Autologous peripheral blood stem cell mobilization and apheresis in pediatric patients with cancer: A single-center report of 64 procedures.

BACKGROUND: The published experience concerning autologous peripheral blood stem cell collection in children is very limited. METHODS: The data of pediatric patients who underwent autologous stem cell mobilization and apheresis between January 2011 and April 2020 were analyzed retrospectively. RESULTS: We studied retrospectively 64 mobilization and apheresis procedures in 48 pediatric patients (34 males, 14 females), mean age of 7.31 ± 5.38 (range, 1.5-19.7) years, the underlying disease was mostly neuroblastoma (NBL). The body weight of 21 patients (43.75%) was 15 kg or less. The targeted autologous peripheral stem cell apheresis (APSCA) was successfully achieved in 98% of patients. Neuroblastoma patients were younger than the rest of the patients and underwent apheresis after receiving fewer chemotherapy cycles than others and all of them mobilized within the first session successfully. Plerixafor was added to mobilization in nine heavily pretreated patients (18.7%), median two doses (range, 1-4 doses). 11 patients (22.9%) underwent radiotherapy (RT) before mobilization with doses of median 24 Gy (range, 10.8-54.0 Gy). Patients with RT were older at the time of apheresis and had received more chemotherapy courses than patients without RT. As a result, patients with a history of RT had significantly lower peripheral CD34+ cells and CD34+ yields than those without RT. In 17 patients (35.4%), 22 different complications were noted. The most common complications were catheter-related infections (n:10, 20.8%), followed by catheter-related thrombosis in eight patients (16.7%). CONCLUSIONS: Patients who had far less therapy before apheresis were more likely to mobilize successfully. Our study provides a detailed practice approach including complications during APSCA aiming to increase the success rates of apheresis in transplantation centers.

Clinical outcome of pediatric medulloblastoma patients with Li-Fraumeni syndrome.

BACKGROUND: The prognosis for Li-Fraumeni syndrome (LFS) patients with medulloblastoma (MB) is poor. Comprehensive clinical data for this patient group is lacking, challenging the development of novel therapeutic strategies. Here, we present clinical and molecular data on a retrospective cohort of pediatric LFS MB patients. METHODS: In this multinational, multicenter retrospective cohort study, LFS patients under 21 years with MB and class 5 or class 4 constitutional TP53 variants were included. TP53 mutation status, methylation subgroup, treatment, progression free- (PFS) and overall survival (OS), recurrence patterns, and incidence of subsequent neoplasms were evaluated. RESULTS: The study evaluated 47 LFS individuals diagnosed with MB, mainly classified as DNA methylation subgroup "SHH_3" (86%). The majority (74%) of constitutional TP53 variants represented missense variants. The 2- and 5-year (y-) PFS were 36% and 20%, and 2- and 5y-OS were 53% and 23%, respectively. Patients who received postoperative radiotherapy (RT) (2y-PFS: 44%, 2y-OS: 60%) or chemotherapy before RT (2y-PFS: 32%, 2y-OS: 48%) had significantly better clinical outcome then patients who were not treated with RT (2y-PFS: 0%, 2y-OS: 25%). Patients treated according to protocols including high-intensity chemotherapy and patients who received only maintenance-type chemotherapy showed similar outcomes (2y-PFS: 42% and 35%, 2y-OS: 68% and 53%, respectively). CONCLUSIONS: LFS MB patients have a dismal prognosis. In the presented cohort use of RT significantly increased survival rates, whereas chemotherapy intensity did not influence their clinical outcome. Prospective collection of clinical data and development of novel treatments are required to improve the outcome of LFS MB patients.

The Resilience Scale for Parents of Children with Cancer: Scale development and psychometric evaluation.

