Isolated central nervous system relapse in two adolescents with primary mediastinal large B-cell lymphoma after treatment with R-DA-EPOCH.

The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.

Outcomes of proton therapy to infradiaphragmatic sites in pediatric patients with Hodgkin lymphoma.

BACKGROUND: Proton therapy (PT) has potential advantages in pediatric Hodgkin lymphoma (pHL). However, there are limited data on PT, specifically to infradiaphragmatic targets. We report on PT planning details, doses achieved to organs at risk (OARs), and clinical and toxicity outcomes for patients with pHL who received PT to infradiaphragmatic regions. METHODS: This is a retrospective study including patients treated between 2011 and 2022. Demographic and clinical factors were collected, and toxicity was reported using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Dosimetric and clinical factors associated with key outcomes were assessed via Cox regression. Photon plans were generated for all patients, and the paired t-tests or Wilcoxon signed rank sum tests were used for dosimetric comparisons. RESULTS: Twenty-one patients comprising 22 PT courses were included. Median follow-up was 5.0 years, and mean age was 14.2 years. Median dose was 21 Gray equivalent (GyE) over 14 fractions. Top acute grade 1 (G1) toxicities included fatigue (59%) and anorexia (36%). Rates of acute G2 and G3+ toxicity were 18% and 0%, respectively. After PT, no local or marginal failures occurred. Five percent experienced disease progression, who were all successfully salvaged, and all patients were alive and disease-free at last follow-up. No secondary malignancies developed. Compared to photon radiotherapy, PT achieved significantly lower doses to the bowels, stomach, spleen, pancreatic tail, liver, kidneys, and pelvic bones. CONCLUSIONS: PT is well-tolerated and leads to excellent oncologic and toxicity outcomes with long-term follow-up. PT confers dosimetric advantages when compared to photons.

Management considerations of Hodgkin lymphoma for patients with Fontan physiology.

While treatment protocols for Hodgkin lymphoma (HL) are well established, there is no literature available to guide therapy or estimate prognosis for patients with Fontan physiology who develop HL. The physiology of a Fontan procedure can result in the inability to tolerate chemotherapy toxicities, supportive care, and infection. We present a series of three patients with Fontan physiology who were treated for HL and discuss their clinical course and treatment.

Pediatric Hodgkin Lymphoma, Version 3.2021.

Hodgkin lymphoma (HL) is a highly curable form of cancer, and current treatment regimens are focused on improving treatment efficacy while decreasing the risk of late effects of treatment. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric HL provide recommendations on the workup, diagnostic evaluation, and treatment of classic HL, including principles of pathology, imaging, staging, systemic therapy, and radiation therapy. This portion of the NCCN Guidelines focuses on the management of pediatric classic HL in the upfront and relapsed/refractory settings.

Active learning for fellows: The hematopathology "unknown case".

The pediatric hematology/oncology fellowship program at the Children's Hospital of Philadelphia set out to create a case-based learning curriculum for common hematologic malignancies that would apply principles of adult learning theory and improve fellows' retention of information in a supportive, goal-oriented learning environment. A framework we employed in developing this curriculum is that of "flow theory," which parallels many of the tenets of adult learning theory. After implementing this curriculum, which we call "the unknown case," the percentage of fellows correctly identifying a common hematopathologic diagnosis improved from 50% to 85%.

Daily text message assessments of 6-mercaptopurine adherence and its proximal contexts in adolescents and young adults with leukemia: A pilot study.

