Immunotherapy with anti-GD2 monoclonal antibody in infants with high-risk neuroblastoma.

Anti-GD2 monoclonal antibodies (mAb) improve the prognosis of high-risk neuroblastoma (HR-NB). Worldwide experience almost exclusively involves toddlers and older patients treated after multimodality or second-line therapies, that is, many months postdiagnosis. In contrast, at our center, infants received anti-GD2 mAbs because this immunotherapy started during or immediately after induction chemotherapy. We now report on the feasibility, safety, and long-term survival in this vulnerable age group. Thirty-three HR-NB patients were <19 months old when started on 3F8 (murine mAb; n = 21) or naxitamab (humanized-3F8; n = 12), with 30″ to 90″ intravenous infusions. Patients received analgesics and antihistamines. Common toxicities (pain, urticaria, cough) were manageable, allowing outpatient treatment. Capillary leak, posterior reversible encephalopathy syndrome, and mAb-related long-term toxicities did not occur. Two 3F8 cycles were aborted due to bradycardia (a preexisting condition) and asthmatic symptoms, respectively. One patient received ½ dose of Day 1 naxitamab because of hypotension; full doses were subsequently administered. Post-mAb treatments included chemotherapy, radiotherapy, and anti-NB vaccine. Among 3F8 patients, 17/21 are in complete remission off all treatment at 5.6+ to 24.1+ (median 13.4+) years from diagnosis. Among naxitamab patients, 10/12 remain relapse-free post-mAb at 1.7+ to 4.3+ (median 3.1+) years from diagnosis. Toxicity was similar with short outpatient infusions and matched that observed with these and other anti-GD2 mAbs in older patients. These findings were reassuring given that naxitamab is dosed >2.5× higher (~270 mg/m2 /cycle) than 3F8, dinutuximab, and dinutuximab beta (70-100 mg/m2 /cycle). HR-NB in infants proved to be highly curable.

Two Clonally Distinct B-Cell Lymphomas Reveal the Diagnosis of XLP1 in a Male Child and His Asymptomatic Male Relatives: Case Report and Review of the Literature.

X-linked lymphoproliferative disease type 1 (XLP1) is a primary immunodeficiency disorder caused by pathogenic variants in the SH2D1A gene (SH2 domain containing protein 1A). Patients with XLP1 may present acutely with fulminant infectious mononucleosis, hemophagocytic lymphohistiocytosis, and/or B-cell non-Hodgkin lymphoma (B-NHL). We report a boy who developed 2 clonally distinct B-NHL 4 years apart and was found to have previously unrecognized XLP1. The report highlights the importance of clonal analysis and XLP1 testing in males with presumed late recurrences of B-NHL, and the role of allogeneic stem cell transplant (allo-SCT) in XLP1 patients and their affected male relatives.

Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials.

ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.

Anaplastic Lymphoma Kinase Inhibitors for Therapy of Neuroblastoma in Adults.

PURPOSE: Adult-onset neuroblastoma (AON) differs significantly in biology and clinical behavior from childhood-onset disease. AON poses therapeutic challenges since tolerance of intensive multimodality therapies that are standard of care for pediatric neuroblastoma (NB) is poor. AON is enriched for somatic mutations including anaplastic lymphoma kinase (ALK), deemed to be an oncogenic driver in NB. ALK inhibitors (ALKis), therefore, have the potential to be of therapeutic benefit. The purpose of this study is to report on their use in AON. METHODS: A single-center retrospective review of adults with NB receiving ALKi (2012-2022) was performed. Response was evaluated using International Neuroblastoma Response Criteria. RESULTS: Fifteen patients with ALK-mutated AON were treated with US Food and Drug Administration-approved ALKi starting at a median age of 34 (16-71) years. Initial ALKi was lorlatinib, crizotinib, and alectinib in seven, five, and three patients respectively; seven received multiple ALKis due to progressive disease/intolerability of one agent. All patients experienced ≥grade 2 adverse events (AEs): crizotinib and alectinib were associated primarily with gastrointestinal AEs, lorlatinib with neurologic AEs, weight gain, and hyperlipidemia resulting in dose reduction or discontinuation of ALKi in several patients. No responses were observed with crizotinib (n = 5 patients), ceritinib, alectinib, or brigatinib (n = 1 each). Of the 13 patients receiving lorlatinib, four, five, and four patients had a complete or partial response (major response rate 69%), and stable disease, respectively. Responses were noted in all disease compartments; complete metabolic response was seen in two L2 patients. Ten of 13 patients remain progression-free at a median of 19 (6-50) months on lorlatinib. Three (two receiving dose-reduced therapy) had progressive disease. Median survival from start of first ALKi was 43 ± 26 months. CONCLUSION: ALKis, particularly lorlatinib, are effective treatment options for AON. However, AEs necessitating dose reduction are common.

