ALBERT

Description: Introduction Juvenile myelomonocytic leukemia (JMML) is a unique, aggressive hematopoietic disorder of childhood caused by excessive proliferation of cells of monocytic and granulocytic lineages. Childhood JMML is classified as a bridging disorder between myelodysplastic syndrome (MDS) and myeloproliferative diseases.More than 95% of JMML patients are diagnosed under the age of six years. Children with JMML mostly present with hepatosplenomegaly, lymphadenopathy, bleeding, anemia, fever, recurrent infections, rash, failure to thrive and pulmonary disease. Approximately 90% of patients carry either somatic or germline mutations of PTPN-11,K-RAS,N-RAS,CBL or NF-1 in their leukemic cells. Aim We want to describe the clinical and laboratory features in 55 cases of JMML seen at the Hacettepe University Pediatric Hematology Department during a 18 year period (January 2000-June 2018). Patients & Methods There were 38 males and 17 females aged between 1 months and 168 months (median 36 months). On admission mean Hb, WBC and platelet was found to be 9.1±1.9 g/dl (range 5.7-14.6g/dl), 38.7±4.3 x10 3 µ/L (range 1.4 - 214 x10 3 µ/L) and 156 ± 7.8x 109 range (8-1598x109/L) , respectively.Results of cytogenetic analysis showed monosomy 7/7qdel in 16 cases.Somatic PTPN11 mutation was found in 23 children whereas somatic KRAS mutation in 7 and germline mutation in one case, somatic NRAS mutation in 3 cases and c-CBL mutation in 5 cases. On admission 49% of patients had no blast cells on the peripheral blood smear.But 3 of 55 patients had 100% blast cells in peripheral blood smear.Monosomy 7 mutation was positive in all of these 3 patients and one of these case had an history of familial MDS and a positive GATA mutation, one other had NF-1 mutation.All three patients were died despite hematopoietic stem cell transplantation(HSCT). On admission, 7 out of 55 patients had 〉30% blast cells in bone marrow aspiration and 3 of them had %100 blast cells on the peripheral smear. The rest of this group except one who had a positive KRAS mutation and diagnosed as AML-M4 were treated with HSCT and 4/6 were stil alive.On the other hand, 7 out of 55 patients had 20-30% blast cells in bone marrow aspiration on admission and none of these patients had neither monosomy 7/7qdel nor trisomy 8 mutation. c-CBL mutation was found to be positive in 5 case and all were still alive (two siblings with c-CBL and one other patient had a diagnosis of juvenile xanthogranulamatosis), and one patient with c-CBL mutation had a diagnosis of portal hypertension.On the other hand two siblings with monosomy 7 have a diagnosis of GATA mutation and both were died after HSCT.Almost 40% of this pediatric group (20/55) were died after a median follow up time 16 months (1-211 months). Discussion JMML is a clonal hematopoietic disorder of infancy and early childhood which results from oncogenic mutations in genes involved in the Ras pathway and allogeneic HSCT remains the only curative treatment more than 50% of patients.However, the timing of diagnosis and treatment is critical to outcome.Prompt HSCT is recommended for all children with NF1, somatic PTPN11 and KRAS mutations, and for most children with somatic NRAS mutations.'Watch and wait' strategy is usually for the group of patients with germline CBL mutations, specific somatic NRAS mutation, and in Noonan syndrome patients, cause spontaneous resolution has been reported in this group. Our results were compatible with the literature , however it seems that in our group despite allogeneic HSCT, relapse is the main treatment failure. Disclosures Niemeyer: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Description: Pediatric myelodysplastic syndrome (MDS) is a group of heterogeneous clonal disorder with lesser frequency compared to adults. Additionally, there is much rare data in pediatric age group in relation to presentational findings and treatment. The clinical and laboratory data, in addition to therapeutic interventions and outcomes of 47 patients in a single centre who were diagnosed between January 2001-May 2014 were summarized. Median age of the study group was 2.8 years (0.1-16.8). The most common complaints at presentation included fever (27%), fatigue (17%), bleeding (15%), abdominal distention (13%), in addition to other rare presentational complaints including pallor, rash, vomiting, irritability, jaundice, stridor, abdominal pain and easy bruising. The underlying disorder was established as: neurofibromatosis in 5, Down syndrome in 3, secondary to prior chemotherapy in 2 (ALL and PNET), Fanconi anemia in 1, Jacobsen syndrome in 1, Klinefelter in 1. Final diagnosis was MDS in 22, JMML in 19, hypoplastic MDS in 4 and chemotherapy related MDS in 2. Median Hb, WBC, thrombocyte counts at presentation were 8.7 g/dl (4.1-12.7), 10.3x109/L (1.3-117) and 55x109/L (4-1515), respectively. Of the mutations studied related to MDS in 22 of the patients, k-ras positivity was the most common (23%). The most common cytogenetic abnormality was chromosome 7 related abnormalities (25%). Of the patients, 21 (45%) are alive and of these alive patients 62% are alive subsequent to hematopoietic stem cell transplantation. The patients with pediatric MDS may present with various complaints and they may have underlying genetic diseases causing propensity for MDS. The survival is better among patients who underwent hematopoietic stem cell transplantation. Disclosures No relevant conflicts of interest to declare.

