Background Pain is a common and distressing symptom for pediatric patients with acute lymphoblastic leukemia (ALL), arising from the disease itself, its treatment, and associated medical procedures. The early phase of treatment is particularly challenging, as children experience multiple, rapidly evolving sources of pain. Despite its prevalence, pain during this period remains poorly characterized. This study qualitatively examined pain experiences among children with ALL during induction and early consolidation.Methods Twenty caregivers of children with ALL (ages 2-17) and eight patients (ages 8-17) participated in two semi-structured interviews capturing pain experiences across early treatment. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis.Results Eight themes described key dimensions of the pain experience: Sources of Pain, Pain Characteristics, Pain-Related Symptoms, Factors Influencing Pain, Pain Impact, Pain Expression, Pain Management Tools, and Barriers to Pain Management. These themes reflected the evolving, multidimensional nature of pain during early treatment.Conclusions Children with ALL experience substantial and multifaceted pain early in their cancer trajectory. Findings underscore the need for early, developmentally informed, and family-centered approaches to pain assessment and management that address the complex and evolving nature of pain during initial treatment.

BACKGROUND:Despite their increased risk for functional impairment resulting from cancer and its treatments, few adolescents and young adults (AYAs) with a hematological malignancy receive the recommended or therapeutic dose of exercise per week during inpatient hospitalizations. Physical therapy (PT) plays a critical role in promoting and supporting exercise in the hospital setting; however, little is known about the factors that influence AYA engagement in PT. This qualitative study aimed to explore barriers and facilitators to inpatient PT through the perspectives of AYAs and healthcare providers. PROCEDURE:AYAs with cancer (n = 14) and healthcare providers (n = 9) were recruited at a pediatric academic medical center. Participants completed a semi-structured interview assessing barriers and facilitators to inpatient PT adherence. Interviews were video/audio-recorded, transcribed, and coded. Codes and themes were developed iteratively using reflexive thematic analysis. RESULTS:AYAs (15-29 years, M = 18.95, SD = 3.68) and healthcare providers discussed four primary themes affecting inpatient PT engagement. The themes suggested that social support from family and friends, AYAs' individual goals, and individualized PT programs improved motivation to participate. In contrast, treatment side effects and treatment demands limited AYA inpatient PT engagement. CONCLUSIONS:AYA engagement and motivation for inpatient PT vary with the individual's circumstances, goals, health, and social support. Evidence-based behavior change techniques may support future intervention efforts in addressing barriers specific to inpatient PT adherence in AYAs with hematological malignancies.

BACKGROUND/OBJECTIVES:Pain is a prevalent late effect of cancer that can disrupt critical developmental milestones during young adulthood. This study examined the relationship between pain and psychosocial outcomes in young adult (YA) survivors of cancer. METHODS:One hundred YA cancer survivors completed measures assessing pain, anxiety, depression, posttraumatic stress, and alcohol use at baseline and follow-up (2-4 weeks later). RESULTS:In multivariate regression analyses, higher pain predicted poorer outcomes across all domains at follow-up (p's <.05). CONCLUSIONS:Pain predicts psychosocial outcomes in YA cancer survivors, underscoring the need for routine assessment of and early intervention for pain to support psychological well-being.

BACKGROUND/OBJECTIVES:Outcomes for pediatric relapsed/refractory (R/R) acute myeloid leukemia (AML) remain dismal. CPX-351, a liposomal formulation of cytarabine and daunorubicin, may have less off-target toxicities than traditional chemotherapies and has shown improved outcomes for adults with newly diagnosed therapy-related AML. DESIGN/METHODS:In this first-in-pediatric, single center phase 1 study (NCT01943682), 27 patients with R/R acute leukemia (acute lymphoblastic leukemia [ALL, n = 3], AML [n = 23], or mixed phenotype acute leukemia [MPAL, n = 1]) received one cycle of CPX-351 (on days 1, 3, 5) at either 44 mg/m2 daunorubicin/dose or 59 mg/m2 daunorubicin/dose. The primary objectives were to determine the CPX-351 recommended phase 2 dose (RP2D) and to evaluate its tolerability; secondary objectives were to assess marrow overall response rate (ORR) and cardiotoxicity. RESULTS:The RP2D was determined to be 44 mg/m2 daunorubicin/dose. Grade ≥3 non-hematologic toxicities occurred in 89% of patients including febrile neutropenia (85%), infection (52%), and maculo-papular rash (37%). No grade ≥3 acute cardiac toxicities or significant changes in cardiac biomarkers were detected. The marrow ORR for AML patients was 48% (10/21 evaluable patients), despite high-risk genetic findings in most and nearly half of patients having undergone prior hematopoietic stem cell transplant. No patients with ALL or MPAL responded. CONCLUSION:CPX-351 at 44 mg/m2 daunorubicin/dose was safe and tolerable in children with R/R acute leukemia, showing promising activity in heavily pretreated, high-risk AML and is now the FDA-approved pediatric dose for therapy-related AML or AML with myelodysplastic changes.

