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In non-Hodgkin lymphomas (NHLs), the bone marrow (BM) involvement is a sign of extensive disease and the iliac crest BM biopsy (BMB) is the established method for the detection of BM infiltration. However, iliac crest BMB is associated with a high rate of false negative results. We assess the ability of 18-F-fluorodeoxyglucose positron emission tomography (F-FDG PET) scan to ascertain the presence of BM involvement in NHL.After reviewing charts of histologically proven NHLs, 97 patients were eligible for our study. All patients were examined by whole-body F-FDG PET scan for initial staging, and all had unilateral posterior iliac crest BMB. BM involvement was established after the result of unilateral posterior iliac crest BMB and image-guided BMB after positive F-FDG PET scan in selected patients.Our data demonstrate an overall sensitivity of 79% for the F-FDG PET scan detecting BM involvement in all patients and specificity of 91%. Further analysis revealed no significant difference in the ability of the F-FDG PET scan to detect BM involvement between the indolent-NHL and the aggressive/highly aggressive-NHL groups (sensitivity P = 0.23, specificity P = 0.64).F-FDG PET scan shows potential to detect BM involvement in NHL. In particular, image-guided repeat BMB should be considered in patients with negative initial iliac crest BMB, whose F-FDG PET scan demonstrates BM involvement in a different site.

A simple and sensitive spectrophotomteric method has been developed for the determination of Sertraline in pharmaceutical and blood sample. The current method is depend upon the reaction between the sertraline and chloranilic acid in slightly alkaline medium, giving a purple colour complex having maximum absorbance at 527.5 nm. The reaction is selective for sertraline with 0.01mg/mL.The colour reaction obeys Beer’s law from 0.1mg to 5mg/mL of sertraline and relative standard deviation is 0.19%. The quantitative estimation of sertraline in blood sample is also studied. Key Words: Spectrophotometric, Sertraline, chloranilic acid, Beer’s law, quantitative estimation . e-mail: asif_hanif101@yahoo.com INTRODUCTION Sertraline Hydrochloride is a Selective Serotonin Reuptake Inhibitor (SSRI) and is a tricyclic compound with antidepressant activity 1 . The antidepressant effect of sertraline is presumed to be linked to its ability to inhibit the neuronal reuptake of serotonin 2 . It has only very weak effects on norepinephrine and dopamine neuronal reuptake. At clinical doses, sertraline blocks the uptake of serotonin into human platelets

Introduction Patients with solid tumors and venous thromboembolic episodes (VTE) have a high risk of recurrence and bleeding during oral anticoagulant treatment. However, we are unaware of studies expressly evaluating such risks in patients with lymphoma. Therefore, we conducted a retrospective study to determine the frequency of such complications during treatment of lymphoma patients who develop VTE. Methods Charts of patients with histologically proven non-Hodgkin lymphoma and Hodgkin lymphoma were retrospectively reviewed and patients with their first acute symptomatic VTE episode were identified (49 non-Hodgkin lymphoma, 8 Hodgkin lymphoma). Recurrence of VTE episodes and major and minor bleeding during treatment with warfarin or low molecular weight heparin (LMWH) were recorded. Results All 57 patients were initially treated with high-dose-adjusted intravenous heparin or body-weight-adjusted LMWH. Forty-six patients were started on oral warfarin and 11 patients continued LMWH. Recurrent VTE episodes occurred in 14 of 46 patients on warfarin therapy, whereas major bleeding was documented in 6 of 46 patients, and minor bleeding in 9 of 46 patients. Recurrent VTE episodes occurred in 1 of 11 patients treated with LMWH, whereas major bleeding occurred in 0 of 11 and minor bleeding in 3 of 11 patients. Conclusions Lymphoma patients treated with warfarin experienced a 30.4% rate of recurrent thrombosis and 13% major bleeding. During this treatment most (65%), but not all, bleeding and thrombotic complications occurred with an international normalized ratio within the therapeutic range. The percentage of serious complications (recurrent VTE and major bleeding) during warfarin use was 44.5%, and the death rate was 6.5%, compared with 9% and 0%, respectively, during use of LMWH.

