The outcome in pediatric acute myeloblastic leukemia; results of the first-line treatment and contribution of hematopoietic stem cell transplantation to survival of relapsed patients.

Background/aim: To analyze the long-term outcome of pediatric patients with acute myeloblastic leukemia. Materials and methods: Data from 69 patients 0-18 years of age diagnosed between December 2001 and October 2019 were analyzed in April 2023. Patients received MRC-AML10 chemotherapy (2ADE+MACE+MidAC). No maintenance chemotherapy or preventive cranial radiotherapy was administered. Twelve patients with Down syndrome and 15 patients with promyelocytic leukemia were in the cohort. Patients with Down syndrome received reduced chemotherapy (cumulative anthracycline 420 mg/m2, cytarabine 3.4 g/m2, etoposide 1400 mg/m2). ATRA was added to chemotherapy in promyelocytic leukemia. Results: Four patients (5.8%) died in the induction (two typhlitis, one intracranial hemorrhage, and one resistant disease). The complete remission rate of 66 patients was 87.8%. There was one death due to cardiotoxicity. Total infection-related deaths were 7.2%. Seven patients with high-risk criteria and one with resistant disease underwent hematopoietic stem cell transplantation (HSCT) following the first-line treatment. All seven patients in remission were alive and disease-free. The relapse rate was 34.4% (n = 21). Four patients developing marrow relapse were disease-free in the second remission after salvage and maintenance chemotherapy. Thirteen patients (18.84%) underwent HSCT in the second remission and 8 are alive and disease-free. The mean follow-up period of patients from diagnosis was 185 ± 13 months. Thirty-four patients (49.2%) were alive and disease-free in the first remission whereas another two patients in the first remission developed secondary malignancy. In good, standard, and poor risk groups, event-free survival (EFS) rates were 68.2%, 52.9%, and 10%, and overall survival (OS) rates were 86.4%, 79.4%, and 20%, respectively. Fifteen years of EFS and OS of the whole cohort were 49.3% and 69.6%, respectively. Conclusion: When compared with national data and multicenter studies of developed countries, survival rates were acceptable.

Autoimmune Hemolytic Anemia Due to Spondyloenchondrodysplasia with Spastic Paraparesis and Intracranial Calcification due to Mutation in ACP5.

Spondyloenchondrodysplasia (SPENCD) is a rare spondylometaphyseal skeletal dysplasia with characteristic lesions mimicking enchondromatosis and resulting in short stature. A large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders. SPENCD is caused by loss of tartrate-resistant acid phosphatase activity, due to homozygous mutations in ACP5 , playing a role in nonnucleic-acid-related stimulation/regulation of the type I interferon pathway. In this article, we presented a 19-year-old boy with SPENCD, presenting with recurrent autoimmune hemolytic anemia episodes since he was 5 years old. He had short stature, platyspondyly, metaphyseal changes, intracranial calcification, spastic paraparesis, and mild intellectual disability. He also had recurrent pneumonia attacks. The clinical diagnosis of SPENCD was confirmed by sequencing of the ACP5 gene, and a homozygous c.155A > C (p.K52T) variation was found, which was reported before as pathogenic. In conclusion, in early onset chronic autoimmune cytopenias an immune dysregulation may often have a role in the etiology. Associating findings and immunologic functions should be carefully evaluated in such patients in the light of the literature. The present case shows the importance of multisystemic evaluation for the detection of SPENCD that has a monogenic etiology.

Recombinant porcine factor VIII in patients with congenital haemophilia A with inhibitors undergoing surgery: Phase 3, single-arm, open-label study.

INTRODUCTION: Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is predicted to provide functional FVIII activity in patients with congenital haemophilia A with inhibitors (CHAWI). AIMS: To evaluate the efficacy and safety of rpFVIII in patients with CHAWI undergoing invasive procedures. METHODS: This phase 3, multicentre, single-arm, open-label study (NCT02895945) enrolled males aged 12-75 years with severe/moderately severe CHAWI who required surgical/invasive procedures. Patients received a loading dose of rpFVIII 1-2 h before surgery. The primary outcome was the proportion of all procedures with a 'good' or 'excellent' response (treatment success) on the global haemostatic efficacy assessment score. RESULTS: Of the eight dosed patients, five completed the study. Six of seven surgeries (85.7%; 95% confidence interval, 42.1-99.6) achieved treatment success; five were rated 'excellent', one was rated 'good'. Seven surgery-related bleeding episodes occurred in three patients during the study, with none requiring additional surgical intervention. Overall, six of eight patients experienced 17 treatment-emergent adverse events. Three patients developed de novo inhibitors to rpFVIII. Five patients reported anamnestic reactions, three to both human (h) FVIII (i.e., alloantibodies to exogenous FVIII detected with anti-hFVIII assays) and rpFVIII, and two to hFVIII only. Four serious adverse events were considered related to rpFVIII (three anti-rpFVIII antibody positive; one anamnestic reaction to hFVIII and rpFVIII). CONCLUSION: Good haemostasis was achieved with rpFVIII during the immediate perioperative period. The study was terminated early because the study sponsor and health authorities determined that the risk of anamnestic reactions outweighs the benefits in this study population.

