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e13010 Background: Primary CNS Lymphoma (PCNSL) is a rare neoplasm of the brain accounting for 1-2% of all brain tumours. Incidence and histopathologic features of PCNSL in India has been reported; however, reports on therapy outcomes of the disease are lacking. We report treatment outcomes of patients with PCNSL at our institute. Methods: Case records of all patients treated for PCNSL between 2008 and 2012 were retrospectively analysed. Epidemiologic details, treatments given, progression free and overall survival were calculated. Patients who completed at least high dose methotrexate (1.5 gram/ m2) for 5 courses with or without RT were included for analysis. Overall survival (OS) was defined as time from diagnosis till death/lost to follow up. Results: A total of seventeen patients were analysed. The median age at diagnosis was 58 years and M: F ratio was 1.14:1. Thirteen out of seventeen patients were eligible for analysis; six could complete the total treatment protocol which included methotrexate, vincristine, procarbazine, Dexamethasone, Radiation therapy followed by high dose cytarabine. Median overall survival was 20 months (range 2-54 months). Among those who completed the protocol, median survival at 21 months was not reached with 66% survival. Conclusions: Treatment of PCNSL with at least high dose methotrexate with or without whole brain radiation offers moderate results. Completion of treatment protocol is associated with better overall survival.

Adult T cell lymphoma/leukemia is a peripheral T-cell neoplasm caused by human T-cell lymphotrophic virus-1, affects mostly adults with systemic involvement and poor prognosis. Diagnosis of adult T-Cell leukemia/Lymphoma is challenging. The clinico-pathologic and immuno-phenotypic features of the three cases will be presented.

Background : CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A5*3). We investigated the association between CYP3A5*3 polymorphism and acute leukemia. Materials and Methods : Two hundred and eighty nine acute leukemia cases comprising of 145 acute lymphocytic leukemia (ALL), 144 acute myeloid leukemia and 241 control samples were analyzed for CYP3A5*3 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0) to detect the association between CYP3A5*3 polymorphism and acute leukemia. Results : The CYP3A5*3 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ 2 - 133.53; df-2, P 0.000). When the data was analyzed with respect to clinical variables, mean WBC, blast % and LDH levels were increased in both ALL and AML cases with 3/3 genotype. The epidemiological variables did not contribute to the genotype risk to develop either AML or ALL. Conclusion : The results suggest that the CYP3A5*3 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients.

Abstract 2203 Poster Board II-180 Introduction: There is no published data on imatinib mesylate (IM) resistance mutations and responses to dose escalation in Indian patients. This study analysed kinase domain (KD) mutations, response to dose escalation, event free survival (EFS) and overall survival (OS) of chronic phase CML (CP CML) patients resistant to IM 400mg. Patients and Methods: Patients with CP-CML resistant to IM 400 mg by European Leukemia Net (ELN) guidelines were screened for known KD mutations using nested PCR and gene sequencing. The IM dose was escalated to 800mg daily. Patients in accelerated (AP) or blast phases (BC) were excluded. Only patients with at least one cytogenetic evaluation after 6 months of dose escalation were analysed. EFS was defined as time from dose escalation to loss of complete hematologic (CHR) or major cytogenetic response (MCR), progression to AP/BC, no complete hematologic response at 3 months, no cytogenetic response at 6 months, less than MCR at 12 months and no complete cytogenetic response (CCR) at 18 months or death from any cause. OS was defined as time from dose escalation to death. Results: There were 90 patients with a median age of 36 years (range, 18-65) and M: F of 2.4:1. None had been on previous therapies other than IM 400mg. Median duration on IM 400 at resistance detection was 18 months (range, 3-48).Trigger for resistance testing was primary hematologic resistance (HR) in 10 (11.1%), primary cytogenetic resistance (CR) in 20 (22.2%), secondary HR in 55 (61.1%) and secondary CR in 5 (5.5%). Twenty nine (32.2%) patients had KD mutations. Of the 29, the most common were T315I in 9 patients (31.2%), G250E in 8 (27.6%), followed by F359V in 4 (13.8%) and M244V in 2 (6.8%). Y253F, Y253H, N374Y, L248V, H396R, and E355G were detected in 1(3.4%) patient each. Age, gender (male vs female, p=1), Sokal score at diagnosis (low + intermediate vs high, p=0.82), duration of IM prior to resistance (< vs ≥ 2 years, p=0.46) and trigger for testing (hematologic vs cytogenetic failure, p=0.14) did not predict for mutation detection. Of 90 patients, 11 (12.2%) with mutations that conferred absolute resistance to IM (T315I, Y253F, Y253H) were excluded from response, EFS and OS analysis.The median time to cytogenetic evaluation for the remaining 79 patients was 9 months (range, 6-13). The response to dose escalation is in Table 1. The type of resistance (primary vs secondary, p=0.1) and the mutation status (presence or absence, p=1.0) did not influence achievement of MCR. Patients with hematologic failure were less likely to achieve MCR compared to cytogenetic failure, 29 vs 76% (p=0.0002). At a median follow up of 18 months (range, 6-40), 35 (45%) patients are event free and 76 (93%) are alive. There were 44 events: failure to achieve CHR in 29 (66%), loss of CHR in 2 (4%), failure to achieve cytogenetic response in 7 (16%), progression to AP/BC in 3 (7%) and 3 (7%) deaths. Out of 44 patients with an event, 9 (19%) went on a clinical trial, 3 (7%) on dasatinib and 29 (66%) on hydroxyurea or no therapy. The following factors predicted for longer EFS: cytogenetic vs hematologic failure (not reached vs 18 months, p=0.0001), MCR vs others (41 vs 14 months, p= Disclosures: No relevant conflicts of interest to declare.

