Kinetics of humoral deficiency in CART19-treated children and young adults with acute lymphoblastic leukaemia.

CD19-CAR T-cell therapy (CART19) causes B-cell aplasia (BCA) and dysgammaglobulinemia but there is a lack of information about the degree of its secondary immunodeficiency. We conducted a prospective study in children and young adults with acute lymphoblastic leukaemia treated with CART19, analysing the kinetics of BCA and dysgammaglobulinemia during therapy, as well as the B-cell reconstitution in those with CART19 loss. Thirty-four patients were included (14 female) with a median age at CART19 infusion of 8.7 years (2.9-24.9). Median follow-up after infusion was 7.1 months (0.5-42). BCA was observed 7 days after infusion (3-8), with persistence at 24 months in 60% of patients. All patients developed a progressive decrease in IgM and IgA: 71% had undetectable IgM levels at 71 days (41-99) and 13% undetectable IgA levels at 185 days (11-308). Three of 12 patients had protective levels of IgA in saliva. In two of three patients who lost CART19, persistent B-cell dysfunction was observed. No severe infections occurred. In conclusion, BCA occurs soon after CART19 infusion, with a progressive decrease in IgM and IgA, and with less impairment of IgA, suggesting the possibility of an immune reservoir. A persistent B-cell dysfunction might persist after CART19 loss in this population.

Outcome and toxicities associated to chemotherapy in children with acute lymphoblastic leukemia and Gilbert syndrome. Usefulness of UGT1A1 mutational screening.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most frequent cancer in childhood. Although intensive chemotherapy has improved survival in those patients, important side effects, including hyperbilirubinemia, are frequent. Gilbert syndrome (GS) is a frequent condition that causes a reduction in glucuronidation and intermittent hyperbilirubinemia episodes. This could provoke a greater exposure to some cytotoxic agents used in ALL, increasing the risk of toxicity. On the other hand, unexplained hyperbilirubinemia could lead to unnecessary modifications or even treatment withdrawals, which could increase the risk of relapse, but data regarding this in ALL pediatric population are scarce. METHODS: Retrospective study to analyze toxicity, outcome and treatment modifications related to GS in children diagnosed with ALL. RESULTS: A total of 23 of 159 patients were diagnosed with GS. They had statistically higher hyperbilirubinemias during all treatment phases (P < 0.0001) and a slower methotrexate clearance when it was administered during a 24-hr infusion at high doses (patients with GS: 74 hr ± 19 vs. patients without GS: 64 hr ± 8; P < .002). However, no relevant toxicity or delays in treatment were found in them. Finally, changes in treatment due to hyperbilirubinemia were only done in 5 patients with GS. CONCLUSIONS: Differences in outcome were not found in patients with GS. Universal screening for GS appears to be not necessary in pediatric patients with ALL. However, when hyperbilirubinemia is observed, it must be rule out in order to avoid unnecessary changes in treatment.

Revisión y evaluación de las maniobras de reanimación cardiopulmonar en un servicio de urgencias / Review and evaluation of cardiopulmonary resuscitation in an emergency department

Introducción: La baja incidencia de parada cardiorrespiratoria (PCR) en niños ha motivado la creación de registros de datos que permiten valorar las medidas implantadas para poder compararlas y extraer conclusiones. El objetivo de este trabajo era conocer la experiencia del personal de un servicio de urgencias pediátricas (SUP) en la atención de las PCR, describir las medidas de reanimación cardiopulmonar (RCP) empleadas y su evaluación. Métodos: Estudio retrospectivo de las historias clínicas y del registro «tipo Utstein», durante 10 años (2001-2010), de los pacientes a quienes el personal del SUP realizó maniobras de RCP. Resultados: Se analizaron 49 episodios de RCP correspondientes a 46 pacientes (28 varones, con una mediana de edad de 2,1 años). Presentaban alguna enfermedad crónica 28 pacientes. La PCR y la etiología neurológica fueron el motivo de aviso y la causa más frecuente, respectivamente. Se encontraban en medio extrahospitalario 21 pacientes, y se iniciaron maniobras de RCP en 13. En 44 episodios se intubó al paciente, en 35 se realizó masaje cardiaco externo y en 33 se administraron fármacos. En 13 pacientes no se consiguió la recuperación de la circulación espontánea (RECE). La mediana de tiempo de RCP fue de 30 minutos, y resultó superior en los pacientes en quienes no se consiguió la RECE (45 frente a 15 min; p= 0,03). Otros 12 pacientes fallecieron durante el ingreso posterior a la PCR. El personal del SUP consideró mejorables las maniobras de RCP realizadas en 12 de los 43 episodios evaluados. Conclusiones: La realización de RCP por parte del personal del SUP es poco frecuente. La mayoría de los pacientes estaban en PCR en el momento de ser atendidos, por lo que requirieron la realización de RCP avanzada. El personal del SUP evaluó las maniobras de RCP realizadas en 43 casos, y las consideró correctas en 31, mejorables en 10 y deficientes en 2 episodios (AU)

Introduction: The low incidence of cardiac arrest (CA) in children has prompted the creation of data records that allow assessing the measures implemented for comparison and extract conclusions. The aim of this study was to determine the experience of the staff of a pediatric emergency department (PED) in the care of the CA and describe the steps used during the cardiopulmonary resuscitation (CPR) and their evaluation. Methods: A retrospective study of medical records and registration "Utstein type" of patients that PED staff performed CPR for 10 years (2001-2010). Results: We analyzed 49 episodes of CPR corresponding to 46 patients (28 male; median age 2.1 years). Chronic illness was suffered by 28 patients. CA and neurological etiology were the reason for notice and the most frequent cause respectively. They were out-of-hospital 21 patients and initiated CPR in 13. In 44 episodes the patients were intubated, in 35 external cardiac massage was performed and in 33 drugs were administered. In 13 patients recovery was not achieved spontaneous circulation (RSC). Median RCP time was 30 minutes, being higher in patients not able RSC (45 vs 15 min; p= 0.03). Another 12 patients died during hospitalization after the CA. PED staff considered improvable CPR performed in 12 of the 43 episodes that were evaluated. Conclusions: Performing CPR by PED staff is rare. Most patients were in CA at the time of being served requiring advanced CPR. PED staff evaluated CPR performed in 43 cases, considered correct in 31, improved in 10 and poor in 2 patients (AU)