Department Of Pediatric Hematology-Oncology Research Articles

A Pilot Study in a Recently Established Childhood Cancer Center for Evaluating the Priority of National Pediatric Cancer Registry

Background: Pediatric cancers account for nearly 2% of all cancers worldwide. In 2018, there were approximately 200,000 newly diagnosed cases of childhood cancer. Objectives: The aim of this study was to assess the need for a national pediatric cancer registry based on case incidence. Methods: This pilot study was conducted on 100 children with cancer who were treated in a recently established pediatric hematology oncology department of Golestan Hospital. Demographic and epidemiological data were collected and analyzed using SPSS software version 25. Results: Sixty-four percent of children with cancer were girls, and the average age of the patients was 7.6 ± 0.42 years. The most common types of cancer diagnosed were leukemia, brain tumor, lymphoma, and retinoblastoma respectively. Metastasis was confirmed in 11 cases. The most prevalent clinical manifestations of cancer included fever, weakness, loss of appetite, paleness, and weight loss. Conclusions: The results of this study align with global rates and data. Based on the findings, the authors emphasize the necessity and priority of establishing a pediatric cancer registry in Iran's health ministry. Therefore, all healthcare workers and specialists in pediatric hematology and oncology should make concerted efforts to establish this registry.

An Integrative Pediatric Oncology Program Addressing Parents’ Quality of Life-Related Concerns

BackgroundParents of children with cancer face bio-psycho-social-spiritual concerns which can significantly reduce quality of life (QoL). We examined the impact of an integrative oncology (IO) intervention on QoL-related concerns among parents of children in a pediatric hematology-oncology department. MeasuresThe study was prospective, controlled, nonrandomized and patient-preferenced. Parents of children recently (≤6 weeks) diagnosed with cancer were assessed using the measure yourself concerns and wellbeing (MYCaW), Edmonton Symptom Assessment Scale (ESAS) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Parents in both groups were reassessed after three weeks. InterventionAn IO consultation was provided, with training in daily relaxation-breathing and manual treatments, and guidance on herbal medicine. OutcomesOf 68 parents consenting to participate, 37 (54%) underwent the intervention with 31 serving as controls. Multivariate analysis found the IO intervention group to contain more Hebrew-speakers (OR=5.96, 95% CI=1.3-27.3, P=0.022); females (OR=5.23, 95% CI=1.1-24.8, P=0.038); and report pain (OR=1.2, 95% CI=1.0-1.4, P=0.045) and impaired appetite on ESAS (OR=1.23, 95% CI=1.01-1.48, P=0.034) when compared to controls. Only the intervention group showed improved baseline-to-3-week scores for physical functioning (P<0.001), cognitive functioning (0=0.018) and fatigue on EORTC (P<0.001); and for ESAS appetite (P<0.001) and anxiety (P=0.02). ESAS sleep increased only in controls (P=0.029). Conclusions/Lessons LearnedIO interventions in pediatric hematology-oncology addressing QoL-related concerns among parents are feasible, potentially increasing predominantly physical symptoms and functioning. Further research is needed to confirm these “real-world” clinical outcomes, and the role of IO in ”Caring for the Caregiver”.

Epidemiology of Invasive Fungal Diseases: A 10-Year Experience in a Tertiary Pediatric Hematology-Oncology Department in Greece.

Although advances in the management of pediatric neoplasms have profoundly improved infectious disease outcomes, invasive fungal diseases (IFDs) remain a major cause of morbidity and mortality in children and adolescents with high-risk hematological malignancies. A retrospective study was conducted in the Pediatric Hematology-Oncology Department of the University General Hospital of Heraklion for 2013-2022 to estimate the prevalence and describe the clinical and epidemiological characteristics of IFDs for pediatric and adolescent patients with neoplasia. Demographic, clinical, and laboratory parameters were analyzed to identify risk factors for the development of IFD. The overall prevalence of IFDs was estimated to be 7.8% (12/154 patients) throughout the study. The mean age at IFD diagnosis was 9.8 years (SD 6.4 years). The most common IFD was possible/probable invasive pulmonary aspergillosis (IPA; in ≈50%), followed by candidemia/invasive candidiasis (in 44%). Candida parapsilosis was the most prevalent Candida species (4/6 events). Of interest, the majority (75%) of IFDs were breakthrough infections. Patients with increased risk for IFDs were those who were colonized by fungi in sites other than the oral cavity, hospitalized in the intensive care unit for >7 days, received >7 different antimicrobials in the last 3 months, or had severe neutropenia for >44 days. Two children out of a total of 12 with IFD died due to refractory disease or relapse (16.7%). More detailed and prospective epidemiological studies on fungal infections in pediatric patients with hematological or solid neoplasms can contribute to the optimization of prevention and treatment.

