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 and Demographic Characteristics of Cutaneous Mastocytosis in Childhood: Single-center Experience.

INTRODUCTION: Mastocytosis is a rare and heterogenous disease, and in children it is generally limited to the skin and tends to regress spontaneously in adolescence. AIM: In this study, demographic, clinical, and laboratory characteristics of pediatric patients with mastocytosis, and also coexisting diseases were investigated. RESULTS: A total of 61 pediatric patients were included in the study. The male-to-female ratio was 2.2, the median age was 2 years (range, 0.25 to 19 y), and the median follow-up period was 2.0 years (range, 0.25 to 19 y). Types of clinical presentation at diagnosis consisted of mainly urticaria pigmentosa (45.9%). Seven patients were further investigated with suspicion of systemic mastocytosis, they were followed up, median of 9 years (range, 2.5 to 16 y), and none of them developed systemic disease. Coexisting allergic diseases were recorded in total 5 patients (8.2%). Three patients had immunoglobulin A deficiency, 1 patient had elevated immunoglobulin E level. A patient developed mature B-cell lymphoma with a heterozygous mutation in c-KIT exon 11. DISCUSSION: Cutaneous mastocytosis in children may present as a complex disease with different clinical signs and symptoms. Standardized clinical criteria and guidelines for the follow-up of children with mastocytosis are required.

Clinical Profile and Outcomes of Primary Immunodeficiency and Malignancy in Childhood at a Tertiary Oncology Center in Developing Country.

Primary immune deficiencies are a group of heterogenous genetic disorders characterized by frequent infections, autoimmunity and malignancy. In this study, we aimed to evaluate clinical characteristics, outcomes of children with malignancy developed on background of primary immunodeficiency and compare survival rates of patients between malignant lymphoma with primary immunodeficiency and without immunodeficiency from tertiary oncology center in a developing country. A total 23 patients with primary immunodeficiency and malignancy were evaluated retrospectively. A total of 26 malignancies (first or second) in 23 patients were determined. The median age at the time of the first malignancy was 8 years (ranges 2-18 years) with increased male ratio (M/F:14/9). Non-Hodgkin lymphoma (n = 17; 65%) was the most common malignancy, followed by Hodgkin lymphoma (n = 5), anaplastic ependymoma (n = 1), spinal glioblastoma multiforme (n = 1), retinoblastoma (n = 1) and intracranial hemangiopericytoma (n = 1). The median follow-up time of patients was 25 months (ranges between 1 and 189 months). The 5-year overall survival rate of patients with malignant lymphoma associated with primary immunodeficiency (41%) were lower than immunocompetent patients with malignant lymphoma (80%) (p = 0.000). The 5-year overall survival of patients was diagnosed between 2021 and 2013 years (62%) was higher than previous years (22%) (p = 0.03). In conclusion, non-Hodgkin lymphomas were the most common histopathologic type in patients with malignancy associated with primary immunodeficiency in the present study. The survival of patients with malignant lymphoma associated with primary immunodeficiency has improved in recent years, yet it is still lower than immunocompetent patients with lymphoma and new targeted drugs are required for better survival rates.

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.

Focal Nodulary Hyperplasia of the Liver Due to Congenital Portosystemic Shunt: A Rare Condition Mimicking Hepatocellulary Carcinoma.

Congenital portosystemic shunts are rare vascular malformations that lead to several complications including liver tumors, pulmonary hypertension, and metabolic encephalopathy. We describe a rare case of a 17-year-old girl with an extrahepatic portosystemic shunt presenting recurrent syncope episodes and a liver mass mimicking hepatocellulary carcinoma.

NUT Midline Carcinoma of the Lung in a Six-Year-Old Child.

BACKGROUND: Nuclear protein of the testis (NUT) midline carcinoma is genetically defined by rearrangement of NUT or by immunohistochemical expression of NUT. FINDINGS: A 6-year old child had a NUT midline carcinoma of the lung. Despite aggressive therapy, the child died. CONCLUSION: NUT carcinoma, which can be diagnosed immunohistochemically, remains an aggressive tumor.

Pulmonary arterial hypertension in a child with stage-IV neuroblastoma after autologous hematopoietic stem cell transplantation and review of the literature.

PH is a rare condition with high mortality rate after pediatric HSCT. As clinical presentation is non-specific and may mimic other conditions, a high degree of suspicion is required for diagnosis. Here, we present a patient with stage-IV neuroblastoma who developed PAH after autologous HSCT. After exclusion of other causes of PH, we regarded that this condition was secondary to HSCT.

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.

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.

Teratoid Wilms' tumor exhibiting extensive squamous differentiation.

