Adolescents and young adults (AYAs) vs pediatric patients: survival, risks, and barriers to enrollment.

Adolescents and young adults (AYAs; ages 15-39 years) with acute lymphoblastic leukemia (ALL) have worse outcomes than pediatric patients with ALL. Multiple factors contribute to this differential survival. AYAs are more likely to have higher-risk leukemia biology than children with ALL. AYA patients have more choices for treatment facility and treatment protocol, as well as barriers to clinical trial enrollment, both of which can affect survival. AYAs must also navigate psychosocial factors inherent to their unique developmental stage. Furthermore, AYAs typically sustain more treatment-related toxicities than pediatric patients. Treatment on pediatric or pediatric-inspired ALL protocols at pediatric cancer centers has been associated with improved outcomes for AYAs with ALL, but there is still variation in the treatment that AYAs with ALL receive. Clinical trials focused on AYAs with ALL and individualized decision-making regarding choice of treatment facility and treatment protocol are needed to optimize the survival and long-term outcomes of this patient population.

A Case of Pheochromocytoma as a Subsequent Neoplasm in a Survivor of Childhood Embryonal Rhabdomyosarcoma.

Childhood cancer survivors are at risk for subsequent neoplasms. We describe the clinical presentation and genetic testing of a 29-year-old woman diagnosed with a pheochromocytoma 22 years post-treatment for childhood embryonal rhabdomyosarcoma of the bladder. Genetic testing for cancer predisposition revealed a pathogenic variant in BRCA2 and a variant of uncertain significance in MSH2. Pathogenic variants associated with deafness were also identified in GJB2. This article reports a novel subsequent neoplasm following childhood embryonal rhabdomyosarcoma, and discusses the potential contribution of genetic cancer predisposition to this case as well as the clinical implications of genetic testing.

Reticular Dysgenesis: A Rare Immunodeficiency in a Neonate With Cytopenias and Bacterial Sepsis.

Severe combined immunodeficiency (SCID) consists of a group of disorders defined by abnormal B and T cell development that typically results in death within the first year of life if undiagnosed or untreated. Reticular dysgenesis (RD) is a rare but especially severe form of SCID that is caused by adenylate kinase 2 deficiency and is characterized not only by lymphopenia but also by profound neutropenia. RD predisposes patients to viral and fungal infections typical of SCID as well as serious bacterial infections atypical in the neonatal period in other SCID types. RD is also associated with sensorineural hearing loss not typically seen in other forms of SCID. Without rapid diagnosis and curative hematopoietic stem cell transplantation, RD is fatal within days to months due to overwhelming bacterial infection. The inclusion of the T cell receptor excision circle assay nationally in 2017 on the newborn screen has facilitated diagnosis of SCID in the neonatal period. This case reports on a male infant with RD who presented after preterm birth with severe cytopenias and a gastrointestinal anomaly and ultimately developed severe bacterial sepsis. Postmortem bone marrow evaluation and panel-based gene sequencing identifying 2 novel variants in the adenylate kinase 2 gene provided confirmation for a diagnosis of RD. This case emphasizes the importance of thorough diagnostic evaluation, including the newborn screen, in neonates and infants with persistent and unexplained cytopenias. Prompt hematology and/or immunology referral is advised for disease management and to facilitate hematopoietic stem cell transplantation to optimize long-term survival.

Late Effects in Survivors of Neonatal Cancer.

The current 5-year survival rate for cancer in infants is greater than 75% in developed countries. However, survivors of neonatal malignancies have an increased risk of late effects from their tumor or its treatment, which may lead to long-term morbidity and/or early mortality. This article reviews surgical approaches and chemotherapeutic agents commonly used in neonatal malignancies and their associated late effects. It also reviews the increased risk for late effects associated with radiation at a young age and hematopoietic stem cell transplantation at a young age.. It highlights the importance of survivor-specific multidisciplinary care in the long-term management of neonatal cancer survivors.

The association of health status and cancer history of young adult survivors of childhood cancer with parental accompaniment to survivorship clinic visits.

PURPOSE: Adult childhood cancer survivors are frequently accompanied by a parent to survivorship clinic. From clinical evaluations among young adult survivors of childhood cancer we aimed to (1) investigate the association between accompaniment and the survivors' health complexity; and (2) determine whether accompaniment is associated with adherence to recommended surveillance tests and follow-up in clinic. METHODS: This was a cross-sectional study of all patients ≥ 18 years old at their first visit to the regional Yale Childhood Cancer Survivorship Clinic from 2003 to 2018. Patients underwent standardized evaluations for medical, neurocognitive, and emotional late effects of therapy; individuals accompanying patients were documented. RESULTS: The 168 patients were a median of 12.0 (range: 0-17.9) years at diagnosis and 22.7 (range: 18.1-39.9) years at evaluation, and 45.8% were accompanied by a parent. In multivariable analyses, 18.0-24.99 years vs. 25.0-39.99 years at visit (OR = 3.43, p = 0.022) and central nervous system (CNS) tumor diagnosis (OR = 6.09 vs. leukemia/lymphoma diagnosis, p = 0.010) were significantly associated with parental accompaniment. Accompaniment was not associated with number and severity of medical late effects, neurocognitive impairment, or emotional distress. Accompaniment was not associated with completed surveillance tests or a clinic follow-up within 2 years. CONCLUSION: Forty-six percent of survivors were accompanied by a parent, and accompaniment was not associated with survivor health status. Accompaniment was not associated with adherence to recommended surveillance tests or clinic follow-up.

Early lymphocyte recovery and outcomes after umbilical cord blood transplantation (UCBT) for hematologic malignancies.

Rapid lymphocyte recovery after bone marrow or peripheral blood transplantation is associated with improved survival. However, the impact of early lymphocyte recovery has not been examined after umbilical cord blood transplant (UCBT). We evaluated lymphocyte recovery in 360 consecutive patients with hematologic malignancy that underwent UCBT between 2001 and 2007. Uniform myeloablative (MA), reduced intensity conditioning (RIC) and graft-versus-host disease prophylaxis regimens were used. In multivariate analysis, an absolute leukocyte count (ALC) >200 × 10(6)/L at day 30 (n = 73) after MA conditioning was associated with superior 2-year overall survival (OS) (73% versus 61%; P = .02) (relative risk [RR]: 2.29; 95% confidence interval [CI]: 1.15-4.56), progression-free survival (PFS) (68% versus 54%; P = .05) (RR: 1.96; 95% CI: 0.99-3.86) and less transplant-related mortality (8% versus 28%, P < .01) (RR: 4.38; 95% CI: 1.65-11.60) compared to ≤200 × 10(6)/L (n = 43). Similarly, an ALC >200 × 10(6)/L at day 42 (n = 105) after RIC was associated with superior 2-year OS (59% versus 41%, P < .01) (RR: 2.10; 95% CI: 1.3-3.41) and PFS (46% versus 36%, P = .05) (RR: 1.58; 95% CI: 1.01-2.49) compared to ≤200 × 10(6)/L (n = 55). There was no significant relationship between ALC and relapse. Rapid lymphocyte recovery early after UCBT predicts better survival in patients with hematologic malignancies.