Second malignant neoplasms within 5 years from first primary diagnosis in pediatric oncology patients in Canada: a population-based retrospective cohort study.

Introduction: From the advancement of treatment of pediatric cancer diagnosis, the five-year survival rate has increased significantly. However, the adverse consequence of improved survival rate is the second malignant neoplasm. Although previous studies provided information on the incidence and risk of SMN in long term survivors of childhood cancer, there is still scarce information known for short term (< 5 years) prognosis. This study aims to assess the incidence, characteristics, management, and outcome of children who develop SMN malignancies within 5 years of diagnosis of their initial cancer. Method: This is a retrospective cohort study of early Second Malignant Neoplasms (SMN) in pediatric oncology patients. The Cancer in Young People - Canada (CYP-C) national pediatric cancer registry was used and reviewed pediatric patients diagnosed with their first cancer from 2000-2015. Results: A total of 20,272 pediatric patients with a diagnosis of a first malignancy were analyzed. Of them, 0.7% were diagnosed with a SMN within the first 5 years following their first cancer diagnosis. Development of a SMN impacted survival, shown by an inferior survival rate in the SMN cohort (79.1%) after three years compared to that of the non-SMN cohort (89.7%). Several possible risk factors have been identified in the study including the use of epipodophyllotoxins, exposure to radiation, and hematopoietic stem cell 169 transplant. Discussion: This is the first national study assessing the incidence, 170 characteristics, risk factors and outcome of early SMN in Canadian children 171 from age 0-15 from 2000-2015.

How I Treat Philadelphia Chromosome-like Acute Lymphoblastic Leukemia in Children, Adolescents, and Young Adults.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) represents a high-risk B-lineage ALL subtype characterized by adverse clinical features and poor relapse-free survival despite risk-adapted multi-agent chemotherapy regimens. The advent of next-generation sequencing has unraveled the diversity of kinase-activating genetic drivers in Ph-like ALL that are potentially amenable to 'personalized' molecularly-targeted therapies. Based upon robust preclinical data and promising case series of clinical activity of tyrosine kinase inhibitor (TKI)-based treatment in adults and children with relevant genetic Ph-like ALL subtypes, several clinical trials have investigated the efficacy of JAK- or ABL-directed TKIs in CRLF2/JAK pathway-mutant or ABL-class Ph-like ALL, respectively. Final results of these trials are pending, and standard-of-care therapeutic approaches for patients with Ph-like ALL have yet to be defined. In this How I Treat perspective, we review recent literature to guide current evidence-based treatment recommendations via illustrative clinical vignettes of children, adolescents, and young adults with newly-diagnosed or relapsed/refractory Ph-like ALL, and we further highlight open and soon-to-open trials investigating immunotherapy and TKIs specifically for this high-risk patient population.

Novel variant in Nudix hydrolase 15 gene influences 6-mercaptopurine toxicity in childhood acute lymphoblastic leukemia patients.

Acute lymphoblastic leukemia (ALL) is the most frequent pediatric cancer. 6-Mercaptopurine (6-MP) is a key component of ALL treatment. Its use, however, is also associated with adverse drug reactions, particularly myelosuppression. Thiopurine S-methyltransferase (TPMT) and, more recently, Nudix hydrolase 15 (NUDT15) deficiency, due to no-function variants in their respective genes, are well known for their role in the development of this toxicity. Two novel genetic variants, rs12199316 in TPMT and rs73189762 in the NUDT15 gene, were recently identified by targeted sequencing. The latter is particularly interesting because of its potential association with 6-MP intolerance. Here, we assessed the relationship of this variant with the risk of myelosuppression and 6-MP dose intensity in 275 patients treated with Dana Farber Cancer Institute ALL protocols at the Sainte Justine University Health Center. Carriers of the NUDT15 rs73189762 variant allele were at a higher risk of myelosuppression, as shown by absolute phagocyte count reduction during consolidation II and maintenance phases of therapy. Reduction in 6-MP dose intensity was observed in patients with both rs73189762 and known no-function variants in the NUDT15 and TPMT genes. This finding supports the initial observation and suggests that 6-MP dose reduction might be beneficial for individuals with this genotype combination.

Access to innovative therapies in pediatric oncology: Report of the nationwide experience in Canada.

