ALBERT

Description: Poor prognosis DLBCL, including intermediate and high risk disease according to IPI accounts for approximately 20% of new cases of DLBCL. The addition of rituximab to conventional chemotherapy (CHOP) has improved the outcomes in this subset, with a 2-year overall survival (OS) of about 50%. However, 40-50% of these patients still have either primary refractory disease or relapse after an initial response. Rituximab-EPOCH (R-EPOCH), an infusional regimen has a dynamic dose adjustment strategy based on the hematopoietic nadir in previous cycle to achieve an optimal drug concentration. Phase II studies with R-EPOCH in untreated DLBCL with intermediate and high risk IPI have reported improved outcomes, with an estimated 2-year OS of 75% which appears superior to that of R-CHOP. Hence we analysed the outcomes of patients with de-novo, poor prognosis (intermediate and high risk IPI) DLBCL who received R-EPOCH and compared it to the  historical cohort of patients who were treated with R CHOP at our centre. Methods Treatment-naïve patients of DLBCL with intermediate or high risk IPI, registered at our centre between November 2011 to June 2013, who received R-EPOCH regimen, were included for the analysis. Case records were reviewed for – demography, histology, stage, bulk of disease, extranodal sites,  performance status, IPI, LDH, albumin, details of chemotherapy, grade ¾ toxicities (CTCAE version 4) and need for hospitalization.  Responses were evaluated at mid and end of chemotherapy. Overall and progression free survival were calculated. Similar analysis was done for poor prognosis DLBCL patients treated with R-CHOP between Jan 2007 to December 2010. Results Baseline characteristics and treatment outcomes of  32 patients (males-24, females-8) treated with R-EPOCH were compared to 42 patients (males-28, females-14) who received R- CHOP. Median age in R- EPOCH group was 47 years (range-20-75 years) versus 55 years (23-72 years )in R- CHOP. Performance status≥ 2 was seen in 47% in R- EPOCH as compared to 28% in R-CHOP group. Significant proportion of patients in R-EPOCH had bulky disease(81% versus  16%) and stage III/IV disease (90% versus 81%) as compared to R-CHOP. Patients with IPI of two represented 8(25%), IPI of three, 11(34%), and IPI of four and five, 10(32%) on R- EPOCH compared to 21(50%), 19(45%) and 2(5%) on R-CHOP, respectively. Serum albumin

Description: Introduction: Dosing of 6-mercaptopurine (6MP) has remained empirical in acute lymphoblastic leukemia (ALL) with leucocyte count and TPMT genotype guiding clinical decisions. A majority of our patients do not tolerate standard doses of 6MP and require frequent dose interruptions or modifications. There is marked inter-individual variability in the tolerability of 6MP and TPMT genotype alone cannot account for all the variability observed in clinical practice. Better predictors of toxicity are needed to guide hemato-oncologists in dose selection and dose optimization of 6MP to achieve maximum anti-leukemic activity. The present study aims to identify factors that influence tolerability of 6MP, including pharmacokinetic parameters of 6MP and its metabolites, so as to enable the development of predictive models of 6MP toxicity in the future. Methods: Adult ALL patients aged ≥18 years receiving 6MP during interim maintenance (IM) or maintenance (M) phase of MCP841or BFM-90 protocol were enrolled after informed consent. All patients received 6MP at the protocol specified dose of 75mg/m2. Complete blood counts and liver function tests were done at baseline, day 8 and 22 of IM, before each cycle of M Phase and as clinically indicated. Serial blood samples were collected at 0, 1, 2, 4 and 6 hours after 6MP dose on day 1 of IM and M phase and areas under the concentration-time curve (AUC) was estimated by non-compartmental analysis. RBC levels of 6-methylmercaptopurine (6mMP) and 6-thioguanine nucleotide (6TGN) were measured on day8 and day22 using a validated HPLC method. TPMT activity was measured using a validated HPLC method at the time of enrollment. TPMT genotyping was done using Sequenom MassARRAY