Recommendations for screening, monitoring, prevention, and prophylaxis of infections in adult and pediatric patients receiving CAR T-cell therapy: a position paper.

Chimeric antigen receptor (CAR) T-cell therapy is one of the most promising emerging treatments for B-cell malignancies. Recently, two CAR T-cell products (axicabtagene ciloleucel and tisagenlecleucel) have been approved for patients with aggressive B-cell lymphoma and acute lymphoblastic leukemia; many other CAR-T constructs are in research for both hematological and non-hematological diseases. Most of the patients receiving CAR-T therapy will develop fever at some point after infusion, mainly due to cytokine release syndrome (CRS). The onset of CRS is often indistinguishable from an infection, which makes management of these patients challenging. In addition to the lymphodepleting chemotherapy and CAR T cells, the treatment of complications with corticosteroids and/or tocilizumab increases the risk of infection in these patients. Data regarding incidence, risk factors and prevention of infections in patients receiving CAR-T cell therapy are scarce. To assist in patient care, a multidisciplinary team from hospitals designated by the Spanish Ministry of Health to perform CAR-T therapy prepared these recommendations. We reviewed the literature on the incidence, risk factors, and management of infections in adult and pediatric patients receiving CAR-T cell treatment. Recommendations cover different areas: monitoring and treatment of hypogammaglobulinemia, prevention, prophylaxis, and management of bacterial, viral, and fungal infections as well as vaccination prior and after CAR-T cell therapy.

[Hepatotoxicity in healthy infants exposed to nevirapine during pregnancy]. / Hepatotoxicidad en el lactante sano expuesto a nevirapina durante el embarazo.

BACKGROUND: The use of nevirapine in HIV-infected pregnant women is discouraged due to its potential to cause hepatotoxicity. There is limited information available on the toxicity in non-HIV infected newborn exposed to this drug during pregnancy. The aim of the study is to determine the extent of hepatotoxicity in the newborn exposed to nevirapine and HIV during pregnancy. METHODS: A cross-sectional, observational, multicenter study was conducted on a cohort of healthy infants born to HIV-infected mothers, in whom the first determination of alanine aminotransferase (ALT), before 6weeks of age, was collected. Patients were allocated to 2groups according to exposure to nevirapine during pregnancy. Hepatotoxicity was rated according to the AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). RESULTS: This study included 160newborns from 159pregnancies (88exposed to nevirapine-based regimens and 71 exposed to protease inhibitors-based therapies). No cases of hepatotoxicity were observed according to the DAIDS Table for Grading. Two cases of ALT above normal values (2.8%; 95%CI: 0.3-9.8%) were observed in patients not exposed to nevirapine, and one case (1.1%; 95%CI: 0.0-6.1%) in the group exposed to nevirapine (P=.585). CONCLUSION: The lack of differences between groups suggests that highly active antiretroviral treatment regimens including nevirapine administered during pregnancy do not involve a higher risk of liver disease compared to other treatment combinations.

Antiviral Treatment and Risk of Hearing Loss in Asymptomatic and Mild Symptomatic Infants With Congenital Cytomegalovirus.

BACKGROUND: To assess hearing outcomes at 24 months of age in infants with mild congenital cytomegalovirus (cCMV) infection, depending on whether they have received antiviral treatment or not. METHODS: A retrospective study within the European Registry of Children with cCMV was performed. Included children had cCMV diagnosed in utero/in the first 21 days of life, with normal physical examination, alanine aminotransferase <80 U/L and platelets >100,000 cs/mm3 and absence of hearing loss (HL) at birth. Cranial ultrasound (cUS) and/or cranial magnetic resonance imaging was normal or with minor findings (isolated lenticulostriate vasculopathy and/or germinolysis/caudothalamic or subependymal cysts, and/or focal/multifocal white matter involvement). The main outcome was the presence of HL at 24 months of age. RESULTS: One hundred ninety-six patients met inclusion criteria. A total of 34.7% received antiviral treatment with valganciclovir/ganciclovir. Children treated had lower gestational age, birth weight and head circumference, and maternal primary infection was less frequent. Among treated children, 21.3% presented minor findings in cUS versus 6.3% in nontreatment group (P = 0.003). Nine patients (4.6%) developed HL at 24 months. Among children with HL, 20% presented minor findings in cUS versus 11.3% in non-HL group (P = NS). HL rate was similar in treated and nontreated groups (4.6% vs. 6.3%; P = 0.6). CONCLUSIONS: One-third of the children were treated with antivirals and infants with minor neuroimaging findings at birth were more likely to receive antiviral. There were no differences in the prevalence of HL at 2 years of age between treated and not-treated children. Minor neuroimaging findings were not clearly associated with an increased risk of delayed onset HL.

Double-Blind, Placebo-Controlled Study of Bezlotoxumab in Children Receiving Antibacterial Treatment for Clostridioides difficile Infection (MODIFY III).

