Changes in Nutritional Status during Induction Phase and Their Association with Fever and Minimal Residual Disease in Paediatric Acute Lymphoblastic Leukaemia.

Background and objectives: Acute lymphoblastic leukaemia (ALL) is associated with a cytokine imbalance and oxidative stress, which can be aggravated by malnutrition. Malnutrition, defined by the World Health Organisation (WHO) as obesity or undernutrition, can affect treatment complications and outcomes. Therefore, we aimed to analyse the change in the body mass index (BMI) z-score during induction, as well as evaluate the impact of childhood malnutrition on fevers at an ALL presentation and early response to therapy. Methods: An observational cohort study of 50 consecutive children with ALL, diagnosed in 2019-2022, was performed. Patients were divided into age groups of 0-5, 6-11, and 12-17 years. BMI-for-age z-scores were used to define undernutrition and overnutrition according to WHO growth standards. Results: The number of patients with an abnormal BMI increased from 3 (6%) at diagnosis to 10 (20%) at the end of induction (from 2 (4%) to 6 (12%) in overweight/obese, and from 1 (2%) to 4 (8%) in underweight patients). At the end of induction, all overweight/obese patients were 0-5 years old. On the other hand, a statistically significant decrease in the mean BMI z-score among patients aged 12-17 was observed (p = 0.005). The mean BMI z-score differed statistically significantly among children aged 0-5 presenting with and without fever (p = 0.001). The minimal residual disease (MRD) level at the end of induction was not related to BMI at diagnosis. Conclusions: Despite the use of steroids, adolescents are prone to losing weight during an ALL induction, in contrast to preschool children, who tend to gain weight under the same treatment. BMI at diagnosis was related to a fever of ≥38 °C (at ALL presentation) in the 0-5 age group. The results emphasise the importance of careful nutritional status monitoring, with younger and older children as important target groups for weight gain and weight loss interventions, respectively.

Development of a questionnaire to evaluate female fertility care in pediatric oncology, a TREL initiative.

BACKGROUND: Currently the five-year survival of childhood cancer is up to 80% due to improved treatment modalities. However, the majority of childhood cancer survivors develop late effects including infertility. Survivors describe infertility as an important and life-altering late effect. Fertility preservation options are becoming available to pre- and postpubertal patients diagnosed with childhood cancer and fertility care is now an important aspect in cancer treatment. The use of fertility preservation options depends on the quality of counseling on this important and delicate issue. The aim of this manuscript is to present a questionnaire to determine the impact of fertility counseling in patients suffering from childhood cancer, to improve fertility care and evaluate what patients and their parents or guardians consider good fertility care. METHODS: Within the framework of the EU-Horizon 2020 TREL project, a fertility care evaluation questionnaire used in the Netherlands was made applicable for international multi-center use. The questionnaire to be used at least also in Lithuania, incorporates patients' views on fertility care to further improve the quality of fertility care and counseling. Results evaluate fertility care and will be used to improve current fertility care in a national specialized pediatric oncology center in the Netherlands and a pediatric oncology center in Lithuania. CONCLUSION: An oncofertility-care-evaluation questionnaire has been developed for pediatric oncology patients and their families specifically. Results of this questionnaire may contribute to enhancement of fertility care in pediatric oncology in wider settings and thus improve quality of life of childhood cancer patients and survivors.

Early Radiation-Induced Sarcoma in an Adolescent Treated for Relapsed Hodgkin Lymphoma with Nivolumab.

Radiation-induced sarcoma (RIS) has been reported as a late secondary malignancy following radiotherapy for various types of cancer with a median latency of 10 years. We describe an early RIS that developed in an adolescent within three years of treatment (including PD-L1 check-point inhibitor Nivolumab) of a relapsed classic Hodgkin lymphoma (HL) and was diagnosed post-mortem. The patient died of the progressive RIS that was misleadingly assumed to be a resistant HL based on the positive PET/CT scan. Repetitive tumor biopsies are warranted in cases of aggressive and multi-drug resistant HL to validate imaging findings, ensure correct diagnosis and avoid overtreatment.

Increase in peg-asparaginase clearance as a predictor for inactivation in patients with acute lymphoblastic leukemia.

Asparaginase is an essential component of acute lymphoblastic leukemia (ALL) therapy, yet its associated toxicities often lead to treatment discontinuation, increasing the risk of relapse. Hypersensitivity reactions include clinical allergies, silent inactivation, or allergy-like responses. We hypothesized that even moderate increases in asparaginase clearance are related to later inactivation. We therefore explored mandatory monitoring of asparaginase enzyme activity (AEA) in patients with ALL aged 1-45 years treated according to the ALLTogether pilot protocol in the Nordic and Baltic countries to relate mean AEA to inactivation, to build a pharmacokinetic model to better characterize the pharmacokinetics of peg-asparaginase and assess whether an increased clearance relates to subsequent inactivation. The study analyzed 1631 real-time AEA samples from 253 patients, identifying inactivation in 18.2% of the patients. This inactivation presented as mild allergy (28.3%), severe allergy (50.0%), or silent inactivation (21.7%). A pharmacokinetic transit compartment model was used to describe AEA-time profiles, revealing that 93% of patients with inactivation exhibited prior increased clearance, whereas 86% of patients without hypersensitivity maintained stable clearance throughout asparaginase treatment. These findings enable prediction of inactivation and options for either dose increments or a shift to alternative asparaginase formulations to optimize ALL treatment strategies.

Integrated Collection of Patient-Reported Outcomes and Experiences in Children with Kidney and Hematological Diseases: A Pilot Study.

