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Children with Down syndrome (DS) are at a significantly higher risk of developing acute myeloid leukemia, also termed myeloid leukemia associated with DS (ML-DS). In contrast to the highly favorable prognosis of primary ML-DS, the limited data that are available for children who relapse or who have refractory ML-DS (r/r ML-DS) suggest a dismal prognosis. There are few clinical trials and no standardized treatment approach for this population. We conducted a retrospective analysis of international study groups and pediatric oncology centers and identified 62 patients who received treatment with curative intent for r/r ML-DS between 2000-2021. Median time from diagnosis to relapse was 6.8 (range 1.1 - 45.5) months. Three-year event-free (EFS) and overall survival (OS) were 20.9±5.3% and 22.1±5.4%, respectively. Survival was associated with receipt of hematopoietic stem cell transplantation (HSCT) (HR 0.28), duration of first complete remission (CR1) (HR 0.31 for > 12 months) and attainment of remission after relapse (HR 4.03). Patients who achieved CR prior to HSCT, had an improved OS and EFS of 56.0±11.8% and 50.5±11.9% respectively, compared to those who underwent HSCT without CR (3-year OS and EFS of 10.0±9.5%). Treatment failure after HSCT was predominantly due to disease recurrence (52%) followed by treatment related mortality (10%). The prognosis of r/r ML-DS remains dismal even in the current treatment period and serve as a reference point for current prognostication and future interventional studies. Clinical trials aimed at improving the survival of patients with r/r ML-DS are needed.

Introduction Heavy menstrual bleeding (HMB) is a common problem among adolescent girls that affects many aspects of their lives. Estimating the effect of HMB on health-related quality of life (HRQoL) is important but challenging, as there is no instrument that measures menstrual bleeding-specific HRQoL for girls ages < 18 years. Aim To develop and assess the psychometric properties of a menstrual bleeding-specific HRQoL tool adapted for use by girls with HMB aged < 18 years. Methods HMB was defined using a pictorial bleeding assessment chart (PBAC) score >100 and/or hemoglobin >2 SD below age appropriate means. Phase 1 utilized a focus group of girls with HMB to review items of the Menstrual Bleeding Questionnaire (MBQ), validated for use in women ages ≥ 18 years, to generate new items and develop the Adolescent MBQ (aMBQ). In phase 2, participants were divided in two groups: those with and those without HMB. Each participant completed 3 questionnaires (aMBQ, Pediatric Quality of Life core module [PedsQL] and PBAC) at 2 time points. Validity of the aMBQ was measured by Spearman's correlation with the PedsQL. Reliability was calculated using an intra-class correlation (ICC) random effect model in those without HMB who repeated the 3 questionnaires within 30-60 days from baseline. Receiver Operating Characteristic (ROC) curve analysis assessed the ability of the aMBQ to distinguish between participants with and without HMB. Ethics approval and informed consent were obtained prior to participation. Results Phase 1 included 5 girls with previously diagnosed HMB. The MBQ was revised to be appropriate for adolescents by substituting 4 words/phrases that altered 8 of 20 questions (Table 1). With the addition of one new question, a 21-item aMBQ was developed with a score range of 0-77, with 77 representing the worst HRQoL. Phase 2 included 73 participants: 19 with HMB and 56 without HMB. Mean age of participants was 14.7 years (range 11-17 years). The validity of the aMBQ was confirmed by a moderate correlation with PedsQL (rho=-0.61). Test-retest reliability was substantial (ICC=0.71, p=0.03). An aMBQ score of >30 identified those with HMB with excellent discrimination (AUC=0.826, sensitivity 71.4%, specificity 88.0%). Conclusion The aMBQ is a valid and reliable measurement tool to assess HRQoL in adolescents with HMB that is easily implemented in the office setting. Furthermore, it may assist clinicians in identifying those with HMB and aid in the evaluation of treatment effectiveness both in clinical practice and research. Disclosures Belletrutti: Takeda Canada: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk Canada: Membership on an entity's Board of Directors or advisory committees; Bayer Canada: Membership on an entity's Board of Directors or advisory committees; Roche Canada: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees. Matteson:ABOG: Honoraria, Other: Received stipend for being an oral boards examiner.; Myovant: Membership on an entity's Board of Directors or advisory committees; Bayer Ensure: Other: Co-Investigator for longitudinal research study and clinical trial. All funds go to site of research, Research Funding.