Gül Nihal Özdemir

A child presenting with hypercalcemia.

Informed Consent: Written informed consent was obtained from patients’ parents who participated in this case. Peer-review: Externally peer-reviewed. Author Contributions: Literature Review - G.N.O.; Writer - G.N.O., E.C.; / Critical Review - Y.T., H.C., T.C.; Other - G.T. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support.

Rhabdomyosarcoma of the Tongue: Report of a Case and Review of the Literature

Rhabdomyosarcomas are the most common soft tissue tumors in children. Head and neck is one of the most frequently affected site. Within the nonparameningeal, nonorbital head and neck region, rhabdomyosarcomas of the tongue are very rare. We present a 2-year-old boy diagnosed with rhabdomyosarcoma of the tongue. The child was treated with complete surgical resection and chemotherapy. He is followed up with no evidence of disease 6 months after termination of therapy. The literature on rhabdomyosarcoma of the tongue is reviewed.

Secondary Neoplasms in Children Treated for Cancer

The survival of children with cancer has improved dramatically in the last decades. Survivors of childhood cancer are at increased risk of long-term complications of therapeutic exposure. Second malignant neoplasms are one of the most severe side effects of cancer treatment. The frequency and type of secondary cancers may vary depending on the initial diagnosis, treatment administered and genetic predisposition. This review highlights the risk factors in the development of SMNs in survivors of pediatric cancers and their differences according to primary cancer type, genetic predisposition and treatment admistered. Finally, the review emphasizes the need for life-time follow-up of survivors of childhood cancer for the development of second malignancies.

Wernicke's encephalopathy in a child with acute lymphoblastic leukemia.

We read with great interest the article “A rare complication developing after hematopoietic stem cell transplantation: Wernicke’s encephalopathy” by Solmaz et al. [1]. Wernicke’s encephalopathy (WE) is an acute syndrome requiring emergent treatment to prevent death and neurologic morbidity [2]. While most often associated with alcoholism, WE also occurs in the setting of prolonged intravenous feeding without adequate thiamine supplementation, prolonged starvation or unbalanced nutrition, gastrointestinal surgery, systemic malignancy, and transplantation [3]. The classic triad of WE includes encephalopathy, oculomotor dysfunction, and gait ataxia. In their article, Solmaz et al. reported a patient who developed WE following hematopoietic stem cell transplantation (HSCT) and they concluded that this was due to prolonged total parental supplementation and lack of thiamine supplementation. The only other suggested cause was the use of busulfan in the conditioning regimen. In the literature there is a link of WE to HSCT, malignancies, or chemotherapies. Here we report a new patient who developed WE during acute lymphoblastic leukemia (ALL) treatment.

Juvenile Myelomonocytic Leukemia in Turkey: A Retrospective Analysis of 65 Patients

Objective: This study aimed to define the status of juvenile myelomonocytic leukemia (JMML) patients in Turkey in terms of time of diagnosis, clinical characteristics, mutational studies, clinical course, and treatment strategies. Materials and Methods: Data including clinical and laboratory characteristics and treatment strategies of JMML patients were collected retrospectively from pediatric hematology-oncology centers in Turkey. Results: Sixty-five children with JMML diagnosed between 2002 and 2016 in 18 institutions throughout Turkey were enrolled in the study. The median age at diagnosis was 17 months (min-max: 2-117 months). Splenomegaly was present in 92% of patients at the time of diagnosis. The median white blood cell, monocyte, and platelet counts were 32.9x109/L, 5.4x109/L, and 58.3x109/L, respectively. Monosomy 7 was present in 18% of patients. JMML mutational analysis was performed in 32 of 65 patients (49%) and PTPN11 was the most common mutation. Hematopoietic stem cell transplantation (HSCT) could only be performed in 28 patients (44%), the majority being after the year 2012. The most frequent reason for not performing HSCT was the inability to find a suitable donor. The median time from diagnosis to HSCT was 9 months (min-max: 2-63 months). The 5-year cumulative survival rate was 33% and median estimated survival time was 30±17.4 months (95% CI: 0-64.1) for all patients. Survival time was significantly better in the HSCT group (log-rank p=0.019). Older age at diagnosis (>2 years), platelet count of less than 40x109/L, and PTPN11 mutation were the factors significantly associated with shorter survival time. Conclusion: Although there has recently been improvement in terms of definitive diagnosis and HSCT in JMML patients, the overall results are not satisfactory and it is necessary to put more effort into this issue in Turkey.

Bilateral Cystic Adrenal Neuroblastoma with Cystic Liver Metastasis

Bilateral congenital cystic adrenal neuroblastoma (NB) with cystic liver metastasis is a very rare condition and only few cases have been reported in the literature. Herein we report a case of a congenital bilateral cystic adrenal NB with cystic liver metastasis and briefly discuss characteristic imaging features of cystic NB.

