Ferhan Akici

Factor VII Deficiency: A Single-Center Experience.

Congenital factor VII deficiency is the most common form of rare coagulation factor deficiencies. This article presents a retrospective evaluation of 73 factor VII deficiency cases that had been followed at our center. The study consisted of 48 males and 25 females (2 months-19 years). Thirty-one (42.5%) of them were asymptomatic. Out of symptomatic patients, 17 had severe clinical symptoms, whereas 8 presented with moderate and 17 with mild symptoms. The symptoms listed in order of frequency were as follows: epistaxis, petechia or ecchymose, easy bruising, and oral cavity bleeding. The genotype was determined in 8 patients. Recombinant activated factor VII (rFVIIa) was used to treat 49 bleeding episodes in 8 patients after 2002. In 2 patients with repeated central nervous system bleeding prophylaxis with rFVIIa was administered. No allergic and thrombotic events were observed during both treatment and prophylaxis courses. Antibody occurrence was not detected in the patients during treatment.

TREATMENT OF WILMS TUMOR: A Report from the Turkish Pediatric Oncology Group (TPOG)

Aim: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey. Methods and patients: Between 1998 and 2006, WT patients were registered from 19 centers. Patients <16 years with unilateral WT whose treatment started in first postoperative 3 weeks were included. Treatments were stage I favorable (FH) and unfavorable histology (UH) patients, VCR + Act-D; stage IIA FH, VCR + Act-D; stage IIB FH, VCR + Act-D + radiotherapy (RT); stage III–IV FH, VCR + Act-D + adriamycin (ADR) + RT; stages II–IV UH tumors, VCR + Act-D + ADR + etoposide + RT. Results: 165/254 registered cases were eligible (bilateral, 5.9%) [median age 3.0 years; M/F: 0.99; 50/165 cases ≤2 years]. 9.7% cases had UH tumors. Disease stages were stage I 23.6%; IIA 36.4%; IIB 5.5%; III 22.4%; IV 12.1%. Cases >2 years had significantly more advanced disease. 1/11 cases with recurrent disease died; 2/165 had progressive disease, 2/165 had secondary cancers, and all 4 died. In all cases 4-year OS and EFS were 92.8 and 86.5%, respectively. Both OS and EFS were significantly worse in stage IV. Conclusions: Despite problems in patient management and follow-up, treatment results were encouraging in this first national experience with a multicentric study in pediatric oncology. Revisions and modifications are planned to further improve results and minimize short- and long-term side effects.

Successful treatment of multiresistant Achromobacter xylosoxidans bacteremia in a child with acute myeloid leukemia.

Achromobacter xylosoxidans is an aerobic gram-negative bacillus and important cause of bacteremia in immunocompromised patients. We describe a leukemia pediatric patient with severe neutropenia who developed bacteremia with A xylosoxidans resistant to multiple antibiotics, and treated the patient with tigecycline and piperacillin-tazobactam in addition to supportive medications.

Surgical interventions in childhood rare factor deficiencies: a single-center experience from Turkey.

Congenital rare factor deficiencies may present in infancy by life-threatening bleedings or may not show any symptoms until adulthood. It is reported more commonly in countries having consanguineous marriages. Data regarding surgical interventions of rare congenital factor deficiencies are based on case reports and records of guidelines. There are no well documented and separately prepared directories related to pre-surgical and prophylactic approaches of surgical interventions of these deficiencies. Our retrospective study consisted of 171 rare factor deficiencies that were followed up in our clinic, and of whom 61 had 88 surgical interventions between 1990 and 2012. Of these patients, 45 were having factor VII deficiency, and factor V, X, XI, XIII and fibrinogen deficiencies were present in five, four, three, two and two patients, respectively. In 23 patients, factor coagulant activities were under 5% (37.7%), in 15 it was between 5 and 30% (24.6%), and in 23 between 30 and 50% (37.7%). Twenty-eight were symptomatic and 33 were asymptomatic. Information of 51 (83.6%) male and 10 (16.4%) female patients with an age range of 5–25 years (13 ± 5.27), whose age at presentation ranged between 3 weeks and 18 years (7 ± 4.66), were retrieved from patient records and from the records contained in the data-processing environment introduced in 2005. The rate of familial consanguinity was 49.2%. Of the surgical interventions, 24 (27.3%) were major, 24 (27.3%) were minor and 40 (45.4%) were circumcision. We used fresh frozen plasma in 32, recombinant factor (rF)VIIa in 20, prothrombin complex concentrate in five and fibrinogen in three patients during surgical interventions. In 18 patients, antifibrinolytic agents were also used. In 27 patients, surgical interventions were applied without any replacement therapy. No additional doses were required after surgical prophylaxis doses. Thrombotic events were not observed. Antibody occurrence was not detected in these patients. In our study, we evaluated preparation for surgical procedures, factor replacement therapy before surgical intervention and postoperative follow-up in patients with rare coagulation factor deficiency.