BACKGROUND:Pain is a prevalent, frequent, and often persistent symptom among children with acute lymphoblastic leukemia (ALL). Despite its high prevalence, pain has remained understudied, and no evidence-based recommendations exist for how best to assess and treat pain in this population. Without proper assessment, clinical efforts to improve pain management in pediatric ALL will be ineffective. AIMS:Therefore, the purpose of this systematic review is to describe and identify gaps in measurement approaches that have been used to assess pain in pediatric ALL, evaluate the psychometric properties of available pediatric pain measures, and provide recommendations for clinical research and practice. METHODS:Literature searches were performed following Cochrane and PRISMA guidelines for systematic reviews. Domains of pain assessed, measures used to assess pain, measure format, respondent, and timing of pain assessment were extracted from studies that met inclusion criteria. The psychometric properties of included measures were then evaluated. A total of 238 full-text articles were screened and 123 met inclusion criteria. RESULTS:Most studies assessed pain using generic health-related quality of life instruments rather than pain-specific measures. A total of 39 measures were used across the 123 included studies, and the psychometric properties of the measures varied considerably. CONCLUSIONS:Recommendations include a selection of well-validated pain assessment measures that are currently available and can be used to facilitate best practices in ALL pain assessment. Clinicians and investigators are encouraged to utilize a multidimensional pain assessment approach to inform and enhance pain care in pediatric ALL.

BACKGROUND:Adherence to cancer treatment protocol medications is critical for optimizing health outcomes, but up to 60% of adolescents and young adults (AYAs) with cancer miss doses. This randomized pilot trial evaluated the feasibility, usability, and acceptability of a tailored adherence-promotion intervention (Supporting Medication Management with Individualized Treatment, SUMMIT) for AYAs with cancer. METHODS:Seventy AYAs (ages 15-24 years) prescribed an oral chemotherapy or a prophylactic antimicrobial as part of their cancer treatment regimen enrolled in the trial. Of these, 24 met criteria for randomization and were assigned to the intervention (SUMMIT) or control (uniform standard of care) arm. Feasibility data were tracked prospectively. AYAs completed usability and acceptability measures and stored their medication in an electronic adherence monitoring device. Descriptive statistics were used to evaluate achievement of feasibility thresholds. An analysis of covariance (ANCOVA) and a logistic regression were used to explore group differences in electronically monitored adherence. RESULTS:Enrollment (70/77 = 91%), retention (56/65 = 86%), fidelity (100%), and assessment completion (100%) rates exceeded thresholds. The intervention was rated as usable and acceptable. Compared to those randomized to the control arm, AYAs randomized to SUMMIT had 18% higher post-intervention adherence (95% confidence interval [CI] = 3.56, 32.35) and were 12 times more likely to improve their adherence by 10% or more from pre- to post-intervention (odds ratio = 12.00, 95% CI = 1.51, 95.53). CONCLUSIONS:Feasibility, acceptability, and usability data are promising, and results suggest this tailored adherence-promotion intervention has the potential to increase medication adherence among AYAs with cancer. TRIAL REGISTRATION:ClinicalTrials.gov Registration: NCT05706610.