B-NHL Cases in a Tertiary Pediatric Hematology-Oncology Department: A 20-Year Retrospective Cohort Study.

Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies -with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer).

Clinical Profile of Pediatric Oncology Patients Treated by Radiotherapy: A Retrospective Audit from a Tertiary Cancer Care Center in South India

Introduction With the increase in the number of pediatric cancers in India, there is a need for a multimodal approach involving various disciplines of therapy in which radiotherapy is one of the important areas of treatment. As there is a paucity of studies in South India about the profile of pediatric cancer patients who have undergone radiotherapy the present study was undertaken. Methods A record-based retrospective study was conducted at the department of pediatric hematology-oncology and radiotherapy at a tertiary care hospital in South India using a data abstraction form which consisted of sociodemographic details of study participants, primary diagnosis, confirmed diagnosis, site of radiotherapy, current status of the patient, etc. Chi-square test or Fisher's exact test was used to find out significant association between current status of study participants and various determinants influencing it. Results Highest proportion, n = 35 (30.4%), of cases were in the age group of 10 to 14 years. Among them, 48 children were primarily diagnosed to have hematolymphoid malignancy while 67(%) had solid tumor. Majority of the patients, n = 110 (95.6%), were treated on curative intent. Conclusion Radiotherapy remains an important modality of cancer-directed therapy in children with cancer. Radiotherapy still forms an integral part of cancer-directed treatment in children with cancer as demonstrated in our population.

Healthcare-associated Infections in the Department of Pediatric Hematology-oncology; A Single Center Evaluation

Healthcare-associated Infections in the Department of Pediatric Hematology-oncology; A Single Center Evaluation

(305) Contemporary Therapies in Oncofertility: Identifying the Common Consults

Abstract Introduction Fertility inquiries among chemotherapy, immunotherapy, and targeted therapy regimens are increasing in volume and heterogeneity of referrals. There is limited research highlighting the prevalence of contemporary oncologic therapies seen by urologists and patient-specific fertility concerns. Objective This study seeks to identify the most common contemporary chemotherapy, immunotherapy, and targeted therapy regimens referred to urology for oncofertility inquiries and concerns. Methods We performed a retrospective single institutional review of all oncologic agents referred to the department of pediatric hematology oncology for fertility evaluation over the past five years (April, 2018- April, 2023). These included both frontline and salvage treatments. Agents were defined as contemporary if drug approval was received by the Food and Drug Administration 2006 or later. Results We identified 75 patients who underwent 28 unique contemporary agents ranging across 16 different drug classes referred for fertility evaluation (Figure 1). The majority of agents referred were used by 1-2 patients. The most common agents for oncofertility consultation included the monoclonal antibody Brentruximab (9), immune checkpoint inhibitor pembrolizumab (8), and T-cell engager Bilinotumomab (8). The most common agents included immune checkpoint inhibitors (16), monoclonal antibodies (16), and tyrosine kinase inhibitors (15). Conclusions There is significant variability and diversity among modern oncologic agents among patients referred for oncofertility evaluation, demonstrating the need for provider familiarity and future research in the oncofertility space. Disclosure No.

Identification of the core competencies of pediatric hematology-oncology nurses: A Delphi study

PurposeTo identify the core competencies of the pediatric hematology-oncology nurse. MethodsA Delphi study was conducted. After identifying the competencies of the pediatric hematology-oncology nurse through a literature review, a questionnaire was created to be administered to a panel of experts to obtain consensus. The panel of experts consisted of 19 nurses. For each competence identified, it was necessary to evaluate the competence in terms of “understanding” and “relevance”, assigning a score from 0 (not at all) to 4 (completely), according to a Likert scale. Then, the experts identified what could be the necessary “level of work experience” within which a nurse should become autonomous in every competency choosing among the levels: beginner, intermediate, expert. Consensus among the experts was reached in two rounds. ResultsAfter submitting the document to two rounds, a final document was obtained with a total of 126 competencies, divided into nine areas. Fifty-eight competencies fall into the “beginner” level, 46 competencies into the “intermediate” level and 22 competencies into the “expert” level. ConclusionsThe document produced by this study could be a starting point for organizing specific training courses for nurses in the pediatric hematology-oncology department. A clear description of specific competencies for pediatric hematology-oncology nurses would help ensure the best care for the child.

