ALBERT

Description: BACKGROUND. Germinal Center (GC) experience is a basic prognostic feature in B-CLL. Patients with VH-mutated GC-experienced CLL have a good prognosis while those with VH-unmutated GC-inexperienced CLL have a poor prognosis. In a recent study we demonstrated that telomere length (TL) of lymphoproliferative disorders strongly correlates with GC, pre-GC or post-GC origin (Ladetto M et al, Blood 2004). Aims of this study were to further define the relationship between TL and VH mutational status in B-CLL and correlate both these parameters with clinical outcome. PATIENTS AND METHODS. 109 B-CLL patients have been analyzed for telomere restriction fragments (TRF) length and are under evaluation for VH mutational status. All samples were taken at diagnosis or during the "watch and wait" phase. Male were 68, females 41. Median age was 62 years (range 34–87). Fifty-three patients were in stage A, 30 patients were in stage B and 16 were stage C according to Binet staging system. Our patient population has been monitored for a median time of 53 months (range 1–290). Sixty-three patients have been already treated for their disease while 46 have not required treatment, so far. TRF length was evaluated by Southern blot and VH mutational status by direct sequencing, as previously described (Ladetto M et al, Blood 2004). The standard cut-off of 2% deviation from any germ line VH sequence was employed to define VH mutational status. Survival analyses were performed using the Kaplan-Meier method. RESULTS. Overall, median TRF length was 5898bp (range 1737–14837bp). There was no correlation between TRF length and patient age, sex or stage. A cut-off of 4500bp discriminated two subgroups of patients characterized by different clinical outcome in terms of time to first treatment (TTFT) and time to disease progression (TTP) following first line treatment. Patients with TL 〈 4500bp had a median TTFT of 16 months and a median TTP of 14 months while patients with TL 〉 4500bp had a median TTFT of 36 months and a median TTP of 50 months (p

Description: Background: Ischemic stroke is rare in young adults, with an incidence of about 10-15% of all the ischemic strokes. In about one third of these patients a cause is missing. Among patients with antiphospholipid antibodies syndrome (APS), stroke is the first thrombotic event in about 13% of cases. Aims of our project were: to evaluate the prevalence of antiphosfolipid antibodies (aPL),to investigate on the prevalence of conventional risk factors and to define the radiological characteristics of the ischemic lesion. Materials and methods: this is a no profit, observational multicenter prospective study. Inclusion criteria were: age older than 18 and younger than 55 years, informed written consent, a clinical and radiological diagnosis of stroke. Patient's data were collected at diagnosis and after 30 days from stroke. If any aPL positivity was found the patient was referred to our service to further/eventually confirm the diagnosis of APS. For each patient these data were collected: age, sex, body mass index, personal and familial history, concomitant co morbidities and therapies, cardiovascular risk factors, drug abuse. CT scan or angioCT or MRI was always performed at diagnosis, aPL profile was determined at diagnosis and eventually confirmed after 12 weeks according to the Sapporo criteria. None of the patients had a previous diagnosis of APS. Results: enrolled patients from January 2017 to December2018 were 46 out of 425 ischemic stroke (10.8%). We found 11/46 aPL positivity patients. Among these patients, 7 were confirmed at 12 weeks (15%). Baselines characteristics of the study population are detailed in table 1. We found a high prevalence of associated conventional cardiovascular risk factors: hypertension (56%), dyslipidemia ( 50%), obesity (55%), smoke ( 52%). We didn't find any correlation between APS and a clear radiological pattern on MRI and CT scan. Conclusions: Prevalence of APS was 15% in our cohort of young patients with stroke, 85% of which had an high risk aPL profile. The detection frequency is similar to the recent APS-ACTION and literature findings. In our cohort stroke was a relapse of a previous ischemic event in 24% of the patients, while in 15% there was a stroke's relapse. Even if these data should be confirmed with a wider number of patients, it seems to be useful to evaluate the presence of aPL in a young patient with ischemic stroke . Disclosures No relevant conflicts of interest to declare.