OBJECTIVE: This study aimed to develop a Resilience Scale for Parents of Children with Cancer (RSP-CC) designed specifically for parents of children with cancer and to evaluate its psychometric properties. METHODS: Based on the Resilience Model for Families of Children with Cancer, items were created after an extensive literature review and evaluated through expert consultation and a pilot study. Psychometric evaluation was conducted with the parents of 601 children with cancer in the pediatric hematology oncology services of different hospitals in the Ankara and Kayseri provinces in Turkey. RESULTS: A 4-factor structure was illustrated by exploratory factor analysis and confirmed by confirmatory factor analysis, explaining 62.192% of the total variance. In the reliability analysis of the scale, Interclass correlation = 0.993 and Cronbach's alpha = 0.994 were found for the scale. Robust correlation coefficients were found between test-retest, and the correlation between the two measurements was statistically significant (r = 0.990; p Ë‚ 0.001). As a result, the validity of a 24-item scale structure consisting of 4 dimensions was validated. CONCLUSIONS: It may be said that the RSP-CC meets the necessary criteria to examine the resilience in parents of children aged 0-18 with a cancer diagnosis, and its psychometric properties are reasonable sufficient.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on pediatric oncology care in the Middle East, North Africa, and West Asia region: A report from the Pediatric Oncology East and Mediterranean (POEM) group.

BACKGROUND: Childhood cancer is a highly curable disease when timely diagnosis and appropriate therapy are provided. A negative impact of the coronavirus disease 2019 (COVID-19) pandemic on access to care for children with cancer is likely but has not been evaluated. METHODS: A 34-item survey focusing on barriers to pediatric oncology management during the COVID-19 pandemic was distributed to heads of pediatric oncology units within the Pediatric Oncology East and Mediterranean (POEM) collaborative group, from the Middle East, North Africa, and West Asia. Responses were collected on April 11 through 22, 2020. Corresponding rates of proven COVID-19 cases and deaths were retrieved from the World Health Organization database. RESULTS: In total, 34 centers from 19 countries participated. Almost all centers applied guidelines to optimize resource utilization and safety, including delaying off-treatment visits, rotating and reducing staff, and implementing social distancing, hand hygiene measures, and personal protective equipment use. Essential treatments, including chemotherapy, surgery, and radiation therapy, were delayed in 29% to 44% of centers, and 24% of centers restricted acceptance of new patients. Clinical care delivery was reported as negatively affected in 28% of centers. Greater than 70% of centers reported shortages in blood products, and 47% to 62% reported interruptions in surgery and radiation as well as medication shortages. However, bed availability was affected in <30% of centers, reflecting the low rates of COVID-19 hospitalizations in the corresponding countries at the time of the survey. CONCLUSIONS: Mechanisms to approach childhood cancer treatment delivery during crises need to be re-evaluated, because treatment interruptions and delays are expected to affect patient outcomes in this otherwise largely curable disease.

Evaluation of Serum Trace Element and Vitamin Levels in Children With Cancer in the First 6 Months After Diagnosis.

Adequate nutrient intake should be provided for the cure of children diagnosed with cancer. The aim of this study was to evaluate serum trace elements and vitamins of children with cancer at diagnosis and during treatment. Children with newly diagnosed cancer who were admitted to our center were evaluated for serum selenium, iron, ferritin, C-reactive protein, vitamin B12, folate, and 25-OH vitamin D levels at presentation, and at the third and sixth months of cancer treatment. Forty-two children (male/female: 15/27) with a median age of 8 years (range, 2 to 17) were included in the study. Mean serum B12, folate, and iron levels were within normal ranges, but selenium and 25-OH vitamin D were low at presentation and during the 6-month period. Serum ferritin levels were high in all 3 measures, but they decreased significantly at the sixth month (P=0.04). There was no relation between micronutrient deficiency and sex, or primary disease, or stage, or place of residence of the patient. In conclusion, serum trace element and vitamin deficiencies are common in children with cancer, and there is a need for further studies with larger patient series.

Total estimated effective doses from radiologic imaging modalities of children with cancer: a single center experience.