Mucoepidermoid Carcinoma of the Parotid Gland in Childhood Survivor of Acute Lymphoblastic Leukemia With Need of Radiotherapy for Treatment and Review of the Literature

Diagnosis of secondary malignancies began with the increasing survival in childhood cancer. Children treated for acute lymphoblastic leukemia (ALL) have an increased risk for developing mucoepidermoid carcinoma (MEC) of the parotid gland. The latent period ranges from 5 to 16 years. A 2 6/12-year-old girl was treated for pro-B ALL. Treatment included multidrug chemotherapy, prophylactic intrathecal methotrexate, and cranial radiotherapy. MEC of the left parotid gland was diagnosed at the age of 8 years, 3 years after completing treatment. She was treated with multiple surgery and radiotherapy. The authors aimed to emphasize the need for concern about second cancers of the parotid gland in children treated for ALL.

How do we encounter rare factor deficiencies in children? Single-centre results from Turkey.

BackgroundRare factor deficiencies (RFDs) are autosomal recessively inherited coagulation factor deficiencies encountered at a frequency of between one in 500 000 and one in two million. Materials and methodsOne hundred and ninety-two patients, diagnosed as having RFD, followed and treated in our clinic between 1990 and 2013 were retrospectively evaluated in this study. ResultsFrom the 192 patients, 142 had FVII, 15 had FX, 14 had FXI, 10 had fibrinogen, six had FV, two had FXIII, two had FV + FVIII and one had FII deficiency. One hundred and thirty of the cases were boys and 62 were girls. The age range was 2 weeks to 24 years and the ages at the admission were between 2 weeks and 16 years. The rate of consanguinity was 49.4%. Eighty-eight of our patients were asymptomatic (45.8%) and 104 were symptomatic (54.2%). Asymptomatic patients were diagnosed by family histories (39.8%), preoperative laboratory studies (54.6%) and operational bleeding (5.6%). Sixty-eight of our symptomatic patients displayed grade II (65.4%) and 36 displayed grade III bleeding symptoms (34.6%). First bleeding regions were skin (33%), nose (28%), central nervous system (CNS) (15.5%), oral cavity (10.5%), soft tissue (6%), joint (3%), urinary system (2%) and gastrointestinal system (GIS) (2%), respectively. The bleeding prevalence rates of our symptomatic patients are listed as epistaxis 62.5%, skin bleedings 53%, oral cavity bleeding 28.8%, haematomas 18.3%, CNS bleedings 17.3%, haemarthrosis 14.4%, GIS bleedings 3.8%, menorrhagia 2.9%, haematuria 1.9%, bleeding because of operations 1.9% and iliopsoas bleedings 1.9%. CNS bleedings (41%) take the first place among the serious bleedings of our cases, followed by haemarthrosis (36.4%), GIS bleedings (18.1%) and iliopsoas bleedings (4.5%). Prophylaxy was applied to nine patients (five patients with FVII, two patients with fibrinogen and one each with FV and FX deficiency). ConclusionsThe characteristics of clinical presentations, first bleeding attacks, bleeding prevalence and severe bleedings as well as prophylactic approaches are discussed in this article.

Insidious Renal Damage in Patients with Thalassemia Major: Is it More Seriousthan Appreciated?

Aim: To investigate early renal injury in thalassemia major patients by using novel serum markers and demonstrate the factors leading to renal injury. Material and Methods: Seventy-one thalassemia major patients (37 males) who were on regular transfusion and chelation programme with deferasirox have been enrolled in this study. Thirty-five healthy children of the same age served as a control group. Serum urea-creatinine, electrolytes, cystatin C and glomerular filtration rate were all noted in our cohort and compared with the control group. Proteinuria was also investigated by calculating UPr/UCr ratio. Results: The median serum creatinine level was 0.4 mg/dL (range; 0.2-0.76 mg/dL ) and the median glomerular filtration rate level was 192 mL/min/1.73 m2 (range; 106-308 mL/min/1.73 m2 ) in patients. More than half of the patients had glomerular hyperfiltration (n=48, 67.6%). Hyperfiltration was prominent in thalassemia group (66.2% vs. 19.4%) (p=0.0001). Mean serum cystatin C levels were found to be statistically elevated in patient group comparing with controls (p=0.0001). Serum cystatin C level was above >1 mg/L in 46 patients (64.7%) whereas only three in controls (p=0.0001). Sex, age, hemoglobin level and cardiac T2* MRI results were not related to the elevated cystatin C levels. On the other hand, liver iron burden and serum ferritin levels were noted to be statistically correlated to elevated cystatin C level (p=0.024 and p=0.04). Deferasirox dose below 25 mg/kg/day was also found in relation with elevated cystatin C levels. Conclusion: Renal injury is multifactorial, insidious but progressive in thalassemia patients. High index of suspicion and routine use of novel markers are required for detection of renal injury during the follow up of thalassemia patients.

