© F e r r a t a S t o r t i F o u n d a t i o ndren who present over 4 years of age are in fact suffering from sporadic AML occurring in a child with DS, rather than from 'true' ML-DS. 18 In addition, ML-DS patients with a history of transient myeloproliferative disease have a significantly better outcome than children with ML-DS without documented transient myeloproliferative disease. 19 Until now, no other prognostic factors have been identified in ML-DS.The leukemic blasts from the majority of patients with ML-DS (72%) show additional cytogenetic changes apart from the constitutional trisomy 21. 20 A previous international-BFM study, performed by Forestier et al., showed that the most frequent gains involved chromosomes 8 (27%), 21 (23%), 11 (8.1%), and 19 (7.4%), whereas chromosomes X (3.2%; only females), 5 (1.5%), and 7 (2.2%) were commonly monosomic. The most frequent partial imbalances were duplication 1q (16%), deletion 7p (10%), and deletion 16q (7.4%). 20 However, the potential clinical impact of these cytogenetic abnormalities is not known and has not been well studied, mainly due to the small numbers of patients in individual series. 9,10,[20][21][22] In current treatment protocols of non-DS pediatric AML patients, stratification is based on cytogenetics and response to therapy. 23 In ML-DS, no prognostic cytogenetic groups have yet been identified, nor any other prognostic factors allowing a risk-stratified approach.We, therefore, conducted a large international study of clinical and outcome data including cytogenetic records from children with ML-DS collected from 13 collaborative study groups. Our aim was to identify differences in outcome related to cytogenetics and clinical characteristics in ML-DS. This was approached by analyzing differences in the cumulative incidence of relapse (CIR), reflecting leukemia resistance, and hence avoiding the influence of toxic (non-leukemic) events on survival estimates. This may result in risk-group stratification and risk-group directed therapy for these patients in the future. In addition, we compared the outcome of ML-DS patients in the different cytogenetic groups with that of non-DS AML patients from the same era treated on AML-BFM regimens as a reference cohort. Methods PatientsData on 451 patients with ML-DS were collected from 13 collaborative study groups participating in the International AML-BFM Study Group. For comparison, a reference cohort of non-DS AML patients (n=543) from the same treatment era, kindly provided by the AML-BFM Study Group, was used. This study was approved by the Institutional Review Boards in accordance with local legislation and guidelines.Patients were eligible if diagnosed between January 1, 1995 and January 1, 2005. Patients who were not treated with curative intent from diagnosis were excluded. The data collected at diagnosis comprised karyotype, sex, age, white blood cell (WBC) count, hemoglobin level, platelet count, immunophenotypic data and FAB morphology. In addition, we collected data on treatment, such a...

Few complete reports exist regarding treatment of venous thromboembolism in children undergoing chemotherapy. We designed this study to unify the treatment of venous thromboembolism in oncology pediatric patients at our department. At the same time, we wanted to evaluate the safety and efficacy of our newly designed treatment schedule. Data from pediatric oncology patients with deep venous thrombosis (DVT) treated at the Department of Pediatric Oncology, Brno, was collected prospectively over a 2-year period (1 January 2006 to 31 December 2007). All patients received low molecular weight heparin (LMWH) at an initial dose of 1.2-1.5 mg/kg body weight subcutaneously (s.c.) twice daily for the first 7-10 days. Afterwards, the dose was lowered to 1.5 mg/kg s.c. once daily. We kept this dose unchanged for a minimum of 3 months. For the first 6 weeks of treatment, the platelet count was maintained 20 x 10/l or more with no concomitant LMWH withdrawal. For the rest of the treatment, LMWH was interrupted once platelets dropped below 20 x 10/l. A total of 33 patients were followed for a median of 6 months. DVT was symptomatic in 15 of 33 patients (46%) and asymptomatic in 18 of 33 (54%) patients. Complete thrombus resolution occurred in 22 of 33 (67%) patients, partial or no recanalization was achieved in 11 of 33 (33%) patients. Eight patients (eight of 33, 24%) were diagnosed with postthrombotic syndrome (PTS). The risk of PTS was significantly higher for patients with symptomatic DVT than in those with asymptomatic DVT. Neither patency rates nor the risk of PTS showed a positive correlation with the achievement of therapeutic anti-Xa activity. Thrombocytopenia less than 20 x 10/l occurred at least once during LMWH treatment in 30/33 (91%) patients. None of the patients experienced severe bleeding, whereas mild bleeding episodes were observed in five of 33 (15%) patients. Our treatment schedule has proved to be both well tolerated and reasonably efficient in treating DVT in children undergoing chemotherapy. Further studies on larger patient groups are warranted.