platform. Dose interruptions, cumulative duration of interruption and dose reduction were recorded as measures of intolerance to 6MP. Statistical analysis: Descriptive data is either expressed as mean±SD or median(range). Difference in TPMT activity or 6TGN levels between groups was compared using Mann-Whitney test. Proportions were compared using Chi-Square/Fischer Exact test. Spearman's correlation was used to study the correlation between two continuous variables. Results: Forty five patients (males-36, females-9) were enrolled on the study from November 2012 to November 2014. The median age was 28(range:16-50) years. The baseline hemoglobin concentration and absolute neutrophil count (ANC) was 8.75±1.2 g/dl and 3.24±2.57X103 cells/µl respectively.Dose was interrupted in 36 patients (80%) patients, median number of interruptions being 2(1-6). The cumulative duration of dose interruption was 23 (4-67) days. Twenty patients (44%) required dose reduction due to grade 4 cytopenias, median number of dose reductions being 1(1-2). TPMT genotype was available for 33 patients (28 WT, 5 heterozygotes). The average TPMT activity was 1.44±1.35units/ml RBCs. No correlation was observed between TPMT genotype and TPMT activity. Genotype was not a significant determinant of dose reduction, dose interruption or cumulative duration of interruption. On the other hand, marked difference in TPMT activity was observed between those who required dose reduction versus those who did not (0.92±0.65 vs. 2.16±1.77, P

Description: Background: Improved molecular and immunophenotypic characterization of AML offers the opportunity to define markers in individual patients which can be used to monitor minimal residual disease (MRD). Immunophenotypic analyses are based on the multiparametric flow cytometry (MPFC) detection of leukemia-associated immunophenotypes. The most useful molecular prognostic markers implicated in AML characterization are NPM1 mutations, FLT3 ITD, CEBPA mutations, MLL -PTD, RUNX1 and ASXL1 mutations. Deregulated expression of genes have also been identified as prognostic markers eg BAALC, WT1 and ERG. In this study, gene mutations (NPM1, FLT3, CEBPA, MLL-PTD), gene expression (WT1 and BAALC)and immunophenotyping were prospectively assessed to detect MRD. Methods: Diagnostic Marrow/peripheral blood samples from 98 AML patients (excluding AML-M3) were included between March 2012 and July 2014. Patients received standard induction chemotherapy with daunorubicin 60 mg/m2 for 3 days and cytosine arabinoside 100 mg/m2 iv for 7 days. Marrow was done 21-28 days after start of induction chemotherapy for assessment of morphology, MPFC and molecular markers. If marrow was in remission (CR), then patients received 1st consolidation therapy with 18 gm/m2 of cytosine arabinoside (HiDAC). Marrow was repeated 21-28 days after 1st consolidation chemotherapy for assessment of same parameters as above. Patients then received 2 more HiDAC or underwent allogeneic transplant according to cytogenetic risk. Cytogenetic analyses were performed using standard techniques of chromosome banding and FISH. All cases were divided into three cytogenetic risk groups (i.e. good, intermediate and poor) based on NCCN guidelines. Immunophenotyping was done using 8 color MPFC. The same panel of antibodies was used to characterize the leukemic cells at diagnosis, post induction and post consolidation. MRD was calculated as a percentage of abnormal leukemic cells per total nucleated cells. cDNA synthesis and quantitative real time PCR (RQ-PCR) assays for WT1 and BAALCwere carried out according to Europe Against Cancer guidelines. Mutation profiling was carried out by capillary electrophoresis and direct DNA sequencing methods as described previously. Chi-square method was used to detect any association between risk groups and gene mutations. Probabilities of relapse-free survival (RFS) were estimated using Kaplan-Meier method. Univariate comparisons of RFS for potential prognostic markers (molecular and MPFC) were made using log-rank test. Results: Of 98 patients enrolled in this prospective study, 86 patients completed induction