BACKGROUND: The need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to "out-of-trial" use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020. METHODS: Innovative therapies were defined as cancer-directed drugs used (a) off-label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics. We excluded cytotoxic chemotherapy, cellular products, and cytokines. RESULTS: We retrieved data on 352 innovative therapy drug requests. Underlying diagnosis was primary CNS tumor 31%; extracranial solid tumor 37%, leukemia/lymphoma 22%, LCH 2%, and plexiform neurofibroma 6%. RAS/MAP kinase pathway inhibitors were the most frequently requested innovative therapies in 28% of all requests followed by multi-targeted tyrosine kinase inhibitors (17%), inhibitors of the PIK3CA-mTOR-AKT pathway (8%), immune checkpoints inhibitors (8%), and antibody drug conjugates (8%). In 112 out of 352 requests, innovative therapies were used in combination with another anticancer agent. 48% of requests were motivated by the presence of an actionable molecular target. Compassionate access accounted for 52% of all requests while public insurance was used in 27%. Mechanisms of funding varied between provinces. CONCLUSION: This real-world data collection illustrates an increasing use of "out-of-trial" innovative therapies in pediatric oncology. This new field of practice warrants further studies to understand the impact on patient trajectory and equity in access to innovative therapies.

Risk factors and clinical impact of thrombosis during induction chemotherapy for pediatric acute lymphoblastic leukemia: A report from CYP-C.

Thromboembolism (TE) is associated with reduced survival in pediatric acute lymphoblastic leukemia (ALL). It has been hypothesized that TE might signal leukemic aggressiveness. The objective was to determine risk factors for TE during ALL induction (TEind ) therapy and whether TEind is associated with treatment refractoriness. This retrospective cohort study using the population-based Cancer in Young People Canada (CYP-C) registry included children <15 years of age diagnosed with ALL (2000-2019) and treated at one of 12 Canadian pediatric centers outside of Ontario. Univariate and multivariable logistic regression models were used to determine risk factors for TEind and whether TEind predicted induction failure and ALL treatment intensification. The impact of TEind on overall and event-free survival was estimated using Cox proportional hazard regression models. The study included 2589 children, of which 45 (1.7%) developed a TEind . Age (<1 year and ≥10 years vs. 1-<10 years), T-cell phenotype, high-risk ALL, and central nervous system involvement were all associated with TEind in univariate analysis. Age and T-cell phenotype remained independent predictors of TEind in multivariable analysis. Induction failure occurred in 53 patients (2.1%). TEind was not associated with induction failure (OR: not estimable) or treatment intensification (adjusted OR [95% CI]: 0.66 [0.26-1.69]). TEind was independently associated with overall survival (adjusted HR [95% CI]: 2.54 [1.20-5.03]) but not event-free survival (adjusted HR [95% CI] 1.86 [0.98-3.51]). In this population-based study of children treated with contemporary chemotherapy protocols, TEind was associated with age and T-cell phenotype and mortality but did not predict induction failure.

CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia is sensitive to BCL-XL inhibition by navitoclax and DT2216.

ABSTRACT: Acute megakaryoblastic leukemia (AMKL) is a rare, developmentally restricted, and highly lethal cancer of early childhood. The paucity and hypocellularity (due to myelofibrosis) of primary patient samples hamper the discovery of cell- and genotype-specific treatments. AMKL is driven by mutually exclusive chimeric fusion oncogenes in two-thirds of the cases, with CBFA2T3::GLIS2 (CG2) and NUP98 fusions (NUP98r) representing the highest-fatality subgroups. We established CD34+ cord blood-derived CG2 models (n = 6) that sustain serial transplantation and recapitulate human leukemia regarding immunophenotype, leukemia-initiating cell frequencies, comutational landscape, and gene expression signature, with distinct upregulation of the prosurvival factor B-cell lymphoma 2 (BCL2). Cell membrane proteomic analyses highlighted CG2 surface markers preferentially expressed on leukemic cells compared with CD34+ cells (eg, NCAM1 and CD151). AMKL differentiation block in the mega-erythroid progenitor space was confirmed by single-cell profiling. Although CG2 cells were rather resistant to BCL2 genetic knockdown or selective pharmacological inhibition with venetoclax, they were vulnerable to strategies that target the megakaryocytic prosurvival factor BCL-XL (BCL2L1), including in vitro and in vivo treatment with BCL2/BCL-XL/BCL-W inhibitor navitoclax and DT2216, a selective BCL-XL proteolysis-targeting chimera degrader developed to limit thrombocytopenia in patients. NUP98r AMKL were also sensitive to BCL-XL inhibition but not the NUP98r monocytic leukemia, pointing to a lineage-specific dependency. Navitoclax or DT2216 treatment in combination with low-dose cytarabine further reduced leukemic burden in mice. This work extends the cellular and molecular diversity set of human AMKL models and uncovers BCL-XL as a therapeutic vulnerability in CG2 and NUP98r AMKL.

Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial.

BACKGROUND: The outcome of children with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia significantly improved with the combination of imatinib and intensive chemotherapy. We aimed to investigate the efficacy of dasatinib, a second-generation ABL-class inhibitor, with intensive chemotherapy in children with newly diagnosed Ph-positive acute lymphoblastic leukaemia. METHODS: CA180-372/COG AALL1122 was a joint Children's Oncology Group (COG) and European intergroup study of post-induction treatment of Ph-positive acute lymphoblastic leukaemia (EsPhALL) open-label, single-arm, phase 2 study. Eligible patients (aged >1 year to <18 years) with newly diagnosed Ph-positive acute lymphoblastic leukaemia and performance status of at least 60% received EsPhALL chemotherapy plus dasatinib 60 mg/m2 orally once daily from day 15 of induction. Patients with minimal residual disease of at least 0·05% after induction 1B or who were positive for minimal residual disease after the three consolidation blocks were classified as high risk and allocated to receive haematopoietic stem-cell transplantation (HSCT) in first complete remission. The remaining patients were considered standard risk and received chemotherapy plus dasatinib for 2 years. The primary endpoint was the 3-year event-free survival of dasatinib plus chemotherapy compared with external historical controls. The trial was considered positive if one of the following conditions was met: superiority over chemotherapy alone in the AIEOP-BFM 2000 high-risk group; or non-inferiority (with a margin of -5%) or superiority to imatinib plus chemotherapy in the EsPhALL 2010 cohort. All participants who received at least one dose of dasatinib were included in the safety and efficacy analyses. This trial was registered with ClinicalTrials.gov, NCT01460160, and recruitment is closed. FINDINGS: Between March 13, 2012, and May 27, 2014, 109 patients were enrolled at 69 sites (including 51 COG sites in the USA, Canada, and Australia, and 18 EsPhALL sites in Italy and the UK). Three patients were ineligible and did not receive dasatinib. 106 patients were treated and included in analyses (49 [46%] female and 57 [54%] male; 85 [80%] White, 13 [12%] Black or African American, five [5%] Asian, and three [3%] other races; 24 [23%] Hispanic or Latino ethnicity). All 106 treated patients reached complete remission; 87 (82%) were classified as standard risk and 19 (18%) met HSCT criteria and were classified as high risk, but only 15 (14%) received HSCT in first complete remission. The 3-year event-free survival of dasatinib plus chemotherapy was superior to chemotherapy alone (65·5% [90% Clopper-Pearson CI 57·7 to 73·7] vs 49·2% [38·0 to 60·4]; p=0·032), and was non-inferior to imatinib plus chemotherapy (59·1% [51·8 to 66·2], 90% CI of the treatment difference: -3·3 to 17·2), but not superior to imatinib plus chemotherapy (65·5% vs 59·1%; p=0·27). The most frequent grade 3-5 adverse events were febrile neutropenia (n=93) and bacteraemia (n=21). Nine remission deaths occurred, which were due to infections (n=5), transplantation-related (n=2), due to cardiac arrest (n=1), or had an unknown cause (n=1). No dasatinib-related deaths occurred. INTERPRETATION: Dasatinib plus EsPhALL chemotherapy is safe and active in paediatric Ph-positive acute lymphoblastic leukaemia. 3-year event-free survival was similar to that of previous Ph-positive acute lymphoblastic leukaemia trials despite the limited use of HSCT in first complete remission. FUNDING: Bristol Myers Squibb.

Outlier Expression of Isoforms by Targeted or Total RNA Sequencing Identifies Clinically Significant Genomic Variants in Hematolymphoid Tumors.

