Differences in the clinical course of heparin induced thrombocytopenia before and after the availability of HIT IgG class testing.

INTRODUCTION: To determine whether the HIT IgG class platelet factor 4 (PF4) enzyme immunoabsorbant assay (EIA) influenced the duration of parenteral direct thrombin inhibitor (pDTI) therapy or bleeding risk in patients started on pDTI for a presumed diagnosis of HIT. MATERIALS/METHODS: 187 patients started on pDTI for presumed HIT were assessed in two time periods before (period 1, n=88 patients) and after the introduction of an IgG-specific assay (period 2, n=99 patients). RESULTS: Patients in period 2 were treated with pDTI therapy for a median of 5 days less (p<0.0001) however the incidence of Grade III and IV bleeding episodes was not different. Bleeding was observed to occur early during the hospital course at a median of 2-3 days after initiation of the pDTI. The average pDTI drug acquisition cost was markedly decreased in period 2 when compared to period 1 (p<0.0001). CONCLUSIONS: Implementation of the IgG class HIT EIA resulted in a decrease in the number of days on a pDTI and a decrease in the average pDTI acquisition cost per patient without an observed change in serious bleeding events.

Obesity is associated with increased relative risk of diffuse large B-cell lymphoma: a meta-analysis of observational studies.

BACKGROUND: The relation between body mass index (BMI) and incidence of diffuse large B-cell lymphoma (DLBCL) has been suggested, but no systematic review has been undertaken. MATERIAL AND METHODS: We performed a literature search through December 2012. Meta-analyses were performed to quantify the relative risk (RR) of DLBCL incidence in overweight and obese persons compared with normal weight individuals using the random-effects model. Subset analyses were performed according to study design, sex, and geographic region. Overweight was defined as a BMI 25 to 29.9 kg/m(2), and obesity was defined as a BMI of 30 kg/m(2). Meta-regression, using an unrestricted maximum likelihood model, was performed to evaluate the linear association between BMI and odds of DLBCL. RESULTS: Our study included 6 case-control and 10 cohort studies. The RR of DLBCL in overweight individuals was 1.14 (95% confidence interval [CI], 1.04-1.24; P = .004), and in obese individuals, RR was 1.29 (95% CI, 1.16-1.43; P < .001). The RR of DLBCL in overweight men and women was 1.22 and 1.27, respectively. In overweight individuals, both prospective and case-control studies showed an RR of 1.13. The RR of DLBCL in obese men and women was 1.40 and 1.34, respectively. In obese individuals, the RR in prospective studies was 1.25 and in case-control studies it was 1.33. Meta-regression analysis showed a 14% increase in DLBCL incidence for each 10 kg/m(2) increase in BMI. CONCLUSION: An increased BMI is associated with higher RR of DLBCL regardless of sex. Also, there seems to be a linear association between BMI and DLBCL incidence.

PCI-32765: a novel Bruton's tyrosine kinase inhibitor for the treatment of lymphoid malignancies.

INTRODUCTION: There has been a significant paradigm shift in the manner in which lymphoid malignancies are treated and managed. Treatment has been moving away from conventional chemotherapy and towards targeted therapy. The success of new classes of agents such as monoclonal antibodies, proteasome inhibitors and immunomodulatory derivatives has sparked further searches for novel pathways to inhibit. The Bruton's tyrosine kinase (Btk) pathway is a downstream mediator of the B-cell receptor (BCR) pathway, which is crucial in B-cell production and maintenance, and a potential therapeutic target. AREAS COVERED: This review will summarize the current knowledge of the Btk pathway and its role in lymphoid malignancies. It will also discuss the present data about PCI-32765 in both the preclinical and clinical setting. EXPERT OPINION: PCI-32765 is an oral irreversible Btk inhibitor with high potency and both preclinical and clinical activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). Phase I studies have demonstrated that it is well tolerated and has an excellent safety profile. Further studies are ongoing as a single agent and in combination with other targeted and conventional therapies. PCI-32765 is a very promising targeted therapy, and the data from these trials will ultimately decide its future role and success.

Obesity but not overweight increases the incidence and mortality of leukemia in adults: a meta-analysis of prospective cohort studies.

The main objectives of the present meta-analysis of prospective cohort studies were to evaluate the role of obesity on the incidence and mortality of leukemia in adults. Obesity was associated with a relative risk (RR) of 1.26 (95% CI 1.17-1.37; p < 0.001) for leukemia incidence and 1.29 (95% CI 1.11-1.49; p = 0.001) for mortality. Obesity was also associated with an increased incidence of acute myeloid leukemia (RR 1.53, 95% CI 1.26-1.85; p<0.001), chronic lymphocytic leukemia (RR 1.17, 95% CI 1.08-1.27; p < 0.001), chronic myeloid leukemia (RR 1.16, 95% CI 1.04-1.30; p = 0.007) and acute lymphoblastic leukemia (RR 1.62, 95% CI 1.12-2.32; p = 0.009). The risk of incidence and mortality of leukemia in adults was consistently higher in obese men.