A unique case of ALL in three monozygotic triplets diagnosed at the age of 24, 27 and 37 months is described. Archived bone marrow smears were available for molecular analysis of immunoglobulin heavy chain (IGH) and IGK genes and T-cell receptor (TCR)-delta and gamma gene rearrangements. A shared IGH rearrangement was found in triplets "A" and "B", and an identical rearrangement of TCR-delta in triplets "B" and "C". These data suggest a common, monoclonal initiation of ALL in one of these three triplets, followed by dissemination of clonal progeny to the other twins via vascular anastomoses within the single, monochorionic placenta that they shared in utero. Differences in IGH rearrangements in diagnostic samples also indicates divergent subclonal evolution of the original "pre-leukaemic" clone.

References RENAL VEIN THROMBOSIS WITH PULMONARY EMBOLISM: FIRST MANIFESTATION OF LUPUS NEPHRITISSystemic lupus erythematosus (SLE) is a chronic autoimmune disease that can affect almost any organ system, with renal involvement occurring in 90% of patients, while 50% of patients already have renal involvement at diagnosis. 1,2 Venous or arterial thrombosis can occur in SLE either as a result of anti-phospholipid syndrome or as a result of hypercoagulable state, related to nephrotic syndrome. 1,[3][4][5][6][7] The risk factors for thromboembolic complications include hypoalbuminaemia, proteinuria, low plasma anti-thrombin-III (AT-III), increased fibrinogen level, hypofibrinolysis, decreased functional activity of protein C and its cofactor protein S, high haematocrit, thrombocytosis, increased platelet aggregation, hyperlipidaemia and reduced plasma volume.1,3-7 An 11-year-old girl was admitted for a 2 months' history of fatigue and shortness of breath, and exercise-induced dyspnoea, headache and myalgia that occurred within the last 2 weeks. Three months prior to admission, there was a transient oedema of lower extremities. Her height was 141 cm (-1.2 standard deviation (SD) ), weight was 29 kg (-1.4 SD) and body mass index was 14.6 (-1.2 SD); she presented with normal respiratory rate of 20/min, tachycardia (heart rate 111/min), elevated blood pressure (141/88 mm Hg), pallor, oedema of eyelids and lower extremities, and left flank pain with loin tenderness on palpation. Laboratory findings revealed anaemia: red blood cells 2.89 ¥ 10 12 /L (normal 4.10-5.10 ¥ 10 12 /L) and haemoglobin 7.6 g/dL (normal 11.5-15.5 g/ dL . Anti-phospholipid antibodies were negative. Concerning hepatitis B and C status, hepatitis B surface antigen (HBsAg) and antibodies against hepatitis C (anti H-CV) antibodies were negative. There was mild hyperimmunoglobulinaemia (immunoglobulin (IgG) 22.9 g/L; normal 8.4-22.4 g/L) with elevated circulating immune complexes of 63 IU/L (normal <50 IU/L). C3 complement was in the normal range; C4 complement was low (0.13 g/L; normal 0.15-0.4 g/ L). Renal biopsy was performed on day 4, resulting in the histological diagnosis of membranous nephropathy. Immunofluorescence on renal biopsy was positive in all IgG classes and C3 at the basal membrane with negative fibrinogen. Arthritis was diagnosed on magnetic resonance imaging of the joints. Therefore, the girl had severe nephrotic syndrome with left RVT and bilateral pulmonary embolism, and she fulfilled 6 criteria for the diagnosis of SLE (polyserositis, nephropathy, arthritis, haemolytic anaemia and leukopenia, positivity of anti-Smith antibodies and positivity of anti-nuclear antibodies) of 11. 2,3Anti-thrombotic, immunosupressive and supportive therapy were started. She received low-molecular weight heparin (LMWH) 150 IU/kg/day for 3 weeks, three intravenous methylprednisolone pulses (30 mg/kg) followed by seven intravenous cyclophosphamide pulses (750-1000 mg/m 2 ) every 3-4 weeks, and further maintenance therapy with azathioprine (2 mg/kg/day) and...

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