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Aim: We previously conducted exome-wide association study in acute lymphoblastic leukemia patients and identified association of five SNPs with asparaginase-related thrombosis. Here we aimed to replicate these findings in an independent patient cohort and through analyses in vitro. Patients & methods: SNPs located in IL16, MYBBP1A, PKD2L1, RIN3 and MPEG1 genes were analyzed in patients receiving Dana-Farber Cancer Institute acute lymphoblastic leukemia treatment protocols 05-001 and 11-001. Thrombophilia-related variations were also analysed. Results: IL16 rs11556218 conferred higher risk of thrombosis and higher in vitro sensitivity to asparaginase. The association was modulated by the treatment protocol, risk group and immunophenotype. A crosstalk between factor V Leiden, non-O blood groups and higher risk of thrombosis was also seen. Conclusion: IL16 and factor V Leiden variations are implicated in asparaginase-related thrombosis.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a common subtype of B-lineage acute lymphoblastic leukemia (B-ALL) with increasing frequency across the age spectrum. Characterized by a kinase-activated gene expression profile and driven by a variety of genetic alterations involving cytokine receptors and kinases, Ph-like ALL is associated with high rates of residual disease and relapse in patients treated with conventional chemotherapy. In this case-based review, we describe the biology of the 2 major ABL-class and JAK pathway genetic subtypes of Ph-like ALL, discuss current diagnostic testing methodologies, and highlight targeted inhibitor and chemo/immunotherapy approaches under clinical investigation in children, adolescents, and adults with these high-risk leukemias.

The epidemiology of infant acute lymphoblastic leukemia (ALL), hypodiploid ALL, and mixed-phenotype acute leukemia (MPAL) in Canada is unknown. The main objective was to describe the prevalence, prognostic factors, and outcomes of three rare and high-risk ALL subtypes in Canada. This is a retrospective study using the Cancer in Young People-Canada (CYP-C) database. Event-free survival (EFS) and overall survival (OS) were described by the Kaplan-Meier method and compared using the log-rank test. Among 2626 children aged 0-14 years diagnosed with B-cell acute lymphoblastic leukemia (B-ALL) between 2001 and 2018, 227 (8.6%) patients were identified to be infant ALL (

Black and Hispanic children with leukemia experience inferior survival compared to non-Hispanic White (NHW) children. Identifying modifiable social determinants of health can inform intervention targets to address inequities. We characterized the frequency of income poverty and household material hardship (HMH) by race/ethnicity in a clinical trial cohort with de novo acute lymphoblastic leukemia. Compared to NHW families, Black and Hispanic families reported more frequent HMH (19% vs. 47% vs. 68% respectively); low-income (27% vs. 52% vs. 74%), and combined low-income and HMH (12% vs. 37% vs. 52%) poverty exposures. Disparate poverty exposures are interventional targets to address racial/ethnic outcome inequities.

Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.

Pazopanib, a receptor tyrosine kinase inhibitor, exhibits anti-tumor activity in adult bone and soft-tissue sarcomas (STS), but has not yet been approved for pediatric tumors. The primary objective was to evaluate pazopanib efficacy when used alone or in combination with topotecan. This real-world multicenter retrospective study included patients with solid tumors, aged 25 years or less at the time of initial diagnosis, treated with pazopanib outside of a clinical trial. Nineteen patients were eligible for efficacy analysis: 14 bone tumors and 5 STS. At pazopanib initiation, the median age was 16.9 years, 18 patients had metastatic disease with a median of 2 prior therapeutic lines. With 6.2 months of median follow-up, no objective response was observed, but 10 patients (52.6%) had stable disease at 8 weeks and the 6-month disease control rate was 26.3%. The median progression free (PFS) and overall survival (OS) were 3.0 months and 6.2 months, respectively. Multivariate analysis showed an inverse relationship between the number of prior treatment lines and PFS and OS (hazard ratio = 1.73 (p = 0.04) and 1.76 (p = 0.03), respectively). Our study showed a potential tumor control activity of pazopanib in pediatric bone and soft tissue sarcomas. Further studies are warranted to determine the optimal timing and condition for pazopanib introduction to maximize the effect.

