Prognosis of Second Primary Malignancies in Pediatric Acute Lymphoblastic Leukemia Survivors: A Multicenter Study by the Turkish Pediatric Hematology Society.

The improved survival rates of childhood cancers raise the long-term risk of second primary malignancy (SPM) in childhood and adolescent cancer survivors. The intensity of the treatment protocol used, the use of some groups of chemotherapeutics, and radiotherapy were found to be risk factors for the development of second primary malignancies (SPMs). Forty-one patients who developed acute myelocytic leukemia or any solid organ cancer within 25 years of follow-up, after completion of pediatric acute lymphoblastic leukemia (ALL) treatment, were included in the study. The mean duration of initial ALL diagnosis to SPM was 9.3 ± 6.1 years. The 3 most common SPMs were acute myelocytic leukemia, glial tumors, and thyroid cancer. Thirteen (81%) of 16 patients exposed to cranial irradiation had cancer related to the radiation field. In total 13/41 (32%) patients died, and the 5-year overall survival rate was 70 ± 8%. Patients older than 5 years old at ALL diagnosis had significantly worse overall survival than cases younger than 5 years old. In conclusion, children and adolescents who survive ALL have an increased risk of developing SPM compared with healthy populations, and physicians following these patients should screen for SPMs at regular intervals.

Laboratory and clinical features of tumor lysis syndrome in children with non-Hodgkin lymphoma and evaluation of long-term renal functions in survivors.

OBJECTIVE: The purpose of our study is to investigate the laboratory and clinical features of tumor lysis syndrome (TLS) and acute kidney injury (AKI) in childhood non-Hodgkin lymphomas (NHL) and to reveal their impact on long term kidney function in survivors. METHODS: Our single-center retrospective study included 107 patients (0-18 years old) with NHL who were admitted and treated at our hospital between 1998 and 2020. The relationship between TLS and age, gender, histopathological subgroup, tumor stage, lactate dehydrogenase (LDH) level at presentation, bone marrow and kidney involvement were assessed. The long-term renal functions of the patients were investigated. RESULTS: 80.3% of the patients were male with a median age of 9.8 years. The most common detected histopathological subgroup was Burkitt lymphoma. Hyperhydration with or without alkalinisation, and allopurinol were used in first-line treatment and prophylaxis of TLS. Laboratory TLS and clinical TLS was observed in 30.8% and 12.1% of patients, respectively. A significant correlation was found between young age, advanced stage, high LDH level at presentation, and TLS. AKI was observed in 12.1% of the patients. When the glomerular filtration rate values of the patients at the first and last admissions were compared after an average of 6.9 years, a mean decrease of 10 mL/min/1.73 m2 was found. It was not, however, found to be statistically significant. CONCLUSION: Lower age, advanced stage, and high LDH level at presentation were found to be risk factors for TLS in our study. Long-term renal function loss was not observed in the survivors who received early and careful prophylaxis/treatment for TLS. The survivors are still being followed up.

Amyloidosis in a Patient With Congenital Neutropenia Because of G6PC3 Deficiency.

Glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency is a recently identified form of congenital neutropenia associated with developmental anomalies. The severity of neutropenia and the clinical spectrum are highly variable. Aside from infectious complications and extrahematologic features, inflammatory bowel disease and autoinflammatory complications are less frequently observed manifestations. However, amyloidosis has never been reported in G6PC3 deficiency. Here, we present a 12-year-old patient with incidentally discovered neutropenia because of the p.E65A (c.194A>C) variant of the G6PC3 gene. He had recurrent aphthae and abdominal pain episodes, and developed nephrotic-range proteinuria, amyloidosis, and end-stage renal failure during follow-up.

Cutaneous manifestations in pediatric oncology patients.

