Characterisation of children and adolescents with acute lymphoblastic leukaemia who presented without peripheral blood blasts at diagnosis.

Of 1003 children with acute lymphoblastic leukaemia (ALL), 147 (14.7%) presented without peripheral blood blasts (PBB). While absence of PBB was not independently associated with survival outcomes when compared to those with PBB, patients without PBB had distinct genetic and clinical characteristics. Notably, we identified a novel genotype-phenotype relationship, in that the patients without PBB had a significantly higher incidence of hyperdiploid B-ALL, accounting for almost half of all patients without PBB (46.9% vs. 22.7%, p < 0.001). Further, absence of PBB was associated with decreased rates of leukaemia involvement of the central nervous system (p < 0.001).

Fusion-negative rhabdomyosarcoma with diffuse bony metastases and remarkable chemosensitivity.

In this report, we describe the case of an adolescent male with an unusual case of fusion-negative, paratesticular alveolar rhabdomyosarcoma who presented with spontaneous tumour lysis syndrome and diffuse bony metastases throughout the axial and appendicular skeleton with additional significant bone marrow involvement. Both spontaneous tumour lysis syndrome and diffuse bony metastases are extremely unusual for rhabdomyosarcoma. On the backbone of standard vincristine, dactinomycin and cyclophosphamide (VAC) chemotherapy, the only local control was orchiectomy at 15 weeks, with no radiation administered due to the initially diffuse nature of the disease and rapid response to chemotherapy. Following 43 weeks of VAC, a year-long maintenance phase with pazopanib was given which was well tolerated. The patient remains in remission now 4 years after completion of therapy.

The two-hit hypothesis in practice: Monozygotic twins with simultaneous hyperdiploid acute lymphoblastic leukemia.

Approximately 25% of B-cell acute lymphoblastic leukemia (B-ALL) cases are defined by hyperdiploidy, with RAS mutations occurring in 30% of hyperdiploid B-ALL patients. It is believed that hyperdiploidy is an in utero event with RAS mutations occurring postnatally, but clinical evidence of this is based on relatively few patients. We present a case of monozygotic, monochorionic twins who developed concordant hyperdiploid B-ALL with identical chromosomal gains but different RAS mutations, adding further evidence that hyperdiploidy is occurring prenatally, with RAS mutations developing postnatally. Environmental exposures were reviewed with the family without identification of a clear association.

Association of Combined Focal 22q11.22 Deletion and IKZF1 Alterations With Outcomes in Childhood Acute Lymphoblastic Leukemia.

IMPORTANCE: Alterations in the IKZF1 gene drive B-cell acute lymphoblastic leukemia (B-ALL) but are not routinely used to stratify patients by risk because of inconsistent associations with outcomes. We describe a novel deletion in 22q11.22 that was consistently associated with very poor outcomes in patients with B-ALL with IKZF1 alterations. OBJECTIVE: To determine whether focal deletions within the λ variable chain region in chromosome 22q11.22 were associated with patients with B-ALL with IKZF1 alterations with the highest risk of relapse and/or death. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 1310 primarily high-risk pediatric patients with B-ALL who were taken from 6 independent clinical cohorts, consisting of 3 multicenter cohorts (AALL0232 [2004-2011], P9906 [2000-2003], and patients with Down syndrome who were pooled from national and international studies) and 3 single-institution cohorts (University of Utah [Salt Lake City], Children's Hospital of Philadelphia [Philadelphia, Pennsylvania], and St. Jude Children's Hospital [Memphis, Tennessee]). Data analysis began in 2011 using patients from the older studies first, and data analysis concluded in 2021. EXPOSURES: Focal 22q11.22 deletions. MAIN OUTCOMES AND MEASURES: Event-free and overall survival was investigated. The hypothesis that 22q11.22 deletions stratified the prognostic effect of IKZF1 alterations was formulated while investigating nearby deletions in VPREB1 in 2 initial cohorts (n = 270). Four additional cohorts were then obtained to further study this association (n = 1040). RESULTS: This study of 1310 patients with B-ALL (717 male [56.1%] and 562 female patients [43.9%]) found that focal 22q11.22 deletions are frequent (518 of 1310 [39.5%]) in B-ALL and inconsistent with physiologic V(D)J recombination. A total of 299 of 1310 patients with B-ALL had IKZF1 alterations. Among patients with IKZF1 alterations, more than half shared concomitant focal 22q11.22 deletions (159 of 299 [53.0%]). Patients with combined IKZF1 alterations and 22q11.22 deletions had worse outcomes compared with patients with IKZF1 alterations and wild-type 22q11.22 alleles in every cohort examined (combined cohorts: 5-year event-free survival rates, 43.3% vs 68.5%; hazard ratio [HR], 2.18; 95% CI, 1.54-3.07; P < .001; 5-year overall survival rates, 66.9% vs 83.9%; HR, 2.05; 95% CI, 1.32-3.21; P = .001). While 22q11.22 deletions were not prognostic in patients with wild-type IKZF1 , concomitant 22q11.22 deletions in patients with IKZF1 alterations stratified outcomes across additional risk groups, including patients who met the IKZF1plus criteria, and maintained independent significance in multivariate analysis for event-free survival (HR, 2.05; 95% CI, 1.27-3.29; P = .003) and overall survival (HR, 1.83; 95% CI, 1.01-3.34; P = .05). CONCLUSIONS AND RELEVANCE: This cohort study suggests that 22q11.22 deletions identify patients with B-ALL and IKZF1 alterations who have very poor outcomes and may offer a new genetic biomarker to further refine B-ALL risk stratification and treatment strategies.

A comparison of central lines in pediatric oncology patients: Early removal and patient centered outcomes.

BACKGROUND: While there is increasing evidence supporting the choice of subcutaneous ports (SPs) over external venous catheters (EVCs) in pediatric oncology patients, prior conflicting studies exist and little data have been gathered as to which type of central line is preferred from the patient/family perspective. PROCEDURE: We performed a single institution, 10 years, retrospective analysis of central lines in pediatric oncology patients (n = 878) to evaluate unplanned early removal and cause of removal while simultaneously obtaining a cross sectional survey of 143 of the primary caretakers/parents of these patients to evaluate their overall satisfaction with the line. RESULTS: EVCs have significantly higher odds of unplanned early removal in comparison to SPs (6.7% of SPs vs. 27.3% of EVCs, odds ratio (OR) = 6.3, P < 0.0001 when controlling for age and diagnosis) secondary to increased infection, malfunction and patient preference. Patients with SPs felt like their central line was easier to care for, had less daily impact in their life, and were overall more satisfied with their central line compared to patients with EVCs, even when controlling for early removal (P < 0.0001 for all). SP patients were much more likely to state that they would choose the same type of line again (OR = 15, P < 0.0001) than EVC patients. CONCLUSION: SPs demonstrated lower removal rates and greater patient satisfaction than EVCs. These data should be considered when choosing a central line for pediatric cancer patients.