Standardized Clinical Pathways Improve Management of Vaso-Occlusive Episodes in the Pediatric Emergency Department

Introduction: Pain secondary to vaso-occlusive episodes (VOE) is one of the most common and debilitating complications of sickle cell disease (SCD). Although there are guidelines for pain management, these are often not well-followed. Pain management is entrenched in subjectivity and susceptible to implicit bias. Research has shown that clinical pathways improve care for patients which is especially important in vulnerable populations such as pediatric patients with SCD. Following a quality improvement project at our institution that resulted in significantly improved inpatient care for pediatric patients with SCD, the goal of this project was to create an accessible clinical pathway with multidisciplinary input to streamline management of VOE in the emergency department (ED) and assure equitable care for all. We aimed to improve time to analgesics, increase the percent of patients receiving pain medications within 30 minutes, and increase intranasal fentanyl and patient-controlled anesthesia (PCA) utilization in the pediatric ED. Methods: The care signature clinical pathway was created using a multidisciplinary approach with individuals representing the department of pediatric hematology-oncology, pediatric emergency, anesthesiology, pharmacy, and nurse management. The pathway was developed based on updated American Society of Hematology guidelines for pain management in pediatric VOE. The pathway became available for use via electronic medical record on July 12 th, 2022. Outcome measures regarding pain management were evaluated for one year prior to pathway publication and compared to outcomes one year after publication. Patients with a primary or secondary diagnosis of SCD presenting to the Yale pediatric ED with vaso-occlusive pain were included. Results: A total of 214 ED visits were evaluated. The pre-pathway cohort included 108 encounters from July 1 st, 2021 to June 30 th, 2022 and the post-pathway cohort included 106 ED encounters from August 1 st, 2022 to July 21 st, 2023. During the first year post implementation, a provider utilized the clinical pathway a total of 534 times (121 individuals) with an average of 1 time per day. An analgesic was ordered for 63 (58.3%) patients and administered for 31 (28.7%) patients within 30 minutes of arrival in the pre-pathway cohort. An analgesic was ordered for 73 (68.9%) and administered for 32 (30.2%) patients within 30 minutes of arrival in the post-pathway cohort. Comparing pre- and post-pathway cohorts, the median time to pain medication order was 22 vs 17 minutes and pain medication administration was 42 vs 40 minutes respectively. Intranasal fentanyl was used for 2 (1.9%) patients in the pre-pathway cohort and 12 (11.3%) patients in the post-pathway cohort. A total of 0 (0%) hydromorphone PCAs were administered in the ED in the pre-pathway cohort compared to 4 (3.8%) hydromorphone PCA administered in the ED in the post-pathway cohort. Conclusion: Standardizing pain management using a clinical pathway has shown improvement in ED management of VOE in the first year post implementation with increased utilization of intranasal fentanyl and PCAs. Our goal of increased percentage of patients receiving pain medication within 30 minutes and decreased time to first analgesic was not achieved, however this is an ongoing project and with education in implementation of the clinical pathway we hope to continue to see long term progress. Additionally, in the future, we plan to expand use of this pathway to additional sites within our health care system.

MDB-10. EPIDEMIOLOGICAL PROFILE OF MEDULLOBLASTOMA IN MOROCCO: A 2-YEAR RETROSPECTIVE STUDY

Abstract Medulloblastoma is a malignant, invasive embryonal tumor of the central nervous system. This pathology is the leading malignancy in children, accounting for 30% of central nervous system pediatric tumors. This study aimed to present the epidemiological profile of medulloblastoma in Morocco. It was a retrospective study including all children aged 0 to 16 years and diagnosed with medulloblastoma at the pediatric hematology-oncology department of the children’s hospital in Rabat (Morocco) over two years, from January 1, 2021, to December 31, 2022. A total of 12 patients were included in the study, 7 boys and 5 girls (M/F ratio 1.4). The mean age was 9 ± 3 years. The majority (91.7%) of children were over 5 years of age. Only one child was aged 18 months. over half of the patients were from a rural areas. Most cases were living over 30 Km from the center. Among them, 40% were more than 150 km. A low socio-economic level was reported by 75% of the families. Two children were born to consanguineous parents. A familial cancer history was noted in 41.7% of patients. Clinical symptoms were dominated by headache (83.3%) and vomiting (66.7%). Regarding treatment, two patients were treated with surgery and seven with a combination of surgery, radiotherapy, and chemotherapy. During the period of study, there were no cases of death. A good outcome was noted in 91.7% of patients. Only one child received palliative care. Childhood cancer in general, and medulloblastoma in particular, is on the rise in Morocco. Given the scarcity of publications on this type of cancer in our country, a national registry is necessary for the monitoring and appropriate management of this disease.