Dolor agudo neonatal con estímulos dolorosos repetitivos, estudio randomizado comparando tres métodos analgésicos no farmacológicos / Neonatal acute pain with repetitive painful stimuli, randomized trial comparing three analgesic non pharmacological methods

Introducción: La analgesia no farmacología es raramente utilizada en las unidades de neonatología. Los estímulos dolorosos repetitivos tienen efectos negativos a largo plazo. Objetivos: Verificar que los métodos analgésicos no farmacológicos son afectivos en estímulos dolorosos repetitivos; determinar cuál método es más efectivo. Material y método; Se realice un ensayo clínica, randomizado, con tres grupos formados de manera aleatoria, con recién nacidos sanos a termino por grupo. Fueron sometidos a tres estímulos dolorosos durante los tres primero días de vida (vacuna contra hepatitis B, BCG y muestra para grupo sanguíneo). El primer grupo (A) recibió lactancia materna y contacto piel como método analgésico no farmacológico durante el estímulo doloroso, el grupo (B) recibió dextrosa al 10 por ciento y el grupo (C) una tetina sin nada. Se utilizó la escala para el Dolor Agudo Neonatal (DAN, Carbajal y col.) y la Escala ABC (Bellieni y col.) para la cuantificación del dolor. Fueron comparados los 3 grupos en cada uno de los tres estímulos repetitivos. Resultados: Para ambas escalas el grupo B expresó menor dolor en los tres estímulos, con 97,5 por ciento de NO DOLOR vs 87,5 por ciento (A) y 85 por ciento (C) (p<0.036) en la escala ABC, y 95 por ciento vs 85 por ciento (A) y 70 por ciento (C) para la categoría NO DOLOR con a categoría DAN (p<0.022). Esta diferencia se mantuvo en las otras categorías de dolor. Se observó que el efecto analgésico es mayor con el estimulo repetitivos. Siendo la categoría NO DOLOR en el grupo B para el primer estimulo 70 por ciento, 85 por ciento en el segundo y 95 por ciento en el tercero (p<0.020). Este efecto se observó también en los grupos A y C. Conclusiones: la dextrosa al 10 por ciento tuvo mayor efecto analgésico comparada con los otros grupos. Los métodos analgésicos no farmacológicos estudiados aumentan su efectividad con estimulo dolorosos repetitivos.

Introduction: Non pharmacological methods are rarely used in neonatal units. repeated painful stimuli have long noxious effects. Objective: To verify the effectiveness of non pharmacological methods in repeated painful procedures; to determine which method is more effective. Material and methods: We conducted a randomized controlled trial. Newborns were randomly assigned into 3 groups (n=40 per group). All of them underwent painful procedures during the first 3 days of life (hepatitis B, BCG and blood sample for determine group and factor). Group A received breast feeding and skin to skin contact as non pharmacological method during the painful stimuli, group B receive dextrose 10 por ciento and group C only suction. Douleur Aigue Nouveauûne scores (DAN, Carvajal et al.) and ABC scale (Bellieni et al.) were used to assess neonatal pain. The 3 groups were compared in each stimulus to determine the most effective method, and the effectiveness in repeated painful stimuli. Results: Group B showed the most analgesic effect in the stimuli, with 97, 5 percent for NO PAIN vs. 87, 5 percent (A) and 85 percent (C) (p<0,036) with ABC scale, and 95 percent vs. 85 (A) and 70 percent (C) for NO PAIN with DAN scale (p<0,022). This difference was constant with all categories of pain. We observed that analgesic effect is greater in repeated painful stimuli. NO PAIN category was 70 percent in group B in the first stimuli, 85 percent in the second and 95 percent in third (9<0,020). This effect was also observed in groups A and C. Conclusions: Dextrose 10 percent seems to offer the best analgesic effect compared with breast feeding and suction. Non pharmacological methods studied increase their effectiveness in repeated painful stimuli.