Recognition of aberrant gene isoforms due to DNA events can impact risk stratification and molecular classification of hematolymphoid tumors. In myelodysplastic syndromes, KMT2A partial tandem duplication (PTD) was one of the top adverse predictors in the International Prognostic Scoring System-Molecular study. In B-cell acute lymphoblastic leukemia (B-ALL), ERG isoforms have been proposed as markers of favorable-risk DUX4 rearrangements, whereas deletion-mediated IKZF1 isoforms are associated with adverse prognosis and have been extended to the high-risk IKZF1plus signature defined by codeletions, including PAX5. In this limited study, outlier expression of isoforms as markers of IKZF1 intragenic or 3' deletions, DUX4 rearrangements, or PAX5 intragenic deletions were 92.3% (48/52), 90% (9/10), or 100% (9/9) sensitive, respectively, and 98.7% (368/373), 100% (35/35), or 97.1% (102/105) specific, respectively, by targeted RNA sequencing, and 84.0% (21/25), 85.7% (6/7), or 81.8% (9/11) sensitive, respectively, and 98.2% (109/111), 98.4% (127/129), or 98.7% (78/79) specific, respectively, by total RNA sequencing. Comprehensive split-read analysis identified expressed DNA breakpoints, cryptic splice sites associated with IKZF1 3' deletions, PTD of IKZF1 exon 5 spanning N159Y in B-ALL with mutated IKZF1 N159Y, and truncated KMT2A-PTD isoforms. Outlier isoforms were also effective targeted RNA markers for PAX5 intragenic amplifications (B-ALL), KMT2A-PTD (myeloid malignant cancers), and rare NOTCH1 intragenic deletions (T-cell acute lymphoblastic leukemia). These findings support the use of outlier isoform analysis as a robust strategy for detecting clinically significant DNA events.

Disparities in parental distress in a multicenter clinical trial for pediatric acute lymphoblastic leukemia.

BACKGROUND: Parent psychological distress during childhood cancer treatment has short- and long-term implications for parent, child, and family well-being. Identifying targetable predictors of parental distress is essential to inform interventions. We investigated the association between household material hardship (HMH), a modifiable poverty-exposure defined as housing, food, or utility insecurity, and severe psychological distress among parents of children aged 1-17 years with acute lymphoblastic leukemia (ALL) enrolled on the multicenter Dana-Farber ALL Consortium Trial 16-001. METHODS: This was a secondary analysis of parent-reported data. Parents completed an HMH survey within 32 days of clinical trial enrollment (T0) and again at 6 months into therapy (T1). The primary exposure was HMH at T0 and primary outcome was severe parental distress at T0 and T1, defined as a score greater than or equal to 13 on the Kessler-6 Psychological Distress Scale. Multivariable models were adjusted for ALL risk group and single parent status. RESULTS: Among 375 evaluable parents, one-third (32%; n = 120/375) reported HMH at T0. In multivariable analyses, T0 HMH was associated with over twice the odds of severe psychological distress at T0 and T1 HMH was associated with over 5 times the odds of severe distress at T1. CONCLUSIONS: Despite uniform clinical trial treatment of their children at well-resourced pediatric centers, HMH-exposed parents-compared with unexposed parents-experienced statistically significantly increased odds of severe psychological distress at the time of their child's leukemia diagnosis, which worsened 6 months into therapy. These data identify a high-risk parental population who may benefit from early psychosocial and HMH-targeted interventions to mitigate disparities in well-being.

Novel Thiosemicarbazone Quantum Dots in the Treatment of Alzheimer's Disease Combining In Silico Models Using Fingerprints and Physicochemical Descriptors.

