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.

Local evidence in sub-Saharan Africa; the CANCaRe Africa experience-Lessons learned and shared thoughts about the way forward.

Collaborative research generating local evidence is key to closing the research and survival gap between sub-Saharan Africa and high-income countries. Lessons learned by CANCaRe Africa, the Collaborative African Network for Childhood Cancer Care and Research while pioneering such research are being discussed together with recommendations for the future.

Brochure intervention to manage bothersome taste changes in pediatric patients receiving cancer therapy.

BACKGROUND: Primary objective was to determine if a patient informational brochure describing potentially useful strategies could help manage specific taste changes. Secondary objective was to describe the specific strategies used and whether the strategies were perceived as being helpful. PROCEDURE: This single-center study included pediatric patients with cancer or hematopoietic cell transplant recipients receiving active treatment who experienced bothersome taste changes in the last month. Participants participated in baseline and follow-up interviews conducted 14-21 days apart. A brochure that listed 16 potentially helpful strategies was provided at baseline. At follow-up, we asked about brochure use and whether it helped. At both interviews, we asked about experienced taste changes, strategies used, and whether strategy helped. RESULTS: Of 100 enrolled participants, different (87%) and bad (72%) taste were most common at baseline. Following the brochure intervention, statistically significant reductions were observed in food tasting different, bad, bland, bitter, sour, and metallic. For most strategies, the proportion of patients who used specific strategies or found them helpful was not significantly different between baseline and follow-up. However, "eating foods you like" was considered helpful in significantly more participants who used the strategy in follow-up (72 out of 89, 80.9%) compared with baseline (55 out of 95, 57.9%; p = .008). Between visits, 81.2% looked at the brochure. Among participants, 53.1% found the brochure helpful, very helpful, or extremely helpful. CONCLUSIONS: A brochure that offered strategies to manage changes in taste helped participants cope with them. Further research should evaluate the brochure using randomized and multicenter trials.

Clinical practice guideline-inconsistent management of fever and neutropenia in pediatric oncology: A Children's Oncology Group study.

BACKGROUND: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described. METHODS: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children's Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December 2015. Patients were randomly selected for chart review by participating sites from a COG-generated list. Care delivered in each episode was adjudicated (CPG-consistent or CPG-inconsistent) against each of five selected recommendations. RESULTS: A total of 107 patients from 22 sites, representing 157 FN episodes, were included. The most common CPG-inconsistent care delivered was omission of pulmonary computerized tomography in patients with persistent FN (60.3%). Of 74 episodes where assessment of four (episodes without persistent FN) or five (episodes with persistent FN) recommendations was possible, CPG-inconsistent care was delivered with respect to at least one recommendation in 63 (85%) episodes. Site size was not associated with CPG-inconsistent care delivery. No statistically significant association between CPG-inconsistent care and fever recurrence was observed. CONCLUSIONS: In this cohort of pediatric patients at high risk of poor FN outcomes, CPG-inconsistent care was common. Opportunities to optimize resource stewardship by boosting supportive care CPG implementation are highlighted.

Prevention of treatment abandonment remains an important challenge to increase survival of Wilms tumor in sub-Saharan Africa: A report from Wilms Africa-CANCaRe Africa.

BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.

Outcomes of chemotherapy-induced nausea and vomiting guideline adherence in pediatric and adult patients: a systematic review.

PURPOSE: This study describes chemotherapy-induced nausea and vomiting (CINV) control rates in pediatric and adult patients who did or did not receive guideline-consistent CINV prophylaxis. METHODS: We conducted a systematic literature review of studies published in 2000 or later that evaluated CINV control in patients receiving guideline-consistent vs. guideline-inconsistent CINV prophylaxis and reported at least one CINV-related patient outcome. Studies were excluded if the guideline evaluated was not publicly available or not developed by a professional organization. Over-prophylaxis was defined as antiemetic use recommended for a higher level of chemotherapy emetogenicity than a patient was receiving. RESULTS: We identified 7060 citations and retrieved 141 publications for full-text evaluation. Of these, 21 publications (14 prospective and seven retrospective studies) evaluating guidelines developed by six organizations were included. The terms used to describe CINV endpoints and definition of guideline-consistent CINV prophylaxis varied among studies. Included studies either did not address over-prophylaxis in their definition of guideline-consistent CINV prophylaxis (48%; 10/21) or defined it as guideline-inconsistent (38%; 8/21) or guideline-consistent (3/21; 14%). Eleven included studies (52%; 11/21) reported a clinically meaningful improvement in at least one CINV endpoint in patients receiving guideline-consistent CINV prophylaxis. Ten reported a statistically significant improvement. CONCLUSIONS: This evidence supports the use of guideline-consistent prophylaxis to optimize CINV control. Institutions caring for patients with cancer should systematically adapt CINV CPGs for local implementation and routinely evaluate CINV outcomes.

