Vitamin D Deficiency in Pediatric Oncology Patients: A Single-Center Experience in Saudi Arabia.

Background There is a lack of local studies on vitamin D deficiency in children with cancer. This study aims to estimate the prevalence of vitamin D deficiency in the pediatric oncology population at King Abdul-Aziz Medical City (KAMC) in Jeddah, addressing knowledge gaps for improved clinical practice and future research. Methods This retrospective observational study was conducted from 2016 to 2021 at the pediatric oncology clinic in National Guard Hospital, Jeddah. The study focused on children aged 14 or younger at cancer diagnosis, data encompassed patient demographics, cancer details, and treatment information, including serum measurements of vitamin D (25(OH)D, calcium, phosphate, alkaline phosphatase). Vitamin D levels were categorized as deficient (<25 ng/ml), insufficient (25-49 ng/ml), sufficient (≥50- 125 ng/ml), or hypervitaminosis (>125 ng/ml), based on our center reference range and the validation of the assay. Results In this retrospective study of 155 pediatric oncology patients, the majority aged 0 to 10 years (78%), findings reveal a male preponderance (54.2%) and a more prevalent in patients with hematological malignancies (85%). Chemotherapy was administered to 98%, with 7% underwent radiotherapy, and 89% received steroids. Analysis of serum 25-OH vitamin D levels indicated an overall deficiency and insufficiency at diagnosis (63%) and post-therapy (43%). Age and gender had a significant influence on vitamin D levels at diagnosis, with older children and females exhibiting lower concentrations. However, these differences diminished by the end of therapy. Notably, hematological malignancy patients often presented insufficient vitamin D levels, while solid tumor patients frequently had sufficient levels. Clinical outcomes showed a high survival rate (90.7%), limited bone density assessments (18.1%), and a 14.2% prevalence of hypervitaminosis. Conclusion In summary, our study reveals that over two-thirds of pediatric oncology patients experience vitamin D deficiency and insufficiency at the time of diagnosis, particularly notable in females and older children. Notably, those with solid tumors exhibit higher baseline 25-OH vitamin D concentrations compared to counterparts with hematological malignancies. The findings underscore the importance of educating both patients and caregivers on supplementation and sun exposure to mitigate the prevalence of deficient and insufficient vitamin D levels in pediatric oncology cases.

The perception of pediatric sickle cell anemia patient's caregivers toward hematopoietic stem cell transplantation (single-center experience, Saudi Arabia).

Background: Sickle cell disease (SCD) is a relatively common genetic disorder in Saudi Arabia characterized by the predominance of sickle hemoglobin (HbS). Although multiple supportive care options exist for patients with SCD, hematopoietic stem cell transplantation (HSCT) is the only cure available and has become highly successful, with an almost 91% overall survival rate. However, pursuing this procedure is still restrained as a curative treatment option. Therefore, this study aimed to evaluate the perception of parents' caregivers at the National Guard Hospital pediatric hematology clinic regarding using HSCT as a curative approach for their children with SCD. Methods: This is a cross-sectional study of the interviewer-administered survey distributed utilizing electronic devices to caregivers of pediatric patients with SCD. Subjects were recruited from Pediatric Hematology & Oncology clinics at National Guard Hospital Affairs in King Abdulaziz Medical City, Jeddah, Saudi Arabia. An estimated sample size of 100 was initially calculated out of 140 pediatric SCD patients; 72 responses were collected from participants. All study participants gave informed consent. All results were analyzed using SPSS; moreover, statistics were set at a CI of 95% and a p < 0.05. In addition, inferential and descriptive statistics were done. Results: Of all respondents, 42 (67.8%) would accept HSCT if their hematologist recommended it. However, approximately 7 (11.3%) were not interested in the procedure, and the rest, 13 (21%), were uncertain. The most reported reasons for HSCT rejection among all respondents were attributed to side effects 31 (50.8%), lack of knowledge 8 (13.1%), and misconception toward the procedure 22 (36.1%). Conclusion: The results of this study were consistent with the fact that most caregivers would follow along with HSCT if it seemed to be fit and was recommended by their hematologists. However, to the best of our knowledge, our study being the first of its kind in the region, further research in the kingdom on the perception of HSCT is needed. Nonetheless, further patient education, an increase in caregivers' knowledge, and enlightenment of the medical team on HSCT as a curative option for sickle cell disease are vital.

Clinical and pathological characteristics of extra-cranial germ cell tumors: A 30-year single-center experience in Saudi Arabia.