BackgroundRequests for secondary interpretation of imaging examinations adds clinical work and generates additional charges.ObjectiveTo understand the impact of secondary interpretations of pediatric nuclear medicine examinations at a quaternary academic center.Materials and methodsIn this IRB approved study, we retrospectively reviewed nuclear medicine examinations submitted for secondary interpretation by a pediatric radiologist with a nuclear medicine focus at our institution between 08/2019 and 08/2024. A single reviewer compared the primary and secondary reports to identify discrepancies that would likely impact clinical management, and discrepancies were confirmed by additional reviewers. Pediatric hematology/oncology faculty (n=29) and fellows (n=18) at our institution were surveyed to understand requests for, and the impact of, secondary interpretations. Results are summarized with descriptive statistics.ResultsThree hundred fifty-eight examinations (median patient age=8 years) were included, 237 were 18F-FDG PET body scans, 97 were 123I-MIBG scans, and 24 were other examinations. Secondary interpretations yielded meaningful changes in 17% (60/358). Of these, 20% (12/60) changed from negative/normal to positive, 20% (12/60) changed from positive to negative/normal, and 57% (34/60) included additional positive findings/diagnoses. Sixteen survey responses (34%; n=16/47 response rate) were received, with providers indicating that secondary interpretations were clinically useful even when they agreed with the primary impression.ConclusionSecondary interpretation of pediatric nuclear medicine examinations by pediatric radiologists with nuclear medicine focus resulted in changes that have potential impact on clinical management in 17% of cases. Secondary interpretations completely changed the impression regarding the presence or absence of malignant disease in 40% of these cases. Referring providers identified benefit in secondary interpretations even when they confirmed the primary impression.

Adolescents and young adults (AYAs) with cancer face unique demands, which result in barriers to psychosocial/behavioral trial retention. Theory-informed and patient-engaged strategies have the potential to increase retention. The purpose of this manuscript is to illustrate how to partner with AYAs and leverage the Theoretical Domains Framework to identify barriers to retention and behavior change techniques (BCTs) targeting these barriers to create retention strategies. Exemplar strategies developed using this approach and implemented in our trial of an adherence-promotion intervention are discussed, and a roadmap is included for teams interested in developing similar strategies to meet their unique needs.

This cross-sectional study described prevalent body image (BI) concerns among adolescents and young adults (AYAs) with neoplasms who received treatment at a quaternary care children's hospital. Thirty-two AYAs, aged 15-39 years, completed questionnaires assessing BI within six months of diagnosis. The most frequently endorsed questionnaire items included the following: desire for increased physical fitness (62.5%), self-consciousness about hair (45.2%), weight dissatisfaction (40.6%), lack of strength (37.5%), wearing loose clothing to hide one's body (37.5%), decreased agility (34.4%), shape dissatisfaction (32.2%), and self-perception of too much body fat (31.3%). Awareness of AYA BI concerns during treatment may generate early intervention targeting this complex issue.