Impact of dexamethasone on transplant-related mortality in pediatric patients: a multi-site, propensity score-weighted, retrospective assessment.

Dexamethasone use during hematopoietic cell transplant (HCT) conditioning varies between pediatric centers. This study aimed to estimate the difference in 1-year treatment-related mortality (TRM) between patients who did or did not receive dexamethasone during HCT conditioning. Secondary objectives were to estimate the difference between dexamethasone-exposed and dexamethasone-unexposed groups in 1-year event-free survival (EFS), time to neutrophil engraftment, acute graft-versus-host disease (aGVHD), and invasive fungal disease (IFD) at day + 100. This was a seven-site, international, retrospective cohort study. Patients < 18 years old undergoing their first allogeneic or autologous myeloablative HCT for hematologic malignancy or aplastic anemia between January 1, 2012, and July 31, 2017, were included. To control for potential confounders, propensity score weighting was used to calculate the standardized mean difference for all endpoints. Among 242 patients, 140 received dexamethasone during HCT conditioning and 102 did not. TRM was unaffected by dexamethasone exposure (1.7%; 95% CI - 7.4, 10.2%). Between-group differences in secondary outcomes were small. However, dexamethasone exposure significantly increased possible, probable, and proven IFD incidence (9.0%, 95% CI 0.8, 17.3%). TRM is not increased in pediatric patients who receive dexamethasone during HCT conditioning. Clinicians should consider potential IFD risk when selecting chemotherapy-induced vomiting prophylaxis for pediatric HCT patients.

Healthcare professional perspectives following implementation of an infection management care pathway for pediatric patients with cancer: a qualitative study.

PURPOSE: The Pediatric Oncology Group of Ontario (POGO) supported an effort to implement infection management care pathways based on clinical practice guidelines, to improve the consistency of infection management in pediatric cancer patients. The objective of this qualitative study was to describe the perspective of healthcare professionals (HCPs) following implementation. METHODS: Four tertiary pediatric oncology centers in Ontario, Canada, implemented the pathways. We randomly identified three HCPs per group (clinical pharmacists; nurse case managers, educators or practitioners and physician assistants; pediatric oncology fellows; or pediatric oncology staff physicians) per site and invited them to participate in a qualitative interview. One-on-one interviews were conducted remotely, followed by thematic analysis of interview transcripts. RESULTS: A total of 66 invitations were extended and 42 HCPs participated. Identified themes were: (1) implementation approach, (2) access and navigation, (3) engagement, (4) concerns, (5) workplace benefits, (6) reception, and (7) provincial harmonization. HCPs preferred in-person implementation strategies over e-mail communication. They identified teaching/educational utility and benefits to non-oncology departments and non-tertiary centers participating in shared care of patients. Other positive aspects related to evidence-based practice, safety, supporting oncology HCPs, and benefits to patients and families. Concerns included need to ensure users applied clinical judgement and loss of autonomy. Provincial harmonization of practice was viewed positively, although potential logistical and institutional cultural barriers were raised. CONCLUSIONS: Following infection management care pathway implementation, HCPs described educational utility and benefits to non-oncology departments, oncology HCPs, patients, and families. Our findings may facilitate future infection management care pathway provincial harmonization.

Do Thresholds for Invasive Ventilation in Hypoxemic Respiratory Failure Exist? A Cohort Study.