BACKGROUND/OBJECTIVES: Oncology patients present with various skin manifestations related to primary disease and treatments. Although these skin toxicities are well described in adults, studies of pediatric oncology patients are limited. The objective of this study was to evaluate the cutaneous findings in pediatric oncology patients receiving chemotherapy. METHODS: In this prospective cohort study conducted from December 2018 to March 2020, all pediatric oncology patients were examined and patients who had a dermatologic finding at any point during their treatments were recorded. Dermatologic examinations were performed by the same dermatologists, and biopsy and microbiologic tests were performed according to clinical need. Patients were grouped according to their oncologic diagnoses and types of chemotherapies. RESULTS: A total of 80 patients with a mean age of 9.1 ± 5.0 years were included in the study. Seventy-five (93.7%) of them developed a dermatologic manifestation during the study period. Most of the patients had hematologic malignancies (n = 48, 60%). Antimetabolites were the most frequently used class of chemotherapeutic agents. Anagen effluvium was the most common dermatologic finding (61.3%, n = 49), followed by inflammatory dermatoses (51.2%, n = 41, most commonly diaper dermatitis in 33 patients), xerosis (35%, n = 28), and nail changes (20%, n = 16, most commonly nail pigmentation in seven patients). Mucositis was seen in 13 (16.2%) patients. Five patients (6.2%) had drug-induced cutaneous hyperpigmentation, and five (6.2%) had toxic erythema of chemotherapy. The highest percentage of xerosis (45.4%) was detected in patients using antitumor antibiotics, whereas inflammatory dermatoses were observed more in patients using antimetabolites (48.6% of patients using antimetabolites), and pigmentation changes were more frequently detected in patients using alkylating agents. CONCLUSION: Identification, diagnosis, and treatment of these reactions are important to dermatologists and oncologists so that appropriate management may be provided to pediatric oncology patients.

Graft-versus-host disease in a child with neuroblastoma after autologous stem cell transplantation.

In the pediatric population, hematopoietic stem cell transplantation (HSCT) is used to treat a wide variety of diseases, both malignant and nonmalignant. For many of these diseases, HSCT is a well-established treatment. Acute graft-versus-host disease (GVHD) continues to be a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Graft versus host disease is a common complication of allo-SCT which is induced by donor T cell recognition of recipient alloantigens. The occurrence of autologous GVHD suggests that inappropriate recognition of host self-antigens may occur. GVHD in patients who received autologous HSCT is extremely rare compared to patients who received allogeneic HSCT. We present the case of a 4-year-old girl with metastatic neuroblastoma who spontaneously developed autologous GVHD after autologous HSCT.

The Incidence of and Factors Associated with Vitamin D Deficiency in Newly Diagnosed Children with Cancer.

This retrospective chart review study aimed to assess vitamin D status and identify risk factors associated with vitamin D deficiency and bone parameters in children with cancer at admission. The data of 86 (50 males and 36 females) patients between April 2013 and June 2015 were analyzed. Calcium, phosphorus, alkaline phosphatase (ALP), 25(OH)D, age, gender, diagnostic category, body mass index, duration of complaints, and season of blood sampling were recorded. Median age was 7.17 years (range 0.31-17.40) in 29 hematological malignancy and 57 solid tumor patients. According to cut-off level of 20 ng/ml, 63% of children with cancer had vitamin D deficiency at diagnosis with a median 25(OH)D of 16.75 ng/ml. The mean vitamin D value of children >10 years was significantly low in comparison to that observed in younger children [11.83, 95% confidence interval (CI) = = 8.85-14.81 ng/ml vs. 19.81, 95% CI = = 17.02-22.60 ng/ml]. Vitamin D measurement between November and May was a risk factor for vitamin D deficiency (P < 0.05). The frequency of hypocalcemia and hypophosphatemia was not different between two groups of vitamin D. Further longitudinal studies are needed to investigate whether monitoring vitamin D status and supplementation in children with cancer might prevent future complications related to vitamin D deficiency.

Severe hepatic sinusoidal obstruction syndrome in a patient with Wilms tumor and hereditary spherocytosis.

