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.

Comparative evaluation of fluoride-free remineralization agents with and without Er,Cr:YSGG laser on artificial enamel remineralization.

This study aimed to evaluate the efficacy of fluoride-free remineralizing agents in initial enamel caries, with and without combined Er,Cr:YSGG laser application. The remineralization effect of various agents and their combinations on artificial initial caries was investigated using 10 experimental groups (n = 7): NC, negative control; PC, positive control; TM, calcium-phosphate compounds (CPP-ACP); TD, theobromine-containing toothpaste; RG, ROCS® remineralizing gel; L, Er,Cr:YSGG laser (2780 nm; 0.25 W; repetition rate, 20 Hz; pulse duration, 140 µs; tip diameter, 600 µm; without air/water cooling); L + fluoride toothpaste; L + TM; L + TD; and L + RG. The demineralized bovine enamel specimens were subjected to an 8-day pH cycle by daily application of the remineralizing agents and laser therapy once prior to the pH cycle and paste application. The enamel samples underwent the Vickers surface microhardness test, and one sample per group was analyzed with scanning electron microscopy. The Kruskal Wallis test was used to compare the microhardness recovery percentage (SMHR%) for each group, and multiple comparisons were made with the Dunn test. Groups L (p = 0.003), RG (p = 0.019), L + TM (p < 0.001), L + fluoride toothpaste (p = 0.001),and L + RG (p = 0.036) exhibited significant increase in SMHR%. The tested remineralizing agents exhibited no statistically significant difference in effect when used alone and in combination with Er,Cr:YSGG laser. Combined application of Er,Cr:YSGG laser and ROCS® remineralization gel effectively promoted enamel remineralization, while use of CPP-ACP and fluoride toothpaste alone was ineffective. Theobromine-containing toothpaste exhibited the least SMHR%. Long-term evaluation of these agents is recommended.

The Mutation of CD27 Deficiency Presented With Familial Hodgkin Lymphoma and a Review of the Literature.

This study aimed to report 4 siblings with CD27 deficiency presented with Hodgkin lymphoma. The father of the family, his 2 wives, and 17 children born from these wives were included into the study. CD27 mutation of all the family members with, and without Hodgkin lymphoma were studied. The variants detected by the exome sequencing analysis were verified by Sanger sequencing and analyzed using SeqScape Software 3. It was determined that both the father of the family and his 2 wives carried the same variant heterozygously. Of the children born to the first mother, 2 children were normal, 3 were heterozygous and 5 were homozygous. Four of these 5 homozygous children were diagnosed with Hodgkin lymphoma. Of the children born to the second mother, 1 child was normal, 3 children were heterozygous and 2 children were homozygous, and none of them had developed a malignant event. We also showed that CD27 deficiency may enhance Treg differentiation. According to our information, this study augmented the relationship of Hodgkin lymphoma and CD27 deficiency. The detection of homozygous CD27 variant in all siblings who developed lymphoma strengthened the place of this mutation in the etiology of Hodgkin lymphoma. In contrast, the presence of homozygous siblings with no malignant event suggested the possible contributions of environmental factors on the etiology.

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.

Hepatitis-Associated Aplastic Anemia: Etiology, Clinical Characteristics and Outcome.

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were <3 to 5×upper limit of normal (ULN) in 2 patients, <5 to 10×ULN in 2 patients, and >10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed.

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.

Ovarian Mucinous Carcinoma in a Pediatric Patient With Maroteaux-Lamy Syndrome.

Mucopolysaccharidoses (MPS) are autosomal recessive lysosomal storage disorder (LSD). Mucinous ovarian cancer is a rare tumor and seldom encounters among adolescents. Here we describe an adolescent female with MPS type VI diagnosed with mucinous ovarian cancer. To our knowledge, this is the first case report of ovarian mucinous carcinoma in a patient with MPS. The association between MPS and cancer has never been described so far, but some LSD are known to have an increased risk of malignancies. The pathogenetic link between LSD and cancer is not well understood. Several potential mechanisms have been proposed for pathogenesis, which include chronic inflammation, abnormal function of activated macrophages, and genetic modifiers. Further studies are required, to understand the role of LSD in cancer.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

Management of acquired aplastic anemia in children : A single center experience.