Rationale: Invasive ventilation is a significant event for patients with respiratory failure. Physiologic thresholds standardize the use of invasive ventilation in clinical trials, but it is unknown whether thresholds prompt invasive ventilation in clinical practice. Objectives: To measure, in patients with hypoxemic respiratory failure, the probability of invasive ventilation within 3 hours after meeting physiologic thresholds. Methods: We studied patients admitted to intensive care receiving FiO2 of 0.4 or more via nonrebreather mask, noninvasive positive pressure ventilation, or high-flow nasal cannula, using data from the Medical Information Mart for Intensive Care (MIMIC)-IV database (2008-2019) and the Amsterdam University Medical Centers Database (AmsterdamUMCdb) (2003-2016). We evaluated 17 thresholds, including the ratio of arterial to inspired oxygen, the ratio of saturation to inspired oxygen ratio, composite scores, and criteria from randomized trials. We report the probability of invasive ventilation within 3 hours of meeting each threshold and its association with covariates using odds ratios (ORs) and 95% credible intervals (CrIs). Measurements and Main Results: We studied 4,726 patients (3,365 from MIMIC, 1,361 from AmsterdamUMCdb). Invasive ventilation occurred in 28% (1,320). In MIMIC, the highest probability of invasive ventilation within 3 hours of meeting a threshold was 20%, after meeting prespecified neurologic or respiratory criteria while on vasopressors, and 19%, after a ratio of arterial to inspired oxygen of <80 mm Hg. In AmsterdamUMCdb, the highest probability was 34%, after vasopressor initiation, and 25%, after a ratio of saturation to inspired oxygen of <90. The probability after meeting the threshold from randomized trials was 9% (MIMIC) and 13% (AmsterdamUMCdb). In MIMIC, a race/ethnicity of Black (OR, 0.75; 95% CrI, 0.57-0.96) or Asian (OR, 0.6; 95% CrI, 0.35-0.95) compared with White was associated with decreased probability of invasive ventilation after meeting a threshold. Conclusions: The probability of invasive ventilation within 3 hours of meeting physiologic thresholds was low and associated with patient race/ethnicity.

Characterizing the limitations of using diagnosis codes in the context of machine learning for healthcare.

BACKGROUND: Diagnostic codes are commonly used as inputs for clinical prediction models, to create labels for prediction tasks, and to identify cohorts for multicenter network studies. However, the coverage rates of diagnostic codes and their variability across institutions are underexplored. The primary objective was to describe lab- and diagnosis-based labels for 7 selected outcomes at three institutions. Secondary objectives were to describe agreement, sensitivity, and specificity of diagnosis-based labels against lab-based labels. METHODS: This study included three cohorts: SickKids from The Hospital for Sick Children, and StanfordPeds and StanfordAdults from Stanford Medicine. We included seven clinical outcomes with lab-based definitions: acute kidney injury, hyperkalemia, hypoglycemia, hyponatremia, anemia, neutropenia and thrombocytopenia. For each outcome, we created four lab-based labels (abnormal, mild, moderate and severe) based on test result and one diagnosis-based label. Proportion of admissions with a positive label were presented for each outcome stratified by cohort. Using lab-based labels as the gold standard, agreement using Cohen's Kappa, sensitivity and specificity were calculated for each lab-based severity level. RESULTS: The number of admissions included were: SickKids (n = 59,298), StanfordPeds (n = 24,639) and StanfordAdults (n = 159,985). The proportion of admissions with a positive diagnosis-based label was significantly higher for StanfordPeds compared to SickKids across all outcomes, with odds ratio (99.9% confidence interval) for abnormal diagnosis-based label ranging from 2.2 (1.7-2.7) for neutropenia to 18.4 (10.1-33.4) for hyperkalemia. Lab-based labels were more similar by institution. When using lab-based labels as the gold standard, Cohen's Kappa and sensitivity were lower at SickKids for all severity levels compared to StanfordPeds. CONCLUSIONS: Across multiple outcomes, diagnosis codes were consistently different between the two pediatric institutions. This difference was not explained by differences in test results. These results may have implications for machine learning model development and deployment.

Opportunities for Continuing Education by Hematology Societies Available to International Trainees.

Continuing education in hematology is a key for stimulating the development around the world and improving patient outcomes. However, access to training and education is not equally distributed worldwide, and disparities in hematology exist for under-represented groups such as trainees living in low- and middle-income countries (LMICs). To identify and review the different educational and career development opportunities offered by hematology-focused international academic societies directed at healthcare professionals in this field. We conducted an online search to screen the official websites of international hematology societies and extracted data regarding continuing education opportunities in hematology. Twenty hematology societies were identified with 850 continuing medical education opportunities extracted and reviewed. We recorded 55 grants and funding opportunities from 13 societies. More than half required a membership to apply, 9.1% were available globally, and 12.7% were designed for persons living in LMICs. The current state of continuing education in hematology offers numerous opportunities for healthcare trainees. However, disparities persist for LMICs.