Background and Significance: Overweight and obesity (OW/OB) are well-characterized risk factors for relapse in children,adolescents, and adults with high-risk acute lymphoblastic leukemia (HR-ALL). Children presenting with OW/OB at ALL diagnosis have a 30-50% higher risk for relapse, a finding replicated in adults with ALL treated on the inter-consortia CALGB 10403 trial (Stock Blood 2019). The mechanisms by which OW/OB induce chemoresistance are emerging and include systemic effects on ALL cells from insulin resistance, and local interactions with marrow adipocytes. Past clinical data and mouse models of dietary modification in ALL show that the adverse impact of OW/OB on relapse is modifiable, with the initial Induction chemotherapy phase of particular importance. Risk for minimal residual disease (MRD) positivity (≥0.01% by flow cytometry) at end of induction was >2-fold higher in patients beginning ALL chemotherapy with OW/OB. Following these translational observations, we conducted the Improving Diet and Exercise in ALL [IDEAL-1] trial in 40 pediatric patients investigating whether caloric restriction could reduce risk for MRD positivity (Orgel Blood Adv 2021). The IDEAL-1 intervention consisted of a 10% caloric dietary deficit via a low carbohydrate, low glycemic load, low-fat, and high protein dietary plan accompanied by a guided home exercise program. Despite intensive chemotherapy and steroid-induced hyperphagia, >90% adherence to caloric restriction was achieved. However, poor adherence to home exercise (<50% of daily goals) and sedentary behavior (SB, <2,000 steps/day) were common. As compared to historical controls, the IDEAL-1 intervention successfully reduced fat gain in those with OW/OB. Importantly, the IDEAL-1 trial also found that caloric restriction reduced odds for MRD positivity by ~70% (p=0.02). Trial Design & Update: Following proof-of-principle from IDEAL-1, we designed the successor IDEAL-2 randomized Phase 2 trial. IDEAL-2 is actively accruing within the Therapeutic Advances in Childhood Leukemia/Lymphoma consortium with a target enrollment goal of 220 evaluable pediatric HR-ALL patients (T2020-003, NCT05082519). Subjects receive health promotion education and are then randomized within strata (±OW/OB, ±presenting WBC≥50K/uL) 1:1 to institutional routine care versus the IDEAL-2 intervention. Chemotherapy is not prescribed by the trial; patients may receive any eligible four-drug Induction regimen. IDEAL-2 incorporated lessons from the prior trial. Based on excellent dietary adherence in IDEAL-1, IDEAL-2 targets an augmented 15% caloric deficit, with the same macronutrient goals. Conversely, limited home exercise and SB in IDEAL-1 prompted integration of supervised exercise >1x/week and a new SB intervention consisting of step goals and movement reminders via a wearable fitness tracker device. Correlative biology uses metabolomics, cytometry, and RNA sequencing to investigate the impact in ALL cells of OW/OB and the IDEAL-2 intervention on insulin signaling, AKT, and chemoresistance. During the trial, we identified the logistical challenges of national variability in the availability of dietitians and physical therapists at sites to implement the intervention and travel barriers to study visits. As such, the trial is being amended to reduce these barriers through use of telehealth and incorporation of supervised exercise trainers. In acknowledging the resource-intensive nature of diet and exercise interventions on families, the trial will add an integrated assessment of household material hardship. Disparities in ALL outcomes remain a critical challenge across populations. These design changes will reduce real-life obstacles to support widespread clinical implementation of a diet and exercise intervention.

SummaryVenetoclax (VEN) combined with hypomethylating agents (HMA) decitabine or azacitidine is used for adult acute myeloid leukaemia (AML), but its application in paediatric, adolescent and young adult (AYA) AML lacks prospective studies. We performed a retrospective chart review of paediatric and AYA AML patients treated with HMA + VEN at Cincinnati Children's Hospital Medical Centre. Twenty‐seven patients received 30 HMA + VEN treatment courses for relapsed/refractory (R/R, n = 21) or newly diagnosed (n = 9) AML due to ineligibility for intensive chemotherapy. The R/R cohort had high‐risk cytomolecular genetic alterations and prior extensive treatments, with 50% (n = 9) of relapse patients (n = 18) having undergone haematopoietic stem cell transplantation (HSCT). Venetoclax treatment using the 400 mg adult exposure‐equivelant dosing (AED) had a median duration of 21 days (range 7–30 days). Grade 3–4 toxicities included neutropenia (90%), anaemia (64%), thrombocytopenia (64%) and febrile neutropenia (44%). The overall complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 73% (77% minimal residual disease [MRD] negativity <0.1%), with 60% undergoing HSCT. Among newly diagnosed patients (n = 9), 89% achieved CR/CRi (78% MRD negativity) and 78% proceeded to HSCT. The R/R cohort (n = 21) showed a 67% CR/CRi rate (71% MRD negativity), with 52% undergoing HSCT. These findings support the safety and efficacy of HMA + VEN in paediatric/AYA AML, indicating it as a viable option for patients unfit for intensive chemotherapy. Further studies are necessary to determine optimal venetoclax dosing, chemotherapy combinations and pharmacokinetics in this population.

Background: Medication non-adherence is common among adolescents and young adults (AYAs) with cancer and associated with poor health outcomes. AYAs with cancer endorse multiple barriers to adherence that differ across individuals, suggesting that tailoring intervention content to an AYA 's specific barriers may have the potential to improve adherence. The purpose of this manuscript is to report on ORBIT-guided Phase I design efforts to create the first tailored adherence-promotion intervention for AYAs with cancer and the study protocol for the ongoing Phase II pilot feasibility trial. Methods: Phase I design included qualitative interviews ( n = 15 AYAs) to understand patient preferences for adherence-promotion care, development and refinement of a best-worst scaling exercise barriers tool ( n = 5 AYAs), and development of intervention modules and a tailoring algorithm. In the ongoing Phase II pilot feasibility trial, AYAs (ages 15 -24 years) with cancer currently taking oral chemotherapy or prophylactic medication will be recruited from three children 's hospitals. Feasibility, acceptability, and usability will be assessed and these outcomes along with data on medication adherence will be used to inform the next phases of intervention development and testing. Conclusions: If promising, this program of research ultimately has the potential to equip clinicians with additional strategies for supporting adherence among AYAs with cancer. NCT05706610

Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis <18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI. Primary endpoint was event-free survival (EFS) based on independent committee-confirmed events. Fifty-one patients were enrolled. Median age was 15 years; Burkitt lymphoma, Burkitt leukemia, and Burkitt-like lymphoma (total: 45%) and diffuse large B-cell lymphoma/primary mediastinal B-cell lymphoma (51%) were the most common subtypes. At the preplanned interim analysis, median EFS was 6.1 vs 7.0 months with ibrutinib plus RICE/RVICI vs RICE/ RVICI, respectively (hazard ratio, 0.9; 90% confidence interval, 0.5-1.6; P = .387); further enrollment was ceased. With ibrutinib plus RICE/RVICI vs RICE/RVICI, median overall survival was 14.1 vs 11.1 months, overall response rate was 69% vs 81%, and 46% vs 44% proceeded to stem cell transplantation. In both treatment arms, 100% of patients experienced grade >= 3 treatment-emergent adverse events. No EFS benefit was seen with ibrutinib. Salvage was generally poor in patients who received prior rituximab, regardless of treatment arm. No new safety signals were observed. Ibrutinib exposure in pediatric patients fell within the target range of exposure in adults. Trial is registered on www.clinicaltrials.gov (NCT02703272)

Given the relative rarity of many childhood diseases, multicenter research studies are necessary in pediatrics. This is particularly true for pediatric malignancies. Running a multicenter study requires substantial infrastructure and cross-discipline coordination and requires protocols that can be reliably executed across the breadth of participating sites. Simple protocols that use or align with routine clinical techniques and standard clinical processes have the highest likelihood of being successfully executed. Image-determined response is a common endpoint in therapy trials, serving as a surrogate for disease response or recurrence. Because of the central role imaging plays as a response criterion, high-quality images are a necessity. Locally established clinical imaging: sometimes referred to in trial protocols as "standard-of-care imaging," imaging performed on clinical equipment according to routine, locally established, imaging techniques that are used for everyday clinical care. Research imaging: imaging according to study-specified parameters. Study protocols that utilize locally established clinical imaging are the easiest to activate and conduct. Some study protocols will provide participating sites with recommended or optimal imaging parameters that sites are able to implement, if feasible and as they see fit. These recommendations, particularly when informed by established expert guidelines, can serve to educate sites about best practice and to elevate the quality of both clinical and research imaging being performed. As recommendations, as opposed to requirements, they do not have negative impacts in terms of operational complications or burden on participating sites. Study protocols that require research imaging, inclusive of study-specific imaging parameters, are more challenging to execute, may require specialized skillsets to implement at participating sites, and should be expected to require additional funding. Study protocols that stipulate what the protocol authors consider to be "standard-of-care imaging" through required parameters, yet provide no funding for imaging, are particularly problematic as they may create conflict with locally established clinical imaging. When considering participation in such trials, sites are forced to not participate in the trial, modify their local clinical imaging technique to match the trial protocol, or build separate/dedicated imaging examinations for study participants. Participation then creates a significant operational burden, particularly when sites participate in multiple clinical trials each with its own unique required imaging, claiming to be "standard of care." Managing the multiple, varied, required imaging parameters across trials, particularly clinical trials for the same or similar diagnoses, is untenable. The consequences of not following protocol required imaging, including protocol deviations, failed patient enrollments, or repeat imaging, are unacceptable. Further, required imaging parameters that diverge from locally established clinical imaging create a burden on patients who may have to be re-imaged to enroll in a trial after a new diagnosis on a clinical examination. In summary, it is not the purview of clinical trials, which enroll only a small fraction of patients imaged at a participating site, to dictate clinical standard-of-care imaging through trial protocols. As much as possible, allow sites to use locally established clinical imaging without modification. Sites can be counted on to complete this successfully and relatively reproducibly. Be reasonable, and avoid, when possible, building required imaging parameters into study protocols. Define as required only what is needed to assess response and maintain alignment with disease-specific imaging standards (see item 4). Recognize that requirements may cause a study imaging technique to diverge from locally established clinical imaging. Imaging sequences that are not critical but have the potential to add pertinent information can be defined in the protocol, but should be recommended not required. Involve imaging professionals from diverse clinical centers as early as possible in clinical trial design and planning. Imaging professionals can provide useful perspective on common practice, current standard of care, imaging technique availability, imaging protocol feasibility, and study conduct considerations. Imaging standards/expert guidelines for assessment of specific diseases should be developed by multidisciplinary groups, widely accepted, easily accessible, easily implemented on clinical imaging equipment, and ideally as flexible as possible. Once agreed upon, standards should not change unnecessarily, and trials focused on diseases with accepted imaging standards should avoid deviating (even augmenting) from these standards. Among others, the Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria,1 the European Society for Paediatric Oncology (SIOPE) magnetic resonance imaging (MRI) guidelines for imaging patients with central nervous system tumors,2 and the recently published Children's Oncology Group Diagnostic Imaging Committee/The Society for Pediatric Radiology Oncology Committee white papers (in press) are meant to serve as recommended standard imaging protocols for many pediatric malignancies. Unless supported by additional funding, avoid exploratory imaging aims that impose imaging requirements beyond locally established clinical imaging. Exploratory aims and application of new or promising but unproven imaging techniques are best accomplished through research imaging with dedicated funding. Protocols requiring specific imaging beyond locally established clinical imaging should utilize research imaging with imaging-related costs, including physicist support for set-up, planned for, and covered by the research study. If there is concern about the quality of locally established clinical imaging, consider asking sites to submit a sample clinical examination, or a scanned phantom, prior to site approval to verify adequacy for disease assessment. Volunteer or phantom scans specifically acquired for site qualification should be supported by study funding. The faithful conduct of clinical trials is critical to generating high-quality data needed to make determinations about the efficacy of therapy. It is tempting to mischaracterize "ideal" imaging parameters as "standard of care" to avoid study costs related to research imaging and to avoid raising questions about risks of imaging-related anesthesia for patients. However, study protocols with unnecessary imaging requirements and those that incorporate rigid (required) imaging techniques into protocols, particularly those that do so while claiming to use "standard-of-care" imaging, make it difficult to accurately execute clinical trials at the local level.