and 59 patients 3 courses of HiDAC. The median age was 27 years (range 15-58). Based on cytogenetic risk groups 24.4%, 47% and 28.6% were good, intermediate and poor risk cases respectively. Twelve patients died during induction due to sepsis and 16 patients were refractory to induction chemotherapy. Baseline frequencies of FLT3-ITD, MLL-PTD, NPM1-type A and CEBPA gene mutations were 20.4%, 10.2%, 20.4% and 25.5% respectively. The biallelic (TAD1 and ZIP mutations) and monoalleleic CEBPA mutations were found in 4.1% and 21.4% patients respectively. No significant association was found between different risk groups and gene mutations except NPM1-type A mutations were associated with good risk group (P=0.015). MRD by RQ-PCR for BAALC/WT1 and MPFC was assessed after post induction and post first consolidation therapy. There was one log reduction in mean copy number of WT1 (5312 vs 430) and BAALC (19648 vs 3298) between diagnosis and post consolidation samples. No significant differences were found between high expressors of WT1/BAALC and RFS. MPFC analyses revealed that 48% of post induction samples were MRD positive (range: 0.05-38%, mean 6.6%) Similarly, 53% of post consolidation samples were MRD positive (range: 0.01-85%, mean 10.9%). Univariate analysis showed that MRD positivity by MPFC at post induction (RFS at 1.5 years- 85% vs 30%, P=0.012) and post consolidation (RFS at 1.5 years- 90% vs 42%, P=0.015) was associated with poor RFS. Patients without MLL-PTD mutation showed better RFS (P=0.003) as compared to mutated cases and TAD2positivity at post induction showed a trend to better RFS (P=0.097). Conclusion: Our results suggest that MRD by MPFC predicts RFS more accurately than over-expression of WI1 and BAALC. Disclosures No relevant conflicts of interest to declare.

Description: Background: Rituximab is a chimeric IgG1 monoclonal antibody targeting the CD20 surface antigen on normal and neoplastic B cells. Its use in combination with chemotherapy in CD20 positive B cell lymphomas has translated into better progression free and disease free survival making its incorporation, a standard of care in treatment of these lymphomas. However, the benefits of this important molecule may not have been available to a majority of patient in the developing countries but for the emergence of biosimilars in the market. The lack of defined regulatory norms in approving biosimilars for patient care has left some doubts regarding their true efficacy in comparison to the innovator MabThera® (Roche). Although our clinical experience suggests comparable efficacy and safety for the biosimilar, we embarked on a formal pharmacokinetic study of the biosimilar, Reditux®, used in combination with standard CHOP or CHOP like regimen in patients with diffuse large B cell lymphoma planned for chemo-immunotherapy. We present our data on twenty-one prospectively treated patients and compared it with the published data on MabThera®. Methods: This was a prospective, single centre pharmacokinetic study conducted between Nov 2011 and June 2013. Patients diagnosed with DLBCL, and treated with Reditux® in combination with chemotherapy, were enrolled into the study. All patients received six cycles of R-CHOP, wherein they received 375mg/m2 Reditux as a graded infusion of 50mg, 100mg and maximum 200mg during the first, second and third hour respectively on day 1 of first cycle. The chemotherapy consisted of standard CHOP including cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2 and vincristine 1.4 mg/m2 (for a maximum single dose of 2 mg), administered intravenously on day 1 after Rituximab infusion, along with 100 mg oral prednisone for 5 days from first day. Serial blood sampling was done during the first cycle of R-CHOP at pre-dose, immediately post infusion and thereafter at 24, 48, 144 hours post infusion with a last sample collected on day 21. The plasma level of rituximab was determined by ELISA (Life Technologies, USA) with a sensitivity of 50 ng/mL. Rituximab AUC and other pharmacokinetic parameters were calculated from the observed concentrations at each time point using WinNonlin® version 6.3. The