso del hígado y corresponde a una condición heterogénea tanto en presentación como en manejo terapéutico. A continuación, presentamos un estudio retrospectivo de pacientes con diagnóstico de BCS, atendidos por el grupo de hepatología del el Hospital Pablo Tobón Uribe. Los resultados se expresan como proporciones en las variables categóricas y como medias y rangos para las variables continuas. La edad promedio de presentación fue de 37,7 años y no hubo preponderancia por el género. Los principales síntomas fueron dolor abdominal (91,4 %), ascitis (71,4 %) y hepatomegalia (60 %). Asimismo, 11 pacientes (31,4 %) presentaron hipercoagulabilidad primaria, mientras que en 7 (20 %) se encontró algún síndrome mieloproliferativo. Además, 6 (17,1 %) tenían neoplasias extrahepáticas: 3 con compresión mecánica y 3 por hipercoagulabilidad asociada; solo en 1 caso se documentaron membranas en la vena cava inferior. Y en 5 casos no fue posible determinar la causa de trombosis. De igual forma, 32 pacientes (91,4 %) recibieron anticoagulación como primer manejo; solo 4 sujetos fueron remitidos a procedimientos: 2 a angioplastia, 1 a derivación portosistémica intrahepática transyugular (Transjugular Intrahepatic Portosystemic Shunt, TIPS) y 1 a trasplante ortotópico hepático (TOH). Luego de ello, 17 (48,5 %) recibieron procedimientos invasivos como segunda línea: 8 (22,8 %) se condujeron a angioplastia y endoprótesis (stent), 5 (14,29 %) a TIPS y 4 necesitaron TOH. Así, los 6 pacientes que se llevaron a TIPS no necesitaron trasplante hepático. El BCS continúa siendo una condición poco frecuente que afecta la salud de personas jóvenes, tanto hombres como mujeres, con una presentación clínica heterogénea. Sin embargo, en la mayoría de los casos ocurre por una causa desencadenante clara, entre las cuales predominan las trombofilias y los síndromes mieloproliferativos. El uso de medidas terapéuticas invasivas, especialmente de la selección temprana de los enfermos que se benefician de TIPS, ha cambiado la historia natural y el pronóstico de este grupo de pacientes.

Abstract Budd-Chiari syndrome (BCS) is a rare disorder characterized by the obstruction of the veins of the liver. Both its presentation and therapeutic management are heterogenous. The following is a retrospective study of patients diagnosed with BCS treated by the hepatology service at the Hospital Pablo Tobón Uribe. The results of the categorical variables are expressed as proportions and the continuous variables as means and ranges. The average age of onset of this disease was 37.7 years and it was not predominant in neither sex. The most common symptoms were abdominal pain (91.4%), ascites (71.4%) and hepatomegaly (60%). Out of 35 patients, 11 (31.4%) had primary hypercoagulability, 7 (20%) had some myeloproliferative disorder, 6 (17.1%) had extrahepatic malignancies -3 with mechanical compression and 3 due to associated hypercoagulability-, and 1 case had a membranous obstruction of the inferior vena cava. 32 patients (91.4%) received anticoagulation as first-line therapy and only 4 were taken to surgery: 2 to angioplasty, 1 to transjugular intrahepatic portosystemic shunt (TIPS) and 1 to orthotopic liver transplantation (OLT). On the other hand, 17 (48.5%) individuals underwent invasive procedures as a second-line therapy, of which 8 (22.8%) underwent angioplasty and stenting, 5 (14.29%) underwent TIPS and 4 needed OLT. The 6 patients who were taken to TIPS did not need liver transplants. Budd-Chiari syndrome remains a rare condition affecting the health of young men and women alike, with a heterogeneous clinical presentation but, in most cases, with a clear trigger where thrombophilic and myeloproliferative disorders predominate. The use of invasive therapeutic measures, especially the early selection of patients who may benefit from TIPS, has changed the natural course and prognosis of this group of patients.