Background Cyclin D has been shown to play an essential role in acute lymphoblastic leukemia (ALL) initiation and progression, providing rationale for targeting the CDK4/6-cyclin D complex that regulates cell cycle progression. Procedure The Children’s Oncology Group AINV18P1 phase 1 trial evaluated the CDK4/6 inhibitor, palbociclib, in combination with standard four-drug reinduction chemotherapy in children and young adults with relapsed/refractory B- and T-cell lymphoblastic leukemia (ALL) and lymphoma. Palbociclib (50 mg/m /dose) was administered orally once daily for 21 consecutive days, first as a single agent (days 1-3) and subsequently combined with reinduction chemotherapy. This two-part study was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) followed by an expansion pharmacokinetic (PK) cohort. Results Twelve heavily pretreated patients enrolled, all of whom were evaluable for toxicity. One dose-limiting hematologic toxicity (DLT) occurred at the starting dose of 50 mg/m /dose orally for 21 days. No additional DLTs were observed in the dose determination or PK expansion cohorts and overall rates of grade 3/4 non-hematologic toxicities were comparable to those observed with the chemotherapy platform alone. Five complete responses were observed, two among four patients with T-ALL and three among seven patients with B-ALL. Pharmacokinetic studies showed similar profiles with both liquid and capsule formulations of palbociclib. Conclusions Palbociclib in combination with reinduction chemotherapy was well tolerated with a RP2D of 50 mg/m /day for 21 days. Complete responses were observed among heavily pretreated patients.

