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The hypereosinophilic syndromes (HES) include a group of heterogeneous diseases characterized by the persistent increase of the number of eosinophils in blood and bone marrow. Few cases of paediatric hypereosinophilia (pHES) have been described in the literature. Early identification of pHES that may evolve towards a lymphomyeloproliferative disease is relevant in light of prognostic and therapeutic implications. Molecular features of 10 pHES patients were analysed at presentation and during their clinical course, including analysis of BCR-ABL1 and FIP1L1/PDGFRA fusion genes, quantitation of WT1 gene copy number and clonality of T-cell receptor (TCR) and immunoglobulin heavy chain (IGH). All patients had normal karyotype and germline TCR configuration. Five children showed IGH clonality at presentation: of these, two developed a B non-Hodgkin lymphoma and a B-lineage acute lymphocytic leukaemia at six and 12 months respectively, two spontaneously reverted to a polyclonal IGH profile during the follow-up, and the last one persisted with pHES without B-clonal evolution after 19 months. One patient had a PDGFRA/FIP1L1 fusion and achieved hematologic and molecular remission after imatinib therapy. IGH rearrangement was observed to be a frequent molecular feature of pHES and may precede B-cell clonal expansion and evolution into B-cell malignancies in children.

Idiopathic thrombocytopenic purpura in children remits spontaneously in the majority of cases but most children require treatment. Between 1995 and 2005, 265 children (0-15 years old) have been consecutively observed and treated: 28 children with high doses of methylprednisolone (HDMP) (15 mg/kgx4 days), 63 with HDMP (7.5 mg/kgx4 days), 37 with HD dexamethasone (DXM) pulses, 29 with low doses of MP, and 51 with different doses of intravenous immunoglobulins (IVIG) (0.4 or 0.8 g/kg). Fifty-seven children have not been treated because of a platelet count>or=10x10(9)/L and no significant bleeding. Two hundred forty-four (92.1%) children reached a persistent CR, 237 (89.4%) after a first-line treatment or the wait and see strategy. No statistically significant differences in CR related to different treatments have been observed. IVIG and HDMP (7.5 mg/kg for 4 days) are the best treatments to reach quickly safe platelet levels>or=30x10(9)/L (3-6 days) and CR (7-11 days). Among non-responding (NR) patients, seven have been splenectomized and three reached stable CR. These results emphasize differences with adult ITP.

The venous thromboembolism is a serious and complex pathological condition especially for its potential complications. It is related to both congenital and acquired factors. Among the congenital factors, different mutations have been identified leading to a reduced activity of enzymes (even higher than 50%) involved in the homocysteine-methyonine methabolic pathway, such as the methylenetetrahydrofolate reductase enzyme (MTHFR). The homozygotic TT genotype is found in approximately 10–12% of the population and is associated with a 25% higher homocisteine level in these patients than those without this mutation. The heterozygotic genotype is found in 40% of the population. The aim of this study is to define in children the correlation between venous thrombosis and MTHFR mutations. Between december 2002 and april 2008 nine children aged between 1–132 months were admitted in the Department of Hematology of Children Hospital Bambino Gesù in Rome. They were affected by deep venous thrombosis and were submitted to thrombophilic screening and vascular imaging. The MTHFR polymorphism C677CT was found in all the patients (four in homozygosis and seven in heterozygosis) and also in their parents. Four heterozygous and three homozygous patients presented increased plasmatic and urinary levels of homocysteine. Since venous thrombosis was only referred in the clinical history, two patients did not received treatments. Nine were treated with low molecular weight heparin (enoxaparin 100 U/kg s.c. × 2 daily), then seven continued the treatment with oral anticoagulant for 6–12 months and all of them performed long term profilaxis with folic acid and B group vitamins. Only one patient presented further thrombotic event and restarded the oral anticoagulant therapy. These data confirm that the measurement of homocysteinemia and MTHFR may be indicated in unexplained idiopathic venous thrombosis or recurrent episodes or venous thrombosis occurred at an early age or at an uncommon site. It is to be discussed whether to perform anticoagulant profilaxis in all patients with MTHFR mutation, in homozygosis or heterozygosis, with or without hyperhomocysteinaemia, with previous thrombotic events, with other thrombotic risk factors (pregnancy, oral contracceptives, sepsis and immobilization). In addition in presence of hyperhomocysteinemia, it might be reccomended to perform therapy with folic acid and B6 vitamin.

Introduction: Myelodysplatic syndromes (MDS) are characterized by ineffective and dysplastic hematopoiesis and peripheral cytopenias. Moreover, autoimmune phenomena, mainly directed against RBC, are described in early MDS, i.e. refractory anemia (RA) and RA with ringed sideroblasts (RARS). We already reported an autoimmune reactivity against erythroblasts in 50% of RA and RARS adult patients, along with peripheral signs of hemolysis, increased BM erythroblasts; and efficacy of steroid therapy. It has become evident that there are significant differences between MDS in children and adults. Most importantly, the cure is the aim of therapy in all children with MDS, while therapeutic possibilities are often limited in adults. MDS and myeloproliferative disorders are rare in childhood and there is no widely accepted system for their diagnosis and classification. Aims of this study were: To evaluate BM autoimmunity in 9 pediatric patients with MDS by the same method used in adults, named mitogen-stimulated-direct antiglobulin test (MS-DAT), to correlate BM MS-DAT positivity with clinical parameters and therapy. Methods: MS-DAT was performed by stimulating BM with PMA and PHA and antibodies were detected in supernatants by competitive solid phase ELISA. Results: We demonstrated the presence of anti-erythroblast autoimmunity in roughly half of pediatric MDS patients, as already reported in adult MDS. More precisely, 4 out of 9 patients showed positive MS-DAT in BM. At variance with adult MDS, positive patients do not show increased erythroblast counts and peripheral signs of hemolysis (i.e higher reticulocytes, indirect bilirubin, and LDH, and lower haptoglobin) compared with MS-DAT negative ones. One of the four patients with anti-erithroblasts autoimmunity has RA, the other three show peripheral and medullary signs of refractory cytopenia with multilineage dysplasia (RCMD). Two out of four were successfully treated with steroid therapy (with a follow up respectively of 6 and 1 months). Discussion: Although the short follow up and the limited number of patients does not allow definitive conclusions, we retain useful to investigate anti-erythroid autoimmunity in all pediatric MDS in order to identify selected patients with low risk MDS who display autoimmune phenomena. In these cases immunosoppressive therapy may be an effective treatment option.