Social determinants of health (SDoH) are associated with stark disparities in cancer outcomes, but systematic SDoH data collection is virtually absent from oncology clinical trials. Trial-based SDoH data are essential to ensure representation of marginalized populations, contextualize outcome disparities, and identify health-equity intervention opportunities. We report the feasibility of a pediatric oncology multicenter therapeutic trial-embedded SDoH investigation. Among 448 trial participants, 392 (87.5%) opted-in to the embedded SDoH study; 375 (95.7%) completed baseline surveys, with high longitudinal response rates (88.9-93.1%) over 24 months. Trial-embedded SDoH data collection is feasible and acceptable and must be consistently included within future oncology trials.

Recognition of aberrant gene isoforms indicative of underlying DNA events can impact molecular classification and risk stratification of B lymphoblastic leukemia (B-ALL). Aberrant ERG isoforms have been proposed as markers of the favorable-risk DUX4-rearranged (DUX4r) subtype while deletion-mediated IKZF1 isoforms are associated with adverse prognosis in non-DUX4r B-ALL. The high-risk IKZF1plus signature depends on gene deletions including PAX5 while intragenic PAX5 amplifications (PAX5amp) are recurrent in the provisional B-ALL with PAX5-alteration subtype. In this study, we screened for outlier expression of isoforms within targeted RNA sequencing assays designed for fusions. Outlier analysis of known and novel IKZF1, ERG, and PAX5 isoforms was 97.0% (32/33), 90% (9/10), and 100% (6/6) sensitive and 97.8% (226/231), 100% (35/35), and 88.5% (23/26) specific for IKZF1 intragenic or 3’ deletions, DUX4r, and PAX5 intragenic deletions respectively, where false positives were favored to represent low-level deletions below the limit of DNA-based detection. Outlier analysis also identified putative PAX5amp cases and revealed partial tandem duplication (PTD) spanning IKZF1 N159Y in the B-ALL with mutated N159Y subtype. To demonstrate utility in other tumor types, outlier analysis was 100% (9/9) sensitive and 100% (255/255) specific for KMT2A-PTD in hematologic samples and 100% (7/7) sensitive and 100% (79/79) specific for FGFR1 tyrosine kinase domain duplication in brain tumors. These findings support the use of aberrant isoform analysis in targeted RNA sequencing data as a robust strategy for the detection of clinically significant DNA events.

Extensive venous malformations (VM) involving limbs severely impact quality of life, mostly due to chronic pain and functional limitations. Patients can also display coagulopathy with associated risks of life-threatening thromboembolism and bleeding. Current pharmacological VM treatments (e.g. sirolimus) are not universally effective as 10% of patients present intractable debilitating and/or critical disease. Novel therapies are therefore highly needed for treatment-resistant VM. Over 70% of sporadic VM are attributed to activating mutations in the TEK gene, encoding the receptor tyrosine kinase TIE2 expressed by venous endothelial cells. Despite in vitro studies showing the superiority of alpelisib over sirolimus in inhibiting TIE2 signalling pathway and vein remodelling, there are currently no clinical reports of alpelisib use in VM. Our aim was therefore to assess the effect of alpelisib in TIE-2 mutated VM and to assess its pharmacokinetics. Three patients with a VM harboring the TEK L914F mutations were treated with alpelisib in an open-label compassionate use study. All patients experienced significant improvement. Pain was controlled, gait improved, size of the abnormal venous network decreased, and coagulopathy showed dramatic improvement. Drug exposure was highly variable despite similar weight-adjusted doses, suggesting that alpelisib dosing should be individualized to patient’s characteristics and guided by therapeutic drug monitoring to improve clinical response.

Gene expression profiling provides a detailed molecular snapshot of cellular phenotypes that can be used to compare different biological conditions. Nanopore sequencing technology can generate high-resolution transcriptomic data in real-time and at low cost, which heralds new opportunities for molecular medicine. In this study, we demonstrate the clinical utility of real-time transcriptomic profiling by processing RNA sequencing data from childhood acute lymphoblastic leukemia (ALL) patients on-the-fly with a trained neural network classifier. This strategy successfully distinguished 11/12 representative ALL molecular subtypes and one non-leukemia control in as little as 5 minutes of sequencing on a MinION sequencer or in less than 1 hour on disposable, low cost Flongle flow cells. Our findings suggest that real-time transcriptomics constitutes a drastically efficient solution for the molecular diagnosis of ALL and other diseases, where conventional clinical workflows require days if not weeks to achieve similar results.

