6-Mercaptopurine-Associated Sinusoidal Obstructive Syndrome During Interim Maintenance I: A Case Report.

Thiopurine-methyltransferase (TPMT) and nudix-hydrolase-15 (NUDT15) are enzymes relevant to the metabolism of thiopurine medications, used to treat immunologic disorders and malignancies. Standard dosing administered in the setting of TPMT/NUDT15 dysfunction can cause excessive cytotoxic metabolites and life-threatening complications. We describe an adolescent with high-risk B-cell acute lymphoblastic leukemia (ALL) whose TPMT/NUDT15 status was unknown due to lack of insurance approval for genetic testing. He subsequently developed myelosuppression and severe veno-occlusive disease (VOD) after receiving 6-mercaptopurine (6-MP). Our patient provides an example of a very rare 6-MP-related toxicity and the potential benefit of TPMT/NUDT15 screening before initiating thiopurine therapy.

A Midwest Stakeholder Evaluation of an Adolescent and Young Adult Cancer Survivor Needs Assessment Survey.

Purpose: Over 87,000 adolescents and young adults (AYAs) are diagnosed with cancer in the United States each year. Improvement in outcomes in the AYA population has lagged that of both younger and older patients. This decrement may be attributable to several factors, including insufficient supportive care services. Our team modified the Needs Assessment & Service Bridge (NA-SB) tool, utilizing an iterative approach with patient and clinician stakeholders to meet the needs of the AYA population at a large Midwestern Cancer Center. Methods: We recruited a 10-member AYA Advisory Board (AB) from our Cancer Center patients, and met five times over 9 months to discuss supportive care and the NA-SB. We recruited a multidisciplinary group of oncology clinicians to assess content validity and conducted interviews with nine clinician stakeholders to discuss implementation. Results: The AB generated a 59-item-modified NA-SB, retaining most of the original NA-SB items and adding several more. Five items with concerns for relevance and/or clarity were revised to create the final 58-item-modified NA-SB. Priorities for implementation were identified by AB and clinician stakeholders. Conclusions: The modified NA-SB thoroughly reflects supportive care needs of our Midwestern AYA cancer survivors. When implemented, the tool may facilitate patient-care team communication and provide data to prioritize development of new supportive care resources. AYA cancer survivors have unique supportive care needs that are insufficiently addressed by current care models; using the modified NA-SB may help address those needs, leading to improved AYA outcomes.

Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

Benefit of Interdisciplinary Care in Resource Identification in an Adolescent and Young Adult Oncology Care Model.

Purpose: There are limited data to identify the best care model to support the vulnerable adolescent and young adult (AYA) oncology population. We sought to compare the impact of AYA physician visits versus interdisciplinary team (IDT) care on AYA-specific resource identification and utilization, as well as to provide a model of AYA oncology care implementation. Methods: We identified AYA-aged patients 15-39 years with a current or prior history of cancer seen by the University of Wisconsin Carbone Cancer Center (UWCCC) AYA Oncology Program between January 21, 2021 and May 27, 2021. Patients in this program have a one-on-one clinic visit with an AYA oncologist followed 4 days later by presentation at an AYA IDT meeting. We conducted retrospective chart review to quantify AYA-specific resource utilization before the AYA program visit, as well as novel resources identified by the AYA physician visit and the IDT meeting, and conducted a descriptive statistical analysis of the data. Results: We identified 35 patients seen by the UWCCC AYA Oncology Program. Before their AYA clinic visit, patients used an average of 2.51 AYA-specific services. An average of 4.45 novel resources was identified by the AYA Oncology Program per patient. This included an average of 2.54 and 1.91 additional resources identified per patient through the AYA physician visit and IDT meeting, respectively. The most common resource needs identified overall fell into the "other" category, consisting of a wide variety of resource domains (26/35) and peer support (27/35). Conclusions: Our data support increased resource identification through an AYA-specific care model. These objective data support the critical importance of AYA interdisciplinary care, as well as the use of an AYA IDT meeting model as a method to include interdisciplinary care in AYA programs despite possible resource constraints.

Pre-Treatment Left Ventricular Ejection Fraction Assessment and Long-Term Cardiovascular Outcomes in Adolescent and Young Adult Lymphoma Survivors.