Splenic Artery Embolization in a Patient With Intracranial Hemorrhage Due to Refractory Persistent Immune Thrombocytopenia.

BACKGROUND: Managing intracranial bleeding in patients with refractory immune thrombocytopenia is difficult. OBSERVATION: A 16-year-old female refractory to prednisolone, intravenous immunoglobulin, eltrombopag, and cyclosporin exhibited heavy menstrual bleeding requiring packed red blood cell transfusions. Autoimmune antibodies were detected, indicating of lupus, and hydroxychloroquine sulfate was administered. In month 6 following the diagnosis, the patient presented with intracranial hemorrhage. Splenic artery embolization promptly increased platelets, and the patient was discharged without any neurological sequela. In month 5 of embolization, the patient's platelet count continued to exceed 300,000/µL without any medical treatment. CONCLUSIONS: Splenic artery embolization is a life-saving procedure in refractory immune thrombocytopenia.

Pedipacks in the transfusion of pediatric patients to reduce wastage of blood components: an observational study from a tertiary center.

BACKGROUND: Pedipacks prevent wastage of blood components but they are not used efficiently in pediatric clinics. METHODS: Red cell concentrate (RCC) and platelet concentrate volumes transfused in the last eight months in the pediatric clinics were screened. To calculate the wastage of blood components, the number of transfused pedipacks, whole unit RCC, and platelet units were screened from transfusion laboratory digital records to show the number of whole RCC units or platelets units used instead of pedipacks. The study results were shared with physicians and transfusion laboratory staff and they were trained on the subject in meetings. Two years later, the transfusion laboratory records were assessed again to evaluate pedipack usage. A google questionnaire was also submitted to the transfusion laboratories of other hospitals to assess the use of pedipacks. RESULTS: RCC and platelets were used in 82.9% of the transfusions, and 31.2% of RCC and 18.4 % of platelets were transfused to patients ≤12 months. During the study period, 569 pedipacks and 117 random donor or apheresis platelets separated into satellite packs would be required. But only 48 pedipacks of RCCs and 24 units of random donor platelets/apheresis platelets separated into satellite packs were used. After two years, in RCC transfusions of 0-12 month-old patients, the transfusion laboratory release of pedipacks increased to 67.9% from 13.5%. Other centers were not also using pedipacks efficiently. The main reasons were unawareness of the subject, the blood bank delivering two units of pedipacks even when only one unit was ordered and the risk of not using the second pedipack before the expiry date, and the short expiry date of irradiated pedipacks. CONCLUSIONS: By increasing awareness of the subject, the collaboration of the clinic and laboratory and solving bureaucratic problems, rational use of blood components can be achieved.

Management of Hyperleukocytosis in Childhood Acute Leukemia Without Leukapheresis and Rasburicase Prophylaxis.

Indications of leukapheresis (LPh) and the prophylactic use of rasburicase in tumor lysis syndrome (TLS) of patients with acute leukemia with hyperleukocytosis are not clear. In this retrospective single-center pediatric study, the outcomes of patients with hyperleukocytosis were reviewed. There were 48 patients with acute lymphoblastic leukemia (ALL) and 13 patients with acute myeloblastic leukemia (AML). The treatment strategies included hyperhydration, allopurinol administration, strict monitoring, and early initiation of induction chemotherapy (CT). No patient underwent LPh because it was not available. Rasburicase was used only in 3 ALL patients with hyperuricemia when the drug was available. Laboratory and clinical TLS developed in 54.16% and 14.58% of patients with ALL, respectively. Laboratory and clinical TLS developed in 76.92% and 15.38% of patients with AML, respectively. No patient developed grade III to V TLS requiring dialysis. Thirteen patients (21.3%) had pulmonary leukostasis on admission, but recovered with CT and nasal oxygen. During the first 14 days of presentation, cerebral leukostasis/coagulopathy-related early death (ED) was 4.2% and 7.7% in patients with ALL and AML, respectively, and all of these patients had a white blood cell count ≥400,000/µL. There was also 1 infection-related death. Patients with hyperleukocytosis can be treated without LPh and liberal use of rasburicase. Renal failure is no longer a cause of ED. Intracranial hemorrhage is the main cause of ED, especially in patients already presenting with this complication. LPh may be performed in patients with leukostasis, if it is not possible to start induction CT early. When resources are limited, rasburicase should be administered in patients presenting with or developing hyperuricemia and/or renal dysfunction.