OBJECTIVES: To investigate the clinical and pathological characteristics of extracranial germ cell tumors (GCTs) in children aged 0-168 months treated at the National Guard Hospital, Jeddah, Saudi Arabia from 1990 to 2020. METHODS: In this retrospective analysis, the data for all cases of GCTs were collected from 1990 to 2020. Statistical analyses were carried out using JMP software. The data was divided into 4 main categories: demographics, pathological/clinical features, recurrence, treatment and outcome. RESULTS: The study included 50 patients, with a mean age at diagnosis of 56.52 months. The median follow-up duration was 30 months. Most tumors were in the gonads, and among the extragonadal tumors, the sacro-coccyx was the most frequent site of the disease.The most common histological subtype of GCTs is yolk sac tumor, accounting for 28% of cases. Of the 50 patients, 46% received chemotherapy, and 54% underwent surgery without chemotherapy. Ten (20%) patients experienced recurrence after treatment. At the last follow-up, 96% of the patients were alive, and only 2 of the patients died due to advanced disease. CONCLUSION: Our findings were comparable to international data, but improvement in surveillance is required for long-term survivors.

New SAMD9L heterozygous mutation leading to myelodysplastic syndrome and acute myeloid leukemia: A case report and review of the literature.

BACKGROUND: SAMD9L mutation is linked to the development of myeloid neoplasm. The mutation has a wide range of clinical presentations involving neurological, immunological, and hematological manifestations. Until now, limited data regarding different variants of this genetic mutation existed. Here we present a 6-year-old girl who presented with acute myeloid leukemia/myelodysplastic changes and who carries a new germline variant mutation in the SAMD9L gene. CASE PRESENTATION: A 6-year-old girl who presented initially as a case of immune thrombocytopenic purpura (ITP) was later diagnosed with acute myeloid leukemia and myelodysplastic changes. In addition, she was found to have a new germline variant mutation in the SAMD9L gene (other known pathogenic variants known to cause ataxia pancytopenia syndrome). She was treated with chemotherapy followed by haplo identical transplant from her unaffected father. She is alive 30 months post-transplant and in complete remission with full donor chimerism. Her initial brain MRI showed mild prominence of the anterior (superior) vermis folia, suggesting mild atrophy. Ongoing surveillance for accompanied neurological manifestation is ongoing, although the patient is asymptomatic. CONCLUSION: For SAMD-9L-related disorder, a careful approach must be taken when a patient presents with a suspicious clinical feature even without a well-known genetic mutation giving the diverse presentation across affected members within the same family. In addition, other associated abnormalities should be monitored long-term.

Renal outcomes in pediatric patients with sickle cell disease: a single center experience in Saudi Arabia.

Background: Sickle cell nephropathy (SCN) is a significant complication of sickle cell disease (SCD) with an asymptomatic onset in childhood and potential progression to chronic kidney disease (CKD). The clinical findings of SCN include hyposthenuria, hematuria, proteinuria, hyperfiltration, and CKD. Data on renal manifestation among patients with SCD in Saudi Arabia is lacking. Therefore, this study aimed to evaluate renal outcomes in patients with SCD who visited a hematology clinic at the National Guard Hospital, Jeddah. Methods: We conducted a retrospective chart review of renal complications in patients with SCD who are within 0-14 years of age and on regular follow-ups at the pediatric hematology clinic in King Abdulaziz Medical City-Jeddah, Saudi Arabia. Results: Among the 140 patients with SCD, 99 met the inclusion criteria. The median age at diagnosis was 18 (1-108) months. Two SCD phenotypes were observed, with 82 (83%) patients having sickle cell anemia (HbSS) and 17 (17%) having HbS/B+ thalassemia. Of the total patients, 92 (93%) were administered hydroxyurea (HU), with a median starting age of 48 (9-168) months. The most common renal complication observed during routine urinalysis was hematuria (38%), followed by proteinuria (11%). After stratifying the sample into four age groups (0-3 years old, 4-7 years old, 8-11 years old, and 12-14 years old), the mean glomerular filtration rate (GFR) values were 96.16, 101.36, 112.69, and 120.11 ml/min/1.73 m2 respectively. Renal imaging revealed abnormal findings in 27 (29%) patients. The most common abnormality observed on US was increased echogenicity (43%). Conclusion: SCN is a significant complication of SCD. In this study, we assessed the renal outcomes in pediatric patients with SCD. After analyzing the clinical findings of SCN, we concluded that the presence of renal complications in pediatric patients presented a progressive pattern.

Neurological abnormalities among pediatric patients with sickle cell disease in Saudi Arabia: a single-center retrospective study.