peripheral blood B-cell count was done on day 3 and day 21 of chemoimmunotherapy. The absolute B cell percentage was calculated by flow-cytometry using CD45, CD19 and CD20. Influence of covariates on AUC of Reditux was analyzed by linear regression. Results: A total of 21 patients were enrolled into the study including 18 males and 3 females. The median age was 50 years in the Reditux® group (range 24-70). Four patients were above 60. Majority (n=12) had Stage 4 disease. The pharmacokinetic parameters described in the table were comparable with the pharmacokinetic profile of MabThera® from published literature. High inter patient variability in pharmacokinetics was observed (CV=88%). Age and gender did not influence pharmacokinetics of the biosimilar though the numbers are few to derive firm conclusions. The median B cell count on day 3 and day 21 of first cycle was 1.75 ± 0.27 and 5.56 ± 1.24 cells/µl respectively. Of the 21 patients, four were lost to follow up while 2 patients had progressive disease and died. At a median follow of 19 months 70.3% of patients from the Reditux® group were progression free. There was no untoward immediate or late toxicity attributable to Reditux® on follow up. Conclusions: Reditux® has similar pharmacokinetic profile as MabThera®. The B-cell kinetics following Reditux® administration are similar to that reported for MabThera®. This study gives further credence to Reditux® as a suitable alternative to MabThera®in the treatment of CD20 positive B cell lymphomas. Table: Pharmacokinetic parameters of Reditux® and Mabthera® PK parameter (mean ± SD) Reditux®(N=21) MabThera® (published literature) AUC (0-t) hr* µg / mL 54,236 ± 47,555 - C max (µg / mL ) 555.74 ± 141.46 408 Vd ( L) 1.3 ± 0.64 2.7 CL (l/day) 0.15 ± 0.16 0.14 Half life (days ) 10.9 ± 8.6 22 MRT last (days) 2.78 ± 3.08 - Vd=Volume of distribution, CL=Clearance, MRT=Mean Residence Time Disclosures No relevant conflicts of interest to declare.

Description: Introduction: The role of FDG PET-CT in follicular lymphoma is limited to accurate assessment of disease extent in early stage patients and selection of biopsy site in cases of suspected high- grade transformation. Despite the known FDG avidity of follicular lymphoma, FDG PET-CT has not yet been included as part of standard staging procedures in these patients. FDG PET-CT has shown significant correlation with bone marrow biopsy in Hodgkin and diffuse large B-cell lymphomas. In this retrospective analysis we have assessed the correlation of PET-CT with that of bone marrow biopsy, the reference standard for assessment of bone marrow infiltration in follicular lymphoma. Methods: We retrospectively analyzed electronic medical records and database of patients with newly diagnosed follicular lymphoma registered at Tata Memorial Centre from July 2009 to Jun 2014, who underwent complete staging workup as per the current recommendations along with whole body 18FDG-PET/CT. The demographic features, performance status, stage, LDH, nodal sites, haemoglobin, follicular lymphoma international prognostic index (FLIPI), FDG PET-CT findings (bone marrow involvement, pattern of involvement- focal or diffuse, sites of marrow involvement, liver and spleen uptake, SUVmax of most FDG avid lesion) and bone marrow aspiration/biopsy (morphology, immunohistochemistry and immunophenotyping on aspirate, where available) findings were recorded. Focal uptake in marrow on baseline PET-CT was considered as marrow involvement if post therapy PET-CT showed resolution of these lesions. The sensitivity, specificity, negative and positive predictive value of PET-CT in detecting bone marrow infiltration was assessed taking bone marrow biopsy as gold standard. The factors responsible for discordant results were analyzed. Results: A total of 54 patients (males-38, females-16) were included in analysis with median age of 50 years, (range 22-73 years). At diagnosis 83% (45 patients) had stage III or IV disease and 57% patients had high-risk FLIPI score. Approximately 88% patients had good performance status (ECOG-

