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 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.

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.

Thrombolysis with Systemic Recombinant Tissue Plasminogen Activator in Children: A Multicenter Retrospective Study

Objective: This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA). Materials and Methods: Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h. Results: Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p>0.05). Conclusion: Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.

Successful treatment of multiple relapsed-refractory Langerhans cell histiocytosis with cyclosporine.

Langerhans cell histiocytosis is a rare hematologic disorder and patients who fail first-line treatment have a poor prognosis, and require more intensive treatment. We present an infant diagnosed with multisystem Langerhans cell histiocytosis refractory to multimodal therapy who was successfully treated with cyclosporine. Cyclosporine might be an effective alternative drug as nonmyelosuppressive rescue therapy for multiple relapsed-refractory Langerhans cell histiocytosis that has not achieved remission with cladribine and cytarabine therapy.

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.

A case of infective endocarditis due to Herbaspirillum Huttiense in a pediatric oncology patient.

Infective endocarditis (IE) is an infection of the endocardium and/or heart valves that involves thrombus formation (vegetation). This condition might damage the endocardial tissue and/or valves. An indwelling central venous catheter is a major risk factor for bacteremia at-risked pediatric populations such as premature infants; children with cancer and/or connective tissue disorders. Herbaspirillum huttiense is a Gram-negative opportunistic bacillus that may cause bacteremia and pneumonia rarely in this fragile population. Herein we report the very first case of bacteremia and IE in a pediatric oncology patient caused by H. huttiense.

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.

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.

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.

Atypical ß-Catenin Activated Child Hepatocellular Tumor.

Hepatocellular adenomas are a benign, focal, hepatic neoplasm that have been divided into four subtypes according to the genetic and pathological features. The ß-catenin activated subtype accounts for 10-15% of all hepatocellular adenomas and specific magnetic resonance imaging features have been defined for different hepatocellular adenomas subtypes. The current study aimed to report the magnetic resonance imaging features of a well differentiated hepatocellular carcinoma that developed on the basis of ß-catenin activated hepatocellular adenomas in a child. In this case, atypical diffuse steatosis was determined in the lesion. In the literature, diffuse steatosis, which is defined as a feature of the hepatocyte nuclear factor-1α-inactivated hepatocellular adenomas subtype, has not been previously reported in any ß-catenin activated hepatocellular adenomas case. Interlacing magnetic resonance imaging findings between subtypes show that there are still many mysteries about this topic and larger studies are warranted.

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%).

Everolimus: a challenging drug in the treatment of multifocal inoperable cardiac rhabdomyoma.

Primary cardiac tumors are rare in childhood. The most common of these are rhabdomyomas. Considering that rhabdomyomas often show spontaneous regression, close follow-up may be sufficient in hemodynamically stable cases. However, hemodynamically significant cardiac rhabdomyomas confer a risk of morbidity and mortality. Herein, we report a newborn infant with multifocal cardiac rhabdomyomas treated with everolimus. The optimal dose of the drug was 0.25 mg 2 times per day, 2 days per week. Patients with inoperable cardiac rhabdomyomas and with symptoms may be candidates for everolimus treatment.