Single-center "Argentine" analysis of post-transplant lymphoproliferative disorders: incidence, histopathological characteristics and EBV status

ABSTRACT Introduction: Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid proliferations occurring after solid organ or bone marrow transplantation. The primary aims of our study were to characterize cumulative incidence of PTLDs, clinical and pathological features according to the Epstein-Barr virus (EBV) status and survival. Methods: This was a retrospective cohort study on adult and pediatric patients, from January 2001 to December 2017. The cumulative incidence of PTLD was calculated by analyzing all the patients transplanted at our hospital, based on the database of the Organ Donation and Ablation Authority of Argentina (INCUCAI). The Kaplan-Meier method was used to plot the survival. Results: Fifty-eight cases of biopsy-confirmed PTLD were identified and 12 cases of clinical data were incomplete and these patients were excluded. The median age at the time of the PTLD diagnosis was 17.5 years (interquartile range [IQR] 9 - 57). The median interval between transplant and PTLD diagnosis was 39 months (IQR 9 - 113). The most commonly transplanted organ was the liver (24 cases, 52.2%), followed by kidney (20 cases, 43.5%). The Epstein-Barr encoding region in situ hybridization (EBER ISH) was positive in 29 (69.8%) of the 43 evaluable biopsies. The PTLD cumulative incidence was 1.84% (95%CI 1.77 - 1.91) for solid organ and 0.84% (95%CI 0.48 - 1.2) for bone marrow transplant patients. The overall survival rate at 5 years was 0.77 (95%CI 0.61 - 0.87). Subgroups by the EBV EBER status, transplant type, PTLD subtype and age group (adult vs. pediatric) showed no statistically significant association with the overall survival. Conclusion: The PTLD incidence was similar to that of previous series and the EBER did not appear as a relevant factor in our patient survival.

EBER + extranodal NK/T lymphoma in patient with idiopathic CD4 lymphocytopenia / Linfoma T/NK EBER positivo en paciente con linfocitopenia CD4 idiopática

Abstract Idiopathic CD4 lymphocytopenia (ICL) not related to HIV is an infrequent and severe condition with no etiology defined until now. The concomitant presence of an underlying disease, especially an oncohematological process, could be related to the immune physiopathology and the development of the im munosuppressive state. On the other hand, Epstein Barr virus is a well-known oncogenic pathogen described in the development of several types of lymphoma which might be reactivated in the ICL. There is still no specific treatment for this syndrome, so the therapeutic scope for these patients is the treatment of opportunistic diseases and the administration of specific antimicrobials as prophylaxis. We present a patient with an uncommon asso ciation of an ICL and an extranodal T/NK lymphoma with detection of VEB nuclear RNA by in situ hybridization (EBER). Diagnosis was challenging which led the health team to carry out many studies over several months

Resumen La linfocitopenia CD4 idiopática (ICL) no relacionada al HIV es una condición grave e infrecuente sin una etiología aún definida. La presencia de una enfermedad subyacente, especialmente un proceso oncohematológico, podría tener relación en la fisiopatología del proceso inmunológico. Por otro lado, el virus Epstein Barr (VEB) es bien conocido por ser un patógeno oncogénico descrito en el desarrollo de diversos tipos de linfomas, el cual podría ser reactivado en estados de inmunosupresión severa. No existe aún un tratamiento específico para este síndro me, por lo que el objetivo terapéutico en estos pacientes radica en el manejo profiláctico y activo de las distintas enfermedades oportunistas ante las cuales son susceptibles. Se presenta un paciente con un déficit grave de linfocitos CD4 de causa idiopática, y un diagnóstico posterior de linfoma T/NK extraganglionar con detección de RNA nuclear de VEB por hibridización in situ (EBER), una asociación poco descrita en la literatura médica.

Eritrosedimentación extremadamente elevada en una población de adultos en la ciudad de Buenos Aires / Extremely elevated erythrosedimentation in an adult population in the City of Buenos Aires

Resumen Introducción: Una velocidad de eritrosedimentación (VHS) extremadamente elevada, definida como mayor o igual a 100 mm/h, se ha asociado a condiciones graves subyacentes como enfermedades infecciosas, enfermedades del colágeno u oncológicas. Objetivo: Analizar un grupo de pacientes para determinar los diagnósticos de base y las características que se asocian con valores de VHS mayores a 100 mm/h en nuestro medio. Pacientes y Métodos: Estudio tipo observacional de corte transversal, con recolección retrospectiva de datos de pacientes adultos con al menos un valor de VHS mayor o igual a 100 mm/h, registrado en el laboratorio entre enero de 2002 y agosto de 2014 en el Hospital Italiano de Buenos Aires. Resultados: Durante el período evaluado se analizaron 879 pacientes mayores de 18 años. La mediana de los valores de VHS fue 111 mm/h (Rango intercuartil 105-120). La etiología prevalente de VHS elevada fueron las enfermedades infecciosas (41,6%), seguida de malignidad (21,6%) y de autoinmune/inflamatoria (12,9%). El diagnóstico individual más frecuente fue el de neumonía (11,4%), seguido por causa indeterminada (5,9%). Conclusión: En pacientes internados, la causa más frecuente de VHS ≥ 100 mm/h fue las enfermedades infecciosas, mientras que en pacientes ambulatorios la causa más frecuente fue la malignidad.