Myeloid sarcoma of the heart: Extramedullary relapse of acute myeloblastic leukemia, presenting with complete heart block and atrial flutter after second allogeneic stem cell transplantation.

We report isolated extramedullary relapse in a 14-year-old boy, sequentially presenting with intestinal and cardiac myeloid sarcoma (MS). Acute myeloblastic leukemia M5 was diagnosed 41 months ago. On the 14th month of the second HSCT, he presented with ileus and underwent surgical treatment. After 2 weeks, arrhythmia, bradycardia, complete heart block, and atrial flutter developed and echocardiography revealed multiple cardiac masses. There was no bone marrow relapse but pathology of the intestinal biopsy showed leukemic infiltration. Patient was successfully treated with a permanent pacemaker and salvage chemotherapy. To the best of our knowledge, this is the first pediatric cardiac MS developed after HSCT.

Bleeding characteristics and management of minor surgeries in rare bleeding disorders: report from a Turkish Pediatric Hematology Center.

BACKGROUND AND OBJECTIVES: In this retrospective report the aim was to present the experience about bleeding characteristics and management of minor surgeries in rare bleeding disorders (RBDs). METHODS: Twenty-six patients were included; with Factor (F) V, FV+VIII, VII, FXI deficiency and afibrinogenemia. Six of the patients were asymptomatic. RESULTS: Fifty-three percent of the patients suffered from mucosal bleeding. Life-threatening bleedings were observed only in the patients with afibrinogenemia and good hemostatic control could only be provided with plasma-derived (pd)-fibrinogen concentrate. Twelve of the patients had undergone 17 minor surgeries. In the patients with FVII and FXI deficiencies with plasma F:C activity between 20-47%, there was a history of uneventful tooth extractions, circumcisions and a pilonidal sinus operation performed without any replacement treatment, whereas one patient with plasma F:C activity of FVII 47% had a history of poor hemostatic control during an adeno-tonsillectomy operation. Although some of these patients were asymptomatic to be on the safe side, minor operations were performed with preoperative administration of one dose of (pd)-fibrinogen concentrate to one afibrinogenemia patient, recombinant active FVII (rFVIIa) to 2 FVII deficient patients and fresh frozen plasma (FFP) to 3 FXI deficient and 1 FVII deficient patients plus postoperatively tranexamic acid (TXA) for 5-7 days. Only with one dose of the replacement therapy just before surgeries good hemostatic control was achieved and none of them had bleeding neither during nor after the surgeries. CONCLUSION: We suggest that minor operations must be performed with preoperative replacement therapies plus 5-7 days of antifibrinolytics under close observation of the hematologist and the surgeon.

Prognostic gene alterations and clonal changes in childhood B-ALL.

Genomic profiles of leukemia patients lead to characterization of variations that provide the molecular classification of risk groups, prediction of clinical outcome and therapeutic decisions. In this study, we examined the diagnostic (n = 77) and relapsed (n = 31) pediatric B-cell acute lymphoblastic leukemia (B-ALL) samples for the most common leukemia-associated gene variations CRLF2, JAK2, PAX5 and IL7R using deep sequencing and copy number alterations (CNAs) (CDKN2A/2B, PAX5, RB1, BTG1, ETV6, CSF2RA, IL3RA and CRLF2) by multiplex ligation proximity assay (MLPA), and evaluated for the clonal changes through relapse. Single nucleotide variations SNVs were detected in 19% of diagnostic 15.3% of relapse samples. The CNAs were detected in 55% of diagnosed patients; most common affected genes were CDKN2A/2B, PAX5, and CRLF2. Relapse samples did not accumulate a greater number of CNAs or SNVs than the cohort of diagnostic samples, but the clonal dynamics showed the accumulation/disappearance of specific gene variations explained the course of relapse. The CDKN2A/2B were most frequently altered in relapse samples and 32% of relapse samples carried at least one CNA. Moreover, CDKN2A/2B alterations and/or JAK2 variations were associated with decreased relapse-free survival. On the other hand, CRLF2 copy number alterations predicted a better survival rate in B-ALL. These findings contribute to the knowledge of CDKN2A/2B and CRLF2 alterations and their prognostic value in B-ALL. The integration of genomic data in clinical practice will enable better stratification of ALL patients and allow deeper understanding of the nature of relapse.