A 7-year-old girl with a history of splenectomy for hereditary spherocytosis (HS) was diagnosed with renal hematoma after a blunt abdominal trauma while receiving aspirin. Multiple erythrocyte transfusions and transarterial embolization were performed without success. Eventual nephrectomy revealed severely necrotic and perforated Stage III Wilms tumor (WT). Radiochemotherapy was administered, but by the eighth week, she developed severe hepatic sinusoidal obstruction syndrome (HSOS). Her ferritin level at the time was 3406 ng/ml. Defibrotide and aggressive supportive measures provided full recovery. The patient was given deferasirox for iron chelation therapy and finished her treatment without incident. To our knowledge, just one patient with HS and WT has been described in the literature. The role of iron excess in HSOS pathogenesis in non-transplant patients has not been addressed before either. Transfusional hyperferritinemia, in addition to chemotherapeutics and radiation, may have contributed to the development of severe HSOS in our patient.

Non­syndromic first case of pediatric rhabdomyosarcoma originating from the umbilical left medial ligament: A case report.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. The present study reports the case of a 2-year-old female who presented with abdominal pain and a palpable abdominal mass. Radiological investigations failed to reveal the tissue origin of the mass and a tru-cut biopsy confirmed the diagnosis of embryonal RMS. Surgical excision was performed after neo-adjuvant chemotherapy. The pelvic end of the mass was observed to continue with the left medial umbilical ligament. The patient's postoperative course was uneventful, and follow-up imaging showed no evidence of recurrence. Τhe present case report is the first non-syndromic case with left umbilical medial ligament-originated RMS.

Clinical Characteristics and Treatment Outcome of Hereditary Spherocytosis: A Single Center's Experience.

Objectives: The objective of the study is to present the demographic characteristics, clinical and laboratory features and outcome of our patients with hereditary spherocytosis (HS). Methods: Demographic, clinical, and laboratory data; complications; and splenectomy results were analyzed retrospectively. The severity of the disease was scaled according to Eber's criteria. Results: Sixty-nine patients (42 boys, 27 girls, median age: 3 years) were eligible. Sixty-eight percent of the patients had a history of neonatal jaundice. The complaints at admission were jaundice (71%), fatigue (27.5%), fainting (4.3%), and pallor (4.3%). The median follow-up duration was 8.5 years. According to Eber's criteria, three (4.3%), 57 (82.6%), and nine (13.1%) patients had mild, moderate, and severe diseases, respectively. Thirty-six patients (52.1%) had a splenectomy. Following splenectomy, we observed a significant rise in hemoglobin levels and a decline in indirect bilirubin levels. Post-operative thrombocytosis was common, with a tendency to fall and stabilize after 1 month. There were no thromboembolic complications. Conclusion: In spite of the high rate of consanguinity, familial history of HS, and neonatal jaundice in our study group, the majority of the HS patients were identified relatively late, about 3 years. This finding shows that HS might be insufficiently acknowledged by primary care. Splenectomy, in selected cases, may reduce the need for transfusions. Post-splenectomy transient thrombocytosis is common and has a benign course.

Clinical features and management of carboplatin-related hypersensitivity reactions in pediatric low-grade glioma.

PURPOSE: The effectiveness of carboplatin and vincristine chemotherapy in the treatment of low-grade glioma (LGG) is well established. However, carboplatin hypersensitivity reactions (CHR) are a major problem leading to premature cessation of therapy. We aimed to investigate the clinical features and the management strategies in CHR, retrospectively. METHOD: Fifty LGG patients treated between October 1997 and January 2008 with carboplatin and vincristine were included in the study. Clinical features, management strategies, influence of demographic factors on CHR, and success rate in terms of continuation with carboplatin therapy were evaluated. RESULTS: CHR were observed in 20 (40%) patients and grade I reactions were the most common. The median number of carboplatin doses administered at the first episode of CHR was nine (range 1-41). Only younger age was found to be correlated with the presence of CHR. Nine patients had carboplatin desensitization protocol; eight patients were given various combinations of premedication while three had no modification. Treatment was terminated in five patients due to CHR. Overall success rate was 75%. CONCLUSIONS: This is the largest single-center study conducted to investigate the frequency and the management strategies in patients with CHR who were treated with the same chemotherapy protocol for LGG. Premedication and desensitization were the preferred modifications in case of CHR. Overall, the success rate for carboplatin continuation is high in comparison to previous studies. Carboplatin can be continued successfully in many cases with CHR if reactions are managed in a timely fashion.