Description: Polycythemia vera (PV) is a myeloproliferative disorder strongly related to a mutated state of JAK2 tyrosine kynase. Several guide-lines have been published on diagnostic criteria and disease management. However, it is not well known if these recommendations are actually followed in the common clinical practice. Moreover, the recent large ECLAP study (Di Nisio et al.: Br J Haematol 2007) questioned the former strong recommendation of keeping the hematocrit (Hct) value below 0.45. We analysed 290 patients with a PV diagnosis made from January 1995 to December 2006 in different hematological institutions and referred to a single transfusion centre for phlebotomy. Among the whole casistics, 210 patients only satisfied 2001 or 2007 WHO diagnostic criteria for PV. This selected group of patients underwent further evaluation of clinical outcome. JAK2 V617F mutation was found in 80/83 of these patients. Median follow up from diagnosis was 68 months (range 13–161). The 210 patients included 115 males and 95 females with a median age of 65 years (range 18–92). Known risk factors at diagnosis comprehended history of previous thrombosis in 34 and concomitant cardiovascular risk factors (diabetes, smoking habit, hypertension, dyslipidemia) in 124 patients. According to the thrombotic risk stratification (Finazzi et al.: Blood 2005), 36 patients were in the low risk group, 29 in the intermediate one and 145 in the high risk group. All patients received phlebotomy at least in the first month from diagnosis. Eighty patients proceeded with phlebotomy only, whereas 130 also received a cytoreductive treatment for at least 6 months. Almost all patients (205: 98%) received either anti-platelets (195) and/or anti-coagulant (30) therapy. The main cytoreductive treatment was hydroxyurea (HU), used by 127 (97%) patients. In particular, HU was the only cytoreductive agent for 107 patients. Other drugs included pipobroman (18 patients), busulfan (5 patients), alpha interferon (2 patients) and 6-thioguanine (1 patient), used for intolerance or suboptimal response to HU. A thrombotic event was observed at diagnosis in 21 patients (10%). A correlation was observed between thrombosis at diagnosis and both thrombocytosis 〉 600 × 109/l (p: 65 years (p: 〈 0.001), history of thrombosis before diagnosis (p: 0.05) and high risk score according to thrombotic risk stratification (p: 0.05). Forty-five patients (21%) displayed post-diagnosis thrombotic events at a median time of 41 months, which correlated to age at diagnosis 〉 65 years (p: 0.006) and high thrombotic risk score (p: 0.04). Leukemic evolution occurred in 4 patients (2%), while secondary myelofibrosis and non-hematological neoplasia were observed in 8 and 11 patients, respectively. Chemotherapy administration did not affect neither overall nor thrombosis-free survival but correlated to neoplastic events (p: 0.05). Median Hct during follow up was kept at the recommended value 〈 0.45 in 31 patients only (15%). Sixty-three % of patients maintained a median Hct value between 0.45 and 0.48 whereas 21.5 % had median Hct value 〉 0.48. A Hct value 〈 0.48 positively affected overall (p: 0.02) but not thrombosis-free survival. A possible advantage of keeping Hct value 〈 0.45 could not be demonstrated due to the small number of patients in this group. In conclusion, diagnostic procedures were not found adherent to WHO indications in 80/290 (27%) patients with hypothetical PV diagnosis and in most of patients the Hct value could not be maintained below the recommended value. The importance of JAK2 evaluation as a diagnostic criteria was further underlined by the detection of V617F mutation in 96 % of the screened patients with a confirmed diagnosis of PV. Our casistics confirmed the role of known prognostic factors as age, previous thrombosis or concomitant cardiovascular risk factors, while the optimal Hct value during follow up (〈 0.45 or 〈 0.48) and the true advantage of cytoreductive treatments remain to be established.