Predictors of mortality in children with neuroblastoma

Background Neuroblastoma is an extracranial solid tumor originating from neural crest cells which failed to properly migrate. Neuroblastoma is commonly found in children under 12 months of age. The survival rate of these patients is still relatively low, both in developed countries and Indonesia.&#x0D; Objective To determine whether age, sex, primary tumor location, degree of cell differentiation, and patient compliance are associated with the survival of children with neuroblastoma at Dr.Sardjito Hospital.&#x0D; Methods This retrospective cohort study included pediatric neuroblastoma patients at Dr. Sardjito Hospital, Yogyakarta, Central Java, between January 2012 to September 2020, however there has been no evaluation about survival of neuroblastoma. We collected secondary data from medical records and registration data of pediatric cancer patients in the Pediatric Hematology Oncology Department of Dr. Sardjito Hospital, we matched te data based on medicals records and manual data in the ward and olyclinic, which included age at diagnosis, sex, primary tumor location, degree of cell differentiation, and patient adherence to therapy. To confirm weather the information about survived or death, apart from medical record we do tracking by telephone to the parent.&#x0D; Results we do the observation and calculating based on our retrospective data , Of 54 pediatric neuroblastoma patients, 54% were female. The median length of observation was 13.25 months, with an incidence rate of 62/100 person-years and a median survival of 13 months from the time of diagnosis. The 5-year survival rate in our study was 21.3%. Multivariate analysis revealed that stage IV patients had higher risk of death (HR 10.9; 95%CI 1.47 to 81.01; P=0.02) compared to other stages. Sub-group follow-up analysis revealed no significant difference in stage IV male patients compared to female patients (HR 1.62; 95%CI 0.81 to 3.22; P=0.172). The survivial in group with primary tumor location outside the adrenal medulla and stage IV was not significantly different from patients whose tumor location was unknown (HR 2.45; 95%CI 0.71 to 8.43; P=0.155). The group whose primary tumor location was in the adrenal medulla did not have a significant difference in survival compared to patients whose primary tumor location was unknown (HR 2.09; 95%CI 0.84 to 5.22; P=0.114).&#x0D; Conclusion The predictor factors studied are not significantly associated with mortality in children with neuroblastoma.

THE EFFECT OF THE COVID-19 PANDEMIC PROCESS ON TREATMENT COMPLIANCE IN HEMOPHILIA PATIENTS

ObjectiveIt is known that there were transportation problems to the hospital and treatment experienced in many disease groups during the pandemic process. The negative impact of the pandemic is particularly evident in chronic diseases and in situations that require continuous treatment. In this study, data on access to treatment and disease status in patients with bleeding diathesis were collected by questionnaire method, and the effects of the pandemic on these patients were determined.MethodologyFifty patients who were followed up in Istanbul Medical Faculty Pediatric Hematology-Oncology Department between 2010-2022 with the diagnosis of bleeding diathesis and accepted to participate in the survey were included in the study. Questions were answered by telephone. Responses were analyzed using SPSS.ResultsThe mean age of the patients in our study was 13 years, the age range was between 2-26 years. The median age was 13. Of these patients, 44 (88%) were male and 6 (12%) were female. 88% of the patients were diagnosed with Hemophilia A, 12% with Hemophilia B. While 56% of the patients were receiving prophylaxis for the treatment of hemophilia, 44% were receiving treatment in case of bleeding. Sixtyfour percent of the patients went to a health institution or doctor once every 1-3 months, 18% every 6 months, 6% once a year for control and follow-up purposes. The last drug or dose change was made 0-6 months ago in 16% of the patients, 7-12 months ago in 4%, and 22% 1-2 years ago. However, in 6%, more than 2 years had passed since the last change, and 42% did not change. Serious psychiatric problems were observed in our two patients. Fear of death and anxiety disorder has been seen in a 10-year-old patient. During this period, severe hyperactivity developed in 1 patient.While 10% of the patients interrupted their treatment in the last 3-4 months, 90% did not. The reason for the disruption of the patients who interrupt their treatment is Covid infection in 20% and the drug cannot be obtained in 40%. While 94% of the patients had no problem in the supply of the drug due to the Covit-19 pandemic, 6% had a problem in the supply of the drug.While 33% of the patients who had problems in the supply of the drug received support from their doctor, 33% from the patient association to solve the problem, 33% did not receive any support from anyone. Among the reasons for having problems in the administration of the drug, 33% of the patients did not go to the hospital because they were afraid of the pandemic, 33% of them could not get treatment even though they went to the hospital, and 33% of them other reasons were reported.While 48% of the patients want an experienced health personnel to go to their home to perform their treatment, 52% do not want it, stating that they do not need it. None of the patients whose treatment was interrupted did not complain of bleeding during this period.ConclusionIt was seen that the patients experienced disruptions related to access to medication and treatment during the pandemic process. However, there were no major problems in this process, thanks to the help of their physicians and other institutions. It is important to emphasize the importance of treatment in hemophilia patients and to have easy communication with the center followed in order to overcome the pandemic process without complications.