Description: Introduction: Mainstay of chemotherapy in acute myeloid leukemia (AML) is induction with a goal to achieve morphological complete remission (CR) as evident by less than 5% blasts. Post remission strategies then focus on either consolidation chemotherapy or allogeneic bone marrow transplantation (aBMT). However, not all patients by this remission criterion achieve long term remission and a subset of patients' relapse. This relapse originates from further expansion chemoresistant clones. Detection of minimal residual disease (MRD) following chemotherapy, early in the course of treatment, is highly predictive of outcome and offers a window of opportunity to intensify treatment and prevent relapse as seen in ALL. Here, we describe assessment of immunophenotypic MRD using a 10-colour two tube assay and a combination of difference from normal and leukemia associated immunophenotype (LAIP) approach in patients of adult AML. Methods: We accrued 310 patients of adult (〉18 years) AML, other than with t(15;17), over a 66-month period (1st July 2012- 31st December 2017) after obtaining informed consent. All patients received standard induction chemotherapy. MRD testing was done post induction and after first consolidation with high dose cytarabine. Patients accrued from 1st July 2012 to 28th February 2015 (85 patients) were processed using a three tube 8 colour MRD assay. Subsequently samples of 225 patients were processed using a two tube 10 colour MRD assay. Identical panel was used for diagnostic sample, post induction and post consolidation. 500,000 events were acquired per tube with the 3-tube assay and 1.6 million events per tube obtained per tube with the 2 tube, 10 colour assay. Analysis of MRD was done using Kaluza 1.3 by a combination of difference from normal approach that focused on the development of Myeloid progenitors to mature cells and LAIP approaches. Cytogenetic studies by conventional karyotyping and FISH was done as per NCCN version 2 2014 recommendations. Patients were classified into favorable, intermediate and poor cytogenetic risk. The presence of FLT3-ITD, NPM1 and CEBPA mutations were detected by a fragment length analysis-based assay. Overall survival (OS) was calculated from date of diagnosis to time of last follow up or death. Relapse free survival (RFS) was calculated from date of CR till time to relapse or death or last follow up if in CR. Results of the MRD assays, cytogenetic and molecular risk groups were analyzed for their impact on OS and RFS using log rank test. Results: The median age of entire cohort was 33 years (M : F = 1.6 : 1). Based on cytogenetics, 35.1% were classified as favorable risk whereas 52.5% and 12.2% were intermediate and poor risk respectively. FLT3-ITD, NPM1 and CEBPA mutations were detected in 21.9%, 29.0% and 7.7% of patients respectively. Post induction MRD was assessed in 298 patients of which 114 (38.3%) had detectable residual disease (range 0.004-22.6%, median:0.9%). Post consolidation MRD was assessed in 186 patients of which 49 (26.4%) were MRD positive (range 0.002-19.8%, median: 0.37%).The 3 year OS, RFS and median RFS of the entire cohort was 59.0%, 44.8% and 18.7 months respectively. Poor risk cytogenetics as expected was predictive of inferior OS (median OS = 14.6 months vs not reached, p=0.05) as well as RFS (median RFS = 9.3 months vs 18.6 months, p=0.003 respectively). FLT3, NPM1 and CEBPA mutations were not informative as predictors of outcome.The presence of MRD at post induction time point predicted an inferior OS [(p=0.08), HR:1.53; 95% CI (0.93-2.51)] & RFS [(p=0.0002), HR:2.14; 95% CI (1.4-3.3)] as compared to the MRD negative group. Similarly, patients harboring MRD at the end of consolidation had an inferior OS [(p=0.04), HR:1.83; 95% CI (0.94-3.6)] & RFS [(p=0.02), HR:1.79; 95% CI (1.04-3.09)] as compared to the MRD negative group. On multivariate analysis post induction FCM MRD emerged as the most important independent prognostic factor predictive of inferior outcome for RFS [(p=0.01); HR:2.14; 95% CI (1.17 - 3.4)] followed by poor cytogenetic risk [(p=0.05); HR:1.8; 95% CI (1.0 to 3.26)]. Conclusion: Our data demonstrates that MRD by flow cytometry at end of induction as well as consolidation are important prognostic factors together with known factors such as high risk cytogenetics. AML MRD is a very useful guide for post remission strategies in AML and should be incorporated into routine treatment algorithms. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Waldenstrom Macroglobulinemia (WM) harbors a mutation in MYD88 gene (MYD88L265P) with frequencies varying from 67% to 91%. Although of diagnostic use its clinical significance in terms of prognosis and treatment response is unclear. We retrospectively analyzed WM for MYD88 L265P mutation, immunogenetic profile (presence of somatic hypermutations and biased gene usage) & correlated these with standard clinical variables including prognosis and patient outcome. Patients & Methods 32 cases WM (diagnosed as per WHO 2008/2001 criteria) were retrospectively accrued from 2007-2013. Genomic DNA extracted from bone marrow aspirate smears was subjected to an allele specific oligonucleotide PCR to detect the MYD88L265P mutation using fluorescently labeled primers followed by capillary electrophoresis. Immunogenetics was assessed in 29 patients. Clonal FR1/FR2 regions of the VH gene were amplified & sequenced. Sequence data was compared to the closest germline sequences on NCBI & IMGT databases. Laboratory variables (Hb, WBC, platelet, M Protein concentration, S. IgM, b2M level, S. Globulin, LDH, %of lymphoplasmacytic lymphocytes) were evaluated at baseline along with the International Prognostic Index (ISSWM). Response evaluation was done as per VIth International Consensus guidelines after treatment as well as at last follow up. 2-tailed Student's t-Test & Chi squared test were applied for statistical analysis. Results Median age was 60 years (range: 46-77), male predominant (87.5%).Majority of patients had cytopenia (90.6%) of one or more blood lineages. Median IWSSM was 3 (n=26). The median follow up was 21.5 months (range: 1 week to 82 months). Majority of patients were treated with cyclophosphamide/vincristine/prednisone ± rituximab (55.1%), followed in others by bendamustine/rituximab(13.8%) or fludarabine/cyclophosphamide/rituximab,(13.8%) or cyclophosphamide/thalidomide/dexamethasone (10.3%). MYD88 L265P mutation was found in 84.3% (27/32) of patients. The immunogenetic results here pertain only to samples with productive IGHV gene rearrangement [22/29 (∼76%) cases]. 96% of cases revealed somatic hypermutations. 59% of cases showed a biased use for the VH3 gene followed by VH4 (22.7%) and VH1 (18.18%). The commonest gene used was IGHV3-7 (27.3%) followed by IGHV1-18 (18.2%). Clinical features separating MYD88 negative from MYD88 mutated WM are seen in Table 1. MYD88 negative WM presented with lower number of infiltrating tumor cells in the bone marrow (p=0.05), older age (p=0.02) and had a lower IWSSM score at presentation (p=0.03) as compared to mutated WM. Majority of the MYD88 negative group were in VGPR,(very good partial response) or CR (complete response) (75%:VGPR/CR) post treatment as compared to MYD88 mutated patients [21%: VGPR/CR, 31.6%: PR (partial response): 26.3%, SD (stable disease):15.8%, PD (progressive disease):6.3%]. At the last follow up 44.4% of MYD88 mutated WM had PD where as no patient in MYD88 WT had changed their initial post treatment status. Two patients with MYD88 mutation died due to disease related complications. Conclusion Our data indicates that WM is a biologically heterogeneous subset dichotomized by MYD88 mutations. WM patients with MYD88 mutations present at younger age with high tumor burden in the bone marrow, high risk of progression and poor therapeutic response. Although limited in number, MYD88 negative WM patients were not associated with PD as compared to the mutated group. Overall MYD88mutation may be considered as an adverse prognostic factor in WM. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 695 Background Radotinib is a novel, selective Bcr-Abl tyrosine kinase inhibitor (TKI) developed by IL-YANG Pharm, South Korea. Radotinib showed a good efficacy and safety profile to chronic myeloid leukemia (CML) in preclinical and phase 1 clinical studies. To investigate the clinical efficacy and safety of radotinib 400 mg twice daily, data from CML patients treated during phase 2 clinical trial are reported. Methods Philadelphia chromosome (Ph+)-positive chronic phase CML (CP-CML) patients who failed or were intolerable to TKIs (imatinib and/or dasatinib and/or nilotinib) were enrolled between July 2009 and November 2011. Patients were treated with radotinib 400 mg twice daily for 12 cycles (1 cycle=4 weeks). The primary end point was an achievement of major cytogenetic response (MCyR, Ph+£35%) by 12 months. Safety parameters were also analyzed. Results A total of 77 CP CML patients (18 years of age or over) were enrolled from 12 sites in Korea, India, and Thailand. This analysis includes data from last enrolled patient who received at least 3 months of radotinib therapy. The median age of patients was 47 (range; 24–76) years, and 65 (84.4%) were imatinib-resistant and 12 (15.6%) were imatinib-intolerant. Four patients also had intolerance to dasatinib. With a median follow-up of 10.6 months, treatment with radotinib is ongoing in 46 patients (59.7%) and 31 patients (40.3%) discontinued the treatment including two deaths (2.6%). However, there were no CML-related deaths. Median duration of radotinib exposure was 296 (8–798) days. Overall MCyR rate was 63.6%, including 35 patients (45.4%) complete cytogenetic response and 14 patients (18.2%) partial cytogenetic response. The median time to MCyR was 2.8 months (85 days) and the median duration of MCyR was 315 (range; 5–726) days. Of patients achieving complete cytogenetic response, 37% (13/35) achieved major molecular response. Within follow-up durations, 44 patients (57.1%) required dose interruption and 41 patients (53.3%) had dose reduction. Most common grade 3/4 hematologic and laboratory adverse events (AEs) were thrombocytopenia (27.3%), neutropenia (10.4%), anemia (6.5%), and hyperbilirubinemia (31.2%). Common non-hematologic AEs were rash (29.8%), fatigue (14.3%), nausea/vomiting (14.3%), headache (13.0%), and pruritus (11.7%). The majority of AEs were easily manageable with temporal dose interruption and/or reductions. In all patients with CP-CML treated with second-line radotinib, estimated progression-free survival and overall survival rate at 12months was 84.9% (95% CI, 72.7–92.0%) and 97.4% (95% CI, 89.9–99.3% ), respectively. Conclusion Radotinib phase 2 trial confirmed the efficacy and safety of radotinib 400 mg twice daily in patients with CP-CML after failure to TKIs. Most of the AEs occurred in the early treatment period, were tolerable, and were easily controlled by dose interruption or reduction. Disclosures: Off Label Use: Radotinib, new BCR/ABL tyrosine kinase inhibitor, treatment for CML. Lee:IL-YANG Pharm.: Employment. Park:IL-YANG Pharm.: Employment. Woo:IL-YANG Pharm.: Employment. Kim:IL-YANG Pharm.: Employment. Lee:IL-YANG Pharm.: Employment. Cho:IL-YANG Pharm.: Employment. Shin:IL-YANG Pharm.: Employment. Kim:IL-YANG Pharm.: Employment. Kim:IL-YANG Pharm.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Description: Introduction The two relevant questions that emerge and remains unanswered in the management of adult lymphoblastic lymphomas (LBL) are- how to select patients for mediastinal radiation and whom to subject for autologous transplant. Mediastinal radiation or intensification of therapy may reduce the mediastinal recurrence- a common site for relapse. It is also understood that not all patients with residual mediastinal mass relapse. The inability of computed tomography to differentiate between necrotic and viable disease in a residual mediastinal mass post induction therapy led us to explore PET-CT as modality to differentiate the same. In a retrospective analysis we evaluated the role of post-induction chemotherapy PET-CT in predicting the risk of relapse or progression in adult LBL patients. Methods In a single centre retrospective analysis we included newly diagnosed LBL patients (〉15 years) who were treated with ALL- like therapy between January 2010 and February 2013. All patients who underwent PET-CT after