Is the absence of JAK2 mutation a risk factor for bleeding in essential thrombocythemia? An analysis of 106 patients.

BACKGROUND: JAK2(V617F) mutation has been recognized as a possible thrombotic risk factor in essential thrombocythaemia (ET). It's role is probably due to an increased myeloid proliferation and white blood cells (WBC) activation. Only few data are available about the effect of JAK2(V617F) on hemorrhagic risk. The aim of our study was to evaluate the influence of the mutational status on hemorrhagic complication. METHODS: We retrospectively analysed laboratory and clinical findings of 106 consecutive patients with ET to evaluate possible relationships between thrombosis, abnormal bleeding, peripheral blood count, overexpression of PRV1 and JAK2(V617F) mutational status. RESULTS: ON UNIVARIATE ANALYSIS WE FOUND: an association between JAK2(V617F) mutation and thrombotic events before or at diagnosis (p<0.003, OR=4.44, 95% CI=1.74-12.4); no statistical correlation between the median value of JAK2(V617F) burden and an increased risk of thrombosis (p=0.4, 95% CI= -22.8-10.4); significant relationships between mutated status and higher haematocrit, high WBC count and low platelet count; and a strong correlation between JAK2(V617F) and PRV1 overexpression (p<0.0001). Moreover, the presence of the JAK2(V617F) mutation and a WBC count greater than 8.4 x 10(9)/L were found to be independent factors related to thrombotic complications in multivariable analysis (p<0.006, OR=3.85, 95% CI=1.3-11.9; and p<0.002, OR=2.8, 95% CI=1.08-7.03, respectively). The prognostic impact of JAK2 mutation status and WBC count on thrombosis was evaluated in the whole cohort. Only new cases occurring in patients without previous thrombotic events were recorded for the analysis. The multivariable analysis showed a statistical correlation between the presence of the mutation and a WBC count greater than 8.12 x 10(6)/L and an increased risk of thrombosis if no cytoreductive treatment was started at diagnosis (JAK2(V617F) p=0.02; WBC p=0.02; OR=4.97; 95% CI=1.04-23.8). Finally, wild-type JAK2 was associated with a higher haemorrhagic risk (p=0.02) in univariate analysis but only a platelet count greater than 1,022 x 10(9)/L was associated with an increased risk of bleeding in the multivariable analysis. CONCLUSION: Our data confirm the role of both JAK2(V617F) as factor associated with an increased risk of thrombosis at the diagnosis and during follow-up in no treated patients. Moreover a WBC count over 8.4 x 10(9)/L1 was also strictly associated to an increased risk of thrombosis. Regarding bleedings, our statistical analysis allows to exclude the mutation protective role on haemorrhage.

Multidrug-resistant Escherichia fergusonii: a case of acute cystitis.

We report a case in which Escherichia fergusonii, an emerging pathogen in various types of infections, was associated with cystitis in a 52-year-old woman. The offending strain was found to be multidrug resistant. Despite in vitro activity, beta-lactam treatment failed because of a lack of patient compliance with therapy. The work confirms the pathogenic potential of E. fergusonii.

Evaluation of an automated closed fluid management device for processing expanded cytokine-induced killer cells to use in immunotherapy programs for cancer.

BACKGROUND: Cytokine-induced killer (CIK) cells are a heterogeneous population of immune cells derived from peripheral blood lymphocytes with a high proliferative potential ex vivo. This study shows a rapid and reproducible protocol for adoptive immunotherapy with CIK cells in patients with hematologic malignancies. For this purpose a new automatic cell processing device (CytoMate, Baxter Oncology) was tested to improve extensive manipulations of these cells. STUDY DESIGN AND METHODS: Twenty CIK expansions obtained from healthy donors and patients with hematologic malignancies were washed and refilled with fresh medium during culture with the CytoMate. Recovery, viability, and cytotoxic activity were evaluated. Six cryopreserved CIK procedures were thawed and processed for washing out dimethyl sulfoxide automatically. Recovery of cells, viability, and early apoptosis were measured immediately after washing, and cytotoxic activity against target cell lines K562 and Daudi was tested after short culture. RESULTS: Prewash volume of CIK cultures was 3600 mL (range, 1970-6000 mL). After automatic wash, the total CIK cell recovery was 85.3 percent (range, 78.5%-97.5%), and living cells were greater than 95 percent. After thawing, the median recoveries of total nucleated cells and natural killer T (NKT) cells were, respectively, 80.7 percent (range, 65%-95.5%) and 90.5 percent (range, 70.5%-98.5%). Thawed cells preserved their cytotoxic activity after cryopreservation (approx. 50% lysis at effector:target ratio of 40:1). CONCLUSION: The automatic wash with the CytoMate showed a good recovery of viable CIK cells during expansion and allowed an efficient manipulation of thawed cells. The use of this simple and efficient washing technique is suitable for clinical-grade processing in cellular therapy protocols.

Beta-lactam failure in treatment of two group G Streptococcus dysgalactiae subsp. equisimilis Pharyngitis patients.

We present two cases of exudative pharyngitis due to Streptococcus dysgalactiae subsp. equisimilis, Lancefield group G. While the participation of this organism as an agent of pharyngitis is well documented, we focus on failure of beta-lactam therapy, a phenomenon that is well described for pharyngitis due to Streptococcus pyogenes. Therefore, these case reports add to our knowledge of pharyngitis caused by non-S. pyogenes streptococci.

Long-term remission in BCR/ABL-positive AML-M6 patient treated with Imatinib Mesylate.

BCR/ABL-positive acute myeloid leukemia (AML) is a rare disease, characterized by a poor prognosis, with resistance to induction chemotherapy and frequent relapses in responsive patients. Here we report a case of BCR/ABL-positive AML-M6 who, after relapse, was treated with Imatinib Mesylate (600 mg/die) and within 4 months achieved a cytogenetic and molecular complete response. After more than 4 years of continuous Imatinib therapy, nested RT-PCR for BCR/ABL is persistently negative. The case reported shows that the response obtained with Imatinib Mesylate in BCR/ABL-positive AML may be long lasting, offering a chance of successful treatment for this poor prognosis group of patients.

Cancer therapy: switching off oncogenes.

Cancer derives from a cell clone that has accumulated genetic and epigenetic changes that influence its phenotype and finally enable it to escape from the normal controls of proliferation. A recent paper shows that, in myc-induced tumours, the inactivation of this oncogene produces the regression of the tumours and the differentiation of the tumour cells into mature osteocytes.1 In addition, a further reactivation of myc in these cells does not restore the malignant phenotype but induces apoptosis. This discovery could lead to an innovative therapeutic strategy.