Feasibility of three times weekly symptom screening in pediatric cancer patients.

OBJECTIVE: Primary objective was to determine the feasibility of three times weekly symptom reporting by pediatric cancer patients for eight weeks. METHODS: We included English-speaking patients 8-18 years of age with cancer. Patients were sent reminders by text or email to complete Symptom Screening in Pediatrics Tool (SSPedi) three times weekly for eight weeks. When patients reported at least one severely bothersome symptom, the symptom report was emailed to the primary healthcare team. Patient-reported outcomes were obtained at baseline, week 4 ± 1 and week 8 ± 1. Symptom documentation, intervention provision for symptoms and unplanned healthcare encounters were determined by chart review at weeks 4 and 8. The primary endpoint was feasibility, defined as at least 75% patients achieving adherence with at least 60% of SSPedi evaluations. We planned to enroll successive cohorts until this threshold was met. RESULTS: Two cohorts consisting of 30 patients (cohort 1 (n = 20) and cohort 2 (n = 10)) were required to meet the feasibility threshold. In cohort 1, 11/20 (55%) met the SSPedi completion threshold. Interventions applied after cohort 1 included engaging parents to facilitate pediatric patient self-report, offering mechanisms to remember username and password and highlighting potential benefits of symptom feedback to clinicians. In cohort 2, 9/10 (90%) met the SSPedi completion threshold and thus feasibility was met. Patient-reported outcomes and chart review outcomes were obtained for all participants in cohort 2. CONCLUSIONS: Three times weekly symptom reporting by pediatric patients with cancer for eight weeks was feasible. Mechanisms to enhance three times weekly symptom reporting were identified and implemented. Future studies of longitudinal symptom screening can now be planned.

Symptom management care pathway adaptation process and specific adaptation decisions.

BACKGROUND: There is substantial heterogeneity in symptom management provided to pediatric patients with cancer. The primary objective was to describe the adaptation process and specific adaptation decisions related to symptom management care pathways based on clinical practice guidelines. The secondary objective evaluated if institutional factors were associated with adaptation decisions. METHODS: Fourteen previously developed symptom management care pathway templates were reviewed by an institutional adaptation team composed of two clinicians at each of 10 institutions. They worked through each statement for all care pathway templates sequentially. The institutional adaptation team made the decision to adopt, adapt or reject each statement, resulting in institution-specific symptom management care pathway drafts. Institutional adaption teams distributed the 14 care pathway drafts to their respective teams; their feedback led to care pathway modifications. RESULTS: Initial care pathway adaptation decision making was completed over a median of 4.2 (interquartile range 2.0-5.3) weeks per institution. Across all institutions and among 1350 statements, 551 (40.8%) were adopted, 657 (48.7%) were adapted, 86 (6.4%) were rejected and 56 (4.1%) were no longer applicable because of a previous decision. Most commonly, the reason for rejection was not agreeing with the statement (70/86, 81.4%). Institutional-level factors were not significantly associated with statement rejection. CONCLUSIONS: Acceptability of the 14 care pathways was evident by most statements being adopted or adapted. The adaptation process was accomplished over a relatively short timeframe. Future work should focus on evaluation of care pathway compliance and determination of the impact of care pathway-consistent care on patient outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT04614662. Registered 04/11/2020, https://clinicaltrials.gov/ct2/show/NCT04614662?term=NCT04614662&draw=2&rank=1 .

Advancing a comprehensive cancer care agenda for children and their families: Institute of Medicine Workshop highlights and next steps.

