ALBERT

Description: Multiple Myeloma (MM) fits in the group of plasm cell disorders characterized by neoplastic proliferation of single clone of plasma cell engaged in the production of a monoclonal immunoglobulin. The cause of MM is unclear, but a genetic predisposition may play a role and cytogenetic abnormalities are considered to be the most important prognostic factor. The proteomic analysis of MM emerges as a key complement to gene expression profiling, primarily because regulation of protein expression can buffer the magnitude of changes occurring at the gene transcription level. In the present study, to identify biomarkers of initial diagnosis, detection of relapse, monitoring for minimal residual disease and prognostic marker in MM by a lesser invasive method, serum proteins reflecting alteration in their proteomes were analyzed. We compared two-dimensional electrophoresis patterns of human sera of twelve patients with multiple myeloma with that of normal twelve subjects. The differentially expressed spots were identified by matrix-assisted laser desorption/ionization-time-of flight (MALDI-TOF) and electrospray ionization quadupole time of flight (ESI-Q-TOF) mass spectrometry. We identified several proteins altered in sera of MM patients. These results suggest that these proteins can be used as a lesser invasive diagnostic, monitoring and prognositic biomarkers of MM if further studies were done.

Description: Chronic myeloid leukemia(CML) is a clonal myeloproliferative disorder and increased angiogenesis in bone marrow is a feature of CML. Vascular endothelial growth factor(VEGF) is a potent angiogenic peptide and microvessel density(MVD) is increased in bone marrow of CML. In this study, the effect of imatinib mesylate therapy on angiogeneisis was investigated and compared with allogeneic bone marrow transplantation(BMT) with philadelphia chromosome positive/BCR-ABL+ CML in first chronic phase. Immunohistochemical staining for detecting VEGF protein was performed by labeled avidin-biotin method on the formalin-fixed and paraffin embedded bone marrow biopsy samples of 10patients of allogeneic BMT, 20patients of imatinib mesylate therapy and 10normal control. Initial and sequential, after at least 12 months of therapy, bone marrow biopsy examed and all patients achieved complete cytogenetic remission. Microvessel was scored in at least 3 areas(*200 fields) of the highest MVD in representative sections of each bone marrow biopsy specimen using immunohistochemistry for CD32 antigen. Patients with Imatinib mesylate therapy and allogeneic BMT induced a significant reduction of MVD (normalization in comparison with controls). MVD was no significant difference between the patients with imatinib therapy and allogeneic BMT. VEGF was mainly expressed myeloid progenitors and less abundantly megakaryocytes and mature granulomonocytic cells. Expression of VEGF, it was significantly decreased in patients with Imatinib mesylate therapy and allogeneic BMT(normalization in comparison with controls). VEGF expression was no significant difference between the patients with imatinib therapy and allogeneic BMT. First line therapy with imatinib mesylate was normalization of bone marrow vascularity compared with allogeneic bone marrow transplantation of CML in first chronic phase.

