ALBERT

Description: Abstract 4759 Both Dasatinib and Nilotinib have proven themselves as more effective but costly first line therapy in chronic myeloid leukemia (CML) than imatinib mesylate (IM). Hence, IM would continue to be used as first line therapy in developing countries because of economic reasons. Thus simple diagnostic tools are required which can triage CML patients into different risk categories. Presence of bone abnormalities (osteoblastic, osteolytic and mixed) in CML was generally associated with poor outcome in pre-imatinib era. Nuclear bone scintigraphy is a simple test that has universal availability. The significance of these abnormalities in imatinib-era has not been investigated. We proposed to evaluate the significance of bone abnormalities as seen on nuclear scintigraphy in CML at diagnosis and at follow-up. The bone scintigraphy was performed with 99m Tc methylene di phosphonate 3-hours after an intravenous injection of 740 MBq of the radiotracer. Regions of interest (ROI) were marked using standard software. A second ROI was marked on the diaphyseal region of the involved long bone. The ratio of average counts per pixel between the involved and the normal areas was calculated for each long bone. The average ratios of the right and left half of body were calculated separately. This average scintigraphic quantification ratio were compared before and after IM therapy. The standard investigations including bone marrow examination and cytogenetics studies were done at diagnosis and at follow-up. The bone scintigraphic abnormalities were correlated with cytogenetic remission after 6 months of IM therapy. The starting dose of IM in chronic phase was 400 mg/day and in advanced phase 600 mg/day. The study was approved by institute review board and was carried out according the declaration of Helsinki. Forty-three newly diagnosed CML patients gave consent for the study. The mean age of patients was 40.8+14.6 and male female ratio was 25:18. Thirty-two patients were in chronic phase and 11 were in advanced phase (accelerated or blast crisis). The prevalence of bone scintigraphy abnormalities were found in 76.7% patients (75% in chronic phase and 81% in advanced phase, p =0.06). No bone abnormalities were detected in 10 patients. At a median follow-up of 7 months (range 5–8 months of IM therapy), 16% patients achieved completed cytogenetic remission (CCR) and 80% achieved partial cytogenetic remission (pCR). The average bone quantification decreased from 3.34+1.05 to 2.07+0.44 among patients in CCR and 2.47+0.57 among patients in pCR. One CML patient showed increase in bone quantification from 3.61 at baseline to 4.14 at 6 months and on bone marrow examination, he was diagnosed in blast crisis. No relationship of bone abnormalities was found with Sokal score at baseline. Bone abnormalities as seen on nuclear scintigraphy are thus common among patients with CML. They tend to resolve on IM therapy. However, a longer follow-up of patients is required for further evaluation of this technique in CML patients and whether it can replace sophisticated prognostic molecular techniques which are inaccessible in resource-constraints settings. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Acute promyelocytic leukemia (APML) is amongst the most curable malignancies with survival close to 80% [1]. Combination of all-trans- retinoic-acid (ATRA) and anthracyclines is the current standard of care for high-risk APML patients [2]. Literature on combination of arsenic trioxide (ATO) with ATRA in high risk APML, the number of cycles and long-term toxicity of ATO is scarce [3]. Methods: It is a single center retrospective study. Diagnosis of APML was made by bone marrow (BM) and PML-RARα detection by RT PCR. Patients with high risk APML (defined as TLC〉10000/µL) enrolled after 2006 were included and treated with combination of ATO/ATRA as per the protocol (Fig. 1). RT PCR for PML-RARα was done after remission induction, completion of consolidation and 6 monthly thereafter. Results: A total of 39 high risk APML patients were treated during the study period (25 males, 14 females) with median age 31y (range 15-50). Cohort was poorly educated (median - 10th standard) and were from poor socioeconomic strata (mean monthly income - INR 7000, 1USD=65INR). The major presenting complaints were bleeding manifestation and fever (78%, 84% respectively) for a median duration of 30 days (range 3-90d, 95% CI - 14.8). Baseline clinical, hematological and coagulation parameters are as enumerated in Table1.Table 1.Descriptive statistics high risk APML patients at baselineMinimumMaximumMeanStd. DeviationHeight (cm)148180163.109.91Weight (kg)35.080.055.4711.75Peripheral blood smear features at presentationHemoglobin (g/dL)4.113.37.132.36Leucocyte count (/µL)107001237004597635230.92Platelet ( x 109/L)625528944.76Blasts and Promyelocytes (%)010070.8535.57Bone marrow findings at diagnosisBlasts09417.5827.43Promyelocytes29670.2423.14Coagulation parameters at presentationPT (s)113120.104.22aPTT (s)203327.793.34Fibrinogen (g/L)0.683.841.890.81 Complications: DIC was present in 66.7% of the patient at baseline with the median duration to resolution of DIC on ATO/ATRA being 7 days (range 4 - 25d). Thrombosis was present in 17.1% of the patients. Differentiation syndrome (DS) was seen in 59% (n-23) of the patients at mean duration of 5.6 days of starting therapy (range: -4 to 14d). Twenty one percent of patients with DS (n-5) succumbed to death and all these patients had features of spontaneous DS prior to starting ATO/ATRA. Deaths due to differentiation were primarily seen in during the first week of starting therapy (median-D4). In rest all cases DS improved