This article highlights key findings from the "Comprehensive Cancer Care for Children and Their Families" March 2015 joint workshop by the Institute of Medicine (IOM) and the American Cancer Society. This initiative convened more than 100 family members, clinician investigators, advocates, and members of the public to discuss emerging evidence and care models and to determine the next steps for optimizing quality-of-life outcomes and well-being for children and families during pediatric cancer treatment, after treatment completion, and across the life spectrum. Participants affirmed the triple aim of pediatric oncology that strives for every child with cancer to be cured; provides high-quality palliative and psychosocial supportive, restorative, and rehabilitative care to children and families throughout the illness course and survivorship; and assures receipt of high-quality end-of-life care for patients with advancing disease. Workshop outcomes emphasized the need for new pediatric cancer drug development and identified critical opportunities to prioritize palliative care and psychosocial support as an integral part of pediatric cancer research and treatment, including the necessity for adequately resourcing these supportive services to minimize suffering and distress, effectively address quality-of-life needs for children and families at all stages of illness, and mitigate the long-term health risks associated with childhood cancer and its treatment. Next steps include dismantling existing silos and enhancing collaboration between clinical investigators, disease-directed specialists, and supportive care services; expanding the use of patient-reported and parent-reported outcomes; effectively integrating palliative and psychosocial care; and clinical communication skills development. CA Cancer J Clin 2016;66:398-407. © 2016 American Cancer Society.

Reevaluation of sodium thiosulfate otoprotection using the consensus International Society of Paediatric Oncology Ototoxicity Scale: A report from the Children's Oncology Group study ACCL0431.

In two randomized trials (Children's Oncology Group ACCL0431 and International Childhood Liver Tumour Strategy Group SIOPEL-6), sodium thiosulfate (STS) demonstrated efficacy in preventing cisplatin-induced hearing loss (CIHL). However, the measures used in those trials have been superseded by the consensus International Society of Paediatric Oncology (SIOP) Ototoxicity Scale. To provide benchmark data for STS efficacy when using this contemporary scale, we reanalyzed ACCL0431 hearing outcomes with the SIOP scale and using multiple timepoints. Compared to the control arm, STS significantly reduced CIHL when assessed by the SIOP scale across these different approaches. These results provide critical data to inform treatment discussions and support future potential trial designs comparing otoprotectants.

Children's Oncology Group's 2023 blueprint for research: Cancer control and supportive care.

The objective of the Cancer Control and Supportive Care (CCL) Committee in the Children's Oncology Group (COG) is to reduce the overall morbidity and mortality of therapy-related toxicities in children, adolescents, and young adults with cancer. We have targeted five major domains that cause clinically important toxicity: (i) infections and inflammation; (ii) malnutrition and metabolic dysfunction; (iii) chemotherapy-induced nausea and vomiting; (iv) neuro- and oto-toxicty; and (v) patient-reported outcomes and health-related quality of life. Subcommittees for each domain prioritize randomized controlled trials and biology aims to determine which strategies best mitigate the toxicities. The findings of these trials are impactful, informing clinical practice guidelines (CPGs) and directly leading to changes in the standard of care for oncology practice. With the development of new therapies, there will be new toxicities, and the COG CCL Committee is dedicated to developing interventions to minimize acute and delayed toxicities, lessen morbidity and mortality, and improve quality of life in pediatric and young adult patients with cancer.

Children's Oncology Group 2023 blueprint for research: Cancer care delivery research.

The National Cancer Institute (NCI) has a 40-year history of initiatives to encourage the participation of community oncology sites into clinical trials research and clinical care. In 2014, the NCI re-organized to form the NCI Community Oncology Research Program (NCORP) network across seven research bases, including the Children's Oncology Group (COG), and numerous community sites. The COG portfolio for Cancer Care Delivery Research (CCDR), mirroring the larger NCORP network, has included two studies addressing guideline congruence, as an important marker of quality cancer care, and another focusing on financial toxicity, addressing the pervasive problems of healthcare cost. CCDR is a cross-cutting field that frequently examines intersectional aspects of healthcare delivery. With that in mind, we explicitly define domains of CCDR to propel our research agenda into the next phase of the NCORP CCDR program while acknowledging the complex and dynamic fields of clinical care, policy level decisions, research findings, and needs of communities served by the NCORP network that will inform the subsequent research questions. To ensure programmatic success, we will engage a broad interdisciplinary group of investigators and clinicians with expertise and dedication to community oncology and the populations they serve.

Pathologic, cytogenetic, and molecular features of acute myeloid leukemia with megakaryocytic differentiation: A report from the Children's Oncology Group.