Bridging therapy (BT) given during the period between T-cell collection and initiation of lymphodepleting chemotherapy is indicated for most children with B-cell acute lymphoblastic leukemia (B-ALL) undergoing treatment with tisagenlecleucel (tisa-cel), a CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy. Both conventional chemotherapy agents and B-cell directed antibody-based therapies such as antibody-drug conjugates and bispecific T-cell engagers have been used as systemic forms of BT. The purpose of this retrospective study was to evaluate if there are detectable differences in clinical outcomes based on the type of BT given (conventional chemotherapy or inotuzumab). A retrospective analysis was performed on all patients treated with tisa-cel at Cincinnati Children's Hospital Medical Center for B-ALL with bone marrow disease (with or without extramedullary disease). Patients who did not receive systemic BT were excluded. Only 1 patient received blinatumomab as BT and was therefore not included in this analysis to focus the analysis on the use of inotuzumab. Pre-infusion characteristics and post-infusion outcomes were collected. Fisher's exact test was used for categorical variables, and t-test or Mann-Whitney test was used for continuous parametric and non-parametric variables respectively. Mantel-Cox was used for survival analyses. Thirty-two patients received BT before CD19 CAR-T for medullary leukemia; 24 received conventional chemotherapy, and 8 received inotuzumab ozogamicin (InO). Cohorts were evenly matched regarding CAR-T indication, recipient age, and median CAR-T cell dose. There were no significant differences between the groups for attaining a minimal residual disease (MRD)-negative complete response after CAR-T, the percentage of patients who maintained prolonged B-cell aplasia, or the median duration of B-cell aplasia. Thirty-seven percent of patients in the conventional chemotherapy group and 43% in the antibody-based therapy group relapsed, with a median time to relapse in both groups of 5 months. No differences in event-free survival, the cumulative incidence of relapse, or overall survival were seen between the two groups. Initial response to tisa-cel, relapse rate, and survival were similar between patients who received BT with conventional chemotherapy or InO therapy. Because low disease burden at the time of infusion is a positive prognostic factor, choice of bridging regimen should focus on therapy that is anticipated to effectively lower disease burden and minimize treatment-related toxicity. Given the limitations associated with the single center retrospective analysis, a larger, multicenter study is needed to further explore these findings.

Outcomes for children and adolescents with relapsed and refractory Hodgkin lymphoma (HL) are poor, with similar to 50% of patients experiencing a subsequent relapse. The anti-CD30 antibody-drug conjugate brentuximab vedotin improved progression-free survival (PFS) when used as consolidation after autologous stem cell transplantation (ASCT) in adults with high-risk relapsed/refractory HL. Data on brentuximab vedotin as consolidative therapy after ASCT in pediatric patients with HL are extremely limited, with data of only 11 patients reported in the literature. We performed a retrospective analysis of 67 pediatric patients who received brentuximab vedotin as consolidation therapy after ASCT for the treatment of relapsed/refractory HL to describe the experience of this regimen in the pediatric population. This is the largest cohort reported to date. We found that brentuximab vedotin was well tolerated with a safety profile similar to that of adult patients. With a median follow-up of 37 months, the 3-year PFS was 85%. These data suggest a potential role for the use of brentuximab vedotin as consolidation therapy after ASCT for children with relapsed/refractory HL.

BackgroundAdherence promotion is a critical component of adolescent and young adult (AYA) cancer care, but predictors of nonadherence that could be targeted in intervention efforts remain largely unknown. The purpose of this multi-site longitudinal observational study was to examine the relationship between barriers and medication adherence among AYAs with cancer. ProcedureSixty-five AYAs (ages 15-24 years; mean age = 18.97 years, SD = 2.51; Mmean time since diagnosis = 1.42 years, SD = 1.95) with newly diagnosed or relapsed cancer completed self-report measures of barriers and adherence at quarterly study visits and used an electronic adherence monitoring device for 12 months. Longitudinal mixed effects models were used to examine our primary hypothesis that greater barriers are related to lower adherence over time. Descriptive statistics were used to explore our secondary aim of describing the frequency and patterns of barriers endorsed by AYAs with cancer. ResultsAfter controlling for covariates (time, medication type, race, ethnicity, diagnosis, time since diagnosis), a greater number of barriers was associated with lower electronically monitored (beta = -5.99, p = .005) and self-reported (beta = -1.92, p < .001) adherence. The specific barriers endorsed by AYAs differed across participants, and the majority of AYAs endorsed an entirely different pattern of barriers than any other AYA in the study. ConclusionBarriers are associated with nonadherence and may be a promising target for intervention. Individual variability across barriers, however, suggests that tailoring may be necessary, and a promising next step is to explore personalized approaches to adherence promotion.