Introduction: Sickle cell disease (SCD) is a common inherited blood disorder characterized by the production of abnormal sickle-shaped red blood cells. SCD can lead to various complications including neurological issues. Early detection and treatment are crucial for preventing these complications. This study aimed to describe the neurological manifestations, radiological findings, and neurological diagnosis related to SCD in Saudi children with the aim of contributing to the formulation of population-based guidelines for screening and treating SCD-related neurological complications. Methods: This descriptive retrospective study included pediatric patients aged < 14 years diagnosed with SCD who were regularly followed up at the hematology clinic in KAMC, Jeddah, Saudi Arabia, from January 2008 to January 2022. Demographic and clinical data were collected from the clinical charts of 101 participants. Results: This study included 101 patients with SCD with a mean age of 23 months at diagnosis. Among these, 59% had SCD and high fetal hemoglobin (HbF) levels. Neurological sequelae, including seizures, stroke, and other abnormalities, were observed in 26.7% of patients. There were no significant differences in the onset of neurological issues between the patients with SCD-high HbF and those with other SCD phenotypes. Discussion: This study highlights the increased risk of brain injury and neurocognitive deficits in children with SCD. The occurrence of neurological sequelae in many patients emphasizes the need for early detection and intervention. Some patients experience neurological complications despite having high HbF levels, suggesting that further interventions are needed. This study has some limitations, including its small sample size and retrospective nature. Conclusion: Early detection and intervention are crucial for neurological complications in patients with SCD. This study emphasizes the need for further research and effective treatment strategies considering the presence of neurological complications despite the presence of high HbF levels. Large-scale studies and population-specific guidelines are warranted for better understanding and management of SCD-related neurological complications in the Saudi population.

Clinical features at diagnosis of sickle cell disease prior to universal newborn screening in Alberta.

Objectives: Sickle cell disease (SCD) is an inherited multisystem disorder with complications starting in the first year of life. Newborn screening (NBS) can identify infants with SCD and is associated with decreased morbidity and mortality. Variation in availability of NBS in Canada, and lack of standardized screening for immigrant children, may lead to delayed diagnosis. Methods: This was a retrospective cohort study of 126 children aged 0-18 years with SCD registered with the SCD clinic at the Alberta Children's Hospital between January 2003 and January 2018, prior to province-wide universal NBS for SCD. Patient demographic information, circumstances of diagnosis, and other contextual information were collected from patient health records. Descriptive statistics were used to summarize data, with Mood's median test used to compare medians between groups. Results: Forty-three (35%) patients were born in Alberta. Patients were mostly (95.3%) of African descent. Of patients born in Alberta, 63% (26/43) were diagnosed at >12 months of age, with a median age at diagnosis of 18 months (IQR = 4-39). This was significantly older (P < 0.001) than children born in the USA or in Canadian provinces with SCD NBS programs, where the median age at diagnosis was zero months (N = 36). Of the 42% of patients born outside North America, 64% were diagnosed following an acute complication. Conclusions: This study highlights the importance of NBS for early detection and management of SCD, and the importance of screening at-risk immigrants who may not have received NBS for SCD.

Pulmonary function in children and adolescents with sickle cell disease after nonmyeloablative hematopoietic cell transplantation.

BACKGROUND: Pulmonary complications are common in sickle cell disease (SCD). The use of standard myeloablative conditioning regimens may increase the risk of lung injury. We report serial pulmonary function testing (PFT) outcomes in children with SCD who underwent a matched-sibling donor hematopoietic cell transplantation (HCT) using nonmyeloablative (NMA) protocol. METHODS: This is a retrospective chart review describing pulmonary outcomes in pediatric patients post HCT. The conditioning regimen consisted of alemtuzumab and a single fraction of 300 cGy of total body irradiation (TBI), and sirolimus for graft-versus-host disease (GVHD) prophylaxis. Serial PFT testing was performed pre and post HCT. The evaluated pulmonary measures included: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1 ), FEV1 /FVC, and forced expiratory flow (FEF25-75 ). RESULTS: Twelve subjects were included in the analysis. All had HbSS genotype, and five of the 12 patients had one or more episodes of acute chest syndrome prior to HCT. Serial PFT measures were completed per patient. No patient was diagnosed with chronic GVHD of any organ post HCT. The baseline median FVC, FEV1 , FEV1 /FVC, and FEF25-75 were within the normal range and remained relatively unchanged post HCT. A linear mixed effects model, adjusting for gender and time from HCT, suggested no significant relationship between HCT and PFT parameters, including FVC, FEV1 , and FEV1 /FVC. Interestingly, the FEF25-75 results exhibited a shift in the means post HCT (pre-HCT 86.2% predicted and post-HCT 93.05% predicted, p-value = .018). CONCLUSION: Our study suggests that HCT in children with SCD may prevent the anticipated decline in pulmonary function over time.

Neuropsychological, behavioral, and quality-of-life outcomes in children and adolescents with sickle cell disease treated with nonmyeloablative matched sibling donor hematopoietic cell transplantation: A case series.