Difficulties in the treatment of an Infant with Hemophilia B

Dear Editor, Hemophilia B is a X-linked recessive bleeding disorder which occurs as a result of Factor IX (FIX) deficiency (1, 2). In some patients with hemophilia, antibody (inhibitor) and allergic reaction may develop against FIX protein which is administered for treatment (3). While antibody develops against the factor administered in approximately 15–25% of the patients with severe hemophilia A, this rate is much lower in patients with hemophilia B (3%). Life-threatening allergic reactions may develop in 50% of the patients who have inhibitor (4). There is no efficient treatment which can be used to prevent allergic reaction developing secondary to antibody response. In this case report, the difficulties in treatment of an infant with severe hemophilia B who developed antibody and allergic reaction against FIX treatment have been discussed. Our patient was diagnosed with hemophilia B after investigations performed because of severe hemorrhage which developed following circumscision at the age of five months. At presentation, the bleeding tests revealed an activated partial thromboplastin time (aPTT) of 104 seconds and a FIX level of 1%. A concentrate containing FIX protein obtained from 9 doses of plasma was used to stop bleeding. When the patient was 14-month old, he was rehospitalized because of head trauma. His cranial ultrasonography and brain tomography findings were found to be normal. FIX concentrate (Replenine®) was initiated at a dose of 80 IU/kg by way of slow intravenous infusion because of head trauma. However, anaphylactic reaction (diffuse urticaria, blushing in the face, cough, dyspnea, cyanosis) developed during infusion of factor concentrate. Dexamethasone, antihistaminic and adrenaline were administered for treatment. In the following administrations, his treatment was switched to Berinine® which is another FIX concentrate with prophylactic administration of antihistaminic and steroid. A similar anaphylactic reaction developed in the third minute of infusion of this new concentrate and treatment was immediately discontinued. Antihistaminic, dexamethasone and adrenaline were administered again. In the follow-up visit one month later, aPTT was found to be 134 s, the FIX level was found to be 0.1% and the amount of inhibitor was found to be 1.7 BU. As a result of mutation study, CGA>TGA (R252X) mutation was demonstrated in exon 8, n.30875, codon 252. Non-human-derived recombinant active FVIIa (rFVIIa - Novo Seven®) was given for severe bleedings in the following periods because of development of antibody. Allergic reaction may occur against FIX protein in patients with hemophilia B who have developed antibody in contrast to hemophilia A (5). Follow-up and treatment of hemorrhage is difficult in patients with hemophilia who are allergic against external FIX protein and develop FIX-related antibody. Antibodies are involved in morbidity and mortality related with bleeding. FIX concentrates are not appropriate, because these patients develop antibody and allergy against FIX concentrates. Since treatment with active prothrombin complex concentrate (aPCC) involves FIX, it may result in allergic reaction similarly (6). Development of recombinant FVIIa provided an appropriate treatment option for patients with hemophilia who develop inhibitor. However, no consensus has been made in relation with treatment with aPCC and rFVIIa in FIX patients who have developed antibody (7). In our own individual experience, it was observed that hemostasis control was provided with aPCC treatment during surgery in patients with hemophilia B who developed antibody (8). It should be kept in mind that the cost of recombinant FVIIa concentrates is high and they carry a risk of thrombosis. Therefore, inhibitor elimination and desensitization treatment should be considered in these patients (9). Elimination of antibody is considerably difficult and treatment success is poor in patients with hemophilia B who are allergic against Factor IX concentrates and who develop antibody. Immune tolerance induction (ITI) treatment which is commonly used in patients with hemophilia A to eliminate antibody and is successful is generally ineffective in these patients. It is recommended that patients with high-risk in terms of development of antibody (patients with complete gene loss) should be identified with molecular analyses at the time of first diagnosis and monitored closely in the beginning of treatment (5). In patients with hemophilia B, it is recommended that the first 10–20 treatments should be administered in hospital in terms of allergy and family members should be trained in terms of the risk of anaphylaxis (10). In conclusion, we aimed to emphasize the difficulties in follow-up of patients with severe hemophilia B who develop allergic reaction and inhibitor against FIX concentrates. Since life-threatening allergic reactions against Factor IX concentrates may develop, the initial administrations in treatment of patients with newly diagnosed hemophilia B should be definitely performed in hospital environment. Recombinant FVIIa is the only appropriate option for treatment of hemorrhage in these patients. Despite a need for inhibitor elimination and desensitization treatment, there is no current application in this area and further studies are needed.

An infant with chronic hemolytic anemia.

Informed Consent: Written informed consent was obtained from patient’s parents. Peer-review: Externally peer-reviewed. Author Contributions: Concept - G.N.O.; Design - T.C.; Supervision -T.C.; Funding - G.T.; Materials - G.T.; Data Collection and/or Processing - G.T.; Analysis and/or Interpretation - G.T., G.N.O.; Literature Review - G.N.O., G.T.; Writer - G.T.; Critical Review - T.C., G.N.O. Conflict of Interest: No conflict of interest was declared by the authors. Financial Disclosure: The authors declared that this study has received no financial support.