Teratoid Wilms' tumor is a rare renal tumor. Herein, we report an unusual variant of such tumor which simulated renal teratoma because of abundant keratinized squamous epithelium within the 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.

Paraganglioma presenting with marked proteinuria: a case report.

Paragangliomas are rare neuroendocrine tumors that arise from sympathetic and parasympathetic paraganglia. In children, most of them are functional tumors. Presenting symptoms such as sustained or paroxysmal elevations in blood pressure, headache, sweating, and palpitations are related to catecholamine hypersecretion. A previously healthy 8-year-old boy presented with marked proteinuria, hypertension, and heart murmur. Imaging revealed an 81×43×45 mm sized solid mass extending from right retroaortic area to left suprarenal region. Measurements of catecholamines suggested the diagnosis of paraganglioma. Pathologic examination confirmed the diagnosis. Complete tumor resection was performed. Proteinuria, hypertension, and cardiac signs resolved after surgery. Proteinuria has been described as a rare manifestation of paragangliomas in adult patients. This is the first case of a paraganglioma presenting with massive proteinuria 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.

Successful allogeneic hemopoietic stem cell transplantation in a case of Wiskott-Aldrich syndrome and non-Hodgkin lymphoma.

WAS is a severe X-linked recessive disorder characterized by microthrombocytopenia, eczema, and immunodeficiency. A six-yr-old boy with WAS diagnosed as B-cell NHL (Stage III) localized in the liver who underwent successful HSCT from HLA-one antigen mismatch sibling donor has been presented here. His conditioning regimen included ATG, busulfan, and fludarabine. He received 2.3 × 10(6) /kg CD 34+ stem cells and 11 × 10(8) /kg nucleated cells at day 0. Neutrophil engraftment was achieved at day +14 and platelet engraftment at day +20. He has been in CR for more than two yr after transplantation. Thus, HSCT is an effective treatment for children with WAS even after development of lymphoma.

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.

Cardiac rhabdomyomas associated with tuberous sclerosis complex in 11 children: presentation to outcome.

Cardiac rhabdomyomas (CRs) are the most common heart tumors in children and closely associated with tuberous sclerosis complex (TSC). This study was performed to assess the presentation type, clinical course, treatment modalities, and outcome of the patients with rhabdomyoma, associated with TSC. We reviewed our patients with cardiac rhabdomyomas (CRs), who had received a diagnosis of TSC previously or during the follow-up period between June 1996 and January 2012, retrospectively. Thirty-two patients with TSC were evaluated and among them 11 patients (34%) were associated with CRs. Five patients (45%) had multiple tumors and consequently a total of 29 CRs were analyzed in our study. The median follow-up period was 2 years (range: 1 week-15 years). Clinical presentation was cardiac murmur in three patients, cyanosis in two patients and arrhythmia in one patient. Five patients were asymptomatic at the diagnosis and CRs were detected during routine cardiac evaluation for TSC. Cardiac tumors were diagnosed prenatally in two patients. Spontaneous regression rate was 31% and we experienced a complete regression of a tumor with an echogenic bordered tissue defect and septal thinning in a patient. Three patients had hemodynamically significant tumor obstruction; two of them underwent surgery. The other patient, who had multiple CRs, was treated medically with everolimus because of high-risk potential of surgery. Although surgical resection is the preferred treatment in most of the patients with hemodynamic instability, we need novel alternative medical therapies in some critically ill patients who cannot be operated due to various reasons.

Multiple axillary-infraclavicular lymph node metastasis from malignant rhabdoid tumor of unknown primary site.

Malignant rhabdoid tumors (MRT) mostly originate from the kidney and central nervous system. However, they may also originate from retroperitoneal and paravertebral regions, mediastinum, liver, chest wall, extremity, and neck, as well as from the soft tissues. The most important method in the differential diagnosis is the analysis of cytogenetic alterations in the INI1 gene. A six-month-old girl presented with multiple conglomerated lymphadenopathies located in the anterior axillary line. MRT diagnosis was confirmed by loss of INI1 expression in the tumor tissue. This is the first case in the literature with unknown primary focus diagnosed from lymph node metastasis.

Ganglioneuroma in a child with hereditary spherocytosis.

Hereditary spherocytosis (HS) is the most frequent cause of congenital hemolytic anemia. Extramedullary hematopoiesis (EMH) mimicking a mass may develop in the lymph nodes, kidneys, pleura, mediastinum, adrenal gland, and in particular the spleen and liver. Other than EMH, B-cell lymphoma, acute lymphoblastic leukemia, and pancreatic schwannoma cases were reported in patients with HS. We present a 13-year-old female patient with HS and ganglioneuroma in the adrenal gland. This association is probably coincidental; however, with increasing cancer cases in HS and the genetic studies being made, this association will be clarified.