Langerhans Cell Histiocytosis: Single Center Experience of 25 Years.

OBJECTIVES: To review a single center outcome of patients with Langerhans Cell Histiocytosis diagnosed at a tertiary referral hospital from Turkey.Methods: The files between 1989 and 2015 of 80 patients with LCH were retrospectively analyzed. RESULTS: During the 25 years, 80 patients were diagnosed with LCH. The median age at diagnosis was 53 months (2-180 months) and the median follow-up time of patients was 10 years and 9 months (24 months-25 years). Bone was the most frequently affected organ (n:60, 75%). Initially, 43 patients (54%) had single system (SS) disease, 20 patients (25%) had multisystem (MS) disease without risk organ involvement (MS-RO-), and 17 patients (21%) had a multisystem disease with risk-organ involvement (MS-RO+). The overall survival (OS) rate was 91%, and event-free survival (EFS) rate was 67% at 10 years. 10-year OS rate was lower for patients with MS-RO+ (65%) when compared to those with, MS-RO-, and SS (100%, 97%, p value=<0.001). The overall survival rate was also lower in patients with lack of response to systemic chemotherapy on 12th week (p=<0.001), younger age (<2 years) at presentation (p=<0.02), skin involvement (<0.001) and lack of bone lesions at presentation (<0.001). DISCUSSION: In the group with MS-RO+, OS is significantly low compared to other groups. Further efforts are warranted to improve survival in MS-RO+ patients.

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia.

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated ß-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When ß-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL.

Late effects of childhood ALL treatment on body mass index and serum leptin levels.

BACKGROUND: It is well known that survivors of acute lymphoblastic leukemia (ALL) show a tendency to become overweight. Cranial irradiation (CRT), is considered to be the primary risk factor for development of obesity. AIMS: The aim of our study was to evaluate body mass index (BMI) and serum leptin levels in survivors of childhood ALL. METHODS: Subjects (Group I) consisted of 93 survivors of childhood ALL (53 males > or = 9 years old, 40 females > or = 8 years old) diagnosed between January 1975 and December 2002 in the Hematology-Oncology Division in Cerrahpasa Medical Faculty, Istanbul University after a follow up 10.21 +/- 4.90 (mean +/- SD) years. Fifty healthy individuals of similar chronological age were taken as controls (29 males, 21 females). Seventy-four subjects had received radiotherapy (Group IA) and 19 had not (Group I B). RESULTS: In Group I, BMI was significantly higher than in Group II (21.65 +/- 4.02 vs 20.31 +/- 3.49, p = 0.04). However, BMI was significantly higher only in Group I A (21.83 +/- 4.27) than in Group II (p = 0.032). Leptin levels were significantly higher in Group I A females than in Group II females. There was a significant correlation between BMI-SDS and serum leptin levels in group IA females. CONCLUSIONS: Leukemia treatment leads to obesity. Higher leptin levels in girls may suggest that sex may be a differentiating factor for this late effect.

Blue rubber bleb nevus syndrome associated with consumption coagulopathy: treatment with interferon.

The blue rubber bleb nevus syndrome (BRBNS) is a rare vascular malformation syndrome with cutaneous and visceral lesions frequently associated with serious, even fatal bleeding. No systemic therapy is currently available. We report here a case with disseminated skin and gastrointestinal venous malformations and findings of disseminated intravascular coagulation that was treated with interferon beta. The disseminated intravascular coagulation manifestations were cleared with the treatment. The regression of the coagulopathy in our patient led us to think that the use of interferon beta in BRBNS might be beneficial.

Toxic epidermal necrolysis after the use of high-dose cytosine arabinoside.

We report a fatal case of toxic epidermal necrolysis (TEN) resulting from a high dose of cytosine arabinoside (ARA-C). A 13-year-old girl with acute lymphocytic leukemia was treated according to the protocol of the BFM Group (BFM-95, HRG). On the fifth day after administration of a high dose of ARA-C (2 g/m2 intravenously every 12 hours), she developed bullous lesions on the hands and soles that disseminated, evolving to necrosis, sepsis, and death on the 22nd day. ARA-C is frequently associated with dermatologic toxicity, but this is only the second case of toxic epidermal necrolysis described in connection with this drug.

A Case with Micromegakaryocytes.

UNLABELLED: A boy with no previous history of bleeding presented with ecchymoses and splenomegaly. He was followed up for thrombocytopenia and micromegakaryocytes for 20 months till clinically malignancy was diagnosed. Micromegakaryocytes must always be treated with suspicion, as they may provide an important clue for dyshematopoesis. KEY WORDS: Micromegakaryocytes, Leukemia, Dismegakaryopoesis.

A Case with Gaucher-Like Cells.

Gaucher-like cells (GLC) are sometimes indistinguishable from real Gaucher cells. GLC can be detected in various diseases. We present a 4.5 year old boy with massive cervical lympadenopathy and an intraabdominal mass mimicking lymphoma. Many GLC were seen in the fine needle aspiration material of an enlarged lymph node. Ziehl-Neelsen stain of the aspirate revealed many acid-fast bacteria in the GLC. Fine needle aspiration might provide valuable information in the evaluation of enlarged lymph nodes.

Multidisciplinary approach to Wilms' tumor: 18 years of experience.

BACKGROUND: The aim was to evaluate the characteristics of Wilms' tumor and the results of combined modality treatment obtained in our center in Turkey. METHODS: From January 1978 to December 1996, 106 patients with Wilms' tumor were diagnosed. Of these 106 patients, 61 were male and 45 were female (M/F = 1,35); the median age at diagnosis was 39 months. The distribution of the 106 patients according to clinical stage was stage I 10%, stage II 42%, stage III 35%, stage IV 9% and stage V 4%. Histologically, 102 of the cases could be evaluated: favorable histology was diagnosed in 88.2% and unfavorable histology in 11.8% of the patients. Ninety-eight patients were treated according to NWTS and eight patients according to SIOP protocols. RESULTS: The EFS and overall survival rates at 2 years were 74.2 and 79.5% respectively, and at 5 years 72.4 and 76.6% respectively. CONCLUSION: As a developing country we evaluated our survival rates and report an improvement in treatment in recent years.

Tropisetron (Navoban) in the control of nausea and vomiting induced by combined cancer chemotherapy in children.

BACKGROUND: We aimed to assess the potency and efficacy of tropisetron, a 5-HT3 receptor antagonist, in the prevention of nausea and emesis observed in the pediatric patient population taking various chemotherapy protocols. METHODS: Tropisetron (Navoban) was given to 100 children (62 boys and 38 girls aged 6 months to 15 years) with various malignancies. Patients received tropisetron during one or more courses of emetogenic chemotherapy for a total of 350 courses administered intravenously or intravenously and intrathecally. Tropisetron (0.2 mg/kg/day, maximum: 5 mg/day) was administered as a single intravenous dose slowly, before the start of chemotherapy on day 1 and intravenously or by mouth on subsequent days (median treatment duration: 5 days). RESULTS: The patients receiving cytotoxic chemotherapy had a 70% complete response rate and a 24% partial response rate during the first 24 h period of the first course. We observed headache (five courses), diarrhea (three courses) and loss of appetite (one course) as side-effects (2.5%). CONCLUSION: Tropisetron is safe, effective, easy to use, has no serious side-effects and can be recommended for pediatric patients. The efficacy of tropisetron may be enhanced by the addition of corticosteroids in patients receiving highly emetogenic cancer chemotherapy.