Melanomas of the respiratory tract are usually metastatic in origin, and finding a primary melanoma is very rare. We report the case of a 60-year-old man who presented with a 2-month history of cough with associated weight loss. The histopathologic findings were consistent with those of a melanoma. Before considering the diagnosis of primary melanoma of the lung, an extensive diagnostic workup was done to rule out metastasis from an occult primary tumor. In addition, previously reported cases of primary lung melanoma were reviewed, and the established criteria for determining the primary site were applied. Because the precise etiology has not yet been elucidated, the possible mechanism is discussed.

Monoclonal gammopathy of undetermined significance (MGUS) is defined by the presence of a serum M-protein at a concentration of 3 g/dL or less, with less than 10% plasma cells in the bone marrow, and the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the plasma cell proliferative process. The annual risk of MGUS progressing to a symptomatic plasma cell proliferation or other related malignancy is approximately 1%. The association between malignancy and venous thromboembolism (VTE) is well recognized. In this retrospective study of MGUS patients, VTE was seen in 8% (9/112) of patients, a rate that is 22.8-fold higher than that in the general population (P is less than .001). Although many studies have identified VTE as a marker for subsequent malignancy, we did not find a significant difference in the incidence of VTE as a function of the risk factor group.

Aromatase inhibitors (AIs) are an effective treatment for postmenopausal women with hormone receptor-positive breast cancer. However, patients receiving AIs report a higher incidence of musculoskeletal symptoms and bone fractures; the mechanism and risk factors for this correlation are not well studied. The aim of this study was to correlate these musculoskeletal symptoms and bone fractures in patients receiving AIs with bone mineral density (BMD), previous tamoxifen use, and administration of calcium/bisphosphonate (Ca/Bis).We reviewed charts of 856 patients with hormone receptor-positive nonmetastatic breast cancer seen at our institution between January 1999 and October 2007. A total of 316 patients met the inclusion criteria of treatment with one of the AIs foror = 3 months and availability of a dualenergy X-ray absorptiometry (DEXA) during this treatment. Arthralgia, generalized bone pain and/or myalgia, bone fracture after beginning AIs, any tamoxifen treatment, and Ca/Bis therapy were recorded.Our study demonstrates a significant association between symptoms and DEXA-BMD results (P.001). Similarly, the group receiving tamoxifen before AIs had fewer patients with arthralgia or generalized bone pain/myalgia or bone fracture (P.001). Furthermore, the group receiving AIs plus Ca/Bis had more patients without musculoskeletal symptoms and had fewer fractures. Finally, the group receiving steroidal AIs compared with nonsteroidal AIs had more patients with arthralgia or generalized bone pain and/or myalgia, and bone fractures (P.001).Patients on AIs who develop osteoporosis are at increased risk of musculoskeletal symptoms and bone fracture. Comedication with Ca/Bis reduces the likelihood for osteoporosis and musculoskeletal symptoms. Patients who received tamoxifen before AIs were less likely to develop AI-related musculoskeletal symptoms. We recommend that patients on AIs should be offered Ca/Bis to reduce the incidence of musculoskeletal symptoms and fracture, especially if patients are receiving steroidal AI and/or did not receive tamoxifen before AIs.