Purpose: Anthracyclines can cause long-term cardiovascular (CV) morbidity, especially in long-term Adolescent and Young Adult (AYA) lymphoma survivors. Pre-treatment left ventricular ejection fraction (LVEF) evaluation is recommended, although its utility in AYA is not established. We sought to determine the pre-treatment LVEF assessment practices in AYA lymphoma survivors treated with anthracyclines and factors associated with long-term cardiotoxicity. Methods: Through an electronic health records review, we retrospectively identified AYA lymphoma survivors with ≥5 years of follow-up postanthracycline treatment. Pre-treatment and follow-up data were abstracted. CV health conditions were defined as risk factors for CV disease and confirmed CV diagnoses. Survivors who had new CV health conditions at follow-up were compared to those who were not using descriptive statistics and logistic regression. Results: One hundred fifteen AYA lymphoma survivors met the study criteria. Pre-treatment LVEF assessment did not affect chemotherapy decisions. Survivors with pre-treatment CV evaluation had mean follow-up since diagnosis of 8 ± 3.3 years, while survivors without it had 10.3 ± 4.2 years, p < 0.05. Survivors with pre-treatment LVEF assessment received lower cumulative anthracycline dose (240.4 mg/m2 vs. 280.1 mg/m2, p < 0.05) and fewer cycles of chemotherapy (4.8 ± 1.5 vs. 5.6 ± 1.2, p < 0.05). Body mass index (BMI) category at diagnosis and follow-up, in addition to age were associated with development of new CV health conditions, pre-treatment LVEF evaluation was not. Conclusion: Pre-treatment LVEF assessment for AYA lymphoma survivors does not impact oncologic treatment decisions or development of CV health conditions. It may be more valuable to assess and modify CV risk factors such as BMI for CV disease prevention.

Pediatric Aggressive Mature B-Cell Lymphomas, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.

Disparities in Treatment Satisfaction and Supportive Care Receipt for Young Adult Oncology Patients on the Basis of Residential Location.

PURPOSE: Adolescent and young adult oncology programs are critical but exist primarily in academic centers, prompting potential disparities in care on the basis of patient residence. We studied the impact of residential location on supportive care receipt and treatment satisfaction in young adults (YAs) with cancer age 19-39 years treated at the University of Wisconsin Carbone Cancer Center (UWCCC). METHODS: YA patients with cancer age 19-39 years seen at UWCCC from March 30, 2019, to March 29, 2020, were sent a survey assessing supportive care receipt and satisfaction. Survey results were compared with retrospective chart review of YAs seen at UWCCC between April 1, 2011, and April 1, 2021. Data were categorized on the basis of residential location using distance from UWCCC and 2013 Rural-Urban Continuum Code (RUCC). RESULTS: Survey results were obtained for 145 YAs, including 29 from nonmetro RUCC (20.0%) and 81 living > 20 miles from UWCCC (55.9%). YAs from nonmetro locations had lower satisfaction with available treatments (79.3% v 91.4%, P = .005), and distant YAs living > 20 miles from UWCCC more frequently identified location as a barrier to supportive care receipt (35.6% v 15.8%, P = .02). Metro YAs more frequently listed fertility consultations as unavailable (38.0% v 16.0%, P = .04) in the survey despite chart review data showing higher rates of sexual health assessments (48.2% v 20.4%, P = .002) and fertility visits (29.6% v 18.5%, P = .18). CONCLUSION: We identified differences in both supportive care receipt and treatment satisfaction on the basis of residential location. These findings support the need for measures to successfully meet treatment and supportive care needs regardless of residential location.

Disparities Between Provider Assessment and Documentation of Care Needs in the Care of Adolescent and Young Adult Patients With Sarcoma.

PURPOSE: Given the occurrence of cancer during a complex developmental time, adolescent and young adult (AYA) patients have unique psychosocial needs that necessitate supportive care, which is optimally provided using National Comprehensive Cancer Network (NCCN) AYA guidelines. We sought to explore compliance with NCCN AYA guidelines and compare with oncology providers' perceptions of AYA care needs. METHODS: Retrospective chart reviews of AYA patients (15-39 years at time of cancer diagnosis) with sarcoma seen at least once in 2019 at the University of Wisconsin identified documentation of discussions deemed critical per NCCN AYA guidelines. As per the ASCO Quality Oncology Practice Initiative certification, we considered a threshold of these factors being discussed 75% of the time or higher to be compliant. Compliance was compared with an electronic survey of University of Wisconsin oncology providers regarding AYA patient needs, with items determined to have adequate resources if noted sufficient by at least 75% of providers. RESULTS: We identified 43 AYA patients with sarcoma. Less than 75% of patients had documentation of discussion of contraception, sexual health, fertility, finances, genetics, social work referral, and clinical trials indicating noncompliance with NCCN guidelines. Surveys, completed by 38 oncology providers, showed significant discordance between providers' perceptions of AYAs' access to resources and providers' documented discussions of supportive care resources. CONCLUSION: Disparities between oncology provider assessment of AYA care needs and documentation of critical components of AYA patient care demonstrate the need for novel tools to evaluate AYA care needs beyond provider assessments.

Humanism and professionalism training for pediatric hematology-oncology fellows: Results of a multicenter randomized trial.