BACKGROUND: This pilot study explored the feasibility and acceptability of implementing text-based assessments of oral chemotherapy adherence in adolescents and young adults (AYA) with leukemia. METHODS: AYA prescribed maintenance 6-mercaptopurine (6MP) received daily text message surveys and utilized an electronic pill bottle for 28 days. Text surveys assessed 6MP adherence and contextual associates (eg, mood). Feasibility was defined by recruitment/retention rates, survey completion rates, cost, and technical issues. After the 28-day period, AYA completed an acceptability survey. Secondary analyses compared text survey and electronic pill bottle adherence rates, and explored the daily associations between contextual factors and 6MP nonadherence. RESULTS: Eighteen AYA enrolled (M age = 18, range 15-22) and completed study procedures (100% recruitment and retention rates). Adherence survey completion rates were high (M = 88.9%), the technology cost was $204.00, and there were few technical issues. AYA reported high satisfaction with the surveys and perceived them as a helpful medication reminder. While not significantly correlated, survey and electronic pill bottle adherence data converged on the majority of days (>90%). Exploratory analyses showed that AYA were more likely to miss a dose of 6MP on weekends (OR = 2.33, P = .048) and on days when their adherence motivation (OR = 0.28, P = .047) and negative affect (OR = 3.92, P = .02) worsened from their own typical functioning. CONCLUSIONS: For AYA with leukemia, daily text-based surveys are a feasible and acceptable method for delivering medication adherence assessments, and may operate as a short-term intervention. To develop personalized mobile health interventions, findings also highlighted the need to study time-varying predictors of 6MP nonadherence.

An Usual Presentation of Pneumocystis jirovecii Pneumonia in a Woman Treated With Immune Checkpoint Inhibitor.

We describe a case of Pneumocystis jirovecii pneumonia in an 18-year-old female individual with refractory primary mediastinal B-cell lymphoma treated with the immune checkpoint inhibitor pembrolizumab. She received 11 doses of pembrolizumab without immune-related adverse events (irAEs) before the diagnosis of P. jirovecii pneumonia. However, prophylactic trimethoprim/sulfamethoxazole was discontinued 6 months of postautologous stem cell transplant per standard guidelines. This case report highlights the importance of judicious infectious disease evaluation while on immune checkpoint inhibitor therapy as symptoms can often mimic irAEs. Furthermore, the benefits of immunosuppressive therapy for the treatment of presumptive irAEs must be weighed against the possible increased risk for opportunistic infections.

Feasibility and acceptability of a pilot tailored text messaging intervention for adolescents and young adults completing cancer treatment.

PURPOSE: Despite cure, adolescents and young adults (AYA) who complete cancer treatment remain at risk for numerous physical and psychological late effects. However, engagement in recommended follow-up care, knowledge of cancer treatment history and risks, and adoption of health promoting behaviors are often suboptimal. The pilot randomized controlled trial assessed the feasibility and acceptability of a text messaging intervention (THRIVE; Texting Health Resources to Inform, motiVate, and Engage) designed to promote well-being, and health knowledge and behaviors. METHODS: Sixty-one AYA who recently completed cancer therapy enrolled and were randomized to receive THRIVE (n = 31) or an AYA survivor handbook (n = 30). Participants from both groups completed baseline measures and follow-up surveys 16 weeks later. AYA randomized to THRIVE received one to two health-related text messages per day over 16 weeks. RESULTS: THRIVE demonstrated a high level of acceptability and feasibility. Exploratory analyses highlighted promising improvements in knowledge, fruit/vegetable intake, and perceptions of health vulnerability. CONCLUSIONS: Text messaging is an acceptable and feasible intervention approach for improving well-being and health of AYA survivors. Future research is needed to test the impact of text messaging in a larger trial, including whether or not such an intervention can improve clinical outcomes, such as survivors' engagement in follow-up care.

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.

Measuring pediatric hematology-oncology fellows' skills in humanism and professionalism: A novel assessment instrument.