Abstract 3661 Poster Board III-597 Introduction BMB is frequently performed during the staging process of patients (pts) with HL. Previous data suggested routine use of this procedure may be unnecessary. The Ann Arbor classification is currently used to detect pts requiring BMB, despite sensitivity (sen) of 100%, specificity (spec) is only 40%. We sought to determine whether a modified IPS [Hasenclever and Diehl (1998)] would yield greater spec while maintaining good sen. Methods We retrospectively reviewed charts of 1215 histologically proven HL pts from Jan 2000-Dec 2008 at Cleveland Clinic Taussig and Moll Cancer Centers. Of 1215 pts, 1089 had BMB (90%). 876 pts were included in our study. 213 were excluded due tor un-interpretable BMB or missing data. Each component of IPS was equally weighted such that one point is assigned to each positive variable [male sex, age ≥45, albumin (alb) Result 88 pts (10%) had BMI, we used a modified IPS formally by calculating a score that uses “weights” based on the results of a multivariable model including all 7 factors and the relative magnitude of the associated regression coefficients (RC), [modified IPS= WBC+2x(sex+age+hem)+3x(stage+alb)+4xlymph]. This model suggests lymphopenia has a stronger impact on the presence of BMI, while leukocytosis has the least impact. The percentage of BMI was 0.1,17,48, and 87 % for pts with a score of 0-8, 9-10, 11-12, and >12 respectively. Using a score of >8 as a rule for BMI, sensitivity was 99% and specificity was 87%. The prevalence of BMI by histology was 4% lymphocyte-rich, 5% nodular sclerosis, 20% mixed-cellularity and 21% lymphocyte-depleted, further analysis showed using modified IPS, sensitivity and specificity were similar across all types of histologies. Conclusions Using a modified IPS of > 8 for predicting BMI in HL doubled the spec associated with Ann Arbor classification. The implementation of modified IPS is a practical and reliable tool that will allow physicians to predict BMI in HL pts. Therefore eliminate unnecessary painful procedure in many pts. Disclosures: No relevant conflicts of interest to declare.

Introduction: MGUS is considered to be a pre-malignant condition, and previous studies have reported VTE as a marker for a subsequent malignancy. We conducted a retrospective study to evaluate the incidence of VTE among MGUS patients (pts) and to correlate this incidence with different risk groups for developing malignancy in MGUS pts. Methods: The complete medical records of all MGUS pts at Cleveland Clinic Cancer Center at Fairview hospital from Jun/2005–Jun/2008 were retrospectively reviewed. Of 237 pts diagnosed with MGUS, 112 pts (65 males, 47 females) were eligible for our study. These pts were divided into 2 risk groups: low risk (LR)/low-intermediate risk (LIR) group (78 pts.) and high intermediate risk (HIR)/high risk (HR) group (34 pts) based on the Risk Stratification Model using three adverse risk factors; serum M-protein level ≥ 3 gm/dL, non-IgG MGUS, and an abnormal kappa/lambda free light chain ratio. Only pts with ≥ 12 months follow up were included. Exclusion criteria included a personal history of inherited thrombophilia, previous episode of VTE or anticoagulant treatment, thrombocytosis, malignancy, and renal impairment. Risk factors (RF) for VTE were identified in each pt and categorized into four groups: no RF, 0; one RF, 1; two RF, 2; and > 2 RF, >2. RF included > 48 hours of immobilization, surgery in the past 3 months, current hospitalization at the time of VTE occurrence, oral contraceptive use, and congestive heart failure. Objectives: 1. To compare the proportion of pts with MGUS who developed VTE to the proportion of pts in the general population who developed VTE. 2. To compare VTE incidence between the two risk groups. Results: During the study period, 9 pts with MGUS experienced VTE. In the general population, the incidence of VTE is 117/100,000 persons/year (from literature). Therefore, the proportion of pts in the general population over 3 years was 117/100000 × 3 =0.0035. The proportion of VTE in MGUS pts, adjusted for 3 years, of 0.080 is significantly higher than that for the general population (p