BACKGROUND: Recently, awareness of the cumulative radiation exposure for pediatric oncology patients has been increasing, together with increased survival rates and longer life expectancy. The aim of our study was to quantify the amount of ionising radiation from imaging modalities of pediatric oncology patients. METHODS: Eighty-eight patients who were diagnosed with childhood cancer and followed up for 5 years between 2004-2014 in our center were included in the study. Patients' medical files were reviewed retrospectively for imaging history in the first 5 years after diagnosis. Total estimated effective doses from radiologic imaging modalities were determined. Also, the basic demographic data, histologic type, stage, and outcomes of disease were collected for all patients. RESULTS: The individual total estimated effective doses ranged from 8.73 to 167 mSv, with a median of 62.92 mSv. Computed tomography was the greatest contributor of total effective doses. The doses ranged 21.45-113.20 mSv (median: 62.92 mSv) in Hodgkin lymphoma, 12.53-167.10 mSv (median: 52 mSv) in non-Hodgkin lymphoma, 4.13-172.98 mSv (median: 52 mSv) in neuroblastoma, 31-149.89 mSv (median: 63.10 mSv) in Wilms' tumor, 11.50-73.72 mSv (median: 36.90 mSv) in germ cell tumor, 26.46-125.86 mSv (median: 80.90 mSv) in other solid tumor and 0.02-13.31 mSv (5.25 mSv) in brain tumor subgroup. Twenty-two children (25%) died with progressive disease during the 5-year follow-up period. CONCLUSIONS: Similar to previous studies, the total estimated effective doses in children with cancer have been found various according to diagnosis, stage and clinical course. To clarify the harmfull effects of radiation burden, prospective studies should be conducted in children with cancer.

Occipital Hypometabolism on FDG PET/CT Scan in a Child with Hodgkin's Lymphoma.

It is known that Fluorodeoxyglucose (FDG) Positron Emission/Computed Tomography (PET/CT) images may be helpful for evaluation of brain function in newborns. Here we described the fluorine-18 [18-F] FDG PET/CT imaging findings of encephalomalacia due to perinatal asphyxia in a child with refractory Hodgkin's Lymphoma (HL) who underwent PET/CT scan to stage the primary disease. Prominent hypometabolism was incidentally detected in the occipital regions bilaterally apart from the FDG uptakes in the malign lymphatic infiltrations. This case highlights the potential coexistence of a malignancy and a functional brain disorder.

Pediatric bladder/prostate rhabdomyosarcoma: Eight cases from a single center.

In this study, clinical characteristics, treatment modalities and outcome of patients diagnosed with bladder/prostate rhabdomyosarcoma (BP RMS) were evaluated retrospectively. Files of 8 children diagnosed with BP RMS and treated between 2004-2014 were reviewed for clinical characteristics, treatment modalities and outcome. Seven males and one female were diagnosed with BP RMS between 2004-2014. Median age was 33.5 months (range, 2 to 176 months). At presentation the main clinical symptoms were hematuria in 5 patients, and constipation, oliguria and prolonged jaundice in 1 patient each. All patients were non-metastatic and only one had an embryonal histology. Primary resection before chemotherapy was performed on only one patient. Six patients were treated initially with VAC chemotherapy for 12 weeks, two patients were treated PIAV (ifosfamide, cisplatin, doxorubicin, vincristine). Local relapse or progressive disease occurred in 5 of 8 patients, and two of these patients underwent primary or secondary tumor resection without radiotherapy. Three patients developed a local relapse after combination of radiochemotherapy and tumor resection. Radical surgical treatment was performed in 3 patients with local relapse. Only one patient underwent partial cystectomy. Six of 8 patients were alive and under follow-up without disease at a median survival of 53 months (range, 13 to 78 months). BP RMS requires a multidisciplinary treatment approach. There is a general consensus that chemotherapy is the mainstay of treatment in BP RMS, but the method to be used for local control is controversial, and may vary from case to case in this heterogeneous disease.

Occurrence of Wilms' tumor in a child with hereditary spherocytosis.