Acquired aplastic anemia (AAA) is a rare and potentially life threatening disorder. We retrospectively compared the outcomes of 29 children with AAA who received immunosuppressive therapy (IST) or underwent hematopoietic stem cell transplantation (HSCT). Median age at diagnosis was 9.0 years (range, 2-18 years) and median follow-up period was 36 months (range, 3-108 months). Viral infection associated/post hepatitis AAA was in 6 patients (20.6%). According to the initial laboratory findings, 8 patients were classified as very severe AA (vSAA), 8 as severe AA (SAA), and 13 patients as transfusion-dependent moderate AA (MAA). Out of 13, 5 transfusion-dependent MAA patients progressed SAA in median one month (range, 1-5 months), another 6 MAA patients developed remission or became transfusion free during follow-up. Eight patients underwent upfront matched family donor (MFD) HSCT at median 6 months (range, 1-9 months) and achieved complete response (100%). Fifteen cycles of IST were given to 10 (34%) patients lacking MFD at median 3 months (range, 2-6 months). Fifty percent of patients had complete/partial response after IST protocol. Three patients who were unresponsive to IST, proceeded to alternative donor HSCT, in 2nd or 3rd year after the diagnosis and only 1 patient was sustained remission. Several drugs such as mycophenolatemofetil, high-dose cyclophosphamide, levamisole and eltrombopag have been investigated in order to improve the outcome of patients with AAA. Early intervention in AAA patients results in significantly better outcomes.

Do PD-1 and PD-L2 expressions have prognostic impact in hematologic malignancies?

Background/aim: PD-1 (programmed death-1) is an immune checkpoint receptor that modulates T-cell activity in peripheral tissues via interaction with its ligands, PD-L1 (programmed death-ligand 1) and PD-L2 (programmed death-ligand 2). Tumor cells upregulate PD-L1 or PD-L2 to inhibit this T lymphocyte attack. Our goal was to determine the PD-1 and PD-L2 expression rates of various hematologic malignancies, and evaluate whether PD-1 and PD-L2 expressions have an impact on prognosis. Materials and methods: For this purpose, pretreatment bone marrow biopsy specimens of 83 patients [42 multiple myeloma (MM), 21 acute leukemia, and 20 chronic lymphocytic leukemia (CLL)] were stained with monoclonal antibody immunostains of PD-1 and PD-L2. Results: As a result, the overall expression rate of PD-1 was 26.2%, 4.8%, and 60% in patients with MM, acute leukemia, and CLL, respectively, whereas the PD-L2 expression rate was 61.9%, 14.3%, and 10% in patients with MM, acute leukemia, and CLL, respectively. Conclusion: Finally, we concluded that the role of the PD-1 pathway can be demonstrated by immunohistochemistry (IHC). Since we evaluated whether there is a correlation between the (IHC) results and survival of patients with MM, acute leukemia, and CLL, we could not demonstrate meaningful evidence that these markers have an impact on prognosis.

Clinical features and treatment of primary autoimmune hemolytic anemia in childhood.

