Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community.

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell transplant physicians have united their expertise to explore the potential of menin inhibitors in pediatric leukemia treatment internationally. Our efforts aim to provide a comprehensive clinical overview of menin inhibitors, integrating preclinical evidence and insights from ongoing global clinical trials. Additionally, we propose future international, inclusive, and efficient clinical trial designs, integrating pediatric populations in adult trials, to ensure broad access to this promising therapy for all children and adolescents with menin-dependent leukemias.

Biological Markers of High-Risk Childhood Acute Lymphoblastic Leukemia.

Childhood acute lymphoblastic leukemia (ALL) has witnessed substantial improvements in prognosis; however, a subset of patients classified as high-risk continues to face higher rates of relapse and increased mortality. While the National Cancer Institute (NCI) criteria have traditionally guided risk stratification based on initial clinical information, recent advances highlight the pivotal role of biological markers in shaping the prognosis of childhood ALL. This review delves into the emerging understanding of high-risk childhood ALL, focusing on molecular, cytogenetic, and immunophenotypic markers. These markers not only contribute to unraveling the underlying mechanisms of the disease, but also shed light on specific clinical patterns that dictate prognosis. The paradigm shift in treatment strategies, exemplified by the success of tyrosine kinase inhibitors in Philadelphia chromosome-positive leukemia, underscores the importance of recognizing and targeting precise risk factors. Through a comprehensive exploration of high-risk childhood ALL characteristics, this review aims to enhance our comprehension of the disease, offering insights into its molecular landscape and clinical intricacies in the hope of contributing to future targeted and tailored therapies.

Coronavirus Disease 2019 in Pediatric Oncology Patients: A Matched-Cohort Analysis of the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry.

BACKGROUND: There is a paucity of multicenter data describing the impact of coronavirus disease 2019 (COVID-19) on hospitalized pediatric oncology patients. Using a large, multicenter, Society of Critical Care Medicine (SCCM) Discovery Viral Infection and Respiratory Illness University Study (VIRUS) database, we aimed at assessing outcomes of COVID-19 infection in this population. METHOD: This is a matched-cohort study involving children below 18 years of age hospitalized with COVID-19 between March 2020 and January 2021. Using the VIRUS; COVID-19 Registry database, children with oncologic diseases were compared with propensity score matched (age groups, sex, race, and ethnicity) cohort of children without oncologic diseases for the prevalence of Multisystem Inflammatory Syndrome in Children (MIS-C), intensive care unit (ICU) admission, interventions, hospital, and ICU length of stay. RESULTS: The number of children in the case and control groups was 45 and 180, respectively. ICU admission rate was similar in both groups ([47.7 vs 51.7%], P =0.63). The proportion of children requiring noninvasive and invasive mechanical ventilation, and its duration were similar between groups, same as hospital mortality. Interestingly, MIS-C was significantly lower in the oncology group compared with the control (2.4 vs 24.6%; P =0.0002). CONCLUSIONS: In this study using a multicenter VIRUS database, ICU admission rate, interventions, and outcomes of COVID-19 were similar in children with the oncologic disease compared with control patients. The incidence of MIS-C is lower in oncologic patients.

Stroke in Pediatric Cancer Patients: A Systematic Review.

OBJECTIVE: Pediatric cancer patients have an increased risk of stroke. However, there is a knowledge gap regarding stroke in early stages of pediatric cancer. The objective of this project is to describe the current knowledge on stroke in pediatric cancer patients. DESIGN: Systematic review. MATERIALS AND METHODS: After Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, literature search was conducted in PubMed, Cochrane, and Google Scholar from January 1, 1995, up to February 1, 2022. RESULTS: A total of 3499 studies were identified, of which 8 met inclusion criteria. The incidence of stroke in pediatric cancer patients varied between 0.47% and 2.9%, and prevalence between 1% and 3%. The risk factors identified were leukemia diagnosis, cranial radiation, thrombocytopenia, coagulopathy, and infection. There was a higher rate of diagnosis with magnetic resonance imaging than with computed tomography scan. Treatment was inconsistent, and patients with cancer were less likely to receive antithrombotic treatment when compared with patients without cancer. The highest mortality was among hemorrhagic stroke. Recurrence rate was 5% to 19%. CONCLUSIONS: The risk for stroke is increased in the pediatric cancer population and can lead to devastating results. The available reports include few patients, with heterogeneous cancer diagnoses and outcomes. Large-scale multicenter studies are needed, focusing on early diagnosis, risk factors, and management strategies of stroke in children with underlying cancer.

Decompressive Hemicraniectomy and Favorable Outcome in a Pediatric Patient with Malignant Middle Cerebral Artery Infarction.

We report a rare case of middle cerebral artery (MCA) stroke in a teenage girl with initial improvement, followed by progression to malignant MCA infarction, requiring an urgent decompressive hemicraniectomy (DHC). Additionally, we report improvement in all areas, including language, comprehension, and motor skills at discharge and the 4-month follow-up. This rare presentation highlights the importance of monitoring the neurological status of a patient with an MCA infarct for progression to a life-threatening malignant MCA infarct. This case report also highlights the importance of consideration of DHC for a favorable outcome of the MMCA infarction.

Congenital Syphilis and the Prozone Phenomenon: Case Report.

Congenital syphilis represents an important public health challenge in the United States, and its prevalence has been increasing for the past 10 years because of many factors. The diagnosis can be difficult given its various and nonspecific clinical manifestations in newborns, and the possibility of false negative results during prenatal care. The prozone phenomenon, caused by an excess of antibody, which interferes with the regular screening tests, is a cause of false negative tests. This could delay the diagnosis and increase morbidity and mortality in the newborn. We present a case of congenital syphilis in a 3-month-old infant whose mother had prenatal care and negative tests for syphilis, which contributed to the late diagnosis. In the face of clinical findings suggestive of congenital syphilis and negative maternal syphilis tests healthcare providers should consider the possibility of maternal false negative test caused by the prozone phenomenon.