Description: Abstract 4390 Background: The relation between venous thromboembolism (VTE) and cancer is well recognized, and risk of VTE increases with disease progression. However, the information available about VTE in terminally ill cancer patients in palliative care unit (PCU) is limited. We evaluated the incidence, risk factor and outcome of VTE in terminally ill cancer patients in PCU. Methods: The clinical records of Chonbuk National University Hospital were searched for all patients with acute, symptomatic deep-vein thrombosis (DVT) and pulmonary embolism (PE) in PCU from April 2008 through July 2010. Results: A total of 220 patients were included in the study and the median survival after palliative care was 16 days. Ten patients (4.5%) were newly diagnosed with VTE in PCU and nine patients (4%) had a history of VTE. All ten patients presented with DVT and the sites included lower extremities (eight) and upper extremities (two). All patients had more than one risk factor: immobilizations in 6 patients (54%), tumor compression in 3 patients (27%), and central venous catheter in 2 patients (18%). After diagnosis, 7 patients received treatment with low-molecular weight heparin (LMWH) and 4 of them switched to warfarin. The median duration of anticoagulation was 26 days. Major bleeding was noted 2 patients but VTE-related death did not occur. The median survival after diagnosis of VTE was 28 days. Conclusion: The incidence of VTE in PCU was relatively low. All patients had one or more risk factors and DVT of lower extremities was most frequent. Although anticoagulation was acceptable treatment except bleeding risk, the risks vs benefits need to be counterbalanced. Further large scale studies are needed to address many of these issues. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Interim positron emission tomography (PET) scan has shown to be useful for evaluating response in Hodgkin lymphoma. And, there has been increasing interests in using interim PET for predicting outcomes in diffuse large B-cell lymphoma. However, few data are available regarding prognostic value of interim PET in patients with peripheral T cell lymphoma (PTCL). Recently, in an attempt to standardize reporting criteria for interim PET, Deauville five-point scale (5-PS), which visually assess the uptake of lesions in comparison with background mediastinal and liver uptakes, were proposed, but this was not investigated in PTCL. Therefore, the aim of this study was to determine the prognostic role of interim PET, assessed by Deauville 5-PS, in patients with PTCL treated with systemic chemotherapy. Patients and Methods We consecutively enrolled newly diagnosed PTCL patients, treated with systemic chemotherapy (CHOP/CHOP-like or non-anthracycline-based) and had the baseline PET data with ³1 evaluable hypermetabolic lesion between 2006 and 2012 in two Korean institutions. Patients treated with upfront chemoradiotherapy before interim PET scan were excluded. Interim PET scan was performed after 3 cycles of chemotherapy, before 1 week of the next cycle. Interim PET response was visually assessed by 5-PS and four point or higher was regarded as positive. All PET assessment was performed by 2 nuclear medicine specialists at each institution, and the discrepancy of assessment was resolved by the agreement through discussion. Results A total of 35 patients was included in this analysis. The median age was 60 years (range, 31-79) and 26 (74%) were male. Histologic subtypes included were PTCL, not otherwise specified in 10 (29%), extranodal NK/T cell lymphoma in 8 (23%), angioimmunoblastic T cell lymphoma in 7 (20%), anaplastic large cell lymphoma, ALK negative in 4 (11%), and others in 6 (18%). 22 patients (63%) were presented as advanced stage disease and 9 (26%) had B symptoms. ECOG performance status was ≥ 2 in 7 (20%), serum LDH level was elevated in 16 (46%), and bone marrow was involved in 5 (14%). Thus, 14 patients (40%) were classified as high risk (≥ 2 factors) by the prognostic index for PTCL (PIT). 31 patients (89%) completed planned systemic chemotherapy ± involved-field radiotherapy and 25 (71%) achieved complete response by systemic chemotherapy. 