BACKGROUND: Educators in pediatric hematology-oncology lack rigorously developed instruments to assess fellows' skills in humanism and professionalism. PROCEDURE: We developed a novel 15-item self-assessment instrument to address this gap in fellowship training. Fellows (N = 122) were asked to assess their skills in five domains: balancing competing demands of fellowship, caring for the dying patient, confronting depression and burnout, responding to challenging relationships with patients, and practicing humanistic medicine. An expert focus group predefined threshold scores on the instrument that could be used as a cutoff to identify fellows who need support. Reliability and feasibility were assessed and concurrent validity was measured using three established instruments: Maslach Burnout Inventory (MBI), Flourishing Scale (FS), and Jefferson Scale of Physician Empathy (JSPE). RESULTS: For 90 participating fellows (74%), the self-assessment proved feasible to administer and had high internal consistency reliability (Cronbach's α = 0.81). It was moderately correlated with the FS and MBI (Pearson's r = 0.41 and 0.4, respectively) and weakly correlated with the JSPE (Pearson's r = 0.15). Twenty-eight fellows (31%) were identified as needing support. The self-assessment had a sensitivity of 50% (95% confidence interval [CI]: 31-69) and a specificity of 77% (95% CI: 65-87) for identifying fellows who scored poorly on at least one of the three established scales. CONCLUSIONS: We developed a novel assessment instrument for use in pediatric fellowship training. The new scale proved feasible and demonstrated internal consistency reliability. Its moderate correlation with other established instruments shows that the novel assessment instrument provides unique, nonredundant information as compared to existing scales.

Pediatricians' Experience with Clinical Ethics Consultation: A National Survey.

OBJECTIVE: To conduct a national survey of pediatricians' access to and experience with clinical ethics consultation. STUDY DESIGN: We surveyed a randomly selected sample of 3687 physician members of the American Academy of Pediatrics. We asked about their experiences with ethics consultation, the helpfulness of and barriers to consultation, and ethics education. Using a discrete choice experiment with maximum difference scaling, we evaluated which traits of ethics consultants were most valuable. RESULTS: Of the total sample of 3687 physicians, 659 (18%) responded to the survey. One-third of the respondents had no experience with clinical ethics consultation, and 16% reported no access to consultation. General pediatricians were less likely to have access. The vast majority (90%) who had experience with consultation had found it helpful. Those with fewer years in practice were more likely to have training in ethics. The most frequently reported issues leading to consultation concerned end-of-life care and conflicts with patients/families or among the team. Intensive care unit physicians were more likely to have requested consultation. Mediation skills and ethics knowledge were the most highly valued consultant characteristics, and representing the official position of the hospital was the least-valued characteristic. CONCLUSION: There is variability in pediatricians' access to ethics consultation. Most respondents reported that consultation had been helpful in the past. Determining ethically appropriate end-of-life care and mediation of disagreements are common reasons that pediatricians request consultation.

Humanism and professionalism education for pediatric hematology-oncology fellows: A model for pediatric subspecialty training.

BACKGROUND: Humanism and professionalism are virtues intrinsic to the practice of medicine, for which we lack a standard, evidence-based approach for teaching and evaluation. Pediatric hematology-oncology (PHO) fellowship training brings new and significant stressors, making it an attractive setting for innovation in humanism and professionalism training. PROCEDURE: We electronically surveyed a national sample of PHO fellows to identify fellows' educational needs in humanism and professionalism. Next, we developed a case-based, faculty-facilitated discussion curriculum to teach this content within pilot fellowship programs. We assessed whether fellowships would decide to offer the curriculum, feasibility of administering the curriculum, and satisfaction of fellow and faculty participants. RESULTS: Surveys were completed by 187 fellows (35%). A minority (29%) reported that their training program offers a formal curriculum in humanism and/or professionalism. A majority desires more formal teaching on balancing clinical practice and research (85%), coping with death/dying (85%), bereavement (78%), balancing work and personal life (75%), navigating challenging relationships with patients (74%), and depression/burn out (71%). These six topics were condensed into four case-based modules, which proved feasible to deliver at all pilot sites. Ten fellowship programs agreed to administer the novel curriculum. The majority (90%) of responding fellows and faculty reported the sessions touched on issues important for training, stimulated reflective communication, and were valuable. CONCLUSIONS: Pediatric hematology-oncology fellows identify numerous gaps in their training related to humanism and professionalism. This curriculum offers an opportunity to systematically address these educational needs and can serve as a model for wider implementation. Pediatr Blood Cancer 2015;62:335-340. © 2014 Wiley Periodicals, Inc.

Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at United States free-standing children's hospitals with de novo acute lymphoblastic leukemia from health care administrative data.

BACKGROUND: Acute lymphoblastic leukemia (ALL) accounts for almost one quarter of pediatric cancer in the United States. Despite cooperative group therapeutic trials, there remains a paucity of large cohort data on which to conduct epidemiology and comparative effectiveness research studies. RESEARCH DESIGN: We designed a 3-step process utilizing International Classification of Diseases-9 Clinical Modification (ICD-9) discharge diagnoses codes and chemotherapy exposure data contained in the Pediatric Health Information System administrative database to establish a cohort of children with de novo ALL. This process was validated by chart review at 1 of the pediatric centers. RESULTS: An ALL cohort of 8733 patients was identified with a sensitivity of 88% [95% confidence interval (CI), 83%-92%] and a positive predictive value of 93% (95% CI, 89%-96%). The 30-day all cause inpatient case fatality rate using this 3-step process was 0.80% (95% CI, 0.63%-1.01%), which was significantly different than the case fatality rate of 1.40% (95% CI, 1.23%-1.60%) when ICD-9 codes alone were used. CONCLUSIONS: This is the first report of assembly and validation of a cohort of de novo ALL patients from a database representative of free-standing children's hospitals across the United States. Our data demonstrate that the use of ICD-9 codes alone to establish cohorts will lead to substantial patient misclassification and result in biased outcome estimates. Systematic methods beyond the use of just ICD-9 codes must be used before analysis to establish accurate cohorts of patients with malignancy. A similar approach should be followed when establishing future cohorts from administrative data.

CLL/SLL diagnosed in an adolescent.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a disease of older adults. Pediatric CLL/SLL is vanishingly rare in the literature. We present a case of CLL/SLL diagnosed in a 17-year-old male. The pathologic findings of this case were those of classic CLL/SLL with an ATM deletion, a characteristic genetic abnormality in CLL/SLL. Management guidelines for CLL/SLL are tailored to older adults making determination of the optimal therapy for this patient a unique challenge.

Patient and hospital factors associated with induction mortality in acute lymphoblastic leukemia.

BACKGROUND: Deaths during induction chemotherapy for pediatric acute lymphoblastic leukemia (ALL) account for one-tenth of ALL-associated mortality and half of ALL treatment-related mortality. We sought to ascertain patient- and hospital-level factors associated with induction mortality. PROCEDURE: We performed a retrospective cohort analysis of 8,516 children ages 0 to <19 years with newly diagnosed ALL admitted to freestanding US children's hospitals from 1999 to 2009 using the Pediatric Health Information System database. Induction mortality risk was modeled accounting for demographics, intensive care unit-level interventions, and socioeconomic status (SES) using Cox regression. The association of ALL induction mortality with hospital-level factors including volume, hospital-wide mortality and payer mix was analyzed with multiple linear regression. RESULTS: ALL induction mortality was 1.12%. Race and patient-level SES factors were not associated with induction mortality. Patients receiving both mechanical ventilation and vasoactive infusions experienced nearly 50% mortality (hazard ratio 122.30, 95% CI 66.56-224.80). Institutions in the highest induction mortality quartile contributed 27% of all patients but nearly half of all deaths (47 of 95). Hospital payer mix was associated with ALL induction mortality after adjustment for other hospital-level factors (P = 0.046). CONCLUSIONS: The overall risk of induction death is low but substantially increased in patients with cardio-respiratory and other organ failures. Induction mortality varies up to three-fold across hospitals and is correlated with hospital payer mix. Further work is needed to improve induction outcomes in hospitals with higher mortality. These data suggest an induction mortality rate of less than 1% may be an attainable national benchmark.

Oncology house physician model: a response to changes in pediatric resident coverage.

