Cornelia de Lange syndrome (CdLS) is a rare genetic condition related to mutation of various cohesion complex related genes. Its natural history is quite well characterized as regard pediatric age. Relatively little information is available regarding the evolution of the disease in young-adult age. In medical literature, only one specific study has been published on this topic. We report on our experience on 73 Italian CdLS patients (40 males and 33 females) with and age range from 15 to 49 years. Our results confirm the previous study indicating that gastroesophageal reflux disease (GERD) is the main medical problem of these patients in childhood and young-adult age. Other medical features that should be considered in the medical follow-up are tendency to overweight/frank obesity, constipation, discrepancy of limbs' length, epilepsy, hearing, and visual problems. Behavioral problems are particularly frequent as well. For this reason, every source of hidden pain should be actively searched for in evaluating a patient showing such a disorder. Finally, recommendations for medical follow-up in adult age are discussed. © 2016 Wiley Periodicals, Inc.

A multicentre study evaluating the presence of glycosil phosphatidyl-inositol (GPI)-negative populations was performed in 85 children with acquired aplastic anemia (AA). A GPI-negative population was observed in 41% of patients at diagnosis, 48% during immune-suppressive therapy (IST), and 45% in patients off-therapy. No association was found between the presence of a GPI-negative population at diagnosis and the response to IST. In addition, the response rate to IST did not differ between the patients who were GPI-positive at diagnosis and later developed GPI-negative populations and the 11 patients who remained GPI-positive. Two patients with a GPI-negative population >10%, and laboratory signs of hemolysis without hemoglobinuria were considered affected by paroxysmal nocturnal hemoglobinuria (PNH) secondary to AA; no thrombotic event was reported. Excluding the 2 patients with a GPI-negative population greater than 10%, we did not observe a significant correlation between LDH levels and GPI-negative population size. In this study monitoring for laboratory signs of hemolysis was sufficient to diagnose PNH in AA patients. The presence of minor GPI-negative populations at diagnosis in our series did not influence the therapeutic response. As occasionally the appearance of a GPI-negative population was observed at cyclosporine (CSA) tapering or AA relapse, a possible role of GPI-negative population monitoring during IST modulation may need further investigation.