Background: Essential thrombocythemia (ET) and Polycythemia vera (PV) are clonal diseases, present at diverse ends in the spectrum of MPD’s. Recently, there has been an increased interest in the association of leukocytosis, thrombocytosis and the presence of JAK2V617F mutation with the risk of thrombosis in patients with ET. Although, leukocytosis and the presence of JAK2V617F mutation has been proposed as prognostic indicators for thrombosis, the correlation of thrombocytosis with thrombotic risk remains unclear. In the current study, we examined the association of the predictors of thrombosis – leucocytosis, thrombocytosis and JAK2V617F mutation, in patients with both ET and PV in a community hospital cohort. Methods: We conducted a retrospective review of all patients with ET and PV receiving treatment at the Cleveland Clinic Cancer Center at Fairview Hospital between January 2001 and December 2007. Data on risk factors (leucocytosis, thrombocytosis and JAK2V617F mutation status) at diagnosis were collected. Pearson Chi-square test was used to analyze the association between the above-mentioned variables and thrombosis (both arterial and venous). In addition to analyzing the entire cohort, separate subgroup analyses were also performed on the individual groups (patients with PV and those with ET). All analyses were performed using SAS software (Cary, NC). Results: One-hundred and eight patients were identified. The median age was 67 years (range 28–89), and 57 patients (53%) were female. WBC counts and platelet counts were found to be positively associated with the presence of thrombosis (p=10,000 were significantly higher than that for the group with WBC counts =400,000 were significantly higher than that for the group with platelet counts Table 1: Association of risk factors and thrombotic events among patients with MPD. THROMBOSIS Yes No RISK FACTORS Level Total N (%) N (%) P value Leukocyte Count . . . . . =10,000/mm3 65 50 76.9 15 23.1 Platelet Count . . . . . 0.027 =400,000/ml 80 48 60 32 40 JAK2V617F mutation . . . . . Among the cohort with ET (N=59) leucocytosis was significantly associated with thrombosis. The proportion of patients with thrombosis for the group with WBC counts >=10,000 were significantly higher than that for the group with counts =10,000 were significantly higher than that for the group with a count Conclusion: Leucocytosis, thrombocytosis and the presence of JAK2V617F mutation are significant risk factors for thrombotic events among patients with MPD. Additionally, while in both subgroups (patients with PV and ET) leucocytosis and the presence of the JAK2V617F mutation were significant risk factors for thrombosis, thrombocytosis was not found to be significantly associated with presence of thrombosis. Even though the results of this retrospective analysis deserve to be confirmed by prospective studies, it strengthens the view that in the treatment of MPD’s (specifically ET), panmyelosuppression would be more efficacious than targeting platelets alone as a modality of therapy for MPD.

Introduction: Patients (pts) with solid tumors and venous thromboembolic episodes (VTE) have a high risk of complications (recurrent VTE/bleeding) during oral anticoagulant treatment. However, few data are available in pts with lymphoma. We conducted a retrospective study to determine the frequency of complications during oral anticoagulant treatment in lymphoma pts. Methods: Charts of histologically proven non-Hodgkin’s (NHL) and Hodgkin lymphoma (HL) pts at our institution from January 1998 through April 2007 were retrospectively reviewed. After excluding pts with thrombocytosis, solid tumors, hypercoagulability or previous treatment with anticoagulants, pts with their first acute symptomatic VTE were identified (49 NHL, 8 HL). 31 were males and 26 females, with an age range of 40–89 years. The first symptomatic VTE was defined as lymphoma associated if the VTE occurred within 3 months before or after the biopsy diagnosis of the lymphoma but before chemotherapy. These VTE were confirmed by contrast venography or doppler ultrasound for venous thrombosis (neck and upper-lower extremities) and chest computed tomography, ventilation/perfusion scan, or pulmonary angiography for pulmonary embolism. Major bleeding was defined as bleeding that required transfusion, caused a drop of hemoglobin > 2 g/dL, or occurred in critical sites. Minor bleeding was defined as any overt bleeding that required stopping the anticoagulant treatment but not fulfilling the definition of major bleeding. Results: All 57 pts were initially treated with high dose adjusted intravenous heparin or body weight adjusted low molecular weight heparin (LMWH). 46 pts were started on oral warfarin during the first 10 days of the initial treatment witch was continued for at least 3 months after discontinuing heparin. 11 pts received continuing LMWH and no warfarin. Recurrent VTE occurred in 14/46 pts on warfarin therapy. The international normalized ratio (INR) was within the therapeutic range (2.0–3.0) in 10/14 pts, and below the therapeutic INR (< 2.0) in 4/14 pts. Death was directly correlated to recurrent VTE (massive pulmonary embolism) in 2 pts in the warfarin treated group; a third death was caused by massive intracranial bleeding. Major bleeding was documented in 6/46 pts (4 pts had an INR within the therapeutic range, 2 had INR > 3), and minor bleeding in 9/46 pts. Recurrent VTE occurred in 1/11 pts treated with LMWH, major bleeding in 0/11 and minor bleeding in 3/11 pts with no deaths. Conclusions: Previous studies showed an overall incidence of 27.1% recurrent thrombosis and 5.4% major bleeding in pts with malignancy treated with oral anticoagulant for VTE. Our study showed 30.4% recurrent thrombosis and 13% major bleeding in pts with lymphoma. Most bleeding and thrombotic complications occurred with an INR within the therapeutic range (65%). The percentage of serious complications was very high during the use of warfarin (43.5%), and the death rate 6.5%, compared to 9% and 0% during the use of LMWH. A high failure rate of oral anticoagulant treatment in pts with lymphoma suggests the need for alternative treatment. Since the number of pts in this retrospective study is small, a prospective randomized, controlled study comparing warfarin with LMWH is indicated.