Hereditary spherocytosis (HS) is the most frequent cause of congenital hemolytic anemia. It is an autosomal dominant genetic disorder characterized by cell membrane abnormalities, specifically in red blood cells. Although the association between benign, borderline and malignant tumors and HS is not clear, various tumors such as splenoma, adrenal myolipoma, pancreatic schwannoma, ganglioneuroma, extramedullary hematopoiesis, myeloproliferative disorders, multiple myeloma, B-cell lymphoma and acute lymphoblastic leukemia have been presented in case reports concerning HS patients. Here we describe a 6-year-old boy with HS who presented with a mass in the left kidney. Tru-cut biopsy revealed Wilms' tumor (WT). To the best of our knowledge, this is the first case of WT associated with HS to be reported in the literature.

Assessment of Nutritional Status in Children With Cancer and Effectiveness of Oral Nutritional Supplements.

Malnutrition is a common consequence of cancer in children, but the most effective methods of nutrition intervention are under debate. We aimed to evaluate the nutritional status of children diagnosed with cancer, and to investigate the effect of oral nutritional supplements on anthropometric measurements, biochemical parameters, and outcome. A randomized clinical study of 45 newly diagnosed cancer patients was performed. Anthropometric and biochemical data and related factors were assessed at 0, 3, and 6 months after diagnosis. On initial anthropometric assessment, prevalence of malnutrition by weight or height was found to be lower as compared with body mass index (BMI), or weight for height (WFH), or arm anthropometry. Twenty-six of the patients (55%) received oral nutritional supplement. During the second 3 months after diagnosis, there was a statistically significant decrease in number of the patients with WFH <90th percentile and BMI <5th percentile (P = .003 and P = .04, respectively). Infectious complications occurred more frequently in malnourished patients during first 3 months, and survival of children who were malnourished at the 6th month was significantly lower than that of well-nourished children (P = .003). On laboratory assessment, serum prealbumin levels of the all subjects were below normal ranges, but no relation was found for serum prealbumin or albumin levels in patients who were malnourished or not at diagnosis. Nutritional intervention is necessary to promote normal development and increase functional status as a child receives intensive treatment. Protein- and energy-dense oral nutritional supplements are effective for preventing weight loss in malnourished children.

Anaplastic lymphoma kinase gene expression in small round cell tumors of childhood--a comparative immunohistochemical study.

The focus of this study was to investigate anaplastic lymphoma kinase (ALK) expression by immunohistochemistry using a highly specific antibody. Distribution and frequency of ALK expression may provide a clue for ALK inhibitor use in small round cell tumors of childhood. The study group involved 76 small round cell tumors of childhood, which composed of 11 rhabdomyosarcomas, 13 Wilms tumors, 7 Ewing sarcoma/primitive neuroectodermal tumors, 34 peripheral neuroblastic tumors, and 11 acute lymphoblastic lymphoma. Anaplastic lymphoma kinase protein expression in small round cell tumors of childhood is poorly described in the literature. The findings of our study highlight a potential and possible role of targeting ALK in pediatric solid tumors by using ALK immunohistochemistry. Anaplastic lymphoma kinase may also have an oncogenic role in rhabdomyosarcomas and peripheral neuroblastic tumors, and they may possibly be treated with ALK inhibitors. Anaplastic lymphoma kinase expression in Wilms tumors is not reported in the literature, previously. Our study evaluated ALK expression in Wilms tumor samples.

Primary liver tumors in children: Hacettepe experience.

