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.

Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study.

BACKGROUND: In patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients. PROCEDURE: Pediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Türkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined. RESULTS: Data from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%. CONCLUSION: Cerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis.

Hematological disturbances in Down syndrome: single centre experience of thirteen years and review of the literature.

Karakurt N, Uslu I, Aygün C, Albayrak C. Hematological disturbances in Down syndrome: single centre experience of thirteen years and review of the literature. Turk J Pediatr 2019; 61: 664-670. Neonates with Down syndrome (DS) may have hematological abnormalities such as polycythemia, thrombocytopenia and transient leukemia (TL). The primary objective of this study was to report the descriptive data of complete blood counts (CBC) of neonates with DS, which were obtained within first week of life. We wanted to focus on neonates with hematological abnormalities and compare them among those with and without TL. The secondary objective was the description of hematological malignancies in the first six years of life. Medical records of 100 neonates with DS between 2006-2018 were assessed. Hematological abnormalities were present in 73/100. We detected anemia in 16, polycythemia in eight, microcytosis in 10, leukopenia in two, leukocytosis in 11, thrombocytopenia in 26, thrombocytosis in 7 and TL in 11 patients. TL group had higher levels of leukocyte count (115.0±93.0x103/mm3) when compared with neonates without TL (11.7±5.6x103/mm3) (p < 0.001). No other statistically significant difference between groups for hemoglobin, MCV and platelet count levels was detected. In the follow- up period, two patients developed acute lymphoblastic leukemia, one hemophagocytic lymphohistiocytosis and one Burkitt lymphoma. None of the TL survivors developed myeloid leukemia of Down Syndrome (ML-DS). Thrombocytopenia may be detected frequently in DS and it may not be a part of TL. We suggest that CBC with peripheral blood film should be evaluated for every patient to check for TL and other hematological disturbances. Despite the fact that none of our TL survivors developed overt leukemia (ML-DS), we also suggest that patients with DS be followed due to the risk of developing leukemia.

Neonates born to mothers with immune thrombocytopenia: 11 years experience of a single academic center.

: A major problem associated with immune thrombocytopenic purpura (ITP) in pregnancy is neonatal thrombocytopenia. We analyzed newborns born to mothers with ITP and examined predictive factors for thrombocytopenia. This retrospective study was performed in a single academic center from January 2007 to January 2018. Pregnant women with ITP and their babies are included. All neonates had a complete blood count and cranial ultrasound (USG) performed. Twenty seven neonates of 22 mothers were evaluated. A total of 23 (85%) of neonates were thrombocytopenic (<150 × 10/l) and in 20 (74%) platelet count was below 50 × 10/l. Median platelet count was 30 (4-300) × 10/l. One baby experienced intracranial hemorrhage, eight (29.6%) had minor bleeding. When babies with and without minor bleeding were compared; no significant difference was found regarding maternal age, duration of ITP, lowest and 'before delivery' platelet count, treatment during pregnancy and splenectomy. Cutoff value of platelet count for bleeding was calculated as 27 × 10/l with a sensitivity of 0.88 and specifity of 0.79. Strong correlation for postnatal thrombocytopenia was detected among siblings. Although the incidence of neonatal thrombocytopenia might be high, the incidence of poor neonatal outcomes is extremely low. Neonatal thrombocytopenia does not rely on maternal profile. The occurrence of neonatal thrombocytopenia and bleeding may be a risk factor for subsequent pregnancies. We suggest that the cutoff value for neonatal platelet count for bleeding can be used for management and treatment of neonates born to mothers with ITP.

Angiopoietins in the bone marrow microenvironment of acute lymphoblastic leukemia.