Background: An extremely elevated erythrosedimentation rate (ESR), defined as equal or higher than 100 mm/h, has been linked to serious underlying conditions, such as infections, connective tissue and oncologic disease. Aim: To analyze a group of patients in order to determine the underlying diagnosis and the characteristics associated with extremely elevated ESR in our environment. Methods: Cross-sectional study of adult patients, who presented with at least one ESR equal or higher than 100 mm/h at Hospital Italiano, in Buenos Aires (Buenos Aires, Argentina) between January 2002 and August 2014. Results: During the previously stated period of time, we analyzed the results of 879 patients. All patients were over 18 years of age. The median for the ESR results was 111 mm/h (interquartile range 105-120). The most prevalent etiology of an elevated ESR was infectious (41.64%), followed by malignancies (21.62%) and autoimmune / inflammatory diseases (12.97%). The most frequent individual diagnosis found was pneumonia (11.49%), followed by undetermined causes (5.92%). Conclusion: When comparing inpatient versus outpatient populations, the most frequent cause was infectious in the former group, while malignancies were the most frequent diagnosis in the latter.

Características clínicas y mortalidad de pacientes adultos con síndrome hemafagocítico, estudio de cohorte retrospectiva / Hemophagocytic lymphohistiocytosis: experience in 27 patients

Background: Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation Aim: To describe the clinical characteristics, causes and survival associated with HLH. Material and Methods: Review of medical records of patients with HLH attended between 2004 and 2016. They were classified according to their probable cause in: associated with immunosuppression, cancer, post-infectious or idiopathic. Kaplan-Meier survival analysis was performed. Results: Twenty seven patients with HLH aged 18 to 87 years (59% men), were detected. Fourteen (52%) were secondary to immunosuppression, six (22%) were post-infectious, five (18%) were associated with cancer and two (7%) were of unknown cause. There were no significant differences in clinical or laboratory features between these etiologies. Within the immunosuppressed group, 12 (86%) were patients with oncologic or hematologic diseases or bone marrow transplantation. Associated cancers were mostly oncohematologic diseases. Thirty-day mortality was 53.4% (95% confidence intervals (CI) 32.7-70.3%), despite the treatment. Mortality was significantly associated with the presence of renal failure with a hazard ratio (HR) of 3.4 (95% CI of 1.2-9.9, p =0.025). Treatment of the underlying disease proved to be protective against mortality with an HR of 0.3 (95% CI 0.1 to 0.98, p = 0.046). Conclusions: The prognosis of HLH could be related to the treatment of the underlying disease. The study of the pathophysiology of this syndrome will allow a better understanding and treatment.

Desarrollo de neoplasias e infecciones definitorias de sida después de iniciar la terapia antirretroviral de alta eficacia / Development of AIDS-related malignancies and infections after starting HAART

Con el objetivo de evaluar la incidencia de neoplasias e infecciones definitorias de Sida (NIDS) y los posibles factores asociados a su desarrollo luego de iniciada la terapia antirretroviral de alta eficacia (HAART) analizamos las historias clínicas de los pacientes que iniciaron tratamiento entre julio 2003 y octubre 2007. Todos recibieron profilaxis con trimetoprima-sulfametoxazol y azitromicina según la recomendación actual. Evaluamos el desarrollo de NIDS en los 6 meses posteriores al inicio de la terapia y su asociación con variables clínicas y epidemiológicas. Analizamos 235 historias clínicas: 118 mujeres (50.2%) y 117 hombres (49.8%). Observamos 11 casos de NIDS: 3 formas pulmonares y 3 ganglionares de tuberculosis, 3 meningitis por Criptococcus neoformans, 1 chagoma cerebral y 1 linfoma no Hodgkin. Presentar recuento de células CD4 menor a 100 o 150 células/ml se asoció con riesgo de desarrollar NIDS. La media de células CD4 fue 73 en los pacientes que desarrollaron NIDS y 143 en los que no la desarrollaron. No hubo asociación con las otras variables analizadas. En pacientes con CD4 menor a 150 células/ml observamos un caso de chagoma cerebral entre 4 con serología reactiva para Chagas, y ninguno de toxoplasmosis cerebral entre 46 con serología reactiva para toxoplasmosis. Concluimos que la tasa de incidencia de NIDS fue del 4.7%, siendo tuberculosis en primer lugar y criptococosis en segundo las enfermedades más frecuentemente observadas. Presentar bajo recuento de células CD4 se asoció de manera significativa al desarrollo de NIDS. Debería reevaluarse el rol de la quimioprofilaxis.