BACKGROUND: Given decreasing resident duty hours, subspecialty hospitalist models have emerged to help compensate for the restructured presence of residents. We sought to examine the impact of our pediatric oncology hospitalist model on the oncology unit staff. PROCEDURE: The survey was developed after a literature review of subspecialty hospitalist models. The final surveys were designed using a 5-point Likert scale. Descriptive statistics were used to compile baseline demographic characteristics of respondents and overall responses to survey questions. RESULTS: Respondents agreed that house physicians provide better continuity of care (96.8%), are more comfortable with the experience level of the physician (98.4%), and are better able to answer questions (92%). Respondents also agreed that house physicians serve as backup for system-related and patient-related questions and found security knowing an experienced provider was on the floor (87.5%). Responses to open-ended questions indicated that the house physician model has impacted fellow education. CONCLUSIONS: Our oncology house physician model helps account for decreased residency duty hours. This can serve as a model for other institutions requiring subspecialty inpatient coverage, given resident work hour restrictions. Adjustments in the clinical education of hematology/oncology fellows need to be considered in the setting of competent, consistent, and experienced front-line providers.

Protecting pediatric oncology patients from influenza.

Influenza is a common respiratory pathogen. Its severity can be unpredictable, but people with chronic illness are at increased risk of severe infection, complications, and death from influenza. This review examines evidence to support various strategies to protect pediatric oncology patients from influenza-related morbidity. Influenza vaccination should be considered standard. Additional evidence-supported measures include antiviral treatment, antiviral prophylaxis, cohorting of patients, and hospital infection control measures. Data from other high-risk populations support the vaccination of family members, double-dose or high-dose vaccination, and the use of barrier methods. These measures have the potential to optimize patient outcomes because there will be fewer treatment interruptions for acute illness. These strategies can also protect patients from prolonged hospitalizations and morbidity related to influenza.

Immunologic consequences of chemotherapy for acute myeloid leukemia.

There are few data characterizing the immunologic consequences of chemotherapy for acute myeloid leukemia (AML) and almost nothing is known about the effects of chemotherapy in a pediatric AML cohort. We identified T-cell subsets, B-cell subsets, and used Enzyme-linked immunosorbent spot analyses to define the function of T cells and B cells in 7 pediatric patients with AML on chemotherapy. The data show that the effects of chemotherapy disproportionately target the B cell and depletion of B cells is associated with impaired responses to the inactivated influenza vaccine. Diminished T-cell numbers were also observed although the magnitude of the effect was less than what was seen for B cells. Furthermore, measures of T-cell function were largely intact. We conclude that humoral immunity is significantly affected by chemotherapy for AML.

A revision of the intensity of treatment rating scale: classifying the intensity of pediatric cancer treatment.

BACKGROUND: We previously developed a reliable and valid method for classifying the intensity of pediatric cancer treatment. The Intensity of Treatment Rating Scale (ITR-2.0) 1 classifies treatments into four operationally defined levels of intensity and is completed by pediatric oncology specialists based on diagnosis, stage, and treatment data from the medical record. Experience with the ITR-2.0 and recent changes in treatment protocols indicated the need for a minor revision and revalidation. METHODS: Five criterion raters reviewed the prior items, independently proposing additions and/or changes in the classification of diseases/treatments. Subsequent to a group discussion of the proposed changes, a revised 43-item ITR was evaluated. Pediatric oncologists (n = 47) completed a two-part online questionnaire. Validity of the classifications was determined by the oncologists classifying each disease/treatment into one of the four levels of intensity. Inter-rater reliability was calculated by having each oncologist classify the treatments of 12 sample patients using the new version which we call the ITR-3. RESULTS: Agreement between median ratings of the 43 items for the pediatric oncologists and the criterion raters was high (r = 0.88). The median of the raters was either identical (81%) with the criterion ratings or discrepant by one level. Inter-rater reliability was very high when using the ITR-3 to classify 12 sample patients, with a median agreement of 0.90 and an intraclass correlation coefficient (r(ICC) = 0.86). CONCLUSIONS: With these minor modifications and updates, the ITR-3 remains a reliable and valid method for classifying pediatric oncology treatment protocols.