Searching for thiosemicarbazone derivatives with the potential to inhibit acetylcholinesterase for the treatment of Alzheimer's disease (AD) is an important current goal. The QSARKPLS, QSARANN, and QSARSVR models were constructed using binary fingerprints and physicochemical (PC) descriptors of 129 thiosemicarbazone compounds screened from a database of 3791 derivatives. The R 2 and Q 2 values for the QSARKPLS, QSARANN, and QSARSVR models are greater than 0.925 and 0.713 using dendritic fingerprint (DF) and PC descriptors, respectively. The in vitro pIC50 activities of four new design-oriented compounds N1, N2, N3, and N4, from the QSARKPLS model using DFs, are consistent with the experimental results and those from the QSARANN and QSARSVR models. The designed compounds N1, N2, N3, and N4 do not violate Lipinski-5 and Veber rules using the ADME and BoiLED-Egg methods. The binding energy, kcal mol-1, of the novel compounds to the 1ACJ-PDB protein receptor of the AChE enzyme was also obtained by molecular docking and dynamics simulations consistent with those predicted from the QSARANN and QSARSVR models. New compounds N1, N2, N3, and N4 were synthesized, and the experimental in vitro pIC50 activity was determined in agreement with those obtained from in silico models. The newly synthesized thiosemicarbazones N1, N2, N3, and N4 can inhibit 1ACJ-PDB, which is predicted to be able to cross the barrier. The DFT B3LYP/def-SV(P)-ECP quantization calculation method was used to calculate E HOMO and E LUMO to account for the activities of compounds N1, N2, N3, and N4. The quantum calculation results explained are consistent with those obtained in in silico models. The successful results here may contribute to the search for new drugs for the treatment of AD.

A systems approach points to a therapeutic role for retinoids in asparaginase-associated pancreatitis.

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.

IL16 and factor V gene variations are associated with asparaginase-related thrombosis in childhood acute lymphoblastic leukemia patients.

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.

This study looked at how certain genetic variations are related to a higher risk of blood clots in children with a type of cancer called acute lymphoblastic leukemia who are receiving a certain treatment (asparaginase). The study found that one specific genetic variation (IL16 rs11556218) was linked to a higher risk of blood clots (thrombosis), and that this risk was influenced by disease and treatment features. The study also found that a certain genetic variation (factor V Leiden), which makes blood more likely to clot, and blood type (non-O) were linked to a higher risk of thrombosis. The conclusion of this study is that genetic variations may play a role in blood clots in children with acute lymphoblastic leukemia receiving asparaginase, and if further confirmed, these variations can serve to advance personalized treatment strategies.

Multicenter real-world experience of the clinical efficacy and tolerance of pazopanib in high-risk pediatric solid tumors (PazoPed).

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.

COVID-19 outcomes in patients with sickle cell disease and sickle cell trait compared with individuals without sickle cell disease or trait: a systematic review and meta-analysis.

Background: Clinical manifestations and severity of SARS-CoV-2 infection in individuals with sickle cell disease (SCD) and sickle cell trait (SCT) are not well understood yet. Methods: We performed a systematic review and meta-analysis to assess COVID-19 outcomes in individuals with SCD or SCT compared to individuals without sickle cell disease or trait. An electronic search on PubMed, Embase, and Cochrane Library was performed on August 3, 2023. Two authors (IFM and ISP) independently screened (IFM and ISP) and extracted data (IFM and ILC) from included studies. Main exclusion criterion was the absence of the non-SCD/SCT group. Exposure effects for binary endpoints were compared using pooled odds ratio (OR) with 95% confidence intervals (CI). I2 statistics was used to assess the heterogeneity and DerSimonian and Laird random-effects models were applied for all analyses to minimize the impact of differences in methods and outcomes definitions between studies. The overall quality of evidence was assessed using the GRADE system. Review Manager 5.4 and R software (v4.2.2) were used for statistical analyses. Registered with PROSPERO, CRD42022366015. Findings: Overall, 22 studies were included, with a total of 1892 individuals with SCD, 8677 individuals with SCT, and 1,653,369 individuals without SCD/SCT. No difference in all-cause mortality was seen between SCD/SCT and non-SCD/SCT (OR 1.18; 95% CI 0.78-1.77; p = 0.429; I2 = 82%). When considering only studies adjusted for confounders (8 studies), patients with SCD/SCT were shown to be at increased risk of death (OR 1.86; 95% CI 1.30-2.66; p = 0.0007; I2 = 34%). No significant difference was seen between individuals with SCD and SCT (p = 0.863). The adjusted for confounders analysis for hospitalisation revealed higher rates for the SCD (OR 5.44; 95% CI 1.55-19.13; p = 0.008; I2 = 97%) and the SCT groups (OR 1.31; 95% CI 1.10-1.55; p = 0.002; I2 = 0) compared to the non-SCD/SCT population. Moreover, it was significantly higher for the SCD group (test for subgroup difference; p = 0.028). Interpretation: Our findings suggest that patients with SCD or SCT may present with a higher mortality and hospitalisation rates due to COVID-19 infection. Funding: None.