BACKGROUND/OBJECTIVES: Despite advances in the treatment of sickle cell disease (SCD), cerebrovascular and cognitive insults can have lifelong consequences. Hematopoietic cell transplantation (HCT) is an established curative therapy, and recent studies have demonstrated efficacy with reduced toxicity nonmyeloablative (NMA) regimens, but little is known about neuropsychological outcomes. The objective of this study was to describe neuropsychological, behavioral, and quality-of-life outcomes with medical correlates in children with SCD who received an NMA matched sibling donor (MSD) HCT. DESIGN/METHODS: Retrospective cohort analysis of nine recipients with hemoglobin SS SCD who underwent MSD HCT using the National Institutes of Health (NIH) NMA protocol. RESULTS: Mean full-scale intellectual functioning (FSIQ) was average pre-HCT (FSIQ = 92.1, SD 9.0; n = 8) and 2 years post-HCT (mean FSIQ = 96.6; SD 11.1; N = 9). Neuropsychological functioning was largely average across all cognitive domains, and no pre/post-HCT differences were found to be statistically significant given the small sample size. However, effect sizes revealed moderate improvements in processing speed (Cohen's d = .72) and verbal memory (Cohen's d = .60) post-HCT, and declines in measures of attention (Cohen's d = -.54) and fine motor speed and dexterity (Cohen's d = -.94). Parents endorsed better quality of life (Cohen's d = .91), less impact of SCD on their family, and less worry about their child's future (Cohen's d = 1.44). CONCLUSION: Neuropsychological functioning in a sample of children and adolescents treated uniformly with NMA MSD HCT remained stable or improved in most cognitive domains, and improvements in quality of life and family functioning were observed.

Stable renal function in children and adolescents with sickle cell disease after nonmyeloablative hematopoietic stem cell transplantation.

BACKGROUND: Sickle cell disease (SCD) is associated with renal complications starting as early as infancy. Allogeneic hematopoietic stem cell transplant (HSCT) treatments using newer nonmyeloablative (NMA) conditioning regimens show promising results in treating SCD in the pediatric population, but renal outcome parameters after transplantation have not been described. AIM: To describe baseline renal parameters as well as short- and long-term renal outcomes in pediatric patients with SCD who underwent NMA-HSCT. METHODS: A retrospective chart review of pediatric patients who received NMA-HSCT in Alberta, Canada. Short-term renal outcomes evaluated were: (1) acute kidney injury (AKI), (2) fluid overload (FO), and (3) hypertension. Long-term outcomes evaluated were: (1) estimated glomerular filtration rate (eGFR) development and at last follow-up with hyperfiltration defined as eGFR ≥ 150 mL/min/1.73 m2 , (2) proteinuria, and (3) hypertension. RESULTS: The mean follow-up time was 128.6 weeks (standard deviations, 69.3). No posttransplant AKI events or FO were observed. eGFR remained > 90 mL/min/1.73 m2 at last follow-up in all patients, whereas hyperfiltration was present in eight (44.4%) and four (22.2%) patients pre- and post-HSCT, respectively, which are significantly different (P < 0.0001). Consequently, median GFR was significantly higher pre-HSCT compared with 24 months HSCT (P < 0.009). Long-term hypertension post-HSCT was present in six patients (33.3%). CONCLUSION: This study describes stable kidney function in children with SCD after NMA-HSCT without evidence of AKI or FO episodes. Rates of hyperfiltration decreased post-HSCT, which signifies that NMA-HSCT could potentially preserve long-term renal function in this population at risk of progressive chronic kidney disease. Further prospective studies are needed to confirm these novel findings.

Nonmyeloablative Matched Sibling Donor Hematopoietic Cell Transplantation in Children and Adolescents with Sickle Cell Disease.

Sickle cell disease is a potentially debilitating hemoglobinopathy associated with early mortality. The only established curative therapy is hematopoietic cell transplantation (HCT) with a matched sibling donor. The National Institutes of Health nonmyeloablative regimen of alemtuzumab/300 cGy total body irradiation and prolonged sirolimus exposure for graft-versus-host disease (GVHD) prophylaxis was administered to 16 children and adolescents. Infused products were unmanipulated granulocyte colony stimulating factor mobilized peripheral blood stem cells. All patients achieved mixed donor-recipient engraftment with no cases of secondary graft failure to date. Two patients have donor myeloid chimerism in the range of 30% to 40%. No sickling crises post-HCT have been observed. Event-free and overall survival rates are 100% with median follow-up of 19.5 months. No cases of GVHD have been observed. Sirolimus weaning was possible in all but one eligible patient to date. Ongoing follow-up and a larger prospective clinical trial are required to determine the long-term safety and efficacy of this regimen in children.