Description: Background : Mastocytosis is a rare disease in children and it usually resolves by adolesence.However; it causes anxiety in parents and should be taken into consideration in patients with cutaneous eritematous lesions. Aim: To find out the systemic mastocytosis patients who apply to pediatric hematology , pediatric allergy and dermatology policlinics. Material and Methods: The files of 24 patients diagnosed with mastocytosis between January 2018 and August 2018 in our clinic were retrospectively analyzed. Results: All patients had cutaneous mastocytosis, 14 patients had urticaria pigmentosa and 9 patients had solitary mastocytoma and one patient had diffuse cutaneous mastocytosis. The male-female ratio was: 2/1. The median age for onset of disease was 7,2 (0-48 months )months. The patients had different types of skin findings such as macules (n=16), plaques(n=6), papules(n=4) and bullae(n=3). None of the patients had anaphylaxis but two patients had angioedema. The diagnosis was confirmed with skin biopsy in 8 patients. The other were diagnosed due to typical history and physical examination. None of the patients had cytopenia, hepatosplenomegaly.Only one patient triptase level 〉20 ug/l. The bone marrow aspiration and biopsy was done to 3 patients and all were normal.The patients were treated with H2 antihistaminics, local moisturizing creams and topical corticosteroid drugs in case of undesirable pruritus. Conclusions: Most cases of childhood mastocytosis are observed in the form of cutaneous mastocytosis and ıt usually resolves by adolescence. If the patients have cytopenia, hepatosplenomagaly or triptase level 〉20 ug/l the bone marrow aspiration and biopsy is recommended. Disclosures No relevant conflicts of interest to declare.

Description: Disseminated intravascular coagulopathy and bleeding are common manifestations of acute promyelocytic leukemia(APL) which are both associated with significant mortality and morbidity. However APL related thrombosis is very rare and majority of the reported cases are adults in the literature. In the past 14 years, 14 cases with APL were found in our hospital database.There were 6 female and 8 male children with a mean age of 10.7±4.6 years (2-17y). Here, we report two pediatric APL case who presented with cerebral thrombosis at the initial presentation. 8/14(57%) had disseminated intravascular coagulation at the initial presentation and one patient had intracardiac and cerebral sinovenous thrombosis during the induction period. Case 1:A 13-year-old boy was admitted to our hospital with a complaint of headache for two days. His physical examination revealed a papilledema and cranial MRI did show sinovenous thrombosis. At the time of the evaluation his WBC count was found to be low and there were myeloid blasts on his peripheral smear,bone marrow aspiration was done and diagnosed as translocation t(15;17)positive APL. He remain in remission more than 4 years without any event however deceased after relapse. Case 2: A 8-year-old boy was admitted to our hospital with a complaint of right hemiparesis, there was a thrombotic occlusion of the left middle cerebral artery associated cerebral infarct on his MRI.His WBC was 5.9x109/l with 76% blasts and bone marrow aspiration and flow-cytometry were both compatible with APL. Patient died after 2 weeks of admission because of thrombosis and bleeding. The incidence of APL related thrombosis was 4.5 and 5.6% in two large adult cohorts. Both arterial and venous thrombosis may ocur in patients with APL. To the best of our knowledge there were limited number of pediatric APL case reports in the literature who presented with thrombosis. In our small group of pediatric APL patients 14% presented with thrombosis and the total number of thrombotic events were found to be 28% during the follow up. Disclosures No relevant conflicts of interest to declare.