PURPOSE: Although humanism and professionalism are central tenets to the practice of medicine, few formal curricula exist for medical trainees. Following a national needs assessment among pediatric hematology-oncology (PHO) fellows, we created a novel curriculum entitled "Humanism and Professionalism for Pediatric Hematology-Oncology" (HP-PHO). In this study, we measure outcomes of this curricular intervention. METHOD: We cluster-randomized 20 PHO fellowship programs to deliver usual training in humanism and professionalism (UT) or the novel curriculum (intervention) during the 2016-2017 academic year. The primary outcome measure was the Pediatric Hematology-Oncology Self-Assessment in Humanism (PHOSAH). Secondary measures included the Maslach Burnout Inventory, Patient-Provider Orientation Scale, Empowerment at Work Scale, and a 5-point satisfaction scale. Participating fellows completed pre- and posttests at the beginning and end of the academic year, respectively, and we calculated change scores for each study instrument. RESULTS: Cluster randomization yielded 59 intervention and 41 UT fellows. The nine intervention sites administered 33 of 36 modules. Change scores on the PHOSAH were not significantly different between the UT and intervention arms. However, fellows on the intervention arm gave significantly higher ratings on several items within the satisfaction scale related to physician burnout, physician depression, balancing professional duties and personal life, and humanism overall. CONCLUSIONS: Exposure to the HP-PHO curriculum did not alter fellows' self-assessed humanism and professionalism skills. However, intervention fellows expressed significantly higher levels of satisfaction in their humanism training, indicating the curriculum's potential for positive impact on the fellows' perceived learning environment.

Calling Consults: A Workshop to Teach Trainees Using Both Didactic and Small Group-based Learning.

Background: Safe patient care includes effective communication. The Accreditation Council for Graduate Medical Education common program requirements include core requirements for trainees to act in a consultative manner and communicate effectively. However, trainees do not commonly receive formal education on this topic. Objective: We created a 1-hour workshop to teach residents and fellows how to effectively call consults, including how to formulate a cogent and comprehensive consult question. Methods: The workshop, delivered over a 1-hour noon conference, included a didactic portion and interactive small-group case-based learning. We used pre- and postworkshop surveys to assess learners' prior training, knowledge, and comfort levels in calling consults. Subspecialists answered a separate survey about the quality of consults received from trainees before and 30 days after the workshop. Results: Seventy-three trainees attended the workshop (41.2% of total trainees invited). After the workshop, the percentage of learners who identified as very or somewhat comfortable with calling consults increased from 82% to 91%. Before the workshop, 87% of trainees could identify key elements in a consult, which increased to 100% after the workshop. There was not a statistically significant improvement in subspecialists' ratings of the overall quality of consults they received 30 days after the workshop. Conclusion: Training learners on the key components and etiquette of calling consults is crucial for the development of effective communication among providers. This training is generally lacking from undergraduate medical education; thus, it is important to provide education in calling consults during residency and fellowship.

IL12 Abrogates Calcineurin-Dependent Immune Evasion during Leukemia Progression.

Exploitation of the immune system has emerged as an important therapeutic strategy for acute lymphoblastic leukemia (ALL). However, the mechanisms of immune evasion during leukemia progression remain poorly understood. We sought to understand the role of calcineurin in ALL and observed that depletion of calcineurin B (CnB) in leukemia cells dramatically prolongs survival in immune-competent but not immune-deficient recipients. Immune-competent recipients were protected from challenge with leukemia if they were first immunized with CnB-deficient leukemia, suggesting robust adaptive immunity. In the bone marrow (BM), recipients of CnB-deficient leukemia harbored expanded T-cell populations as compared with controls. Gene expression analyses of leukemia cells extracted from the BM identified Cn-dependent significant changes in the expression of immunoregulatory genes. Increased secretion of IL12 from CnB-deficient leukemia cells was sufficient to induce T-cell activation ex vivo, an effect that was abolished when IL12 was neutralized. Strikingly, recombinant IL12 prolonged survival of mice challenged with highly aggressive B-ALL. Moreover, gene expression analyses from children with ALL showed that patients with higher expression of either IL12A or IL12B exhibited prolonged survival. These data suggest that leukemia cells are dependent upon calcineurin for immune evasion by restricting the regulation of proinflammatory genes, particularly IL12. SIGNIFICANCE: This report implicates calcineurin as an intracellular signaling molecule responsible for immune evasion during leukemia progression and raises the prospect of re-examining IL12 as a therapeutic in leukemia.

Multicentric Castleman disease presenting with fever.

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder that usually manifests with nonspecific symptoms, including fever and lymphadenopathy. Treatment of pediatric MCD varies greatly. A 21-month-old child was diagnosed with MCD after presenting with fever. He had incomplete response to initial therapy directed at interleukin-6, but improved with subsequent chemotherapy.