Outcome of Pediatric Neuroblastoma at the Children’s Hospital and Institute of Child Health, Lahore

Objective: To demonstrate outcome of pediatric neuroblastoma at The Children’s Hospital and Institute of Child Health, Lahore. Study design: Descriptive observational study Place and duration: The study was conducted in Pediatric Hematology Oncology department, The Children’s Hospital and the Institute of Child Health, Lahore in twelve months from March 2020 to February 2021. Methodology: Study was conducted on total of 60 patients of diagnosed neuroblastoma. Main variables of study were age, parent’s education, socioeconomic status, traveling distance, LTS, and INSS stage, metastatic sites, tumor size and outcome. SPSS version 23.1 was used for data analysis. Test of significance was applied taking p value ≤0.05 as significant value. Results: Regarding histopathology, fifty eight 96% patients had neuroblastoma while 4% patients had ganglioneuroblastoma. Life threatening symptoms were present in 85% patients. Most common primary sites were suprarenal 45%, retroperitoneum 25%, pre/paravertebral 11%, posterior mediastinal 11%, others 6%. Metastasis were present in 40% patients at diagnosis and most common metastatic sites were bone marrow 21%, bone 8% and both 10%. Six(10%) patients with stage 2 showed complete remission ,2(3%) partial remission, 2(3%) patients with stage 3 achieved complete remission ,19(34%) partial remission, 4(7%) patients with stage3 expired, 18(30%) patients with stage 4 were put on palliation initially, 2(3%) patients with stage 4S showed complete remission. Conclusion: The survival outcomes of children with neuroblastoma who were treated at the children hospital lahore between march-2020 and fab-2021are compareable to those in developed and developing countries. A high level of suspicion for neuroblastoma is necessary, especially in children under five years of age with an abdominal mass. This can only be ensured through proper education of health care providers about this aggressive childhood malignancy. Advanced disease presentation is common, high-risk neuroblastoma is considered challenging and has one of the least favourable outcomes among cancers. Late diagnosis due to cultural and socioeconomic barriers and lack of care at primary care level and poor referral to oncology units owing to deficient health care system are still considered the major contributory factors for poor outcome. However, newer treatment strategies are mandated to improve outcomes in pediatric patients who are at high-risk and display relapse. Moreover, multidisciplinary approach with the establishment of infrastructure is the need of time to provide integrated care. Keywords: Neuroblastoma, Outcome, Management, Children

Adverse effects of Anticancer Chemotherapy in Childhood Cancer: A Prospective Study in a Moroccan hospital

Objective: To determine the incidence and frequency of adverse drug reactions (ADRs) induced by cancer chemotherapy in pediatric inpatients. Patients and methods: This was a six-month prospective observational study in the pediatric hematology-oncology department of the children's hospital of Rabat. This study took into account ADRs manifested by in inpatient children and undergoing cancer chemotherapy. A modified version of the Moroccan Poison Control and Pharmacovigilance Centre's notification form was used to collect demographic, clinical, cancer treatment and ADR-related data. The causality, severity and preventability were assessed for each adverse event. Results: 106 patients out of 118 followed have developed a total of 266 ADRs. The most frequent ADRs were anemia (14.3%), infections (9.4%), leukopenia (8.6%) and fever (8.3%). Vincristine (16.3%), etoposide (14%) and cytarabine (13%) were the most frequently administered products. Cytarabine followed by etoposide were the drugs most involved in ADRs. The majority of ADRs (55.6%) were probable according to the WHO method of causality assessment. Conclusion: Cancer chemotherapy is associated with a high risk of developing ADRs, particularly hematological ADRs in children. Pediatric patients receiving cytarabine and daunorubicin combinations and regimens including anthracyclines should receive more attention. Risk management plans need to be implemented by health care teams in this area.