Introduction: The myelodysplastic syndromes (MDSs) include a group of marrow disorders united by the common feature of ineffective hematopoiesis. Primary MDS is defined as occurring in the absence of exposure to ionizing radiation, chemotherapeutic agents or myelotoxic drugs. Secondary MDS occurs in the presence of such exposure. The reported hematological side effects of hydroxychloroquine include aplastic anemia, agranulocytosis, thrombocytopenia, and hemolytic anemia in individuals with G-6-PD deficiency. However the frequency of secondary MDS after treatment with hydroxychloroquine is unknown. We report four patients who developed MDS after hydroxychloroquine therapy, a previously unrecognized association. Methods: We did a retrospective chart analysis of 217 patients on hydroxychloroquine for rhematological conditions in 2005. None of these patients had exposure to myelosuppressive drugs including methotrexate, radiation, chemotherapeutic agents, or benzene. Amongst these patients, 4 had been diagnosed with MDS in 2005. The demographics, type of MDS, karyotypic abnormalities, dose and duration of treatment with hydroxychloroquine were reviewed. Results: Two patients were male (M) and two female (F); the median age was 69.75 years, (range 65–76). There was no personal or family history of hematopoietic cancer. The dose of hydroxychloroquine for all patients was 400 mg daily, with median treatment duration of 10.5 years and a range of 6–16. All patients had bone marrow biopsy confirmation of the diagnosis of MDS, and two had karyotype abnormalities. Conclusion: The incidence of MDS in a group older than 70 years ranges from 15 to 50/100,000 persons/year. The diagnosis of four cases of MDS among 217 patients in one year is approximately 123–37 fold higher than the risk of MDS in the general population aged more than 70 years (P < 0.001) and suggest that long-term treatment with hydroxychloroquine is associated with an increased risk of developing secondary MDS. Age (years)/sex Dose (daily) / duration of hydroxychloroquine treatment MDS subtype Cytogenetic studies. Two (or more) cytogenetically different populations of cells are indicated by a slanted line (/) between their karyotype notations.The number in brackets [ ] indicates the number of cells seen with the preceding karyotype.del (deletion): loss of part of a chromosome. q: the long arm of the chromosome. +: extra copy of the chromosome. −: random loss of chromosomes. Case 1 65/M 400 mg/6 years Refractory anemia without ringed sideroblasts. 45 XY case 2 73/F 400 mg/7 years Refractory anemia without ringed sideroblasts. 46 XX case 3 76/M 400 mg/16 years Refractory anemia with excess blasts 49,XY,+4,+8,+12[5]/46,idem,−5, −6,−13[1]/46,XY[15] case 4 65/F 400mg/13 years Refractory anemia with ringed sideroblasts 46 XX, del (20) (q11.2q13.3)[2]/46 XX[18]