Congenital Factor Deficiencies in Children: A Report of a Single-Center Experience

Congenital factor deficiencies (CFDs) refer to inherited deficiency of coagulation factors in the blood. A total of 481 patients with CFDs, who were diagnosed and followed at our Pediatric Hematology and Oncology Clinic between 1990 and 2015, were retrospectively evaluated. Of the 481 cases, 134 (27.8%) were hemophilia A, 38 (7.9%) were hemophilia B, 57 (11.8%) were von Willebrand disease (vWD), and 252 (52.3%) were rare bleeding disorders (RBDs). The median age of the patients at the time of diagnosis and at the time of the study was 4.1 years (range: 2 months to 20.4 years) and 13.4 years (range: 7 months to 31.3 years), respectively. The median duration of the follow-up time was 6.8 years (range: 2.5 months to 24.8 years). One hundred nineteen (47.2%) of 252 patients with RBDs were asymptomatic, 49 (41.1%) of whom diagnosed by family histories, 65 (54.6%) through preoperative laboratory studies, and 5 (4.2%) after prolonged bleeding during surgeries. Consanguinity rate for the RBDs was 47.2%. Prophylactic treatment was initiated in 80 patients, 58 of whom were hemophilia A, 7 were hemophilia B, 13 were RBDs, and 2 were vWD. Significant advances have been achieved during the past 2 decades in the treatment of patients with CFDs, particularly in patients with hemophilias. The rarity and clinical heterogeneity of RBDs lead to significant diagnostic challenges and improper management. In this regard, multinational collaborative efforts are needed with the hope that can improve the management of patients with RBDs.

Best treatment option for infantile chronic myeloid leukemia patients: Imatinib or hematopoietic stem cell transplantation?

We were interested in the article by Alchalby and his colleagues about the hematopoietic stem cell transplantation (HSCT) and imatinib therapy in pediatric patients with chronic myeloid leukemia (CML). Philadelphia chromosome (Ph)-positive CML is extremely rare in infants (1). That is why the treatment strategies for infantile CML remain controversial. Treatment with tyrosine kinase inhibitors (TKIs) has replaced HSCT in children especially without a matched sibling donor (MSD) (2). On the other hand, clinical observations in adult patients with CML yielded imatinib as front-line therapy (3). We disagree that this is true for children. The progression to accelerated phase under TKI therapy (4), potential long-term side effects (3) such as osteoporosis and pulmonary hypertension and also higher cost in developing countries (5) are major drawbacks. A 16-month-old girl presented with abdominal distension and anorexia lasting for a month. She had prominent hepatosplenomegaly. Complete blood count showed hemoglobin of 9.4 g/dL, platelet count of 349 9 10/L, and total leukocyte count of 229 9 10/L with a differential count of 17% promyelocyte, 10% myelocyte, 40% stab/ neutrophil, 11% eosinophil, 6% monocyte, 1% basophil, and 15% lymphocyte. Bone marrow aspirate showed no blasts. Leukocyte alkaline phosphatase score was five (range: 20–137), and fetal hemoglobin level was normal. Karyotypic study revealed Ph positivity (46, XX, t(9;22)(q34; q11). RT-PCR showed presence of both b3a3 and b2a2 variants of bcr-abl fusion gene. Imatinib was started at the dose of 340 mg/m. Hematological response was achieved with imatinib therapy at one month. FISH analysis performed after three months showed bcr-abl variants fusion positive in 8.7% b3a3 and 7.4% b2a2 (partial response). After six months of therapy, RT-PCR showed presence of BCR/ABL positivity (0.1006%) (optimal response). She underwent HSCT from matched unrelated donor (MUD) after seven months of imatinib. The patient experienced acute GvHD (grade II) and CMV infection, which were treated successfully. She was fully chimeric, and t(9;22) was negative after HSCT. Chronic GvHD (skin and liver) was detected on +195th day, and CMV pneumonia was diagnosed on +332nd day. She was intubated and admitted to the intensive care unit. But unfortunately, she died due to ARDS on +343th day. Just after the best therapeutic response with TKI in the chronic phase, HSCT with MSD/ MUD is the treatment of choice for children with CML (6, 7). But the high risk of morbidity and mortality even from MSDs should also be taken into account. It has been proposed that imatinib therapy would be more appropriate therapy for patients withoutMSD. Some authors recommend that allo-SCT in children should be postponed until the disease becomes refractory to imatinib (3). To the best of our knowledge, our patient was one of the youngest patients to undergo HSCT in the literature. Although she died of CMV pneumonia, which is one of the complications of HSCT, we still believe that the best curative option for pediatric/infantile CML patients is HSCT until novel drugs with less toxicity and higher efficacy are produced.