The impact of omidubicel on immune reconstitution and infections in cord blood transplant patients.

INTRODUCTION: The success of an allogeneic hematopoietic stem cell transplantation (alloHCT) is measured by cure from the underlying malignancy, immune reconstitution (IR), and freedom from graft-versus-host disease, without the continued need for immunosuppressive therapy. AREAS COVERED: Effective IR is critical to the success of alloHCT wherein poor IR can potentially increase the risk of infection and disease relapse. Different stem cell sources give rise to varying patterns of IR. Particularly with umbilical cord blood transplant, delayed IR is commonly seen with associated increased infection rates and non-relapse mortality, attributable to low CD34+ cell doses and predominance of naïve T cells in the graft. Recent FDA approval of omidubicel, an expanded cord blood graft, was granted due to rapid hematologic recovery and a reduced incidence of high-grade infections associated with improved IR. This review focuses on IR and infections seen with omidubicel and compares those to IR after alloHCT with other graft sources. EXPERT OPINION: Characteristics of omidubicel, such as ready availability, high infused CD34+ cell dose, and rapid hematologic and immune recovery improve upon the shortcomings of standard umbilical cord blood transplantation. We feel that the data support the emergence of omidubicel as an alternative donor product.

Novel Biomarkers and Molecular Targets in ALL.

PURPOSE OF REVIEW: Acute lymphoblastic leukemia (ALL) is a widely heterogeneous disease in terms of genomic alterations, treatment options, and prognosis. While ALL is considered largely curable in children, adults tend to have higher risk disease subtypes and do not respond as favorably to conventional chemotherapy. Identifying genomic drivers of leukemogenesis and applying targeted therapies in an effort to improve disease outcomes is an exciting focus of current ALL research. Here, we review recent updates in ALL targeted therapy and present promising opportunities for future research. RECENT FINDINGS: With the utilization of next-generation sequencing techniques, the genomic landscape of ALL has greatly expanded to encompass novel subtypes characterized by recurrent chromosomal rearrangements, gene fusions, sequence mutations, and distinct gene expression profiles. The evolution of small molecule inhibitors and immunotherapies, and the exploration of unique therapy combinations are some examples of recent advancements in the field. Targeted therapies are becoming increasingly important in the treatment landscape of ALL to improve outcomes and minimize toxicity. Significant recent advancements have been made in the detection of susceptible genomic drivers and the use of novel therapies to target them.

Congenital Ewing Sarcoma Presenting as a Rapidly Growing Neck Mass in a Newborn.

BACKGROUND: Ewing sarcoma (EWS) is an aggressive soft-tissue and bone malignancy. Congenital EWS is extremely rare, and its presenting features can be unique from that of EWS occurring in older children. CLINICAL FINDINGS: A full-term female infant with a neck mass present at birth was admitted to a level I nursery with an otherwise well appearance and normal vital signs. After consultation with a neonatologist, she was transferred to a neonatal intensive care unit where she developed sudden respiratory collapse from rapid growth of the mass causing airway obstruction, leading to emergent intubation. Ultrasound and MRI scans of the neck mass demonstrated cystic and vascular components, and a timely biopsy revealed small round blue cells with diffuse CD99 expression and chromosomal translocation 11;22. PRIMARY DIAGNOSIS: Ewing sarcoma. INTERVENTIONS: An accelerated workup for EWS was done due to the patient's critical status. On day of life (DOL) 8, she was started on treatment of EWS as per the current standard-of-care AEWS0031. On DOL 24, she underwent tracheostomy placement. OUTCOMES: The patient completed 14 total cycles of chemotherapy and is more than 12 months old. Her tracheostomy was decannulated at 6 months of age. PRACTICE RECOMMENDATIONS: The rarity of EWS in neonates and its presentation as a neck mass make this disease difficult to recognize unless clinicians have a high index of suspicion. The aims of this case report are to increase awareness of malignancy as a potential cause of neck masses in neonates and to prompt nurses and physicians to prepare for airway stabilization at appropriate levels of care if a neck mass is present at birth.

Sweet and Salty: Diabetic Ketoacidosis in a Patient With Nephrogenic Diabetes Insipidus.

The co-existence of nephrogenic diabetes insipidus (NDI) with diabetes mellitus (DM) in a patient that presents in diabetic ketoacidosis (DKA) is rare and, to our knowledge, has not been described even in case reports. We report the case of a 16-year-old male with known NDI who presented to the pediatric emergency department (ED) for one day with generalized weakness and decreased appetite, found to be in moderate DKA from new-onset DM. The initial management of his dehydration and hyperosmolar state presented a unique challenge. Fluid resuscitation with isotonic fluids in a patient with NDI poses a risk of worsening hypernatremia, which can lead to seizures and death. However, the use of hypotonic fluids has the potential to lower serum osmolality too quickly, which can result in cerebral edema. Nephrology, endocrinology, and the pediatric intensive care unit (PICU) consultants were notified of this patient, and a discussion was coordinated between sub-specialists to determine the appropriate fluid resuscitation. The patient was allowed to drink free water in addition to receiving intravenous fluids (IVF) of dextrose 5% with 0.2% sodium chloride at a rate of one-and-a-half maintenance (150 mL/hr) in the ED prior to transfer to the PICU where insulin infusion was initiated. This case report provides guidance to inpatient providers on the management of patients with co-existent NDI and DM in DKA, a rare combination that requires thoughtful and urgent management.