Hepatosplenic Fungal Infections in Children With Leukemia-Risk Factors and Outcome: A Multicentric Study.

BACKGROUND: Invasive fungal infections, including hepatosplenic fungal infections (HSFI), cause significant morbidity and mortality in children with leukemia. There are not enough data to support for the best approach to diagnosis of HSFI in children, nor for the best treatment. PROCEDURE: In this multicentric study, we assessed the demographic data, clinical and radiologic features, treatment, and outcome of 40 children with leukemia and HSFI from 12 centers. RESULTS: All cases were radiologically diagnosed with abdominal ultrasound, which was performed at a median of 7 days, of the febrile neutropenic episode. Mucor was identified by histopathology in 1, and Candida was identified in blood cultures in 8 patients. Twenty-two had fungal infection in additional sites, mostly lungs. Nine patients died. Four received a single agent, and 36 a combination of antifungals. CONCLUSIONS: Early diagnosis of HSFI is challenging because signs and symptoms are usually nonspecific. In neutropenic children, persistent fever, back pain extending to the shoulder, widespread muscle pain, and increased serum galactomannan levels should alert clinicians. Abdominal imaging, particularly an abdominal ultrasound, which is easy to perform and available even in most resource-limited countries, should be recommended in children with prolonged neutropenic fever, even in the absence of localizing signs and symptoms.

Juvenile Myelomonocytic Leukemia in Turkey: A Retrospective Analysis of Sixty-five 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.

High Infection-Related Mortality in Pediatric Acute Myeloid Leukemia without Preventive Antibiotics and Antifungals: Retrospective Cohort Study of a Single Center from a Middle-Income Country.

OBJECTIVE: This study aimed to evaluate infection-related mortality in patients with acute myeloid leukemia (AML) treated without preventive antibiotics and antifungals in a middle-income country. MATERIALS AND METHODS: Infection-related mortality was evaluated retrospectively in 49 pediatric patients. RESULTS: A total of 173 chemotherapy courses were administered as first-line chemotherapy. Four patients died during induction: one patient due to intracranial bleeding, two patients due to typhlitis, and one patient due to invasive fungal infection with pulmonary vascular invasion and massive bleeding. Another two patients died with resistant disease. During consolidation there were four infection-related deaths and one death due to cardiotoxicity. In first-line chemotherapy mortality was 22% (11/49); infection-related mortality was 14% (7/49). Event-free survival and overall survival at 6 years were 42.9% and 61.2% (95% CI: 44-76 and 66-99 months), respectively. CONCLUSION: Due to considerable infection-related deaths, antibacterial and mold-active antifungal prophylaxis may be tried during neutropenic periods in pediatric AML.

The Association of Oral Vitamin D and Calcium Supplementation With Bone Mineral Density in Pediatric Acute Lymphoblastic Leukemia Patients.

AIM: To investigate the association of calcium (Ca) and vitamin D (vit D) supplementation with bone mineral density (BMD) in pediatric acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Group I (n=11): de novo ALL patients aged 1 to 18 years. Group II (n=46): pediatric ALL survivors in first complete remission and ALL patients on maintenance chemotherapy. We stratified group II into 3 subgroups according to the postdiagnosis period (group IIa: 8 to 24 mo, group IIb: 24 to 48 mo, group IIc: >48 mo). Group III (n=22): healthy siblings of group II. Daily oral vit D3 and Ca carbonate was given only to group I. In group I, BMD was measured at diagnosis and after completion of intensive chemotherapy (TP1 and TP2). RESULTS: A significant increase in Ca (P=0.024) and 25-OH vit D (P=0.01), and a decrease in magnesium (P=0.023) were detected at TP2 compared with TP1 in group I. Mean plasma levels of 25-OH vit D were <20 ng/mL in all the groups. Total body (P=0.005), total body less head (P=0.005), and L1 to L4 BMD Z scores (P=0.025) decreased significantly at TP2 compared with TP1. The lowest BMD scores were found at 8 to 24 months after diagnosis in unsupplemented patients. A gradual increase in BMD Z scores was shown, with the highest scores in group IIc. CONCLUSION: Vit D and Ca supplementation in pediatric ALL patients during intensive chemotherapy may not prevent bone mineral loss. BMD scores of pediatric ALL patients described by other studies, as a major decrease in the first 2 years and gradual increase afterward, was also observed in our patients.

