INCREASINGLY COMMON PRESENTATION OF EXTRANODAL BURKITTS LYMPHOMA WITH SURPRISINGLY RAISED PLEURAL/ASCITIC FLUID ADENOSINE DEAMINASE LEVELS

Acute onset polyserositis as a presentation of Non Hodgkins lymphoma(NHL) occurs in 20% of individuals.(1-4) Etiology being a jumble between an Extranodal Burkitt lymphoma(ENBL),a pyothorax associated lymphoma and a primary effusion lymphoma as a cause of such effusions.(5) We report a case series of 5 such patients of NHL,four of which received chemotherapy with standard CHOP regimen.However,all patients succumbed.The common ndings of strikingly raised uid adenosine deaminase(ADA) levels in all of these effusions establishes a possible etiopathological link(ENBL).(6) An immunocompetent status renders primary effusion lymphoma unlikely which also has high uid ADA levels.This case series proposes a rational approach towards such cases of suspected ENBL presenting with acute onset lymphocytic polyserositis and a negative HIV antibody status with enormously raised uid ADA levels thereby permitting timely institution of chemotherapy for a better patient prognosis.

Potential anti-proliferative effects of chemical constituents and hemisynthetic derivatives from Scadoxus pseudocaulus (Amarillydaceae)

Background: Biological significance of Amaryllidaceae is well advocated from the literature. In Cameroon, plants from this fam- ily are routinely used for the cure of liver, cancer and cardiovascular diseases. To date, no scientific investigation corresponding to the anti-cancer activity of extracts and isolated compounds of Scadoxus pseudocaulus is available. Objective: Current study is focused to elaborate the anti-proliferative effects of natural isolates (compounds 1-6, 9) and hemi-synthetic analogs (compounds 7-8) extracted from S. pseudocaulu. Methods: Column chromatography of the ethyl acetate extract followed by purification of different fractions led to the isolation of seven compounds (1 – 6, 9). Esterification reaction of compound 6 was carried out using butyroyl chlorides and triethylamin to produce two derivatives (7 – 8). The cytotoxic activity was performed after staining of treated cells with florescent dye propid- ium iodide. Dead cells were detected using cytometer FL2 or FL3 channels/filters. Results: Trans-derivative of narciclasine (a natural isolate from S. pseudocaulus), was found to be most potent among all tested compounds. Its effects were more significant on low malignant follicular lymphoma (DoHH2 cells) as compared to highly ma- lignant (EBV infected) Burkitts lymphoma (Raji cells). Conclusion: From our results, narciclasine appears to hold the potential of a lead molecule that can be used to bridge the ther- apeutic gaps in cancer research. Keywords: Scadoxus pseudocaulus; Amaryllidaceae; 7-deoxy-trans-dihydronarciclasin; farrerol; derivatization; cytotoxic activity.

Rituximab and CODOX-M / IVAC Without Stem Cell Transplantation For Poor Risk Diffuse Large B Cell Lymphoma (IPI3-5) and Burkitts Lymphoma Is Feasible and Gives a High Response Rate: Preliminary Results Of a Phase 2 UK National Cancer Research Institute Trial

Introduction R-CHOP is the standard of care for patients with diffuse large B cell lymphoma (DLBCL) however poor risk patients (IPI 3-5) still have an inadequate outcome. Neither first remission high dose chemotherapy and peripheral blood stem cell transplantation (HDC+PBSCT) nor selection of cases for intensification by interim PET scanning have demonstrated a proven benefit. In the case of Burkitts lymphoma (BL) there is a paucity of data on the addition of Rituximab to the CODOX-M and IVAC regimen. Patients and Methods 113 patients with DLBCL and 37 with BL were recruited from 53 UK sites between May 2008 and April 2013. Median age was 49 years (18-65). For DLBCL patients IPI scores were 3 – 72 ( 64%), 4 -40 (35%) and 5 – 1 (1%). All patients received the modified CODOX-M and IVAC regimen including all CNS directed therapy( Mead et al Ann Oncol. 2002 Aug;13(8):1264-74) and 8 doses of rituximab. The primary end point of the study was Progression Free survival (PFS) and secondary endpoints included toxicity and CR rate. Results The main toxicities reported were neutropenia ( 89% grade 3 or 4), thrombocytopenia (84.2% grade 3 or 4), infection 61.6% grade 3 or 4 and mucositis (30.1% grade 3 or 4). 4 patients were excluded from toxicity assessment as they did not start therapy after registration. There were 8 treatment related deaths observed (infection with neutropenia (5), GI haemorrhage (1), acute cerebral haemorrhage (1) and bowel perforation (1) ). 78 patients with DLBCL and 31 with BL have completed all therapy ( 78.5 % of patients with available data) with an overall response rate of 92 % for DLBCl and 94% for BL. In patients who completed all therapy CR was achieved in 34 (44%), CR (u) in 8 (10%) and PR in 30 (38%) for DLBCL patients and CR was achieved in 21 (68%), CR (u) in 6 (19%) and PR in 2 (6%) in BL patients. 3 patients ( 2 DLBCL and 1 BL) who progressed during therapy have been included in the response analysis. End of treatment PET scanning was not obligatory. 80 patients with DLBCL and 30 patients with BL remain alive and without progression at a median follow up of 18.6 and 19.3 months respectively. Conclusion The R-CODOX-M -R-IVAC regimen can be delivered to patients with poor risk DLBCL in a multicentre setting. High rates of haematological toxicity and consequent infection are inevitable with treatment of this intensity but appear acceptable when compared with other treatments such as HDC+PBSCT. Response rates are encouraging in view of the very poor risk IPI profile of the patients included in this study. Burkitts lymphoma patients also achieved an excellent response rate with no apparent additional toxicity attributable to the addition of rituximab to the regimen. We currently plan the first analysis for the primary endpoint of PFS in 2015. The Trial was supported by Leukaemia and Lymphoma Research (LLR). Disclosures: McMillan: Roche: Consultancy, Honoraria; Amgen: Research Funding. Off Label Use: Rituximab usage in Burkitts Lymphoma. Ardeshna:Roche: Honoraria, Research Funding. Jack:Roche/Genentech: Research Funding. Patmore:Roche: Consultancy, Honoraria. Pettengell:Roche: Honoraria; Amgen: Honoraria. Linch:Roche: Honoraria, Research Funding.