P821: LATE ONSET AND/OR LONG LASTING NEUTROPENIA IN CHILDHOOD: CLINICAL AND HEMATOLOGICAL CHARACTERISTICS AND OUTCOMES

Background: In contrast with primary autoimmune neutropenia of infants and pre-school children, characterized by the presence of anti-polymorphonuclear antibodies (anti-PNN), benign course and spontaneous resolution at age 3-5 years, late onset (LO) and/or long lasting (LL) neutropenia of childhood is vaguely described. Aims: To address characteristics and outcomes in a cohort of children with LO/LL diagnosed and followed by our Department. Methods: Cross-sectional study of patients aged 0-16 years with LO (age >5 years, in accordance with Fioredda et al, 2020) or LL (duration >3 years) neutropenia (1.5 G/L) +/- leukopenia (Z-score ≤2 according to age and gender); with a first visit or continued follow-up in our Department of Pediatric Hematology-Oncology (T.A.O.) during the period 2015-2020. Patients with severe congenital neutropenia (SCN) were excluded. Detection of anti-PNN using GAT and GIFT was centralized. Results: From 1972 to 2021, 534 cases of neutropenia/leukopenia were recorded (5, 40, 82, 134, 273 during 1970-1979, 1980-1989, 1990-1999, 2000-2009, 2010-2021, respectively); 152 were included in the cross-sectional study. Sixty-one (40%) had no LO/LL (age<5 years, resolution within≤3 years), 77 (51%0 had LO and 14 (9%) had LL. Male/female ratio was 47% vs 52% vs 28% in no LO/LL vs LO vs LL, respectively (P=0.27), median age 1 vs 11.1 vs 3.1 years (P<10-4), median neutrophil count 0.5 vs 1.2 vs 0.6 G/L (P<10-4), and with concomitant leukopenia in 27% vs 53% vs 36% (P=0.009) or lymphopenia in 3% vs 10% vs 7% of cases (P=0.27). Anti-PNN were detected in 83% vs 42% vs 60% of patients no LO/LL vs LO vs LL, respectively (P=0.12). Familial neutropenia was observed in three pairs of siblings/cousins with LL, possible ethnic neutropenia in 7 patients, probable genetic predisposition to cancer in 4 patients LO/LL and a congenital metabolic syndrome in one patient LL. Infection, mostly cutaneous, occurred in 17% vs 24% vs 66% no LO/LL vs. LO vs. LL (P=0.02). Bone marrow examination was performed in 8 patients (4 LO, 4 LL) and showed mild hypoplasia in 2 (LO). Mild peripheral blood lymphocytic subsets abnormalities were observed in ¼ of the patients, particularly in LO, and mild reduction of serum immunoglobulin class levels in ¼ of the patients, without difference between no LO/LL and LO. Genetic typing performed in 9% of patients LO/LL (targeted pediatric MDS panel N=2, primary immunodeficiency N=2, SCN N=1, whole-exome sequencing N=2) showed a heterozygous TACI mutation in one patient with LL and frequent infections of moderate severity. In total, MDS, immunodeficiency and autoimmunity was noted in 1%, 5% and 4% of patients LO and immunodeficiency in 14% of patients LL. One patient LL developed B-cell precursor ALL. One patient LO with Evans syndrome received eltrombopag, without response, and MMF with response. All patients are alive. Neutropenia resolved spontaneously in 54% of patients. Two-year probability of unresolved neutropenia was 26% vs 78% vs 100% in patients no LO/LL, LO and LL, respectively (P<10-4). Summary/Conclusion: LO/LL neutropenia might be associated with bone marrow failure syndromes, immunodeficiency or autoimmunity. Long-term follow-up and investigations are needed in children with LO/LL neutropenia. Genetic typing in specialized reference networks, like EuNet-INNOCHRON or EWOG, might identify diagnostic subgroups of clinical relevance.

Efficacy and safety of outpatient based therapy in childhood acute lymphoblastic leukemia.

