Yair Herishanu

Richter syndrome (RS) is the development of an aggressive lymphoid malignancy, in chronic lymphocytic leukemia (CLL). Most are diffuse large B-cell lymphomas (DLBCL), however in 10-15% of RS, there is transformation to Hodgkin lymphoma, termed "Hodgkin variant" (HV). In the present retrospective study we summarize the Israeli experience with HV-RS, and analyze demographic data, relevant laboratory and clinical parameters, and outcome. We collected and analyzed data from 119 patients with RS from 12 Centers in Israel during 1996-2010 and identified 16 cases with "Hodgkin's variant". The median age was 58 years, and 67% were males. The median time from CLL diagnosis to development of HV was 5.9 (range=0.8-11.9) years and the median survival was 39.5 months, compared to 9 months for the cases with RS-DLBCL. Hodgkin variant appears to differ from DLBCL-RS and is clinically less aggressive. However, compared to de novo Hodgkin's lymphoma, HV-RS has a worse prognosis.

Janus kinase-2 (JAK2) is mutated in a high proportion of patients with polycythemia vera and in a smaller number with essential thrombocythemia and primary myelofibrosis. Mutated JAK2 is an important diagnostic marker for myeloproliferative neoplasm (MPN) and may also play a major role in the pathogenesis of MPN. To evaluate the prevalence of mutated JAK2 (JAK2-V617F) among patients with major intraabdominal vein thrombosis who had normal blood counts at diagnosis of the initial event. The medical records of patients who presented with a major intraabdominal venous thrombosis and normal peripheral blood counts were obtained. JAK2-V617F mutation status was determined by real-time polymerase chain reaction. Twenty-two patients were available for this analysis and 9 (41%) were found to have JAK2-V617F. Patients with positive JAK2-V617F were younger and had more frequent clinical splenomegaly than those with wild-type JAK2. A high proportion of patients presenting with "idiopathic" major intraabdominal vein thrombosis and normal blood counts carry JAK2-V617F. We recommend searching for the mutation in this clinical setting to detect patients with occult MPN.

We report the case of an 80-year-old man treated for follicular grade 3B non-Hodgkin’s lymphoma (NHL). Immunochemotherapy consisted of rituximab (375 mg/m²) and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) every 21 days. Since the patient complained of mild dyspnea on effort with bilateral basilar crackles audible on auscultation, PET-CT was performed and showed disappearance of the initial 18F-FDG uptake, but new abnormal sites of 18F-FDG uptake were evident in the sub-pleural areas of the lung, mostly on the right side. After starting the fifth cycle of rituximab-CHOP, the dyspnea worsened. Chest-X ray and HRCT were consistent with an interstitial infiltration, including sub-pleural air-space consolidation, and “ground-glass” opacities, small pulmonary cysts and thickening of the interlobular septa were also seen. Trans-bronchial biopsy was performed and revealed interstitial inflammation of the lung parenchyma, as well as swelling and hyperplasia of atypical type II alveolar cells. Alternative diagnoses than drug-related pulmonary toxicity are discussed, and a literature review is provided.

The white blood cell count and its differential are established inflammation-sensitive biomarkers with a proven prognostic value in the field of atherothrombosis. However, the WBCC count range and determinants havenot been explored in the absence of a significant inflammatory response. To analyze the WBCC range and determinants in a large Israeli sample of individuals, excluding patients with a significant inflammatory response. WBCC and differential count reference ranges were determined in a large sample of apparently heal participants with high sensitivity C-reactive protein concentrations below 10 mg/L. Linear regression models were used to identify the determinants of the WBCC. The central 95% areas under the distribution curves were established for each gender. The study population comprised 8247 individuals (5391 males and 2856 females). The main laboratory and clinical variables found to affect the WBCC were gender, hemoglobin level, smoking status, triglycerides, and body mass index (all P < 0.001). Similar results were obtained for the differential count. The reference ranges for men and women were 3.6-9.9 and 3.4-10.0 x10(3) microl, respectively.The reference ranges for currently smoking men and women were 3.6-11.5 and 3.6-11.2 x10(3) microl, respectively, and were significantly higher compared with those of the never smokers and past smokers. We have demonstrated new limits of normal values for the WBCC in apparently healthy individuals who lack a significant "background" acute-phase response in a large Israeli sample. Our data might be useful for the risk stratification of apparently healthy individuals in the field of atherothrombosis.

Background:  In the light of an emerging role for early‐mid treatment 18 F‐deoxyfluoroglucose positron emission tomography (FDG‐PET) as an important prognostic indicator in aggressive non‐Hodgkin’s lymphoma (NHL) , we attempted to determine whether a simple parameter, such as the early‐mid treatment CRP (C‐reactive protein) level, could also be utilized as a significant prognostic factor in aggressive NHL.Patients and methods:  Serum CRP levels were monitored in 55 patients with aggressive NHL. The lowest value of the early mid‐term CRP levels recorded was compared with the interim PET‐CT results, as well as with the clinical course and eventual outcome.Results:  During chemotherapy, the lowest value of early‐mid treatment CRP levels significantly predicted the results of the interim FDG‐PET (P = 0.04 with an odds ratio of 1.13). Patients who did not achieve an early‐mid treatment CRP level of P = 0.001) as well as a reduced overall survival (OS) (P = 0.016).Conclusions:  The early‐mid treatment serum CRP level is a prognostic factor in aggressive NHL. Patients who do not achieve an early‐mid treatment level of <5 mg/L have quicker disease progression or earlier relapse and also appear to have an inferior OS.

Abstract:  Background: Recently, it was shown that fat tissue produces and releases inflammatory cytokines, and that obesity may be regarded as a state of low‐grade inflammation. In this regard, we aimed to establish an association between obesity and persistent leukocytosis. Patients and methods: We present clinical observations of obese subjects primarily referred for further evaluation of leukocytosis without a cause and validated the link between leukocytosis and elevated body mass index (BMI) in a cross‐sectional study. Results: During 1999–2005, 327 patients were referred for further investigation because of persistent leukocytosis. Of these, 15.3% were asymptomatic obese, mostly females, with mild persistent neutrophilia accompanied by elevated acute‐phase reactants. After careful evaluation, no recognized cause for leukocytosis was found other than the fact that the patients were obese. During a mean follow‐up of 45.6 months, the leukocytosis and the elevated acute‐phase reactants persisted and no new causes for leukocytosis were evident. Furthermore, in a cross‐sectional analysis of 3716 non‐smoker subjects, 62 were found to have leukocytosis. Compared with the population with a normal white blood count range, these subjects with leukocytosis had higher BMI, serum C‐reactive protein (CRP) levels, waist circumference, and neutrophil and platelet count (all P < 0.0005). After logistic regression analysis, only BMI was shown to be associated with leukocytosis (P < 0.0005). Conclusions: Obesity is recognized as a possible cause for reactive leukocytosis. Awareness of this ‘obesity‐associated leukocytosis’ may help the clinician to avoid more extensive and unnecessary diagnostic work‐up, particularly in similar obese subjects.