Renal Ultrasonographic Abnormalities at Initial Presentation of Children Diagnosed with Acute Lymphoblastic Leukemia and Long-Term Renal Functions and Prognosis in Survivors.

Objectives: The kidney is a vulnerable organ for acute lymphoblastic leukemia (ALL), by the disease, and various associated clinical pictures. This retrospective study aims to document renal ultrasound abnormalities in children with newly diagnosed ALL as well as to investigate the correlation between renal findings and clinical/laboratory/survival data. Methods: All children (age <18 years) with ALL were included in the study. An increase in size/nephromegaly (NM) or hyperechogenicity (HE) of the kidneys at first admission was accepted as a pathological renal abnormality. The clinical/laboratory findings, survival, and long-term renal functions were compared between patients with and without NM/HE. Results: The incidence of NM±HE was 12% in 163 patients. Enlargement of spleen, liver, or both and, hypercreatininemia was independently correlated with the presence of NM/HE. After the induction therapy, ultrasound findings were resolved in all patients, and NM/HE did not influence ALL prognosis. All survivors had normal renal functions in long term. Conclusion: The renal ultrasound abnormalities are not uncommon in children with leukemia at admission, without a negative impact on leukemia prognosis and on long-term renal functions.

Treatment results of modified BFM protocol in pediatric high-risk Burkitt lymphoma.

BACKGROUND: Chemotherapy with high dose methotrexate is the mainstay of treatment for Burkitt lymphoma (BL), especially to manage central nervous system (CNS) disease. However, methotrexate administration requires close drug level monitoring for appropriate folinic acid rescue, which might not be readily available in all centers. In this study, we assessed the long-term treatment outcomes of a modified Non-Hodgkin lymphoma (NHL)-Berlin-Frankfurt-Munster (BFM) 90 regimen in pediatric high-risk BL without CNS involvement. METHODS: Between 1999 and 2011, 42 patients (median age: 7 years) with advanced-stage BL were treated with modified NHL-BFM 90 regimen (methotrexate at a dose of 1 g/m2). Demographic data, stage, lactate dehydrogenase (LDH) and treatment results were retrospectively evaluated. The patients were assessed for toxicity, survival and CNS recurrence. RESULTS: Thirty-six patients had Stage III and six had Stage IV disease, respectively. The median LDH level was 1,432 IU/L. Four patients died of infectious and metabolic complications. One patient had local recurrence at the 48 < sup > th < /sup > month of the follow-up and he is in the second remission for 72 months. In Kaplan-Meier analysis, the overall survival and event-free survival rates at 10 years were found as 90 % and 88 %, respectively. None of our patients died of treatment failure. CONCLUSIONS: The administration of the reduced dose of methotrexate seems to not compromise treatment success nor increase the risk of CNS recurrence in high-risk BL without CNS involvement. The limitation of the study is that it is not randomized. Our treatment scheme might be considered for centers without methotrexate measurement facility.

Clinical Characteristics of and Cancer Incidence in Children Evaluated for Lymphadenoapthy Referred to Pediatric Oncology Clinics.