Social determinants of health (SDoH) are associated with stark disparities in cancer outcomes, but systematic SDoH data collection is currently absent from oncology clinical trials. Trial-based SDoH data are essential to ensure representation of marginalized populations, contextualize outcomes, and identify health-equity intervention opportunities. We report the feasibility of the first pediatric oncology multicenter trial-embedded SDoH investigation. Among 448 trial participants, 392 (87.5%) opted-in to the embedded SDoH study; 375 (95.7%) completed baseline surveys, with high longitudinal response rates (87.2-92.8%) over 24-months of therapy. Trial-embedded SDoH data collection is feasible and acceptable, and must be consistently included within future oncology trials.

Background Food insecurity (FI) is an adverse social determinant of health (SDoH) prevalent among pediatric cancer patients and associated with poorer health outcomes in general pediatrics. Receipt of federal SNAP benefits reduces FI in general pediatrics, and is thus a marker of appropriate resource support to mitigate adverse SDoH. Dana-Farber Cancer Institute (DFCI) Acute Lymphoblastic Leukemia (ALL) Consortium Trial 16-001 is the first pediatric oncology clinical trial to prospectively collect parent-reported SDoH, including income, SNAP receipt, and FI. We investigated whether income-eligible pediatric ALL families were successfully receiving SNAP benefits, and whether SNAP receipt was associated with FI. Methods Secondary analysis of children aged 1-17 years with de novo ALL enrolled on the DFCI 16-001-embedded SDoH cohort study at 6 US centers from 2017-2022. We utilized parent-reported SDoH data at diagnosis (T0) and 6-mos (T1) into therapy to identify families as (1) SNAP-eligible, proxied as household income Citation Format: Rahela Aziz-Bose, Yael Flamand, Puja J. Umaretiya, Lenka Ilcisin, Ariana Valenzuela, Peter D. Cole, Lisa M. Gennarini, Justine M. Kahn, Kara M. Kelly, Bruno Michon, Thai-Hoa Tran, Jennifer J. G. Welch, Lewis B. Silverman, Kira Bona. Food insecurity and receipt of Supplemental Nutrition Assistance Program (SNAP) benefits among income-eligible US pediatric acute lymphoblastic leukemia patients enrolled on a multi-center clinical trial [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B096.

The molecular hallmark of childhood acute lymphoblastic leukemia (ALL) is characterized by recurrent, prognostic genetic alterations, many of which are cryptic by conventional cytogenetics. RNA sequencing (RNA-seq) is a powerful next-generation sequencing technology that can simultaneously identify cryptic gene rearrangements, sequence mutations and gene expression profiles in a single assay. We examined the feasibility and utility of incorporating RNA-seq into a prospective multicenter phase 3 clinical trial for children with newly diagnosed ALL. The Dana-Farber Cancer Institute ALL Consortium Protocol 16-001 enrolled 173 patients with ALL who consented to optional studies and had samples available for RNA-seq. RNA-seq identified at least 1 alteration in 157 patients (91%). Fusion detection was 100% concordant with results obtained from conventional cytogenetic analyses. An additional 56 gene fusions were identified by RNA-seq, many of which confer prognostic or therapeutic significance. Gene expression profiling enabled further molecular classification into the following B-cell ALL (B-ALL) subgroups: high hyperdiploid (n = 36), ETV6-RUNX1/-like (n = 31), TCF3-PBX1 (n = 7), KMT2A-rearranged (KMT2A-R; n = 5), intrachromosomal amplification of chromosome 21 (iAMP21) (n = 1), hypodiploid (n = 1), Philadelphia chromosome (Ph)-positive/Ph-like (n = 16), DUX4-R (n = 11), PAX5 alterations (PAX5 alt; n = 11), PAX5 P80R (n = 1), ZNF384-R (n = 4), NUTM1-R (n = 1), MEF2D-R (n = 1), and others (n = 10). RNA-seq identified 141 nonsynonymous mutations in 93 patients (54%); the most frequent were RAS-MAPK pathway mutations. Among 79 patients with both low-density array and RNA-seq data for the Philadelphia chromosome-like gene signature prediction, results were concordant in 74 patients (94%). In conclusion, RNA-seq identified several clinically relevant genetic alterations not detected by conventional methods, which supports the integration of this technology into front-line pediatric ALL trials. This trial was registered at www.clinicaltrials.gov as #NCT03020030.