Acquired von Willebrand syndrome in children with aortic and pulmonary stenosis.

INTRODUCTION: This prospective study was planned to investigate the frequency and relationship of acquired von Willebrand syndrome (AVWS) with aortic and pulmonary stenosis in patients. METHODS: A total of 84 children, ranging from two to 18 years of age, were enrolled in this study. Of these, 28 had isolated aortic stenosis, 32 had isolated pulmonary stenosis and 24 were healthy. Children with aortic and pulmonary stenosis associated with other congenital heart diseases were excluded. Children with hypothyroidism, renal or liver disease, malignancy or autoimmune disease were also excluded. Wholeblood count, blood group, factor VIII level, prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor antigen (VWF:Ag), ristocetin co-factor (VWF:RCo), and bleeding time using a platelet-function analyser (PFA-100) were performed in all patients. All of the children in the study underwent a detailed physical examination and echocardiographic evaluation. RESULTS: A history of bleeding was positive in 18% of the aortic stenosis group, 9% of the pulmonary stenosis group, and 4% of the control group. Seven of 60 (12%) patients had laboratory findings that implied a diagnosis of AVWS, and two of these (28%) had a history of bleeding. The frequency of AVWS was 14% in patients with aortic stenosis and 9% in those with pulmonary stenosis. CONCLUSION: AVWS is not rare in stenotic obstructive cardiac diseases. A detailed history of bleeding should be taken from patients with valvular disease. Even if the history is negative, whole blood count, PT and aPTT should be performed. If necessary, PFA-100 closure time and further tests should be planned for the diagnosis of AVWS.

Nonsyndromic Juvenile Myelomonocytic Leukemia With PTPN11 Mutation in a 9-Year-old Girl.

A 9.5-year-old girl with malaise, fever, massive hepatosplenomegaly, anemia, leukocytosis (37.9 × 10(9)/L), monocytosis (1.48 × 10(9)/L), and thrombocytopenia is presented. Hemoglobin F was increased (18%). Bone marrow erythroid/myeloid ratio was 40/1 with 7% myeloblast and 5% monocyte suggesting erythroleukemia or juvenile myelomonocytic leukemia (JMML). The patient had a fulminant course with respiratory compromise and died in 2 weeks before heterozygous somatic mutation in the PTPN11 gene was shown. JMML must be considered also in the patients older than 6 years. A cytopenic phase may precede JMML. Leucocytosis may be transient and there may be predominance of erythroid precursors in the bone marrow.

The Efficacy and Safety of Procedural Sedoanalgesia with Midazolam and Ketamine in Pediatric Hematology.

OBJECTIVE: The aim of this study is to investigate the efficacy and safety of sedoanalgesia performed outside the operating room by pediatricians trained in advanced airway management and life support. MATERIALS AND METHODS: Midazolam and ketamine were administered consecutively by intravenous route under cardiorespiratory monitoring for painful procedures of pediatric hematology. RESULTS: A total of 115 patients had 237 sedoanalgesia sessions. Sedation time was 24.02±23.37 s and sedation success was 92.5% (Ramsay scores of ≥5). Patient satisfaction was high. The recovery time was 28.81±14.4 min. Although statistically significant (p<0.01) increases in systolic and diastolic blood pressure, heart rate, and respiratory rate were observed without clinical importance, they improved without any intervention. No severe adverse events were observed. CONCLUSION: Sedoanalgesia with intravenous midazolam and ketamine for pediatric hematology and oncology patients' painful minor invasive procedures performed in an optimally equipped setting outside the operating room by pediatricians trained and certificated in advanced airway management and life support is effective and safe.

The effect of childhood cancer therapy on ovarian reserve and pubertal development.