BACKGROUND AND AIM: Autoimmune hemolytic anemia (AIHA) is characterized by autoimmune destruction of erythrocytes. In this retrospective study, the clinical, laboratory features and treatment responses of patients with primary AIHA were evaluated. MATERIAL AND METHODS: 21 consecutive patients diagnosed with primary AIHA in a children's hospital from 2008 to 2016 were included. Clinical, laboratory findings and treatment responses were analyzed. RESULTS: Twenty-one patients, aged 6 months-15 years, with direct antiglobulin test positive anemia were presented. Pallor and jaundice were the common complaints and icterus and hepatomegaly /splenomegaly was the most common physical findings. Thirteen patients (62%) had a previous infection history. At the time of diagnosis, hemoglobin level was 3-10.5 g/dL. Fifty- eight percent of patients had IgG reactivity and 29.4% patients had both IgG and C3d reactivity. Eight patients were given methylprednisolone, 11 patients received prednisone and 14 patients received intravenous immunoglobulin. Five patients (23.8%) were transfused due to severe anemia. Two patients did not need any treatment. The response rate following first-line treatment was 94%. One patient who did not respond any treatment died of infection. CONCLUSION: Primary AIHA is an acute illness mostly self-limiting or requiring short-term steroid therapy. Rarely, it might be resistant to immunosuppressive treatment and be mortal.

Effects of stem cell transplantation on bone mineral density and vitamin D status in children with thalassemia major.

HSCT is a curative treatment in TM, but conditioning and immunosuppressive treatment may affect bone metabolism. In this retrospective study, we aimed to compare BMD, vitamin D status, and growth in children with TM who underwent HSCT to those in children with TD TM. Twenty-three children with TM who underwent HSCT (mean age 7.1 years [1.03-14.7]) and 24 children with TD thalassemia (mean age 9.8 years [1.6-14]) were recruited. Lumbar spine BMD of TD thalassemia patients was higher than those in patients who had HSCT at both baseline and second-year assessments (P=.009, P<.001, respectively). However, BMD Z scores or serum 25-OH vitamin D levels were not different in two groups. Being >10 years of age was a significant risk factor for low BMD, height, and weight Z score for both groups. Patients who underwent HSCT with Pesaro risk class II or III had higher risk for low BMD compared to those risk class I patients (P=.044). In conclusion, children with TM who were >10 years at HSCT are at risk for low BMD and growth retardation. HSCT had no effect on BMD deficit in children with TM.

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.

Comparison of prophylactic use of intravenous immunoglobulin versus Pentaglobin® in pediatric patients after hematopoietic stem cell transplantation.

There are few studies evaluating the use of IgM-enriched IVIG (Pentaglobin(®) ) in HSCT recipients. This study aimed to compare the efficacy of prophylactic use of IVIG versus prophylactic use of Pentaglobin(®) within the first 100 days after allogeneic HSCT. We performed a prospective, randomized study of the use of prophylactic IVIG versus prophylactic use of Pentaglobin(®) in patients after allogeneic HSCT. The first dose of IVIG or Pentaglobin(®) was given before conditioning regimen and after transplant was given on day +1, +8, +15, and +22. And then, it was given if IgG level was below 400 mg/dL. Twenty-seven patients in IVIG group and 32 patients in Pentaglobin(®) group were included in the study. There were no significant differences in the duration of neutropenia, hospitalization, fever, and in the number of pyrexial episode, septicemia, bacteremia, local infection, CMV infection, acute GVHD, VOD, and adverse events between the IVIG group and Pentaglobin(®) group. Randomized placebo-controlled trials are needed to conclude that utilization of IVIG or Pentaglobin(®) has no beneficial effect in HSCT.

Relationship between mandibular incisor irregularity and type of occlusion in ankyloglossia.

PURPOSE: To investigate the relationship between the lingual frenulum length with mandibular incisor irregularity and type of occlusion in children with ankyloglossia. MATERIALS AND METHODS: Eighty children aged between 7 and 12 years with ankyloglossia enrolled in the study. The patients were classified according to Kotlow's classification. Mandibular incisor crowding was measured and the molar relationship was determined. The data were analysed statistically using Fisher's exact test, X2 and Pearson's correlation. RESULTS: Of the 80 patients, 45 (56.3%) had mild, 23 (28.8%) had moderate and 12 (15%) had severe ankyloglossia. Fifty-nine (73.8%) of the patients had mild irregularity, 18 (22.5%) had moderate and 3 (3.8%) had severe irregularity. In 56 (70%) of the patients, Class I occlusion was observed, 17 (21.3%) had Class II and 7 (8.8%) had Class III occlusion. No significant differences were found between types of ankyloglossia with mandibular incisor irregularity and occlusion types. A significant positive correlation was determined between the length of the lingual frenulum length and mandibular incisor irregularity. There were significant positive correlations between the lingual frenulum length, incisor irregularity and age. CONCLUSION: Mild and moderate types of ankyloglossia are unrelated to mandibular incisor crowding and occlusion type.

