We report a case of EBV encephalitis in a seven-yr-old child with Ph+ ALL. Two months after an allogeneic HSCT from his HLA mismatched mother, the patient showed an altered sensorium, generalized seizures, and a left hemiparesis. Brain MRI demonstrated multiple lesions highly suggestive for viral encephalitis. Blood and CSF PCR analyses were negative for the most common viruses involved in immunocompromised patients including EBV. A cerebral biopsy was performed, which showed intense gliosis and perivascular lymphocytic cuffing. PCR analysis performed on brain tissue was positive only for the EBV genome, while extensive investigations for other viral infections were negative. The patient's neurological symptoms rapidly worsened and he died two months later. This case report suggests that in patients presenting neurological and radiological signs of encephalitis after an HSCT, an EBV involvement should be considered, even in the absence of CSF and blood PCR virus detection.

The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9-81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6-176.0), with 2-year disease-free survival rate of 45.1% (95% confidence interval 39.6-50.6). The median overall survival was 14.4 months (range 0.3-177.0), with 2-year overall survival rate of 42.2% (95% confidence interval 37.5-46.9). At univariate analysis for CR achievement, age < 60 years (P < .001), World Health Organization classification (P = .045), low-risk karyotype (P < .001), no high-risk karyotype (P = .006), positivity for AML-ETO (P = .004)/CBFβ-MYH11 (P = .003)/CD15 (P = .006)/CD11b (P = .013), negativity for FLT3-ITD (P = .001), Hb > 8 g/dL (P = .020), and white blood cell < 50 × 10 /L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 10 /L (P = .017), and low-risk/no high-risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement. The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported.

No abstract

Background: Identifying perioperative bleeding risk in pediatric patients undergoing major surgery is challenging because personal history is often not sufficiently informative and laboratory tests are also more susceptible to pre-analytical variables. Children with low Willebrand add further uncertainty in the treatment options. The aim of this study was to evaluate practices to assess hemorrhagic risk and manage bleeding prophylaxis in children with low von Willebrand factor levels (30 and 50 IU/dL; low VWF), known von Willebrand disease (VWD) or healthy controls undergoing ear, nose and throat (ENT) surgery. Methods: In this retrospective observational study, data from consecutive paediatric patients undergoing ENT surgery between January 1, 2010 and December 31, 2017 at the Turin Paediatric Hospital were analysed. All statistical analyses were performed using STATA (StataCorp. 2013. Been Statistical Software: Release 13. College Station, TX: StataCorp LP). Demographic and clinical characteristics of patients were assessed using the absolute frequencies and percentages for qualitative variables and percentiles for quantitative variables. The risk of bleeding was estimated from the number of patients who experienced bleeding within 21 days as a proportion of the number of patients subjected to surgery. 90% confidence intervals (90% CIs) were estimated for the evaluation of bleeding risk, using the Jeffreys method and any differences in the risk of bleeding between patient groups were tested using a proportions test. To investigate any factors associated with the therapeutic strategy used, multinomial logistic regression models were conducted. Results: Major perioperative bleeding was seen in 6.3% (5/79) of low VWF patients, 3.0% (35/1152) of healthy controls and 20.0% (5/25) of patients with VWD. In low VWF patients, perioperative bleeding prophylaxis was given to 59.5% and included subcutaneously desmopressin (n=21) and VWF-containing concentrate (n=26). Oral or intravenous tranexamic acid was administered to all low VWF patients. Of these patients, one major hemorrhagic event occurred in patients who did not receive prophylaxis and the remaining events occurred in patients treated with VWF-containing concentrate. In patients who received a VWF-containing concentrate, lower VWF ristocetin cofactor levels were observed compared with patients who received desmopressin or were untreated during surgery. No differences in clinical and laboratory features were observed between patients with low VWF treated with desmopressin and those who were untreated. Conclusions: Patients with low VWF have a higher risk of perioperative bleeding compared with healthy controls but a significantly lower risk compared with patients with VWD. The perioperative management of these patients is complex with a high risk of overtreatment. In our experience the caution of keeping the VWF-containing concentrate in the operating room available for use in case of bleeding appears to be a balanced approach. Prospective randomized studies to identify accurate methods of assessing bleeding risk and evaluate the most effective perioperative bleeding prevention are warranted. Essential bibliography: Ruchika Sharma and Veronica H. Flood. Advances in the diagnosis and treatment of Von Willebrand disease. Hematology American Society of Hematology Education Program 2017:379-384 Sadler JE. Low von Willebrand factor: sometimes a risk factor and sometimes a disease. Hematology American Society of Hematology Education Program 2009:106-112 Rodeghiero F, Tosetto A, Abshire T, et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost. 2010;8(9):2063-2065. Casey LJ, Tuttle A, Grabell J, et al. Generation and optimization of the self-administered pediatric bleeding questionnaire and its validation as a screening tool for von Willebrand disease. Pediatr Blood Cancer. 2017;64(10) Mannuccio Mannucci P, Kyrle PA, Schulman S, Di Paola J, Schneppenheim R, Cox Gill J. Prophylactic efficacy and pharmacokinetically guided dosing of a von Willebrand factor/factor VIII concentrate in adults and children with von Willebrand's disease undergoing elective surgery: a pooled and comparative analysis of data from USA and European Union clinical trials. Blood Transfus. 2013;11(4):533-540 Disclosures No relevant conflicts of interest to declare.