7076 Background: Recent studies suggest that higher doses of Daunarubicin (DNR) may lead to better complete remission (CR) in patients with de-novo acute myeloid leukemia (AML). Most studies have u...

Paraneoplastic encephalomyelitis (PEM) is a well-characterized neurological syndrome. Its association with ovarian teratoma is rare. A young lady presented with features suggestive of encephalomyelitis with predominant cerebellar syndrome. Magnetic resonance imaging brain was normal. Cerebrospinal fluid showed lymphocytic pleocytosis. Computerized tomography scan of the pelvis revealed a complex left ovarian cyst. With a clinical diagnosis of PEM she underwent a left salpingo-oopherectomy. This was followed by total recovery of the PEM in two weeks. The histopathology revealed immature teratoma. The interesting feature was the clinicopathological correlation between the finding of fetal cerebellar tissue in the tumor and the PEM with predominant cerebellar features.

4086 Background: Gastric cancer is the second most common gastrointestinal cancer in our hospital based cancer registry. This retrospective analysis aims at studying the epidemiology and treatment patterns for gastric cancer at our hospital, which is a tertiary care cancer center for the state of Andhra Pradesh in south India. Methods: A retrospective analysis of the case records of 125 consecutive patients with gastric cancer who presented to our department between Jan 2004 and Dec 2005 were analysed. Data regarding epidemiology, stages at diagnosis and treatment plans were collected. Patients with early gastric cancer received 5FU based chemoradiation or chemotherapy only. Palliative chemotherapy included 5FU/cisplatin based regimens. Results: A total of 125 patients were analysed. The median age was 61years (range 18–82 years). 71% were males and 29% females. Being a tertiary care center, 92% were referred with a confirmed diagnosis on endoscopic biopsy. 30% were smokers, 11% consumed alcohol, 40% had both habits while 29% had neither. The most common part of the stomach involved was the antro-pyloric region (44%) followed by the body (30%), GE junction/cardia (20%) while 6% had diffuse involvement including linitis plastica. At diagnosis, 35% were early stage, 56% metastatic and 8% locally advanced tumors. 90% patients who had surgery for early stage disease had T2,3 tumors. One third had inadequate nodal staging.70% of patients who had curative resections underwent adjuvant chemoradiation and 30% had chemotherapy only. Of all patients with metastatic disease, 65% palliative chemotherapy while 45% opted for best supportive care. Conclusions: The distribution of tumors within the stomach is similar to Japanese data, which may reflect the common etiological factors like high salt diet. The fact that one third of patients had inadequate nodal dissection stresses the relevance of adjuvant chamoradiotherapy protocols. The high incidence of smoking as a contributory factor in the etiology reflects the need for aggressive anti tobacco legislation. The study reiterates the need for inexpensive and novel therapies for palliation of symptoms in patients with advanced disease and widens the scope for collaborative clinical trials. No significant financial relationships to disclose.

Glutathione S-transferase P1 (GSTP1) enzyme plays a key role in biotransformation and bioactivation of certain environmental pollutants such as benzo[a]pyrene-7, 8-diol-9, 10-epoxide (BPDE) and other diol epoxides of polycyclic aromatic hydrocarbons (Hengstler et al. 1998) and catalyses detoxification of base propanols that arise from DNA oxidation thus offering cellular protection against oxidative stress. GSTP1 gene belongs to the pi class gene family, located on chromosome 11q13 (Autrup 2000). It comprises of seven exons (Morrow et al. 1989; Bora et al. 1997) and codes for cytosolic GST enzyme (Fryer et al. 1986). The first polymorphism identified is an A–G polymorphism at nucleotide 313 in exon 5 of GSTP1 gene which leads to an amino acid substitution of isoleucine (IE) by valine (val) at 105 amino acid position (Ile105Val). This substitution results in three GSTP1 genotypes: they are isoleucine/isoleucine (Ile/Ile) homozygous wildtype, isoleucine/valine (Ile/Val) heterozygote and valine/valine (Val/Val) homozygous variant.GSTP1 codon 105 polymorphism might play an important role in leukaemiogenesis, as it potentially alters protein function, diminishing its detoxification ability for certain mutagens and carcinogens, which could result in increased DNA damage and mutation, and a greater risk of developing cancer. Biochemical studies indicated that GSTP1 Val105 allele has a lower thermal stability than GSTP1 Ile105 allele (Zimniak et al. 1994; Johanson et al. 1998), and Val homozygotes had a lower conjugating activity than Ile homozygotes, with heterozygotes displaying intermediate activity (Watson et al. 1998). Individuals with at least one Val allele at codon 105 of GSTP1 enzyme might have an underlying predisposition to cancer when exposed to environmentally derived