Epstein-Barr virus-associated risk factors for post-transplant lymphoproliferative disease in pediatric liver transplant recipients.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) are the most common de novo malignancies after liver transplantation (LT) in children. The aim of our study was to assess the role of pre-LT EBV status and post-LT EBV viral load as risk factors for developing PTLD in a cohort of pediatric LT recipients. METHODS: Data of all children who underwent LT between January 2002 and December 2019 were collected. Two cohorts were built EBV pre-LT primary infected cohort and EBV post-LT primary infected cohort. Moreover, using the maximal EBV viral load, a ROC curve was constructed to find a cutoff point for the diagnosis of PTLD. RESULTS: Among the 251 patients included in the study, fifteen PTLD episodes in 14 LT recipients were detected (2 plasmacytic hyperplasia, 10 polymorphic PTLD, 2 monomorphic PTLD, and 1 Classical-Hodgkin's lymphoma). Patients of the EBV post-LT primary infected cohort were 17.1 times more likely to develop a PTLD than patients of the EBV pre-LT primary infected cohort (2.2-133.5). The EBV viral load value to predict PTLD was set at 211 000 UI/mL (93.3% sensitivity and 77.1% specificity; AUC 93.8%; IC 0.89-0.98). In EBV post-LT primary infected cohort, patients with a viral load above 211 000 were 30 times more likely to develop PTLD than patients with a viral load below this value (OR 29.8; 3.7-241.1; p < 0.001). CONCLUSIONS: The combination of pretransplant EBV serological status with EBV post-transplant viral load could be a powerful tool to stratify the risk of PTLD in pediatric LT patients.

Kaposi sarcoma in a child after hematopoietic stem cell transplantation: Should pre-transplant HHV-8 screening be considered in recipients from high prevalence areas?

Kaposi sarcoma (KS) is an angioproliferative disease associated with human herpesvirus 8 (HHV-8). We report the case of a 10-year-old male from a high HHV-8 prevalence area, diagnosed with severe aplastic anemia who underwent an upfront hematopoietic stem cell transplantation (HSCT). Five months after transplant, the patient was diagnosed with KS with skin, mucosae, lymph nodes and lung involvement. After withdrawal of immunosuppression the patient achieved complete remission without requiring further treatments. KS may occur after HSCT in patients from high HHV-8 prevalence areas. Considering that, we propose that screening of HHV-8 by antibody testing could be considered in HSCT donors/recipients from these areas.

Congenital infection of SARS-CoV-2 in live-born neonates: a population-based descriptive study.

OBJECTIVE: To evaluate the evidence of mother-to-child transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This is a descriptive, multicentre, observational study in nine tertiary care hospitals throughout Spain. The study population was women with coronavirus disease 2019 during pregnancy. Mother-to-child transmission was defined as positive real-time RT-PCR of SARS-CoV-2 in amniotic fluid, cord blood, placenta or neonatal nasopharyngeal swabs taken immediately after birth. RESULTS: We included 43 women with singleton pregnancies and one with a twin pregnancy, as a result we obtained 45 samples of placenta, amniotic fluid and umbilical cord blood. The median gestational age at diagnosis was 34.7 weeks (range 14-41.3 weeks). The median interval between positive RT-PCR and delivery was 21.5 days (range 0-141 days). Fourteen women (31.8%, 95% CI 18.6%-47.6%) were positive at the time of delivery. There was one singleton pregnancy with SARS-CoV-2 RT-PCR positive in the placenta, amniotic fluid and umbilical cord blood (2.2%, 95% CI 0.1%-11.8%). Nasopharyngeal aspiration was performed on 38 neonates at birth, all of which were negative (0%, 95% CI 0%-9.3%). In 11 neonates the nasopharyngeal aspiration was repeated at 24-48 hours, and one returned positive (9.1%, 95% CI 0.2%-41.3%). CONCLUSIONS: The presence of SARS-CoV-2 in placenta, amniotic fluid and cord blood shows that mother-to-child transmission is possible but uncommon.

Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies.

A chromosomal region that includes the gene encoding HER2, a receptor tyrosine kinase (RTK), is amplified in 20% of breast cancers. Although these tumors tend to respond to drugs directed against HER2, they frequently become resistant and resume their malignant progression. Gene amplification in double minutes (DMs), which are extrachromosomal entities whose number can be dynamically regulated, has been suggested to facilitate the acquisition of resistance to therapies targeting RTKs. Here we show that ~30% of HER2-positive tumors show amplification in DMs. However, these tumors respond to trastuzumab in a similar fashion than those with amplification of the HER2 gene within chromosomes. Furthermore, in different models of resistance to anti-HER2 therapies, the number of DMs containing HER2 is maintained, even when the acquisition of resistance is concomitant with loss of HER2 protein expression. Thus, both clinical and preclinical data show that, despite expectations, loss of HER2 protein expression due to loss of DMs containing HER2 is not a likely mechanism of resistance to anti-HER2 therapies.