Seattle Children's, formerly Children's Hospital and Regional Medical Center, formerly Children's Orthopedic Hospital, is a children's hospital in the Laurelhurst neighborhood of Seattle, Washington. The hospital specializes in the care of infants, children, teens, and young adults aged 0–21 in several specialties.
BackgroundThere are increasing policy efforts to restrict gender-affirming care for youth, often citing concern for potential regret and poor evidence base. While previous studies show low decisional regret and high decisional satisfaction in adults following gender-affirming chest surgery, data are needed for individuals under the age of 18. The aim of this study was to compare decisional regret and decisional satisfaction following gender-affirming chest surgery between adolescents and young adults.MethodsA cross-sectional, patient-reported outcomes study was conducted at a pediatric hospital from April to July 2024. All patients met World Professional Association for Transgender Health Standards of Care surgical criteria. Eligible individuals were at least one-year postoperative from gender-affirming chest surgery. Primary outcomes were scores on the Decision Regret Scale and the revised Satisfaction with Decision scale, two validated patient-reported outcome measures. Scores were compared between adolescent (below age 18) and young adult (between ages 18-26) cohorts.ResultsOf the 77 participants who completed the survey, 42 (54.5%) underwent surgery as adolescents and 35 (45.5%) as young adults. The median (IQR) Decision Regret Scale score was 0.0 (0.0-0.0), indicating low decisional regret, and did not differ between cohorts (p = 0.23). The median (IQR) Satisfaction with Decision score was 5.0 (5.0-5.0), indicating high decisional satisfaction, and did not differ between cohorts (p = 0.40).ConclusionsAdolescents who underwent gender-affirming chest surgery had similarly low decisional regret and high decisional satisfaction compared to young adults. These results are also comparable to previously reported data in adult populations. Thus, concerns about potential regret should not be a basis for limiting gender-affirming chest procedures in adolescents.
Background:Atypical teratoid rhabdoid tumor (ATRT) is a rare pediatric central nervous system tumor with little data on the efficacy of upfront treatment strategies. This study reports prognostic factors and survival of children with newly diagnosed ATRT at high-volume centers treated as per the Children's Oncology Group trial ACNS0333. Methods:Data were collected retrospectively from 13 institutions. Included subjects were children with newly diagnosed ATRT, treated as per ACNS0333, a single-arm phase III trial of intensive chemotherapy and radiation therapy (RT). Data were analyzed to assess the prognostication of clinical variables and estimates of event-free survival (EFS) and overall survival (OS). Results:Eighty subjects were included, with a median age at diagnosis of 18 months, 70% had localized disease, and 53% underwent complete tumor resection at the time of diagnosis. Fifty patients (63%) completed all therapy phases, while 12 patients (15%) experienced progression during treatment. Fifty-three patients (66%) received post-induction consolidation with high-dose chemotherapy and stem cell rescue (HDC/SCR), and 55 (69%) received RT. The 4-year EFS and OS for the entire cohort were 49% and 53%, respectively. Patients completing all therapy phases had superior outcomes (4-year EFS: 63%; OS: 67%). Absence of disease post-induction correlated with improved outcomes (4-year EFS: 64%; OS: 70%), and patients with primary spinal cord tumors had poor outcomes despite intensive therapy. Conclusions:Children with ATRT treated as per ACNS0333 with multi-modal therapy, including HDC/SCR and RT, have improved survival compared to those treated without RT and is higher than previously reported on study.
The influence of genetic ancestry on genomics in T-cell acute lymphoblastic leukemia (T-ALL) has not been fully explored. We examined the impact of genetic ancestry on multiomic alterations, survival outcomes, and risk stratification. Among 1,309 children and young adults with T-ALL treated on the Children's Oncology Group trial AALL0434, the prognostic value of five commonly altered T-ALL genes varied by ancestry-including NOTCH1, which was associated with superior overall survival for patients of European ancestry but was nonprognostic among patients of African ancestry. Integrating genetic ancestry with published T-ALL risk classifiers, we identified that an X01 penalized Cox regression classifier stratified patients regardless of ancestry, whereas a European multigene classifier misclassified patients of certain ancestries. Overall, 80% of patients harbored a genomic alteration in at least one gene with differential prognostic impact in an ancestry-specific manner. These data demonstrate the importance of incorporating genetic ancestry into genomic risk classification. SIGNIFICANCE:There is a lack of studies examining the prognostic significance of genomic features by genetic ancestry in T-ALL, especially in non-European ancestral groups. In this study, we demonstrate how the prognostic value of individual alterations differs by genetic ancestry, warranting future studies to identify germline alleles affecting these associations. See related commentary by de Smith, p. xxx.
Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to impact overall survival (OS). The influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium (PIDTC) from 1990-2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and 79.7%, respectively. Age ≥5 years, donor type, and a pre-HCT history of severe infection had a negative impact on OS and EFS, whereas pre-HCT autoimmunity had no impact. Reduced intensity regimens were associated with lower T cell and myeloid donor chimerism, particularly when non-busulfan-based regimens were used. Low myeloid donor chimerism was associated with lower platelet counts. Mixed chimerism was not consistently associated with post-HCT autoimmunity. Patients with class I (exon 1-2 missense and intron 5 hotspot variants) and class II variants (all others) had similar pre-HCT clinical symptom severity and no difference in OS, EFS or platelet recovery post-HCT. In conclusion, our study showed excellent long-term OS and EFS following HCT for WAS, highlighting the importance of early HCT, before the development of severe infections. We confirmed that HCT using busulfan-based conditioning was associated with improved donor chimerism and platelet recovery. This study was registered at www.clinicaltrials.gov as #NCT02064933.
