Douglas Figueroa (lightloaf02)

Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are uniquely classified neoplasms occurring in both children and adults. This category consists of 5 neoplastic subtypes chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL1-negative atypical chronic myeloid leukemia (aCML), MDS/MPN-ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), and MDS/MPN-unclassifiable (U). Cytogenetic abnormalities and somatic copy number variations are uncommon; however, >90% patients harbor gene mutations. Although no single gene mutation is specific to a disease subtype, certain mutational signatures in the context of appropriate clinical and morphological features can be used to establish a diagnosis. In CMML, mutated coexpression of TET2 and SRSF2 results in clonal hematopoiesis skewed toward monocytosis, and the ensuing acquisition of driver mutations including ASXL1, NRAS, and CBL results in overt disease. MDS/MPN-RS-T demonstrates features of SF3B1-mutant MDS with ring sideroblasts (MDS-RS), with the development of thrombocytosis secondary to the acquisition of signaling mutations, most commonly JAK2V617F. JMML, the only pediatric entity, is a bona fide RASopathy, with germline and somatic mutations occurring in the oncogenic RAS pathway giving rise to disease. BCR-ABL1-negative aCML is characterized by dysplastic neutrophilia and is enriched in SETBP1 and ETNK1 mutations, whereas MDS/MPN-U is the least defined and lacks a characteristic mutational signature. Molecular profiling also provides prognostic information, with truncating ASXL1 mutations being universally detrimental and germline CBL mutations in JMML showing spontaneous regression. Sequencing information in certain cases can help identify potential targeted therapies (IDH1, IDH2, and splicing mutations) and should be a mainstay in the diagnosis and management of these neoplasms.The continuing improvement in pediatric cancer survival over time is largely attributable to the availability of intensive therapies. Increasing attention has been focused on addressing the physical and psychosocial impacts of cancer and cancer treatments. Evidence from adult oncology suggests that routine symptom screening and feedback to health care providers can improve patient-clinician communication, reduce distress, and improve quality of life and may even increase survival. Many questions remain regarding implementation of routine symptom screening in pediatric cancer care, including the best symptom assessment instrument and the reporter type and feasibility of integration with electronic health records (EHRs). Nonsymptom adverse events are also important, for both routine clinical care and adverse event reporting for patients enrolled in clinical trials. However, traditional mechanisms for reporting adverse events lead to substantial inaccuracies and are labor intensive. An automated approach for abstraction from EHRs is a potential mechanism for improving accuracy and reducing workload. Finally, identification of symptom and nonsymptom toxicities must be paired with prophylactic and therapeutic strategies. These strategies should be based on clinical practice guidelines that synthesize evidence and use multiprofessional, multidisciplinary expertise to place this evidence in clinical context and create recommendations. How best to implement clinical practice guidelines remains a challenge, but EHR order sets and alerts may be useful. In summary, although survival is excellent for pediatric patients receiving cancer therapies, more focus is needed on identification of symptoms and nonsymptom toxicities and their management. The EHR may be useful for promoting better supportive care through these mechanisms.Next-generation sequencing (NGS) of bone marrow and peripheral blood increasingly guides clinical care in hematological malignancies. NGS data may help to identify single nucleotide variants, insertions/deletions, copy number