We aimed to review our experience with the clinical characteristics and outcome in childhood liver tumors. We investigated the clinical, laboratory and pathological characteristics, treatments and outcome in hepatoblastomas (HBL) and hepatocellular carcinomas (HCC). We identified 91 HBL and 42 HCC cases. Distant metastases were detected in 16% of HBLs and 22% of HCCs. PRETEXT stages were I/II in 34% and III/IV in 66% of HBLs and I/II in 16% and III/IV in 84% of HCCs. Most cases received cisplatin + doxorubicin chemotherapy. At a median of 58 months, 90 cases had died, 28 were alive, and 15 were lost to follow-up. Five-year survival rates were 32.4% for all HBLs and 15.6% for HCCs. Five-year survival rates were 47% in HBLs and 22.8% in HCCs diagnosed after 1990. In HBLs, distant metastases and absence of chemotherapy response indicated poor prognosis. Prognosis for childhood liver tumors has improved over the last two decades with preoperative chemotherapy with cisplatin + doxorubicin. Surgical resectability is important for cure. For HCC, more effective chemotherapy approaches are essential.

Alpha-fetoprotein-producing hepatoid gastric adenocarcinoma in a child presenting with spontaneous gastric perforation.

Gastric adenocarcinoma is a rare entity in the pediatric population. Gastric hepatoid adenocarcinoma with elevated serum alpha-fetoprotein (AFP) is seen extremely rarely in children. A 12-year-old boy was admitted to the hospital with complaint of abdominal pain. X-ray revealed free air density below the diaphragm. Emergent laparotomy showed perforated stomach. Four weeks after the operation, he was readmitted with severe gastrointestinal obstruction symptoms. He underwent an explorative laparotomy, which revealed intestinal edema and diffuse small solid nodules covering the peritoneum. Serum AFP level was mildly elevated. Endoscopic evaluation of the upper gastrointestinal tract was performed, and a gastric mass was detected. All pathological findings were compatible with gastric carcinoma showing hepatoid differentiation. We report an unusual case of AFP-producing hepatoid gastric adenocarcinoma presenting with gastric perforation. This is, to the best of our knowledge, the first reported case of AFP- producing hepatoid gastric adenocarcinoma presenting with gastric perforation in a child.

Use of plerixafor for peripheral blood stem cell mobilization failure in children.

BACKGROUND: Peripheral blood stem cell mobilization is usually performed following chemotherapy plus G-CSF in children. This standard approach may not be successful in some heavily pretreated patients undergoing mobilization. Plerixafor (AMD3100) has been used in adults as a second line mobilizing agent. Our aim is to analyze our experiences with plerixafor in children. METHODS: We retrospectively evaluated three children who received plerixafor as a second line stem cell mobilizing agent in our department in the 2010-2012 period. Data including age, sex, diagnosis, previous chemotherapy, radiotherapy details, previous harvest attempts, adverse reaction, and harvest outcome were analyzed. RESULTS: We used plerixafor in combination with G-CSF and chemotherapy or with only G-CSF seven times in three patients. All three patients were treated with different multiple chemotherapy regimens prior to stem cell harvest and failed earlier mobilization with chemotherapy plus G-CSF. The diagnoses were relapsed Hodgkin lymphoma in two and recurrent Ewing's sarcoma in one patient. We used plerixafor in combination with G-CSF and chemotherapy or with only G-CSF seven times in three patients. The harvest was successful in four of seven attempts. No adverse reaction was observed in the patients. CONCLUSION: The success rate is four out of seven attempts (57%) in our group. Although the data regarding the use of plerixafor in children is scarce, our experience also supports its use in poor mobilizer children. The use of plerixafor in children results in effective increases in peripheral stem cell counts and reduces the risk of mobilization failure.

Primary ovarian malignant melanoma arising in teratomatous component of mixed- germ cell tumor in a child: case report.

Primary ovarian malignant melanoma arising in teratomatous component of germ cell tumors is seen extremely rare with most reports being only of single cases and small series in reproductive aged woman and mostly from cystic teratoma, whereas information on pediatric presentation is sparse. This case is reported for being extremely rare tumor.

Chronic lymphocytic leukemia in a child: a challenging diagnosis in pediatric oncology practice.