with dexamethasone 10mg BD and interruption of ATO/ATRA. Outcomes: Median duration to hematological remission was 31days (range: 2-59d). Bone marrow remission was attained in all patients alive at the end of induction. Molecular remission was attained in 100% of these patients. OS was 84.1% (Fig 2A). Log survival curve (Fig 2B) elucidates the fact that those patients who survived the induction therapy had no mortality further during the course of illness. Event free survival (EFS) was 84.1%, same as OS suggesting no patients relapsed during the therapy. Mean follow up of the cohort was 910 days (range 1 - 2681d, SD - 854.3d). Long term follow up these patients showed no evidence of secondary malignancy as feared by most authors for giving ATO therapy. Conclusions: Four cycles of ATRA/ATO with two years of maintenance therapy produces long-term remission with low risk of relapse and no arsenic induced long term toxicities in patients with high risk APML. REFERENCES: 1. Sanz MA, Lo-Coco F. Modern approaches to treating acute promyelocytic leukemia. J Clin Oncol 2011;29:495-503. 2. National Comprehensive Cancer Network (nccn). NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia. Ver. 2.2013. Fort Washington, PA: nccn; 2013. 3. Seftel MD, Barnett MJ, Couban S, Leber B, Storring J, Assaily W, Fuerth B, Christofides A, Schuh AC. A Canadian consensus on the management of newly diagnosed and relapsed acute promyelocytic leukemia in adults. Curr Oncol. 2014 Oct;21(5):234-50. Figure 1. Protocol of ATO/ATRA therapy. Legend: BM - Bone marrow, Consol - Consolidation, PCR - Polymerase chain reaction, DIC - disseminated intravascular coagulation, ANC - absolute neutrophil count, Wk - week, OD - once daily. Figure 1. Protocol of ATO/ATRA therapy. Legend: BM - Bone marrow, Consol - Consolidation, PCR - Polymerase chain reaction, DIC - disseminated intravascular coagulation, ANC - absolute neutrophil count, Wk - week, OD - once daily. Figure 2. Kaplan Meier curves (A) Cumulative survival curve showing 84% OS. (B) log survival curve showing no mortality after the initial 90 days after starting therapy. Figure 2. Kaplan Meier curves (A) Cumulative survival curve showing 84% OS. (B) log survival curve showing no mortality after the initial 90 days after starting therapy. Disclosures No relevant conflicts of interest to declare.

Description: Introduction Angiogenesis is one of the central dogmas in growth and progression of a malignant tumor including malignant lymphoma. Lymphoma is a tumor originating from immune cells and lymphoid malignancies and it can alter normal immune function. However, nature of the immune dysfunction is not well defined. Inflammatory mediators acting through Th1/Th2 cytokines and growth factors secreted by the infiltrating inflammatory cells are known to have both direct and indirect angiogenic effects on endothelial cells.Whether tumor angiogenesis in lymphoma patients is associated with alteration in inflammatory cytokines is an unexplored area.Whether extent of angiogenesis at baseline and elevation of levels of biomarkers in the serum have any bearing on chemotherapy response in a patient of B-NHL remains an unanswered question. Methods Forty nine cases of de novo DLBCL with available formalin fixed paraffin embedded (FFPE) block, serum (stored at -80˚C)and IPI were reviewed using the diagnostic criteria defined in the Revised European-American Classification of Lymphoid Neoplasm's.BD Pharmigen™cytometric bead analysis (CBA) Human Th1/Th2 Cytokine Kit II (Catalog No. 560484) was used to quantitateInterleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-10 (IL-10), Tumor Necrosis Factor (TNF-α), and Interferon-γ (IFN-γ) protein levels against internal standard controls. BD FCAP ArrayTM software was used to analyze all the cytokines levels respectively. Baseline angiogenesis in tumor was assessed by histopathologic examination for micro vessel density. Microvessel density was examined using CD34 antibody (clone QBEnd 10, Dako, Denmark), an endothelial cell marker. Vascular "Hot Spots" were identified at low power and the visual analog system was used for counting at 40X in at least five independent microscopic fields per tissue section. The mean of five fields was calculated and divided by the field area (1 HPF=0.19 mm2) to obtain the density count in mm2. Precautions were taken to count vessels at the center of the tumor and to avoid the periphery of the tumor to obtain true representation of tumor vasculature. Median value was calculated for the continuous data and CD34, IL-6, IL-10, IL-4, IL-2, IL-17, TNF-α, IFN-γ divided into categorical variables based on median value. Kaplan-Meier method was used to estimate event-free survival (EFS) distribution.Cytokine profile and microvessel density were correlated with EFS for identification of prognostic marker. Informed consent was taken from all the patients enrolled in the study in accordance with IEC, PGIMER guidelines. Results Forty nine DLBCL cases in the study included thirty (61%) males and nineteen (39%) females (male/female, 1.6:1). The median age of patients was 56 years (range, 17 - 80 years). Stage I/II were seen in 40% patients while stage III/IV were seen in 60% patients. Fifty-four patients had extranodal disease. Forty five, 15 and 40% patients had low, intermediate and high risk IPI respectively. All but 3 patients were treated with RCHOP based regimen. Remaining 3 patients 2 received bendamustine with rituximab while one recevied only CHOP. CR rate was 58.8% while ORR was 70%. At the time of analysis three patients had died. On univariate analysis, IL-10, a cytokine of TH2 response, was identified as a promising prognostic factor for EFS (p