The effects of childhood cancer therapy on ovarian reserve tests and on pubertal development within 5 years were compared with a control group. The study group was composed of 41 patients who underwent chemotherapy during pre-menarche (subgroup A; n = 15) and after menarche (subgroup B; n = 26); the control group was composed of 44 patients admitted with non-cancer related diseases (in total n = 85). Mean total ovarian volume and total antral follicle counts on ultrasound examination were significantly lower in the study group compared with the control group (3.5 ± 2.3 versus 5.2 ± 2.4 ml; P = 0.001; and 3.4 ± 3.3 versus 8.6 ± 3.5; P < 0.001, respectively). Mean FSH level was significantly higher in the study group (13.5 ± 16.2 versus 7.3 ± 2.7 mIU/ml; P = 0.017). Anti-Müllerian hormone levels in subgroup A were significantly higher than in subgroup B (1.8 ± 0.1 versus 1.5 ± 0.08 pg/dl; P = 0.034). In conclusion ovarian volume, antral follicle count and FSH can be used for evaluating the harmful effect of cancer chemotherapy on ovarian follicles. Post-menarche, Anti-Müllerian values reveal that ovarian follicles are more sensitive to the devastating effects of cytotoxic treatment.

Homozygous antithrombin deficiency in adolescents presenting with lower extremity thrombosis and renal complications: two case reports from Turkey.

We present 2 cases of lower extremity deep venous thrombosis in 2 gypsy adolescents from related families. The patients had low antithrombin activity levels and inherited homozygous antithrombin deficiency was confirmed by molecular analysis (Leu131Phe mutation). One patient had a history of nephrectomy at the age of 9 due to nonfunctioning kidney and 2 siblings died at 4 months of age. His mother had 3 fetal losses in the third trimester. The other propositus had an elder sister who suffered from postpartum deep vein thrombosis and pulmonary embolism. Heterozygous mutation was demonstrated in both parents.

Screening survivors of childhood acute lymphoblastic leukemia for obesity, metabolic syndrome, and insulin resistance.

Acute lymphoblastic leukemia (ALL) survivors were screened for risk factors of cardiovascular disease. Forty-four ALL survivors in first remission were enrolled. Twenty-six also received 12-18 Gy cranial radiotherapy (RT). Patients' body mass indexes (BMIs) at dignosis and during the study were compared. Metabolic syndrome (MS) evaluation was performed in patients, parents, and siblings older than 6 years. Homeostasis Model Assessment (HOMA) index of the survivors was also calculated. In survivors with impaired fasting glucose levels, oral glucose tolerance test (OGTT) was performed. Thyroid functions and IGF-1 and/or IGFBP-3 levels of the survivors who received cranial RT were evaluated. Median age of the survivors was 11.5 years (6-23). At diagnosis, mean BMI percentile was 46.7 (3-95) and mean z-score was -0.09 ± 1.14; during the study, these values rose to 71.1 ± 25.6 (3-100) and 0.8 ± 0.94, respectively (P < .001). One patient (2.2%) and nine survivors (20%) were obese at diagnosis and during the study, respectively (P = .005). Survivors had significantly higher BMI percentile and BMI z-score compared to their siblings (P = .006 and P = .011, respectively). The study group was small and we could not show a correlation of the patients' obesity with RT, thyroid functions, IGF-1, and IGFBP-3 levels. In three survivors (6.8%), there was MS. Maternal and paternal MS was not found as a risk factor for MS of the survivors (P = .1, P = .5, respectively). The HOMA index revealed insulin resistance (IR) in 12 (27.2%) of the survivors, whereas OGTT revealed abnormal glucose regulation and/or IR in four. As a conclusion, ALL survivors have high risk for obesity and MS.

Analysis of Chromosomal Aberrations and FLT3 gene Mutations in Childhood Acute Myelogenous Leukemia Patients.

OBJECTIVE: To identify the well-known common translocations and FLT3 mutations in childhood acute myelogenousleukemia (AML) patients in Turkey. MATERIAL AND METHODS: The study included 50 newly diagnosed patients in which t(15;17), t(8;21), and inv(16)chromosomal translocations were identified using real-time PCR and FLT3 gene mutations were identified via direct PCR amplification PCR-RE analysis. RESULTS: In all, t(15;17) chromosomal aberrations were observed in 4 patients (8.0%), t(8;21) chromosomal aberrationswere observed in 12 patients (24.0%), inv(16) chromosomal aberrations were observed in 3 patients (6.0%), and FLT3-ITD mutations were observed in 2 patients (4.0%); FLT3-D835 point mutation heterozygosity was observed in only 1patient (2.0%) patient. CONCLUSION: Despite of the known literature, a patient with FLT3-ITD and FLT3-D835 double mutation shows a bettersurvival and this might be due to the complementation effect of the t(15;17) translocation. The reportedmutation ratein this article (4%) of FLT3 gene seems to be one of the first results for Turkish population.