BACKGROUND: Acute myeloid leukemia (AML) with megakaryocytic differentiation (AMkL) is a rare subtype of AML more common in children. Recent literature has identified multiple fusions associated with this type of leukemia. METHODS: Morphology, cytogenetics, and genomic sequencing were assessed in patients from Children's Oncology Group trials AAML0531 and AAML1031 with central-pathology review confirmed non-Down syndrome AMkL. The 5-year event-free survival (EFS), overall survival (OS), and RR were evaluated in these AMkL subcategories. RESULTS: A total of 107 cases of AMkL (5.5%) were included. Distinct fusions were identified in the majority: RBM15::MRTFA (20%), CBFA2T3::GLIS2 (16%), NUP98 (10%), KMT2A (7%), TEC::MLLT10 (2%), MECOM (1%), and FUS::ERG (1%); many of the remaining cases were classified as AMkL with (other) myelodysplasia-related changes (MRC). Very few cases had AML-associated somatic mutations. Cases with CBFA2T3::GLIS2 were enriched in trisomy 3 (p = .015) and the RAM phenotype, with associated high CD56 expression (p < .001). Cases with NUP98 fusions were enriched in trisomy 6 (p < .001), monosomy 13/del(13q) (p < .001), trisomy 21 (p = .026), and/or complex karyotypes (p = .026). While different 5-year EFS and OS were observed in AMkL in each trial, in general, those with CBFA2T3::GLIS2 or KMT2A rearrangements had worse outcomes compared to other AMkL, while those with RBM15::MRTFA or classified as AMkl-MRC fared better. AMkL with NUP98 fusions also had poor outcomes in the AAML1031 trial. CONCLUSION: Given the differences in outcomes, AMkL classification by fusions, cytogenetics, and morphology may be warranted to help in risk stratification and therapeutic options.

Treatment of breakthrough and prevention of refractory chemotherapy-induced nausea and vomiting in pediatric cancer patients: Clinical practice guideline update.

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made.

Oxygenation thresholds for invasive ventilation in hypoxemic respiratory failure: a target trial emulation in two cohorts.

BACKGROUND: The optimal thresholds for the initiation of invasive ventilation in patients with hypoxemic respiratory failure are unknown. Using the saturation-to-inspired oxygen ratio (SF), we compared lower versus higher hypoxemia severity thresholds for initiating invasive ventilation. METHODS: This target trial emulation included patients from the Medical Information Mart for Intensive Care (MIMIC-IV, 2008-2019) and the Amsterdam University Medical Centers (AmsterdamUMCdb, 2003-2016) databases admitted to intensive care and receiving inspired oxygen fraction ≥ 0.4 via non-rebreather mask, noninvasive ventilation, or high-flow nasal cannula. We compared the effect of using invasive ventilation initiation thresholds of SF < 110, < 98, and < 88 on 28-day mortality. MIMIC-IV was used for the primary analysis and AmsterdamUMCdb for the secondary analysis. We obtained posterior means and 95% credible intervals (CrI) with nonparametric Bayesian G-computation. RESULTS: We studied 3,357 patients in the primary analysis. For invasive ventilation initiation thresholds SF < 110, SF < 98, and SF < 88, the predicted 28-day probabilities of invasive ventilation were 72%, 47%, and 19%. Predicted 28-day mortality was lowest with threshold SF < 110 (22.2%, CrI 19.2 to 25.0), compared to SF < 98 (absolute risk increase 1.6%, CrI 0.6 to 2.6) or SF < 88 (absolute risk increase 3.5%, CrI 1.4 to 5.4). In the secondary analysis (1,279 patients), the predicted 28-day probability of invasive ventilation was 50% for initiation threshold SF < 110, 28% for SF < 98, and 19% for SF < 88. In contrast with the primary analysis, predicted mortality was highest with threshold SF < 110 (14.6%, CrI 7.7 to 22.3), compared to SF < 98 (absolute risk decrease 0.5%, CrI 0.0 to 0.9) or SF < 88 (absolute risk decrease 1.9%, CrI 0.9 to 2.8). CONCLUSION: Initiating invasive ventilation at lower hypoxemia severity will increase the rate of invasive ventilation, but this can either increase or decrease the expected mortality, with the direction of effect likely depending on baseline mortality risk and clinical context.