10 patients (29%) underwent consolidative autologous stem cell transplantation (ASCT). Using 5-PS, interim PET scan was visually scored as follows; 1 point in 10 patients (29%), 2 in 6 (17%), 3 in 8 (23%), 4 in 7 (20%), and 5 in 4 (11%). Among these, 11 patients (31%) had 4 point or above were considered positive for interim PET scan. With a median follow-up of 43.4 (range, 4.3-89.8) months, progression-free survival (PFS; median, 5.2 vs 38.0 months, respectively; P=0.001) and overall survival (median, 12.6 months vs not reached, respectively; P=0.004) was significantly worse in patients with positive interim PET than those with negative results. In multivariate analysis for PFS, high risk of PIT (HR, 3.67; 95% CI, 1.13-11.99) and positive interim PET (HR, 4.02; 95% CI, 1.32-12.23) were independently associated with faster disease progression, whereas consolidation with ASCT was independent prognostic factor for better PFS (HR, 0.23; 95% CI, 0.06-0.84). Conclusion Visual assessment of interim PET scan using Deauville 5-PS appears to predict early outcomes of patients with PTCL. Patients with positive interim PET shows highly predictive of extremely poor outcomes. Therefore, our findings suggest further studies regarding early stratification based on interim PET results as a response-adapted treatment strategies in patients with PTCL are needed to improve outcomes. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction Imatinib (IM) is an effective treatment in patients with chronic phase chronic myeloid leukemia (CML-CP). In the previous report (Leukemia research, 2012;36:689-693), we demonstrated that IM could be discontinued in CML patients achieved undetectable minimal residual disease (UMRD) after the treatment of front-line IM therapy. These observations were confirmed by prospective STIM1 and TWISTER studies. However, in both studies, approximately half of patients were treated with front-line interferon therapy, which might be a confounding factor when considering the impact of prior interferon on treatment free remission (TFR) in the previous IM discontinuation studies. Thus, the aim of this study was to investigate the long-term outcomes of IM discontinuation in patients with CML-CP, who have treated with front-line IM therapy and achieved UMRD. Patients and methods We consecutively enrolled patients with CML-CP, discontinued IM therapy after achieving UMRD for at least 12 months in 2 Korean institutions from June 2009 to Jan 2013. Patients with a prior history of any other treatment (〉1 months) for CML before IM administration were excluded. UMRD was defined by undetectable levels of BCR-ABL transcript by RQ-PCR with sensitivity of at least 0.0046%IS. After discontinuation, BCR-ABL/ABL ratio was monitored by RQ-PCR monthly during the first 6 months and every 3 months thereafter, and molecular relapse was defined by detectable levels of BCR-ABL transcript in two successive assays. Results Nineteen patients (8 male, 11 female) with a median age of 52 years (range, 29-78) were included. The reasons for discontinuing IM were shared decision between physicians and patients with long undetectable BCR-ABL transcript (n=9), chronic adverse events of IM (n=6), patient’s request (n=3), and wish for pregnancy (n=1). At initial diagnosis, the Sokal score was low to intermediate in 11 patients and high in 8 patients. All patients started IM at a dose of 400mg/day and median interval between IM initiation and UMRD was 21.5 months (range, 7.0-61.9). IM therapy was then maintained during a median of 34.8 months (range, 12.1-72.4). With a median follow-up of 52.1 months (range, 17.5-60.5), the overall probability of UMRD persistence at 4-year was 22.1% (95% CI, 11.6-32.6). Fourteen patients (73%) lost UMRD after a median of 4.0 months (range, 1.1-22.8). 12 patients relapsed within first 9 months and 2 late relapse were identified at 20.5 and 22.8 months, respectively. No patients included in this analysis were progressed to advanced stage CML or died. IM therapy was resumed in all patients with molecular relapse, but 2 patients were switched to dasatinib owing to chronic adverse events of IM. At the time of this analysis, all patients were still sensitive to IM and dasatinib therapy. 12 patients re-achieved UMRD and 2 patients maintained stable major molecular response. In univariate analysis for molecular relapse, high risk of Sokal score (P