Multiple Myeloma accounts for 10% of malignant hematologic neoplasms. For the past 30 years, a combination of melphalan and prednisone has been the standard treatment for this disease. Nonetheless, it remains an incurable malignancy with a median survival that does not exceed three years. Recent evidence suggests that angiogenesis is increased in multiple myeloma and has prognostic value. Because of its anti-angiogenic properties, thalidomide has been employed as therapy and several trials show that thalidomide alone is active in 25% to 35% of patients with relapsed and refractory myeloma. Among previously untreated patients with more advanced and symptomatic disease, the combination of thalidomide-dexamethasone doubled the response rate to 72 % (in comparison to thalidomide alone) and induced remissions more rapidly. Objectives: To evaluate the efficacy and side effects of thalidomide in combination with glucocorticoid in previously untreated (newly diagnosed) and treated (refractory to other chemotherapies) multiple myeloma patients in a community hospital setting. Patients and Methods: We retrospectively identified eighty-four consecutive patients with multiple myeloma treated between September 1999 and October 2004 at the Cleveland Clinic Center at Fairview Hospital. The sixteen of eighty-four patients (Table 1) who had received thalidomide were selected for further study. The median starting dose was 150 mg/d. The maintenance dosage was 50–100 mg/d in accordance with tolerability. In addition to thalidomide all sixteen patients were receiving dexamethasone. All provided written informed consent prior to receiving treatment. The primary end point of the study was response rate, defined as complete (undetectable monoclonal M protein in the serum) or partial (greater than 50% reduction in serum monoclonal M protein level) Results: Three patients achieved a partial response in the refractory group and 2 in the newly diagnosed group. One patient achieved a complete response in the refractory group and four in newly diagnosed patients. Sixty percent of the patients in the refractory group and 100% of the newly diagnosed patients survived the follow up time (Table 2). Major side effects included sedation in four (25%), deep venous thrombosis in three (18.7%), neuropathy in three (18.7%) and constipation in two (12.5 %) of the patients. Conclusion: The combination of thalidomide and dexamethasone appears to show promising activity in patients with newly diagnosed and possibly with refractory MM. The combination induced a high frequency of response, rapid onset of remission, and low incidence of serious irreversible toxicity. However, ongoing randomized trials are still needed to define further the role of thalidomide with dexamethasone in the treatment of multiple myeloma. Table 1 Patients Characteristics Refractory patients Newly diagnosed patients Number of patients 10 6 Age (years) 66.3 60.5 Sex 7 male, 3 female 1 male, 5 female IgA type 3 3 IgG type 6 2 Biclonal 1 1 Table 2 Refractory patients Newly diagnosed patients Partial response 3 2 Complete response 1 4 No response 6 0 Median follow up (months) 25.2 11.3 Median progression free survival (months) 7.5 10 Diagnosis to start of thalidomide (months) 18.7 2.5 Time on thalidomide (months) 14.2 11.2 Number of deaths (during follow up time) 4 0

The effect of aggregating agents on the hexose monophosphate shunt (HMPS) and the relationship of 14CO2 production to platelet aggregation were studied in normal volunteers. Platelets collected in ACD were suspended in modified Ringer’s bicarbonate buffer without washing and were studied before and after the addition of collagen, adenosine diphosphate (ADP), epinephrine, or thrombin. HMPS and Kreks cycle activities were estimated by the yields of 14CO2 from glucose-1-14C (C1) and glucose-6-14C (C6). 14CO2 production from each substrate was measured continuously during experiments using paired, vibrating reed electrometers and incubation flasks. Both flasks contained aliquots of the same platelet suspension. Baseline 14CO2 production averaged 22 ± 4.5 mµmoles/hr/109 platelets from C6 as compared to 33 ± 6 mµmoles/hr/ 109 platelets from C1. Each aggregating agent gave a prompt and striking increase in 14CO2 production from C1. In contrast, the increase in 14CO2 production from C6 was not detectable for 10 min and then production increased slowly. Inhibition of 14CO2 nate (25 mM) did not interfere with platelet aggregation. Stimulation of 14CO2 production from C1 by aggregating agents was unaffected by malonate. These data indicate that platelet aggregation coincides with stimulation of the HMPS, but the increase in Krebs cycle activity occurs later and is not essential for platelet aggregation.