In order to evaluate the incidence rate and possible risk factors associated with AIDS-related malignancies and infections (ARMI) we performed data analysis of clinical charts of HIV patients in two hospital cohorts, that started high activity antiretroviral therapy (HAART) between July 2003 and October 2007. Trimethoprim-sulfamethoxazole and azytromicin prophylaxis was provided according to current guidelines. We evaluated development of ARMI six months after-starting HAART and its association with clinical and epidemiological variables. Of 235 patients analyzed -118 women (50.2%) and 117 men (49.8%)- 11 presented ARMI: 3 pulmonary TB and 3 lymph nodes TB cases, 3 cases with meningeal Cryptococcus, one Chagas' disease presenting brain mass and one with non-Hodgkin lymphoma. ARMI incidence: 4.7%. A CD4 cell count < 100/150 was associated with risk of developing ARMI. The mean CD4 cell count was 73 in patients who developed ARMI and 143 in those who did not. No association was found with the other analyzed variables. In the CD4 cell count < 150 group one out of 4 patients with reactive serology presented Chagas's disease causing brain mass; none of the 46 patients with reactive serology presented toxoplasmosis encephalitis. The incidence rate of ARMI was 4.7%. TB in first place and cryptococcosis in second were the AIDS events more frequently observed. A low CD4 cell count was the only observed risk factor statistically associated with development of ARMI. The role of prophylaxis in this population should be re-evaluated.

Características de la infección por HIV/sida según sexo en una región del Gran Buenos Aires: Períodos 1998-2002/ 2003-2005 / Characteristics of HIV infection by sex in a suburban district of Buenos Aires for the periods 1998 to 2002 and 2003 to 2005

Con el propósito de evaluar características de la infección por HIV/sida en uno de los distritos más pobres del Gran Buenos Aires, revisamos datos clínicos y epidemiológicos de las historias clínicas de los pacientes con diagnóstico reciente de infección por HIV en el hospital Dr. Diego Paroissien entre 1998 y 2005. Analizamos 524 historias clínicas, 329 (62.8%) correspondientes al período 1998-2002 y 195 (37.2%) al 2003-2005, 241 mujeres (46%) y 283 hombres (54%). El modo dominante de transmisión en las mujeres fue sexual y en los hombres el uso de drogas intravenosas. Las mujeres presentaron al momento del diagnóstico de infección por HIV, de manera estadísticamente significativa, menor estadio clínico, menor edad, mayores valores de recuento de células CD4 y menores de carga viral. No observamos diferencias entre ambos sexos en la frecuencia con que los pacientes continuaron en control clínico al año de seguimiento, iniciaron terapia antirretroviral y continuaron en tratamiento al año de haber iniciado el mismo. Comparando los períodos 1998- 2002 y 2003-2005 se determinó un aumento, estadísticamente significativo, del diagnóstico como parte del control del embarazo en la mujer, del modo primario sexual de adquisición, de la frecuencia de pacientes que continuaron en control clínico al año de seguimiento y de la disminución del uso de drogas inyectables para ambos sexos. Las diferencias de sexo observadas persisten en el período 2003-2005 cuando se excluyeron del análisis las mujeres en las que se realizó el diagnóstico como parte del control del embarazo.

With the aim of evaluating gender differences in one of the poorest districts of Buenos Aires, we reviewed epidemiological and clinical data of newly-diagnosed HIV patients at the Diego Paroissien Hospital between 1998 and 2005.We analyzed 524 clinical charts, 329 (62.8%) of which were from the 1998 to 2002 period and 195 (37.2%) from 2003 to 2005. Women accounted for 241 (46%) of the patients. The dominant mode of transmission was sexual intercourse in women and intravenous drug-use in men. At the time of diagnosis, women were at a significantly lower clinical stage, were younger, and had higher CD4 counts and lower viral loads. No gender differences were found in the rates of continued clinical care or continued antiretroviral therapy at one year follow-up. Comparing the periods 1998 to 2002 and 2003 to 2005, there was a statistically significant increase in diagnoses made during the pregnancy screening in women, in sexual transmission as the primary route of HIV infection, in the frequency of patients (both men and women) who had continued clinical care at one year follow-up, and a decreasing of intravenous drug-use in both sexes.The observed gender differences in the 2003-2005 period persisted even when those women who were diagnosed during their pregnancy screening were excluded from the analysis.