Description: Infantacute lymphoblastic leukemia (ALL) is a rare disease and consist of 4-5% of all childhood ALL. Despite improved survival rates of childhood ALL, infants with ALL have a worse prognosis . There were 206 patients diagnosed with ALL at Hacettepe University, Pediatric Hematology Department between 1 January 2008 and 31 December 2016, 11 out of 206 (5.3%) were diagnosed as infant ALL. We aimed to evaluate clinical findings, laboratory results and treatment outcome of our infant ALL patients retrospectively. There were 9 boys and two girls with a median age of 8 months (range 1-12 months) and nine out of 11 (82%) were older than 6 months of age at the initial diagnosis. Interestingly 2 of 3 siblings born from spontaneous triplet pregnancy diagnosed at the same time when they were 7 months old while the other sibling diagnosed 4 months later when he was 11 months old. Physical examination revealed hepatosplenomegaly in 10 out of 11 patients and 1 patient had extramedullary involvement with subcutaneous nodules on the forehead. On admission median WBC count was found 202x10-9/L (range 37.4-739x10-9/L) with a median hemoglobin level 9 g/dL (range 2.6-12.9 g/dL) and median platelet count 81x10-9/L (range10- 314x10-9/L). Immunophenotyping revealed CALLA+ B cell leukemia in 3 patients, CALLA- B cell in 6 patients and T cell leukemia in 2 patients. Cytogenetic analysis showed t(4;11) positivity in 4 patients and 3 of them were spontaneous triplets. Initial CNS involvement were positive in 2 of the patients. Eight patients (73%) were treated with Interfant protocols (Interfant 99 (n=4), Interfant 06 (n=4)) and 3 patients received Modified St. Jude Total XV protocol. Relapse were observed in 2 patients (one had both CNS and bone marrow relapse one year after the completion of chemotherapy and the other experienced an early bone marrow relapse at the 7thmonth of the treatment). Hematopoetic stem cell transplantation (HSCT) was performed in five patients from matched related donor (n=2), unmatched related donor(n=1), and matched unrelated donor(n=2). Moreover, relapse after HSCT was observed in 2 patients 3 and 4 months later; one received second transplantation and survived while the other died because of progressive disease. Four of the five patients who had HSCT survived 74 months, 45, 18 and 13 months after the initial diagnosis, respectively. After a median of 18 months (range 4- 74 months ) follow-up period 6 patients are alive (45 %) and on remission 4 after HSCT and 2 with only chemotherapy. Infant leukemia usually presents with high hyperleucocytosis and extramedullary involvement. The prognosis is poor and international colloborative studies reprorted that 4 year -event free survival rates were between 28-54%. Our results suggest that bone marrow transplantation seems to be a good and efficient choice of treatment. However there is still a big issue to decide which patient should go under transplantation and more studies are needed to reevaluate the eligibility criteria for HSCT in this group of patients. Moreover to the best of our knowledge infant leukemia in triplets without monozygocity were first time reported. Disclosures No relevant conflicts of interest to declare.