Platinum nanoparticles were synthesized using the gamma-ray irradiation as a reducing factor and chitosan as a stabilizer. The prepared platinum nanoparticles were characterized using ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FT-IR). The saturated conversion dose to reduce the Pt4+ to Pt0 was found to be about 14 kGy for initial Pt4+ concentration of 1 mM. The size of the platinum nanoparticles (1.4–1.6 nm) did almost not change with the increase of chitosan concentration from 0.5 to 2.0%. Thus, gamma Co-60 ray irradiation method is favorable for synthesizing PtNPs with the small sizes.

Introduction: Thrombo-embolic event (TE) is a frequent complication of childhood acute lymphoblastic leukemia (cALL) and is associated with reduced survival. Overexpression of podoplanin or coagulome genes and coagulation pathway activation have been identified in cancer-induced TE but the role of leukemia environment in TE occurrence has not been fully elucidated in ALL. We assessed whether leukemia gene expression (GE) signature at diagnosis was associated with TE development in cALL. Methods: We included children aged 0-18 years old (y.o.), from two hospitals, with newly diagnosed ALL and available RNA sequencing data from bone marrow at diagnosis. The primary outcome was the occurrence of grade ≥2 TE during ALL therapy using the Ponte Di Legno Working Group classification. TEs were classified as early (ET) if they occurred within 6 weeks from treatment start, or late (LT) otherwise. We compared differential gene expression (DE) in children with and without TE, adjusted for age ( Results: We included 80 patients (median age: 5 years [interquartile range, IQR: 3-11 years], 53% male, 83% precursor B-cell ALL) of whom 19 (23.8%) developed a TE (7 ET and 12 LT) at a median of 76 days (IQR: 31-133 days) following cancer diagnosis. Patients with TE were more likely to be ≥10 y.o., while other demographic and clinical characteristics were similar. No genes from the coagulome, podoplanin or Hallmark coagulation pathways were differentially expressed in children with and without TE. The KEGG Ribosome pathway was the most upregulated pathway in the group with TE (normalized enrichment score (NES) = 2.35, adjusted p-value= 0.012) and ET (NES = 2.63, adjusted p-value < 0.001). LT was not significantly associated with ribosome pathway dysregulation. Interestingly, prior reports identified functional enrichment in ribosomal pathway as a biomarker for venous TE. A heatmap classification for ribosomal genes revealed 3 distinct signatures: ribosomal downregulation, moderate and high ribosomal activation. High ribosomal activation profile was seen in 6/7 ET and 9/12 LT, corresponding to a positive and negative predictive value of 0.55 and 0.92 for TE, respectively. Conclusion: TEs in cALL were not associated with dysregulation in coagulation pathways or podoplanin gene at the RNA level. However, ribosomal translational pathway was highly upregulated in the group with thrombosis, particularly with ET. Dysregulation of posttranscriptional machinery might explain the pro-thrombotic effect of leukemia environment in cALL and warrants further investigation including proteomic exploration. Citation Format: Marie-Claude Pelland-Marcotte, Meredith Michelle Rémy, Yan Ma, Jessica Liu, Camille Jimenez-Cortes, Thomas Sontag, Maxime Caron, Pascal Saint-Onge, Sylvie Langlois, Charles Joly-Beauparlant, Daniel Sinnett, Arnaud Droit, Thai Hoa Tran, Raoul Santiago. Ribosomal translational regulation is a potential mechanism for leukemia-related thrombo-embolic event in childhood acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3897.