OBJECTIVE: Angiogenesis have implications in leukemia biology. Angiopoietin 1 (Ang 1) is an angiogenic cytokine which is essential in survival and proliferation of endothelial cells. Angiopoietin 2 (Ang 2) promotes dissociation of pericytes and increases vascular permeability and stromal derived factor 1 alpha (SDF 1α) which is a key player in stem cell traffic in the bone marrow (BM), has stimulating effects on angiogenesis as well. Here, we investigated the role of the leukemic BM microenvironment and specifically, the role of SDF 1α-CXCR4 and Ang 1/Ang 2-Tie 2 axes. METHODS: Here, Ang 1, Ang 2, and SDF 1α levels were measured in the BM plasma and in supernatants of mesenchymal stem/stromal cells (MSCs) of patients with ALL and compared with those of healthy controls. RESULTS: The results showed that at diagnosis, BM plasma levels of Ang 1 and SDF 1α were significantly low and Ang 2 was high when compared to control values. Remission induction was associated with an increase in Ang 1/Ang 2 ratio and SDF levels in BM plasma. DISCUSSION: The results suggest that BM microenvironment and leukemic cell-stroma interaction influences the secretion of Ang 1, 2 and SDF 1α, thus, may affect both angiogenesis, homing and mobilization of leukemic blasts.

Antenatal hydronephrosis: a single center's experience and follow-up strategies.

This study was performed to evaluate the role of postnatal ultrasonography (US) in predicting the final diagnosis and need of surgery of antenatal hydronephrosis patients. One hundred and twenty six renal units (RUs) of 76 patients with diagnosis of antenatal hydronephrosis (ANH) were studied. An early postnatal US no later than the first week of life was requested. Voiding cystourethrography (VCUG) and/or diuretic renogram (MAG3) was performed in children who had persistent or worsening hydronephrosis to make a certain diagnose of etiology. US findings of different etiologies, and operated/nonoperated groups are compared. Regarding the renal pelvic anteroposterior diameter in the first week postnatal US; mild, moderate, severe, and no HN was detected in 48 (38.1%), 31 (24.6%), 24 (19.0%), and 23 (18.3%) RUs respectively. Eight RUs with a normal first postnatal US were found to have renal anomaly during follow up and 63% of these were vesicoureteral reflux (VUR). Kidneys with mild or moderate HN were likely to have transient dilatation while severe HN was likely to have obstruction. Postpartum follow-up of AHN is a dynamic process. Follow-up must be planned with optimum period of intervals according to clinic and US findings, to select the right patient for surgery or close follow-up.

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.

Deferasirox therapy in children with Fanconi aplastic anemia.

Thirty-nine children with Fanconi aplastic anemia (FAA) have been followed up in our center between January 2008 and November 2010. Eight of these children (20%) with a transfusional iron overload had been undergoing deferasirox treatment during the study period. In the English literature, transfusional iron overload and the use of an iron chelator in children with FAA has not yet been evaluated. Here, we have presented the effectivity and tolerability of deferasirox in children with FAA and a transfusional iron overload. Before the deferasirox treatment, the mean serum ferritin level was 3377 ± 2200 ng/mL. After a mean 13.6-month treatment duration, the mean ferritin level decreased to 2274 ± 1300 ng/mL (P<0.05). In our series, 3 patients had renal and 3 had hepatic toxicity during the treatment. Two patients had peliosis hepatis and 2 had congenital renal abnormalities before the treatment. There may be differences in the side-effect profiles of deferasirox treatment in patients with FAA. In our series, despite the low number of cases, nephrotoxicity and hepatotoxicity were common side effects instead of gastrointestinal disturbances reported in other studies. Deferasirox is an oral, easily applicable, and effective iron chelator; baseline hepatotoxicity and nephrotoxicity may increase the development of toxic side effects in children with FAA. Patients with FAA receiving deferasirox treatment should be followed up closely for these side effects.

Pseudotumor cerebri in a Turkish boy with Fanconi anemia.

Pseudotumor cerebri (PC) is a clinical syndrome characterized by increased intracranial pressure with a normal cerebrospinal fluid cell count and protein level in the absence of a space-occupying lesion or apparent obstruction to the cerebrospinal fluid pathway. Although PC is described in patients with various hematological diseases including iron-deficiency anemia, megaloblastic anemia, acquired aplastic anemia, hemolytic anemia, sickle cell disease, and paroxysmal nocturnal hemoglobinuria, there is no case of PC with Fanconi anemia in the English literature. Here, we report a first case of PC in an 11-year-old boy with a diagnosis of Fanconi anemia.