e22001 Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. With the improvements in effective antileukemic drugs and the risk stratification treatment approach, the cure rate for pediatric ALL has increased to &gt;90%. The effect of outpatient treatment and developing supportive care have a very important role in this success. We evaluated the disease outcomes and severe complications (complication causes hospitalization in ICU, encephalitis) of children who had been treated with the Children’s Oncology Group (COG) protocols, and follow-up protocol during a 20-year study period. Methods: From 1999 to 2020, 134 patients who had been diagnosed with ALL in the Department of Pediatric Hematology-Oncology at the Istanbul University Oncology Institute were included in the present study. Nine patients excluded from all analysis that 5 of them admitted with relapse, 2 had been diagnosed with mature aggressive B-cell acute leukemia, and 2 had been diagnosed with mixed phenotype and 7 who had been lost to follow-up were also excluded from survival analyses. Results: Mean age was 7.7±4.89 years old in 125 patients (Table). The 5- and 10-year and 20-year Event Free Survival (EFS) rates were 90.2% (standard error [SE], 4.2%) in standart risk B-ALL (n=54) and Overall Survival (OS) rates were 100%, 96% and 96% ([SE], 3.9%), respectively. In high risk group B-ALL (n=53) 5-year EFS was 80.7% (standard error [SE], 5.8%) and 78.2% ([SE], 6.1%) for both 10 and 20 year period and OS rates were 76.9% ([SE], 5.9%) for all periods. Although the number of patients is low in T-ALL (n=11), 5- and 10-year and 20-year EFS and OS rates were 63.6% (standard error [SE], 14.5%) for all periods. Fifteen severe complication recorded in 12 patients (10 B-ALL, 2 T-ALL). One patient hospitalized in ICU due to gram negative sepsis for 3-times and epidural hemorrhage. Conclusions: The survival rate for pediatric ALL has increased in recent years according to improvements of treatment.In our cohort, 20-year OS rate is 96% for standart risk B-ALL and 76.9% for high risk B-ALL. Additionally, regularly and closely monitored patients, complications can be effectively prevented, treated, and eliminated. In our study, the short hospitalization period, rapid analysis of laboratory tests, continuous supportive care, efficient education given to the parents of children increased the success of the therapy and ensured low complication rates. [Table: see text]

ALL-098: COVID-19 in Children with Cancer: What We Learned from the First Wave

Context:COVID-19 is associated with morbidity and mortality in children with cancer, who are treated mainly in outpatient settings, where hospital visits are unavoidable for appropriate delivery of therapy, increasing their exposure risk to SARS-CoV-2.Objective:To measure the frequency of SARS-CoV-2 infection among hospitalized children with cancer and to detect the associated clinical manifestations and outcomes.Design:A prospective, nonintervention study recruited all hospitalized children with cancer with confirmed SARS-CoV-2 between mid-April and mid-June 2020 (NCT04404244).Setting:The study was carried out at a tertiary Pediatric Hematology Oncology Department at Ain Shams University in Egypt.Methodology:On admission and upon suspicion of COVID-19, patient clinical report forms, including demographic data, clinical assessments, epidemiological data (history of contact with a COVID-19 case), underlying oncologic disorders, and cause of admission, were completed. Baseline laboratory investigations, including complete blood count, C-reactive protein, serum ferritin, lactate dehydrogenase, and D-dimer, were performed. COVID-19 was confirmed by SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test by nasopharyngeal swab. Chest radiograph and/or high-resolution computed tomography (HRCT) chest scan was performed.Results:Over the study course, 61 children with cancer were admitted: 42 (68.9%) had acute lymphoblastic leukemia (ALL), 4 (6.5%) had lymphoma, and 15 patients had other malignancy. Fifteen were diagnosed with SARS-CoV-2. Most had hematological malignancies: 10 (76.9%) had ALL, 1 (6.7%) had acute myeloid leukemia, and 2 (13.4%) had lymphoma. Their mean age was 8.3 ± 3.5 years. Initially, 10 (66.7%) were asymptomatic, and 5 (33.3%) were symptomatic with fever and/or cough. Baseline laboratory tests other than SARS-CoV-2 RT-PCR were not diagnostic; the mean absolute lymphocyte count was 8.7 ± 2.4 × 109/L. C-reactive protein was mildly elevated in most of the patients. Imaging was performed in 10 (66.7%) patients, with significant radiologic findings detected in 4 (40%) patients. Treatment was mainly supportive with antibiotics, as per the febrile neutropenia protocol and local Children’s Hospital guidance for management of COVID-19 in children.Conclusions:Pediatric cancer patients with COVID-19 were mainly asymptomatic or with mild symptoms. A high index of suspicion and regular screening with nasopharyngeal swabs in asymptomatic hospitalized cancer patients is recommended.