10023 Background: Minimal residual disease (MRD) assessment by immunoglobulin/T-cell receptor (Ig/TCR) polymerase chain reaction (PCR) is currently being used in the international pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) trial EsPhALL2017/AALL1631 for risk stratification. MRD concordance has previously been demonstrated between Ig/TCR PCR and flow cytometry in Ph+ALL. We sought to assess concordance of MRD assessment between conventional Ig/TCR PCR and next-generation sequencing (NGS) assays. Methods: MRD was assessed in all pts on AALL1631 by Ig/TCR PCR at end-induction IB; those with MRD -4 were classified as standard-risk (SR) and randomized to treatment with imatinib and one of two chemotherapy regimens without hematopoietic stem cell transplant (HSCT), whereas pts with end-induction 1B MRD ≥ 5x10-4 were considered high-risk (HR) and assigned to HSCT after consolidation chemotherapy. Residual diagnostic and end-induction IB samples from consenting pts were assessed for NGS MRD by the clonoSEQ assay (Adaptive Biotechnologies) in blinded fashion and subsequently compared to Ig/TCR MRD to determine concordance as related to MRD-based HSCT recommendations ( ie, MRD ≥ 5x10-4 consistent with HR group assignment). MRD values were calculated using the kappa statistic for agreement above chance. Results: Sixty-seven pts had matched samples available for MRD assessment at end-induction 1B by both Ig/TCR PCR and NGS (Table). NGS MRD was evaluable for all 67 pts and stratified as 62 SR (-4) and 5 HR (≥5x10-4). In contrast, Ig/TCR PCR results were inevaluable for 3 pts (unsatisfactory sample quality) and indeterminate (positive, but not quantifiable) in 4 pts. Of the remaining 60 pts, 55 met SR and 5 HR criteria using Ig/TCR PCR. There was only 1 discordant case between the two methods for MRD-based HSCT recommendation among these 60 pts with a kappa statistic for agreement above chance of 0.88. Conclusions: NGS and Ig/TCR PCR assays were highly concordant in MRD assessment for risk stratification at a threshold of 5x10-4 in pediatric pts with Ph+ALL enrolled on AALL1631. Of note, the NGS assay yielded MRD results amenable for risk stratification in 100% pts compared to 89.6% for the Ig/TCR PCR methodology. These data support the use of NGS MRD testing for risk stratification in pediatric Ph+ALL.[Table: see text]

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently identified high-risk subtype of B-lineage ALL (B-ALL), characterized by a gene expression profile similar to that of Philadelphia-positive (Ph+) ALL, but without the hallmark BCR-ABL1 oncoprotein. Ph-like ALL represents approximately 15% of childhood ALL and its frequency rises with age, peaking among adolescents, and young adults with B-ALL. This subtype is associated with adverse clinical features, persistence of minimal residual disease, and a poor prognosis despite modern chemotherapy regimens. While Ph-like ALL lacks the BCR-ABL1 fusion, it is characterized by a diverse spectrum of kinase fusions and cytokine receptor gene rearrangements that may be similarly amenable to molecularly targeted therapies. While survival rates for childhood ALL have drastically improved with intensive conventional chemotherapy, Ph-like ALL represents a novel paradigm of precision medicine in ALL. This review aims to provide a comprehensive review of the clinical picture and genetic basis of Ph-like ALL and to illustrate how these findings can translate into tailored targeted therapies with the hopes of improving the outcomes of Ph-like ALL patients.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and constitutes approximately 25 % of cancer diagnoses among children under the age of 15 (Howlader et al., 2013) [ 1 ]. Overall, about half of ALL cases occur in children and adolescents and it is the most common acute leukemia until the early 20s, after which acute myeloid leukemia predominates. ALL is the most successful treatment paradigm in pediatric cancer medicine as illustrated by the significant survival rate improvement from ∼10 % in the 1960s to >90 % today (Hunger et al., 2015) [ 2 ]. This remarkable success stems from the progressive improvement in the efficacy of risk-adapted multiagent chemotherapy regimens with effective central nervous system (CNS) prophylaxis via well-designed randomized clinical trials conducted by international collaborative consortia, enhanced supportive care measures to decrease treatment-related mortality, in-depth understanding of the genetic basis of ALL, and refinement in treatment response assessment through serial minimal residual disease (MRD) monitoring (Pui et al., 2015) [ 3 ]. These advances collectively contribute to a decline in mortality rate of 23.5% for children diagnosed with ALL in the US from 2000 to 2010 (Smith et al., 2014) [ 4 ]. Nevertheless, outcomes of older adolescents and young adults with ALL still lag behind those of their younger counterparts despite pediatric-inspired chemotherapy regimens (Stock et al., 2019) [ 5 ], relapsed/refractory childhood ALL is associated with poor outcomes (Rheingold et al., 2019) [ 6 ], and ALL still represents the leading causes of cancer-related deaths (Smith et al., 2010) [ 7 ]. The last two decades have witnessed important genomic discoveries in ALL, enabled by advances in next-generation sequencing (NGS) technologies to characterize the landscape of germline and somatic alterations in ALL, some of which have important diagnostic, prognostic and therapeutic implications. Comprehensive genomic analysis of large cohorts of children and adults with ALL has revised the taxonomy of ALL in the molecular era by identifying novel clonal, subtype-defined chromosomal alterations associated with distinct gene expression signatures, thus reducing the proportion of patients previously labelled as “Others” from 25 % to approximately 5 % (Mullighan et al., 2019) [ 8 ]. Insights into the genomics of ALL further provide compelling biologic rationale to expand the scope of precision medicine therapies for childhood ALL. Herein, we summarize a decade of genomic discoveries to highlight three different facets of precision medicine in pediatric ALL: 1) inherited predispositions of ALL; 2) relevant molecularly targeted therapies in genomically-defined ALL subtypes; and 3) treatment response monitoring via pharmacogenomics and novel MRD biomarkers.