The CD15 antigen is an adhesion molecule normally expressed on neutrophils that mediates phagocytosis and chemiotaxis: it is also expressed on blasts of patients with acute myeloid leukemia (AML). Its prognostic role has been tested in different studies, including or not acute promyelocytic leukemia (APL), with conflicting results and its significance still remains unclear. To address this issue, a cohort of 460 AML patients of all ages with, the exclusion of APL, [M/F 243/217, median age 50.6 years (range 0.9 – 81.2)] intensively treated at our Institute between 1/1999 and 12/2010 was retrospectively evaluated. Overall, 61 patients (13.3%) evolved from a documented myelodysplastic phase (MDS): AML-ETO, CBFβ-MYH11, FLT3-ITD and NPM were positive in 35/438 (8.2%), 30/427 (7.0%), 55/409 (13.4%) and 67/200 (14.6%) evaluable patients, respectively. A favorable karyotype was found in 90/436 patients (20.6%) while an unfavorable profile was documented in 60/436 cases (13.8%). CD15 positivity was found in 171/406 evaluable patients (42.1%): in particular, CD15 was positive in 13/42 evaluable patients evolved from MDS (31.0%) compared with 158/364 evaluable patients without previous MDS (43.4%) (p=0.123). Induction treatments consisted of anthracycline (ACY) + cytarabine (Ara-C) +/- etoposide in 448 patients and of a fludarabine-based regimen in 12 patients. A complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6 – 176.0), with a 2-year disease-free survival (DFS) rate of 45.1% (95% CI 39.6 – 50.6). The median overall survival (OS) was 14.4 months (range 0.3 – 177.0), with a 2-year OS rate of 42.2% (95% CI 37.5 – 46.9). Among the several variables tested at univariate analysis for CR achievement, age <60 years (p<0.001), WHO classification (p=0.045), low-risk karyotype (p<0.001), no high-risk karyotype (p=0.006), positivity for AML-ETO (p=0.004)/CBFβ-MYH11 (p=0.003)/CD15 (p=0.006)/CD11b (p=0.013), negativity for FLT3-ITD (p=0.001), Hb >8 g/dl (p=0.020) and WBC <50 x 109/l (p=0.034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (p=0.002 – OR 2.96,95%CI 1.51 – 5.89), age <60 years (p=0.008 – OR 2.28, 95%CI 1.23 – 4.21), WBC <50 x 109/l (p=0.017 – OR 2.34, 95%CI 1.16 – 4.73) retained an independent prognostic role on CR achievement. In conclusion, the baseline assessment of CD15 positivity could have a role in the risk evaluation for CR achievement in non-APL AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biological features already reported. Disclosures Breccia: novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy. Latagliata:Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Shire: Consultancy.