Viral respiratory infection among children treated in hemato-oncology department – Clinical and epidemiological characteristics

BackgroundRespiratory viral infections may be associated with high morbidity and mortality among immunosuppressed children. Our aim was to characterize clinical course and epidemiology of respiratory infections suspected as viral among children treated in a single hematology-oncology department in a tertiary hospital. MethodsProspective, observational study during 1.10.2014–1.10.2015. All children with respiratory infection event in the Pediatric Hematology-oncology department at the Ruth Rappaport Children Hospital, Haifa, who were tested for respiratory viruses, were included. Collected data included signs and symptoms, pathogens, background disease, epidemiological characteristics, complications and duration of illness. Viruses were detected by molecular methods. Results159 events were observed among 102 children (55 males). Age range: 3 months-19 years. Single event was observed in 62%. In 79 events (50%) a respiratory virus was detected. Children who underwent allogeneic bone marrow transplantation had more events compared with those with other diseases (58% vs. 32%, p = 0.018). Viral detection was positively associated with symptoms of cough and rhinitis (p < 0.001) and with treatment with biological agents, methotrexate, cyclosporine and tacrolimus (p = 0.006), and negatively associated with hospitalization due to the acute infection illness compared to outpatient and infections during hospitalization related to the basic hemato-oncology disease (p = 0.007). There was no prolonged hospitalization, secondary infections or significant delay in chemotherapy. No patient was admitted to the intensive care unit and there was no mortality. ConclusionsThe probability for viral etiology in immunosuppressed children with respiratory infection was associated with degree of immunosuppression. Otherwise, there was no difference in the course of the disease between those with or without viral detection. No severe course of illness was observed.

Evaluation of endocrine and cardiac complications in survivors of childhood acute lymphoblastic leukemia: A single center study from south Punjab.

Objectives: The objective of our study was to evaluate the endocrine and cardiac complications in survivors of childhood ALL. Study Design: Descriptive Cross Sectional study. Setting: Department of Pediatric Hematology-oncology, Endocrinology and Cardiology at The Children Hospital &amp; Institute of Child health Multan (CH&amp; ICH). Period: January 2019 to June 2019. Material &amp; Methods: Sixty patients were enrolled after taking informed consent from patient/parents. Endocrine complications include (growth failure, overweight/obesity, hyperlipidemia, thyroid disorders, precocious puberty) and cardiac complications include hypertension and low ejection fraction were evaluated. Results: Out of 60 ALL survivors 32 were males (53.3%) and 28 were females (46.7%). At diagnosis patient’s age range was 7-17 years with median age of 11.6 years. At study median age was 17 years with age range of 13 to 23 years. Among our ALL survivors 56.6% had one complication and 25% had multiple problems. Obesity (25%), overweight (20%) and hyperlipidemia (26.4%) were the three common complications followed by short stature (5%), thyroid disorders (3.3%) and hypertension (3.3%). Conclusion: We report high prevalence (56.6%) of these complications from south Punjab. Therefore extended follow up of ALL survivors is needed in order to identify an abnormality and timely treatment and improved quality of life.

Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia: An Analysis of Day-One Versus Day-Eight Lumbar Punctures in Remission Induction Therapy.

IntroductionTraumatic lumbar puncture (TLP+) can lead to the iatrogenic infiltration of the central nervous system (CNS) by circulating leukemic blast cells in childhood acute lymphoblastic leukemia (ALL). The risk of TLP+ is increased by a number of factors at the time of presentation of the disease, such as a high white cell count (WCC), T-ALL phenotype, and unstable clinical condition of the patient. For this reason, the first lumbar puncture (LP) was deferred until Day Eight of prednisolone prophase during remission induction therapy in one set of patients. The objective was to compare the historical cohort of Day-One LP with Day-Eight LP with respect to the incidence of TLP+ and de novo CNS leukemia.MethodsA retrospective comparative data analysis of 1,185 childhood ALL patients aged 1-16 years was conducted based on the electronic medical records of the pediatric hematology-oncology department of The Indus Hospital (TIH), Karachi, from January 2010 to August 2018. A total of 600 patients whose LP was done on Day One (January 2010-May 2015) were placed in cohort A, whereas 585 patients whose LP was performed on Day Eight (June 2015-August 2018) were placed in cohort B. After the examination of the cerebrospinal fluid (CSF), the status of CNS infiltration was classified as CNS-1, CNS-2, CNS-3, and TLP+.ResultsA total of 1,185 patients were included in the study, of whom 600 patients were in cohort A and 585 patients in cohort B. The incidence of TLP+ was found to be lower in cohort B (1.7%) as compared with the incidence in cohort A (4.3%) (p-value=0.009). However, there was an increase in the incidence of CNS-3 cases in cohort B (8%) as compared to cohort A (3%) (p-value: <0.001). When the CNS status of both the cohorts was compared with that of the internationally published data, a low incidence of TLP+ cases was noted in patients with LP on Day Eight.ConclusionThe modified approach of performing the first LP on Day Eight significantly reduced the incidence of TLP+ cases. However, an unusual finding of a significant increase in the CNS-3 leukemia was noted. More prospective studies are needed to investigate this significant increase in CNS-3 cases.