Caracterización, manejo y pronóstico de una cohorte de pacientes cirróticos con carcinoma hepatocelular. Hospital Pablo Tobón Uribe 2012-2018 / Characterization, management and prognosis of a cohort of cirrhotic patients with hepatocellular carcinoma. Pablo Tobón Uribe Hospital 2012-2018

Introducción. El carcinoma hepatocelular (CHC) en los pacientes con cirrosis hepática es una indicación frecuente de trasplante de hígado y una causa de muerte por diagnóstico tardío. El objetivo de este estudio fue describir las características demográficas, clínicas y de laboratorio de pacientes con CHC sobre hígado cirrótico, así como el estadio al momento del diagnóstico, el manejo ofrecido y la supervivencia en función del estadio, según la clasificación BCLC. Metodología. Estudio observacional de cohorte retrospectiva que incluyó pacientes atendidos en un centro en Colombia entre el 1 de enero de 2012 y el 31 de diciembre de 2018, mayores de 18 años con hepatocarcinoma. La recolección de la información se realizó a partir de la revisión de historias clínicas. Para el análisis estadístico se utilizó SPSS versión 23.0. Resultados. En el estudio se incluyeron 219 pacientes con CHC y cirrosis hepática de base. El 58,9% fueron de sexo masculino y la mediana de edad fue de 65 años. La distribución etiológica de la cirrosis para alcohol, esteatohepatitis no alcohólica (NASH), criptogénica, infección por virus de la hepatitis B y C fue de 30,6%, 21,4%, 19,1%, 12,2% y 7,7%, respectivamente. El 49,3% tenían clasificación Child-Pugh A, el 37% B y el 13,7% C, al momento del diagnóstico. La clasificación del estadio BCLC se distribuyó así: 0=4 (1,8%), A=94 (42,9%), B=26 (11,9%), C=39 (17,8%) y D=56 (25,6%). La supervivencia, de acuerdo con la clasificación BCLC, fue para BCLC 0=60 meses, A=84,6 meses, B=28,7 meses, C=10,7 meses y para BCLC D=7 meses. Conclusión. A pesar de encontrarse una mejor supervivencia en esta serie, en comparación con la hallada en otra serie realizada en nuestro centro en 2009, y similar a lo reportado en el mundo, el diagnóstico tardío continúa siendo la principal causa de mortalidad en los pacientes con CHC.

Introduction. Hepatocellular carcinoma (HCC) in patients with liver cirrhosis is a frequent indication for liver transplantation and a cause of death if not diagnosed promptly. The aim of this study was to describe the demographics, and clinical and laboratory characteristics of patients with HCC in a cirrhotic liver, as well as the stage at the time of diagnosis, type of treatment offered, and survival, according to BCLC classification. Methodology. Retrospective observational cohort study, which included patients treated at a center in Colombia between January 1 2012 and December 31 2018, aged ≥18 years, with hepatocarcinoma. Information was collected from medical records. Collected data was analyzed using SPSS 23.0. Results. We included 219 patients with HCC and underlying liver cirrhosis. Males were 58.9% and median age was 65 years. Etiological distribution of cirrhosis for alcohol, non-alcoholic steatohepatitis (NASH), cryptogenic, and hepatitis B and C viral infection was 30.6%, 21.4%, 19.1%, 12.2% and 7.7%, respectively. At diagnosis, 49.3% had Child-Pugh A score, 37% B and 13.7% C. BCLC classification was distributed as follows: 0=4 (1.8%), A=94 (42.9%), B=26 (11.9%), C=39 (17.8%) and D=56 (25.6%). Survival, according to BCLC classification, was for BCLC 0=60 months, A=84.6 months, B=28.7 months, C=10.7 months and for BCLC D=7 months. Conclusion. Despite finding better survival in this series, compared to that found in another series from our center in 2009, and similar to that reported worldwide, a delayed diagnosis continues to be the main cause of mortality in patients with HCC.