Description: In TM chronic anemia, blood transfusions and iron over load result in impairments in many organs. Little is known about the changes in blood pressure (BP) patterns of children with TM. To evaluate ABPM changes and associated laboratory and clinical features in children with TM. ABPM was performed in 20 TM patients with no cardiac or renal dysfunction (12M, 8F; 11.3+/−3.8 years), and 20 healthy children (11M, 9F; 11.6+/−2.4 years). Blood and timed urine samples were collected for hematological and biochemical tests. [Dipping: a fall in the mean systolic (diastolic) BP during nighttime of more than 10% of the mean daytime systolic (diastolic) BP]. Mean daytime (8AM–8PM) and nighttime (midnight to 6AM) systolic (SBP) and diastolic (DBP) blood pressures were comparable. No patient in TM and control group had mean 24-h, day time, nighttime SBP or DBP above 90th percentile. SBP and DBP- loads were always less than 20% in control group. In TM group: SBP-load was more than 20% in 1, and 1 patient during daytime and nighttime, respectively; and DBP- load was more than 20% in 1, and 2 patients during daytime and nighttime, respectively. The percentage of systolic (60% vs 35%; p:0.102) and diastolic (30% vs 20%; p:0.118) non-dippers among TM patients were higher, compared to control group. In TM group: the percentage of systolic (80% vs 40%; p:0.063) and diastolic (50% vs 10%; p:0.044) non-dippers among older (12–16 years) patients were higher, compared to younger (5–11 years) patients. There was no association between non-dipping pattern and hemoglobin, ferritin or albuminuria level. Our preliminary results suggest that BP anomalies in TM occur before the development of cardiac or renal dysfunction. There is an association between non-dipping and the age of the patient. Long-term follow-up will make clear whether abnormalities in ABPM patterns have a predictive value in the development of renal and cardiac dysfunction in TM patients.

Description: Introduction: Hematopoietic stem cell transplantation (HSCT) is being increasingly used as curative therapy for severe disorders of the hematopoietic system and transfusional iron overload (TIO) contributes considerably to treatment-related morbidity and mortality after HSCT. Management of iron overload in the post-HSCT setting may be complicated since the use of therapeutic phlebotomies is often not feasible due to ongoing anemia and compliance to deferoxamine is low. Studies that evaluate the safety dose of deferasirox (DFX), which is the most commonly used chelation therapy, in this setting are limited. Purpose & Methods: This is a prospective, phase 2, multicenter, single-arm study to evaluate the efficacy and safety of iron chelation with oral DFX in beta-thalassemia major (TM) patients who have undergone HSCT. The study was conducted in 7 centers from Turkey. The primary objective was to evaluate if DFX could provide clinically safe chelation in a target pool of 26 pediatric patients with TIO within a minimum of 6 months and maximum of 2 years after related/unrelated HSCT. Patients had to be transfusion-independent and have iron overload at screening defined by serum ferritin (SF) of 〉1000 μg/L or cardiac MRI T2*

Description: Introduction: Childhood acute lymphoblastic leukemia (ALL) treatment with St. Jude Total therapies showed superior outcome with event-free and overall survival rates 85.6 ± 2.9% and 93.5 ± 1.9%, respectively. Here, we studied prognostic features and the outcome of Turkish children with newly diagnosed ALL treated with modified St. Jude Total Therapy XV Protocol. Patients and methods: There were 182 newly diagnosed ALL patients aged 1-18 years old and treated with modified Total Therapy XV between 1 January 2008 and 30 January 2016. According to our previous successful results with high dose methylprednisolone (HDMP), each patient received 7 days of HDMP as an initial treatment and randomized at doses of 20 mg/kg/d or 10mg/kg/d HDMP, not exceeding at maximum 1000 mg MP. After the first 7-day steroid treatment, concomitant chemotherapy was given and the steroid doses were tapered to 10mg/kg/d and 5mg/kg/d during the next week in each group, respectively. Afterwards, the whole group received 2 mg/kg/d MP for the following two weeks. Also, there were a third group received lower doses (