induction chemotherapy were analysed. SUVmax was used to assess the response. Details of demographic variables, diagnosis, subtype, baseline LDH, bone marrow involvement, cerebrospinal fluid analysis, chemotherapy, radiotherapy, responses, relapse/progression, death and its cause and last follow up date were taken from electronic medical records. Results Twenty-two patients (17 males and 5 females) with median age 24.5 years (range, 16-44 years) were analysed. All patients had T- LBL. Thirteen patients (13/22) had stage IV disease (Ann Arbor stage) and all had bulky mediastinal mass at diagnosis. None of the patient had CSF or bone marrow involvement. Raised LDH and low albumin were present in 80% and 60% of patients respectively. Median WBC was 10,200/cumm (range, 4400-15300/cumm). All but 4 patients received BFM-90 ALL protocol based therapy. After induction 19 patients achieved complete remission on PET-CT. Patients who had residual mediastinal masses on PET-CT relapsed during later phase of therapy (all within 6 months) in mediastinum and died subsequently. Mediastinal radiation was given to one of these patients but it did not prevent a subsequent relapse. One patient who achieved complete response had bone marrow relapse after 16 months of therapy. Three patients had treatment related death (sepsis). At median follow up of 14 months 1-year overall survival was 69% and progression free survival was 78%. Conclusion Post induction therapy PET-CT seems to have prognostic role and may predict relapse for patients with residual disease activity. Such patients should be considered for treatment intensification. However, the role and timing of mediastinal radiation in such patients remains investigational. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Plasmacytoid dendritic cells (pDCs) are a subset of immune cells that secrete type 1 interferons and serve as antigen presenting cells. In many tumors increased pDC frequencies have been observed and are involved in tumor response initiation. However, there is not much data in acute myeloid leukemia especially in the context of minimal residual disease and outcome. Here we evaluated the frequencies of pDCs in the post induction bone marrow and found a significant correlation with post induction MRD levels. Furthermore, we found that high levels of pDCs in MRD positive patients confer a better overall survival (OS). Methods: All adult (〉18 years ) of patients who were treated for AML [other than AML with t(15;17)] were accrued over a 2 year period. All patients received "3+7" induction therapy with daunorubicin and cytarabine. If patients were in morphological CR at end of induction, they either received 3 courses of 12-18 gm/m2 high dose cytarabine (HiDAC) or aBMT if feasible. The presence of MRD was assessed using 8 colour flow cytometry on a post induction bone marrows using CD45, CD36, CD38, CD123, CD33, CD117, CD34, HLADR, CD7, CD56, CD13, CD19, CD16, CD11b, CD15 and CD14. Minimum of 500,000 events were acquired/tube on an 8 colour BD FACS Canto II or a 10 colour BC Navios instruments. Kaluza software (v1.3) was used to analyze the .fcs files. MRD was calculated as a percentage of abnormal leukemic cells per total viable cells as gated in forward scatter v side scatter plot. pDCs were calculated as CD123 bright population which expressed HLA-DR (while gating on the progenitors and monocytes based on their expression of CD45 and side scatter). The pDC percentages were counted as a fraction of all viable cells. pDCs were divided into pDC High and pDC Low groups, based on a median pDC value of 0.1%. OS was calculated from start of induction therapy to time of last follow up or death. Chi Squared test was used to analyse categorical values of pDC (hi v/s low) and MRD (positive v/s negative). Log rank test was used to compare pDC groups in MRD positive subset. Results: At a median follow up of 16 months, OS was 47.8%. After exclusion of induction deaths, a total of 94 patients of adult AML was assessed for the presence of MRD at the end of induction. Of these MRD was detected in 48 (51.1%, range 0.01-40%). pDC values ranged from