We aimed to explore the feasibility and potential relevance of integrated electronic collection of patient-reported outcome and experience measures (PROM and PREM) in children with special healthcare needs (CSHCN) by using the example of children with kidney and hematological diseases. We performed a cross-sectional, single-center study of children <18 years of age. Children (≥10 years) and their parents received Generic PedsQL Core Scale 4.0 and custom PREM surveys to their email addresses via the REDCap platform, and the results were integrated into the hospital's electronic health records system. A total of 192 patients (98 with kidney diseases and 94 with hematological diseases) were enrolled. The overall response rate was 51%, and the median time for completion of each proxy questionnaire was approximately three minutes. The lowest PROM scores were observed in the emotional and school functioning dimensions. More favorable experiences in the diagnosis establishment process were associated with higher scores in physical, social, school functioning, and total PROM scores. A better evaluation of the hospital's environment was associated with higher social functioning, while better information provision correlated with higher physical functioning and total PROM scores. Our data indicates that integrated electronic collection of PROMs and PREMs in the population of CSHCN is feasible, but efforts to increase the response rate are needed. The associations between PROMs and PREMs suggest that future studies exploring targeted interventions at the healthcare service level to improve subjective patient outcomes are needed.

Development and Integration of Patient-Reported Measures into E-Health System: Pilot Feasibility Study.

Patient-centered care is recognized as a key element in recent healthcare management strategies. However, the integrated collection of patient feedback capturing the entire journey of patients with complex medical conditions remains understudied. Herein, we aimed to describe the development of an instrument prototype for the collection of PROMs and PREMs that would encompass a whole patient journey at a single time point. We further describe the process of its integration into a hospital's information system (HIS) and the results of a pilot feasibility study in adult patients with kidney and hematological diseases. We developed an instrument consisting of original PREM and generic EQ-5D-5L questionnaires. E-questionnaires were handled with REDCap software (version 12.5.14) and integrated into the HIS. Patients refusing to use e-questionnaires (48%) were offered paper administration and were older (64 vs. 50 years). The overall response rate for e-questionnaires was 57.1% with a median completion time of 2.0 and 3.7 min for PROM and PREM, respectively. Psychological and social services and primary care setting (diagnosis establishment and involvement in continuous care) were identified as most problematic. The majority of PREM dimensions encompassing different levels of care significantly correlated with PROM responses. Our data indicate the feasibility and potential relevance of the proposed approach, although wider-scale studies in diverse settings are needed.

Evaluation of oncofertility care in childhood cancer patients: the EU-Horizon 2020 twinning project TREL initiative.

Background: The 5-year survival rate of childhood cancer exceeds 80%, however, many survivors develop late effects including infertility. The aim of this study was to evaluate the current status of oncofertility care at Vilnius University Hospital Santaros Klinikos (VULSK) within the framework of the EU-Horizon 2020 TREL project. Methods: All parents or patients aged 12-17.9 years treated from July 1, 2021 until July 1, 2022 were invited to complete an oncofertility-care-evaluation questionnaire. After completing the questionnaire, patients were triaged to low-risk (LR) or high-risk (HR) of gonadal damage using a risk stratification tool (triage). Data was assessed using descriptive statistics. Results: Questionnaires were completed by 48 parents and 13 children triaged as 36 (59%) LR and 25 (41%) HR patients. Most HR respondents (21/25, 84%) were not counseled by a fertility specialist. Six boys (4 HR, 2 LR) were counseled, none of the girls was counseled. Three HR boys underwent sperm cryopreservation. Only 17 (27.9%, 9 HR, 8 LR) respondents correctly estimated their risk. All counseled boys (n = 6) agreed the risk for fertility impairment had been mentioned as compared to 49.1% (n = 27) of uncounseled. All counseled respondents agreed they knew enough about fertility (vs. 42%). Conclusions: Respondents counseled by a fertility specialist were provided more information on fertility than uncounseled. HR patients were not sufficiently counseled by a fertility specialist. Based on the current experience oncofertility care at VULSK will be improved.

Case Report: Specific ABL-Inhibitor Imatinib Is an Effective Targeted Agent as the First Line Therapy to Treat B-Cell Acute Lymphoblastic Leukemia With a Cryptic NUP214::ABL1 Gene Fusion.

Acute lymphoblastic leukemia (ALL) with recurrent genetic lesions, affecting a series of kinase genes, is associated with unfavorable prognosis, however, it could benefit from treatment with tyrosine kinase inhibitors (TKI). NUP214::ABL1 fusion is detected in 6% of T-cell acute lymphoblastic leukemia (T-ALL), and is very rare in B-ALL. We present a case of adolescent with B-ALL and a cryptic NUP214::ABL1 fusion which was initially missed during diagnostic screening and was detected by additional RNA sequencing. Treatment with specific ABL-inhibitor Imatinib was added later in therapy with a good effect. Initial treatment according to conventional chemotherapy was complicated by severe side effects. At the end of Consolidation, the patient was stratified to a high risk group with allogeneic hematopoietic stem cell transplantation because of insufficient response to therapy. At that time, targeted RNA sequencing detected NUP214::ABL1 gene fusion which was previously missed due to a small microduplication in the 9q34 chromosome region. Gene variant analysis revealed no TKI-resistant ABL1 mutations; therefore, treatment with Imatinib was added to target the NUP214::ABL1 fusion protein. A negative minimal residual disease was achieved, and treatment was downgraded to intermediate risk protocol. Combining routine genetic assays with next-generation sequencing methods could prevent from missing atypical gene alterations. Identification of rare targetable genetic subtypes is of importance in order to introduce targeted therapy as early as possible that may improve survival and reduce toxicity. Treatment with ABL1 inhibitor imatinib mesylate revealed as a highly effective targeted therapy against the leukemia driving protein kinase.