Description: Background Interim 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan may predict outcomes in patients with diffuse large B-cell lymphoma (DLBCL). However, overall accuracy in predicting treatment outcomes on adopting 5-point Deauville score (DS) was considerably low in DLBCL because of mainly low positive predictive value of interim PET-CT scans. This suggested that additional tool might be needed to more accurately predict treatment outcomes. International prognostic index (IPI) was greatly associated with outcomes for DLBCL and considered to reflect biologic aggressiveness of DLBCL. Thus, we hypothesized that combined assessments using DS on interim PET-CT scan and baseline IPI might improve the prediction of treatment outcomes in DLBCL patients. In this study, we aimed to establish the risk predicting model integrating DS on interim PET-CT as an estimate of early metabolic response and baseline IPI as a predictor of biologic aggressiveness in patients with newly diagnosed DLBCL. Methods In this retrospective cohort study, we consecutively enrolled patients with newly diagnosed DLBCL. Patients were eligible if they were histologically confirmed with DLBCL from Jan 2007 to June 2016, received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), and had PET-CT scan data at baseline and at interim after 3 cycles of R-CHOP. Primary CNS or transformed DLBCLs were excluded. Interim PET-CT was assessed using 5-point DS and four point or higher was regarded as positive. All PET-CT scans were assessed by 2 experienced nuclear medicine physicians, who were masked to treatment outcomes of the patients. Discrepant interpretations between 2 nuclear medicine physicians were resolved by consensus through mutual discussion. Results A total of 316 patients were screened for eligibility. Ninety-six patients were excluded from the analysis due to following reasons: unavailable baseline (n=9) or interim PET-CT scans (n=48), early death before interim PET-CT (n=16), Primary CNS or transformed DLBCLs (n=15), and insufficient medical records (n=8). Thus, 220 patients were analyzed. Median age was 64 years (range, 19-87) and 132 (60%) were male. Based on the IPI risk, patients were classified as the low or low-intermediate (LI; N=126, 57%), and high-intermediate (HI) or high (N=94, 43%) groups. Interim DS was determined as 1 (n=67, 30.5%), 2 (n=65, 29.5%), 3 (n=39, 17.7%), 4 (n=36, 16.4%), and 5 (n=13, 5.9%). With a median follow-up of 56.6 months (IQR 36.0-71.8), 5-year progression-free survival (PFS) rate was 65.2% (95% CI, 58.1-72.3) and overall survival (OS) rate was 69.9% (95% CI, 63.2-76.6). Interim DS (1-3 vs 4-5) and the IPI (low-LI vs HI-high) were independently associated with PFS (for interim DS of 4-5, hazard ratio [HR], 2.96 [95% CI, 1.83-4.78], P 〈 0.001; for HI-high IPI, HR, 4.84 [2.84-8.24], P 〈 0.001) and OS (for interim DS of 4-5, HR, 2.98 [1.79-4.98], P 〈 0.001; for HI-high IPI, HR, 5.75 [3.14-10.51], P 〈 0.001) in the multivariate analysis. We stratified patients into 3 groups based on the risk of progression: Low (low-LI IPI and interim DS 1-3), Intermediate (low-LI IPI with interim DS 4-5, or HI-high IPI with interim DS 1-3), and High (HI-high IPI and interim DS 4-5) risk groups. The risk stratification model showed a significant association with PFS (for low risk vs intermediate risk, HR 3.98 [95% CI, 2.10-7.54], P

Description: Acute Myeloid Leukemia (AML) develops as the consequence of a series of genetic changes in a hematopoietic precursor cell. However, the definitive diagnostic protein-biomarkers for AML are still unclear, and monitoring these markers has not yet been completely achieved. In our study, to identify the biomarkers for an initial diagnosis, detection of relapse and monitoring the minimal residual disease in acute myeloid leukemia (AML) by a lesser invasive method, serum proteins reflecting alteration in their proteomes were analyzed. We compared two-dimensional electrophoresis patterns of human sera of twelve patients with acute myeloid leukemia with that of normal twelve subjects. The differentially expressed spots were identified by matrix-assisted laser desorption/ionization-time-of flight (MALDI-TOF) and electrospray ionization quadupole time of flight (ESI-Q-TOF) mass spectrometry. Eight proteins that expressed differentially in AML group were found. The expression levels of alpha-2-HS-glycoprotein, complement-associated protein SP-40,40, RBP4 gene product, lipoprotein C-III and an unknown protein were down-regulated in serum of AML patients, whereas the other three proteins including immunoglobulin heavy chain variant, proteosome 26S ATPase subunit 1 and haptoglobin-1 up-regulated. These results suggest that these proteins can be used as less invasive diagnostic and monitoring biomarkers of AML if further studies were done.