Chronic lymphocytic leukemia/lymphoma (CLL) is an extremely rare disease during childhood. We report a 16-year-old female who presented with lymphadenopathies and she was diagnosed as T cell lymphoblastic lymphoma. Her chemotherapy response was minimal and clinical findings were unusual. Therefore, her biopsy specimen was re-examined and diagnosis was changed to CLL. Chemotherapy protocol including fludarabine, cyclophosphamide, rituximab was administrated and good response was observed. In our patient deletion at 1q21.2 region that includes aryl hydrocarbon receptor nuclear translocator (ARNT) gene was detected via comparative genomic hybridization method. ARNT gene deletion may be a new mutation in chronic lymphocytic leukemia development.

Spindle cell rhabdomyosarcoma displaying CD34 positivity: a potential diagnostic pitfall; report of two pediatric cases.

Spindle cell rhabdomyosarcoma is a rare subtype of rhabdomyosarcoma mainly seen in children. Occasional aberrant staining with a variety of immunohistochemical markers has been noted. The aberrantly expressed markers include alpha-smooth muscle actin, cytokeratin, S100, neurofilaments, CD20, immunoglobins, and CD117. We report herein two pediatric cases displaying strong CD34 positivity and one with additional focal CD117 positivity, causing considerable difficulty in distinction from solitary fibrous tumor and extra-gastrointestinal stromal tumor. To our knowledge, CD34 staining has been merely reported in rhabdomyosarcoma. Spindle cell rhabdomyosarcoma has to be considered in the differential diagnosis of childhood spindle cell tumors. Post-chemotherapy specimens should be evaluated in caution, since chemotherapy can cause considerable changes in tumor antigen expression. Since CD117 and CD34 are stem cell markers, their positivity in pediatric tumors should be interpreted with caution. Even if the morphology is not supportive, a wide immunohistochemical panel should be applied in childhood malignant solid tumors.

Two-stage multilevel cervical spondylectomy for aneurysmal bone cyst.

Aneurysmal bone cyst is a benign tumor-like bony lesion with a propensity to develop in the pediatric population. It generally involves one vertebral level when localized to the spine. The degree of resection correlates highly with fewer recurrences. En bloc spondylectomy is the procedure of choice for this reason, but its high complication rate has led to the development of alternative surgical methods. This paper presents a three-level aneurysmal bone cyst that was excised totally in two stages, and the safety and efficacy of this method especially in the pediatric population are emphasized. This paper also states that anterior and posterior instrumented fusions are necessary in spite of the growing spine.

Characteristics of children with non-hodgkin lymphoma associated with primary immune deficiency diseases: descriptions of five patients.

BACKGROUND: An increased incidence of non-Hodgkin lymphoma (NHL) has been seen in various primary immune deficiency (PID) cases. The present study aimed to evaluate the clinical characteristics and treatment outcomes of five cases with NHL associated with primary immunodeficiency. METHODS: We retrospectively evaluated five patients with primary immunodeficiency who developed NHL. Two patients had ataxia-telangiectasia (A-T), one patient had common variable immunodeficiency (CVID), one patient had Bloom's Syndrome, and one patient had Wiskott-Aldrich syndrome (WAS). RESULTS: All patients were male (median age, 8 years). Stage distribution was stage III in three patients and stage IV in two patients. Three patients had B-cell lymphoma and two had T-cell lymphoma. Reduced doses of Berlin-Frankfurt-Münster (BFM) and French Society of Pediatric Oncology (SFOP) regimens were used in four patients according to histopathological subtype. The two patients with ataxia and one patient with Bloom's Syndrome died of progressive/relapsed disease at months 5, 19, and 6, respectively. The patient with CVID associated with T-cell lymphoma has been in remission for 7 years. A full-dosage regimen of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was successfully used in the patient with WAS and B-cell lymphoma; he was still in remission after 3 years. CONCLUSION: Primary immunodeficiency diseases are one of the strongest known risk factors for the development of NHL. Management of these patients remains problematic. There is a great need to develop new therapeutic approaches in this group. The use of rituximab in combination with CHOP may provide a promising treatment option for B-cell lymphomas associated with immunodeficiency.