Neurological complications after allogeneic hematopoietic stem cell transplantation in children, a single center experience.

In this study, we retrospectively examined the data of children who underwent allo-HSCT from HLA-matched family donors. We analyzed the incidence, etiological factors, clinical characteristics, possible reasons, risk factors, and follow-up of neurologic complications. BU-based conditioning regimens were used in most of the cases (n = 62). The median duration of follow-up for the 89 patients was 20 months (range 1-41 months). Eleven percent of transplanted children developed one or more neurological symptoms after HSCT with a median observation time of two months (range -6 days to 18 months). The median age of the four girls and six boys with neurological complication was 13 yr (range 5.3-17.6 yr). Cylosporine A neurotoxicity was diagnosed in five children, four of them were PRES. The rest of complications were BU and lorazepam toxicity, an intracranial hemorrhage, a sinovenous thrombosis, and a transient ischemic attack during extracorpereal photopheresis. No difference was found between groups of neurological complication according to age, gender, diagnosis, hospitalization time, neutrophil and platelet engraftment time, stem cell source, and conditioning regimen, acute and chronic GVHD or VOD. Neurological complication was the cause of death in one patient (1.1%).

Massive splenic infarction and portal vein thrombosis in children with chronic myeloid leukemia.

Massive splenic infarction and portal vein thrombosis (PVT) due to chronic myeloid leukemia (CML) is extremely rare. We describe 2 children who were presented with massive splenic infarction and PVT in the course of CML. Massive splenic infarction and PVT treated with splenectomy in one and with medical treatment in another in whom PVT resolved by cytoreductive treatment, led to downsizing of spleen or splenectomy. Splenic infarct and PVT should be considered in CML patients with long-lasting severe abdominal pain despite appropriate medical attempts. Splenectomy should be spared for persistent symptoms and complications.

Knowledge of sports participants about dental emergency procedures and the use of mouthguards.

AIM: The aim of this study was to evaluate the knowledge of sports participants regarding emergency management of dental trauma and the awareness about mouthguards. METHODS: A specific questionnaire regarding knowledge, experiences and behaviours after dental trauma and the use of mouthguard was distributed to 359 sports participants up to 18 years of age. The sports involved were basketball, swimming, volleyball, soccer, tennis, badminton, handball, athleticism, golf, gymnastics, water polo and karate. The questions were focused on personal experience, awareness of first aid and dental emergency procedures and knowledge about mouthguards. RESULTS: The results showed that 10.9% had experienced a kind of dental trauma, and 12.5% would look for a dentist for treatment in emergency. 34.5% would re-implant the avulsed tooth, 33.4% would maintain the avulsed tooth in handkerchief and 25.3% would maintain it in saline solution. 41.1% were aware of the possibility of oral injuries during sports practice, and 55.4% knew about mouthguards, but only 11.2% of the participants reported to use them. There was a statistically significant difference between the experienced participants (>5 years) and less-experienced group (<5 years) in knowledge about dental emergency procedures and mouthguards. Reasons given for not wearing mouthguards include 'lack of aesthetic' was significantly high in experienced participants. The less-experienced participants significantly stated that they had never heard about mouthguards before. CONCLUSION: Our results showed a lack of knowledge of sports participants about management and prevention of traumatic dental injuries. Educational programs should be organized to give information about emergency treatment and promote the use of mouthguards to sport participants.

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.