Introduction Studies suggest that patients with cancer are more likely to experience severe outcomes from COVID-19. Therefore, cancer centers have undertaken efforts to care for patients with cancer in COVID-free units. Nevertheless, the frequency and relevance of nosocomial transmission of COVID-19 in patients with cancer remain unknown. The goal of this study was to determine the incidence and impact of hospital-acquired COVID-19 in this population and identify predictive factors for COVID-19 severity in patients with cancer. Methods Patients with cancer and a laboratory-confirmed diagnosis of COVID-19 were prospectively identified using provincial registries and hospital databases between March 3rd and May 23rd, 2020 in the provinces of Quebec and British Columbia in Canada. Patient’s baseline characteristics including age, sex, comorbidities, cancer type, and type of anti-cancer treatment were collected. The exposure of interest was incidence of hospital-acquired infection defined by diagnosis of SARS-CoV-2 ≥ 5 days after hospital admission for COVID-unrelated cause. Co-primary outcomes were death or composite outcomes of severe illness from COVID-19 such as hospitalization, supplemental oxygen, intensive-care unit (ICU) admission and/or mechanical ventilation. Results A total of 252 patients (N=249 adult, and N=3 pediatric) with COVID-19 and cancer were identified, and the majority were residents of Quebec (N=233). One-hundred-and-six patients (42.1%) received active anti-cancer treatment in the last 3 months prior to COVID-19 diagnosis. During a median follow-up of 25 days, 33 (13.1%) required admission to the ICU, and 71 (28.2%) died. Forty-seven (19.1%) had a diagnosis of hospital-acquired COVID-19. Median overall survival was shorter in those with hospital-acquired infection, compared to a contemporary community-acquired population (27 days vs unreached, HR 2.3, 95% CI 1.2-4.4, p=0.0006). Multivariate analysis demonstrated that hospital-acquired COVID-19, age, ECOG status, and advanced stage of cancer were independently associated with death. Interpretation Our study demonstrates a high rate of nosocomial transmission of COVID-19, associated with increased mortality in both univariate and multivariate analysis in the cancer population, reinforcing the importance of treating patients with cancer in COVID-free units. We also validated that age and advanced cancer were negative predictive factors for COVID-19 severity in patients with cancer., Highlights • We found a high rate of nosocomial transmission of COVID-19 in patients with cancer. • Nosocomial COVID-19 increased mortality compared to community-acquired infection. • Nosocomial COVID-19, age, ECOG, and stage were independently associated with death. • COVID-free units and infection control procedures are required to protect patients.

ABL-class fusions other than

Aim: To evaluate the association between human leukocyte antigen (HLA) alleles and native Escherichia coli asparaginase hypersensitivity (AH) in children with acute lymphoblastic leukemia (ALL) who received Dana-Farber Cancer Institute treatment protocols. Patients & methods: HLA-DQA1, HLA-DRB1 and HLA-DQB1 alleles were retrieved from available whole exome sequencing data of a subset of childhood ALL patients from Quebec ALL cohort and analyzed for an association with AH. PCR assay was developed to analyze associated alleles in the entire discovery and replication cohorts. Results: Two alleles in linkage disequilibrium ( HLA-DRB1*07:01 and DQA1*02:01) were associated with AH. Additional analyses, performed to distinguish between HLA-DRB1*07:01 haplotypes with and without DQB1*02:02 allele, showed that the association was dependent on the presence of DQB1*02:02. Conclusion: This study confirms the implication of HLA-DRB1*07:01, DQA1*02:01 and DQB1*02:02 alleles in developing AH in childhood ALL.