No abstract

1269 Introduction. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic disorder characterized by the clonal expansion of a PIG-A mutated stem cell and consequent defective synthesis of glycosil phosphatidyl-inositol-anchored proteins, complement-mediated hemolysis, increased incidence of thrombosis, bone marrow failure. PNH and acquired aplastic anemia (AA) are closely related and a reciprocal progression is possible. A relative resistance of the PNH stem cell to the immune-mediated damage can explain the PNH clonal expansion in AA. High resolution flow cytometry analysis (FCA) has revealed a high incidence of minor PNH clones in adult AA patients at diagnosis, predictive for some Authors of a favourable response to the immunosuppressive therapy (IST) (Maciejevki et al, 2001; Ishiyama et al, 2003; Sugimori et al, 2006). “Pure” PNH is a very rare disease in children. Only a few studies have so far evaluated longitudinally PNH clones in pediatric AA patients. Materials and Methods. Ninety AA patients diagnosed in 8 AIEOP (Italian Association of Pediatric Hematology-Oncology) Centers (age at diagnosis 1–20 years, median =10.8, 51 severe AA, 30 very severe AA, 9 non severe AA) were studied: forty-one since diagnosis, 25 during IST, 20 off therapy and 4 selected cases after hematopoietic stem cell transplantation (HSCT). Among the patients followed since diagnosis, 8 received an HLA matched sibling donor HSCT as first line therapy, whereas the other 33 patients were treated with IST according to EBMT protocols (anti-lymphocyte globulin/anti-thymocyte, ciclosporin ± granulocyte colony stimulating factor). The study started in 1998. Peripheral blood PNH cells were detected by lack of CD59 expression on granulocytes by a two-color FCA for CD59 (clone p282-FITC Becton-Dickinson) and CD11b (clone D12-PE Becton-Dickinson); at least 105 cells were analyzed, for a total of 1104 tests. The presence of a population CD11b+/CD59- > 0.15% was defined as abnormal; the cut off value was established in 1998 by evaluating 87 normal controls (PNH clones: median = 0.001%, mean+2SD=0.10%). Since 2009 FCA results were confirmed by more sensitive techniques with three or six-color sequential gating analysis for CD45/33/66b or CD45/33/15/24/14/FLAER. Results. A PNH+ clone was observed in 15 patients (36.6%) at diagnosis (clone size 0.17–10.4%), in 10 patients (40%) during IST (clone size 0.16–12.6%) and in 8 patients (40%) off-therapy (clone size 0.16–4.0%). The presence of a PNH+ clone at diagnosis did not predict a favourable response to IST, both in ALG and ATG-treated patients. In 33 patients (16 at diagnosis, 9 in IST, 8 off therapy), the presence of the PNH clone was sporadic or intermittent, whereas in 13 patients (9 at diagnosis, 3 in IST, 1 off therapy) the clone persisted for more than 3 following controls (follow up 6–60 months). Among the 26 PNH- patients at diagnosis, in 10 a PNH clone (clone size 0.16–1.7%) appeared later during IST. Among the 25 patients studied during IST, in one patient PNH clone appearance was associated with the tapering of cyclosporine (figure 1), in two with the relapse when off therapy. In one out of 4 patients treated with HSCT, a PNH clone appeared at time of relapse and disappeared after starting IST with cyclosporine (figure 2). A mild hemolysis was observed in the only 2 patients with a major PNH clone (clone size 12.6 and 10.4% respectively). No thrombotic events were reported. Conclusions. We have observed a significant incidence of minor PNH clones in pediatric AA at diagnosis, as reported in adults. Whereas previous studies in adults correlated the presence of pre-treatment minor PNH clones with a favourable response to IST, we do not confirm those observations both in the present multi-centre as in our previous single-centre study (Timeus et al, 2010), in agreement with Yoshida et al (2008) and Scheinberg et al (2010). The appearance of a PNH clone in a PNH- patient at diagnosis is described as uncommon (Sugimori et al, 2009), however in our series this was observed in 38% of previously PNH- patients. In AA the presence of PNH clones seems related to complex interactions between stem cells, immune-mediated damage and immunosuppressive therapy. A periodic screening for PNH clones in patients with AA is recommended, permitting modulation in IST, early identification of major PNH clones and prompt diagnosis of a frank PNH. Disclosures: Timeus: Alexion Pharma Italy s.r.l.: Research Funding. Dufour:Pfizer: Consultancy.

IntroduzIoneLe talassemie sono disordini genetici in cui la produzione di emoglobina normale è soppressa, in parte o completamente, a causa di un difetto di sintesi di una o più catene globiniche. Vi sono diversi tipi di talassemie; quelle di maggiore rilevanza clinica comprendono le α-talassemie, le δβ-talassemie e le β-talassemie. Il trattamento raccomandato per la talassemia major comprende regolari trasfusioni di sangue, con intervalli da due a cinque settimane, per mantenere il livello di emoglobina (Hb) pre-trasfusionale al di sopra di 9-10,5 g/dl. Questo regime trasfusionale permette una crescita normale, assicura un'attività fisica normale e sopprime adeguatamente l'attività del midollo osseo [1].Tuttavia vi sono casi in cui la trasfusione non risulta praticabile, ad esempio per l'insorgenza di complicanze quali anemia emolitica autoimmune, reazioni avverse, reazioni trasfusionali febbrili non-emolitiche ed emolitiche, ecc.Riportiamo qui il caso di una ragazza affetta da β-talassemia (β+/β°) che presentava una situazione clinica molto grave dal momento che non poteva più ricevere ulteriori trasfusioni a causa di pregresse gravi reazioni emolitiche post-trasfusionali e che ha mostrato una risposta eccezionale a talidomide.Il caso che descriviamo di seguito è in parte ripreso da una precedente pubblicazione, un caso di beta-talassemia major resistente alle terapie convenzionali AbstractWe report the case of a 22-year-old woman from Albania, with thalassaemia major, in severe clinical condition who could no longer be transfused due to the occurrence of severe, acute, post-transfusional reactions. After 10 years of treatment, she failed to respond to hydroxyurea. When she received thalidomide, haemoglobin levels increased from 3.7 g/dl to 9 g/dl. Since then, at 22 months of follow-up, the therapy is still effective and well tolerated. The case gives the opportunity to describe the clinical use of thalidomide, and its potential in the management of beta-thalassaemia. Keywords: thalassaemia, thalidomide, foetal haemoglobin