BACKGROUND: Therapies to prevent recurrence of Clostridioides difficile infection (CDI) in pediatric patients are needed. Bezlotoxumab is a fully human monoclonal antibody approved for prevention of recurrent CDI in adults. We assessed the pharmacokinetics, safety, tolerability, and efficacy of bezlotoxumab in pediatric patients. METHODS: MODIFY III was a multicenter, double-blind, placebo-controlled study of bezlotoxumab in children (1 to <18 years) receiving antibacterial treatment for CDI. Participants were randomized 3:1 to receive a single infusion of bezlotoxumab (10 mg/kg) or placebo and were stratified by age at randomization (cohort 1: 12 to <18 years, cohort 2: 1 to <12 years). The primary objective was to characterize bezlotoxumab pharmacokinetics to support dose selection for pediatric patients; the primary endpoint was the area under the bezlotoxumab serum concentration-time curve (AUC0-inf). Safety, tolerability, and efficacy were monitored for 12 weeks post-infusion. RESULTS: A total of 148 participants were randomized and 143 were treated: 107 with bezlotoxumab and 36 with placebo (cohort 1 n = 60, cohort 2 n = 83; median age 9.0 years); 52.4% of participants were male and 80.4% were white. Geometric mean ratios (90% CI) for bezlotoxumab AUC0-inf were 1.06 (0.95, 1.18) and 0.82 (0.75, 0.89) h * µg/mL for cohorts 1 and 2, respectively. Bezlotoxumab 10 mg/kg was generally well-tolerated with an adverse event profile similar to placebo, including no treatment discontinuations due to adverse events. CDI recurrence was low and comparable for bezlotoxumab (11.2%) and placebo (14.7%). CONCLUSIONS: The results of this study support the bezlotoxumab dose of 10 mg/kg for pediatric patients. TRIAL REGISTRATION: NCT03182907 at ClinicalTrials.gov.

Hepatotoxicidad en el lactante sano expuesto a nevirapina durante el embarazo / Hepatotoxicity in healthy infants exposed to nevirapine during pregnancy

INTRODUCCIÓN: En nuestro medio, el uso de nevirapina en la embarazada infectada por el VIH se desaconseja por su potencial hepatotoxicidad. Existen pocos datos sobre dicha toxicidad en el neonato no infectado por el VIH y expuesto a este fármaco durante la gestación. Se pretende determinar el grado de hepatotoxicidad en el recién nacido expuesto a nevirapina y VIH durante la gestación. MÉTODOS: Estudio transversal observacional multicéntrico en una cohorte de recién nacidos hijos de madre VIH positivas no infectados en los que se revisó la primera determinación de alanina aminotransferasa antes de las 6 semanas de vida. Se establecieron 2 grupos según hubieran estado expuestos o no a nevirapina durante la gestación. La hepatotoxicidad se clasificó según el AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). RESULTADOS: Se incluyeron 160 recién nacidos de 159 gestaciones (88 expuestos a tratamientos combinados con nevirapina y 71 a inhibidores de proteasa). No se observó ningún caso de hepatotoxicidad según laGrading Table del DAIDS, pero se registraron 2 casos de ALT superior a los valores de normalidad (2,8%, IC 95%: 0,3-9,8) en los no expuestos a nevirapina y uno (1,1%, IC 95%: 0,0-6,1) en el grupo expuesto (p = 0,585). CONCLUSIONES: La ausencia de diferencias entre ambos grupos sugiere que los regímenes de tratamiento antirretroviral de gran actividad que incluyen nevirapina durante la gestación no asocian un riesgo aumentado de hepatopatía en el lactante con respecto a otros regímenes

BACKGROUND: The use of nevirapine in HIV-infected pregnant women is discouraged due to its potential to cause hepatotoxicity. There is limited information available on the toxicity in non-HIV infected newborn exposed to this drug during pregnancy. The aim of the study is to determine the extent of hepatotoxicity in the newborn exposed to nevirapine and HIV during pregnancy. METHODS: A cross-sectional, observational, multicenter study was conducted on a cohort of healthy infants born to HIV-infected mothers, in whom the first determination of alanine aminotransferase (ALT), before 6 weeks of age, was collected. Patients were allocated to 2 groups according to exposure to nevirapine during pregnancy. Hepatotoxicity was rated according to the AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS). RESULTS: This study included 160 newborns from 159 pregnancies (88 exposed to nevirapine-based regimens and 71 exposed to protease inhibitors-based therapies). No cases of hepatotoxicity were observed according to the DAIDS Table for Grading. Two cases of ALT above normal values (2.8%; 95% CI: 0.3-9.8%) were observed in patients not exposed to nevirapine, and one case (1.1%; 95% CI: 0.0-6.1%) in the group exposed to nevirapine (P = .585). CONCLUSION: The lack of differences between groups suggests that highly active antiretroviral treatment regimens including nevirapine administered during pregnancy do not involve a higher risk of liver disease compared to other treatment combinations

Infeccions de transmissió sexual en els adolescents / No disponible

No disponible