OBJECTIVES: In our study, we aimed to investigate the clinical characteristics and cancer frequency in patients referred to our pediatric oncology outpatient clinic for lymphadenopathy. METHODS: The charts of patients admitted to our pediatric oncology outpatient clinics for lymphadenopathy between January 2014, and December 2016 were retrospectively reviewed in this study. Age, gender, duration of complaints, previous therapies, systemic signs and symptoms, lymph node characteristics and laboratory findings were recorded. The frequency of malignancy was calculated. RESULTS: One hundred thirty-four patients (34 girls) with a median age of six years (range four months-17 years) were included in our study. The majority of the patients (98%) had localized lymphadenopathy and the head and neck region was the most common site of involvement (87%). The median long-axis diameter of lymph nodes ranged between 0.5 cm and 5 cm (median 2 cm) by physical examination. Twenty-one patients (15.6%) had lymph node biopsy. Four patients had ruptured epidermal cyst, lymphangioma, pilomatricoma and ectopic thymus. Of the other biopsies, nine patients were diagnosed with reactive LAP, four with lymphadenitis, and four with Hodgkin's disease. The lymphoma patients had lymph node size greater than 2.5 cm and the duration of lymphadenopathy was longer than four weeks. Three out of four patients had systemic clinical findings accompanying lymph node enlargement. CONCLUSION: Three percent of the patients with lymphadenopathy who were referred for suspected malignancy received a cancer diagnosis. This rate, which is too low for a reference center, suggested that the patients might be referred to the pediatric oncology outpatient clinic without a thorough evaluation in primary health care.

Thrombotic thrombocytopenic purpura as a rare cause of anemia with thrombocytopenia in childhood: report of 2 cases.

Köker O, Yildirmak ZY, Genç DB, Kiliçaslan Ö. Thrombotic thrombocytopenic purpura as a rare cause of anemia with thrombocytopenia in childhood: report of 2 cases. Turk J Pediatr 2019; 61: 418-423. Thrombotic thrombocytopenic purpura (TTP) is a rare multisystem disorder characterized by single or recurrent episodes of thrombocytopenia, microangiopathic hemolytic anemia and widespread microvascular thrombosis, which causes significant morbidity and mortality unless promptly recognized and treated. The underlying pathogenesis is a defect in von Willebrand factor (vWF) cleaving protease, called `A Disintegrin and Metalloproteinase with Thrombospondin Type 1 Repeats 13 (ADAMTS-13)`. There are 2 forms: congenital TTP (ADAMTS-13 gene mutations) and acquired TTP (autoantibodies and ADAMTS-13 deficiency). We presented two patients who initially presented with thrombotic microangiopathy and were later diagnosed with TTP upon demonstration of the deficiency in ADAMTS-13 activity.

Parameters indicative of persistence of valvular pathology at initial diagnosis in acute rheumatic carditis: the role of albumin and CD19 expression.

OBJECTIVE: The aim of this study is to define the predictors of chronic carditis in patients with acute rheumatic carditis (ARC). METHODS: Patients diagnosed with ARC between May 2010 and May 2011 were included in the study. Echocardiography, electrocardiography, lymphocyte subset analysis, acute phase reactants, plasma albumin levels, and antistreptolysin-O (ASO) tests were performed at initial presentation. The echocardiographic assessments were repeated at the sixth month of follow-up. The patients were divided into two groups according to persistence of valvular pathology at 6th month as Group 1 and Group 2, and all clinical and laboratory parameters at admission were compared between two groups of valvular involvement. RESULTS: During the one-year study period, 22 patients had valvular disease. Seventeen (77.2%) patients showed regression in valvular pathology. An initial mild regurgitation disappeared in eight patients (36.3%). Among seven (31.8%) patients with moderate regurgitation initially, the regurgitation disappeared in three, and four patients improved to mild regurgitation. Two patients with a severe regurgitation initially improved to moderate regurgitation (9.1%). In five (22.8%) patients, the grade of regurgitation [moderate regurgitation in one (4.6%), and severe regurgitation in 4 (18.2%)] remained unchanged. The albumin level was significantly lower at diagnosis in Group 2 (2.6±0.48g/dL). Lymphocyte subset analysis showed a significant decrease in the CD8 percentage and a significant increase in CD19 percentage at diagnosis in Group 2 compared to Group 1. CONCLUSION: The blood albumin level and the percentage of CD8 and CD19 (+) lymphocytes at diagnosis may help to predict chronic valvular disease risk in patients with acute rheumatic carditis.