Search

BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

The incidence and outcomes of aplastic anemia (AA) in Asia remain limited. This study aimed to explore the incidence and outcomes of patients with adult AA across the country of Thailand. This is a prospective multi-center nationwide population-based observational study of AA patients aged at least 15 years old, diagnosed from August 2014 to July 2016, with a longitudinal follow-up period over 2 years. There were 348 newly diagnosed adult AA patients during the enrollment period, giving an annual incidence of 4.6 per million. The incidence of severe (SAA) and very severe aplastic anemia (VSAA) (3.8 per million) was higher than non-severe AA (NSAA, 0.8 per million). The peak incidence was observed in the patients aged from 80 to 89 years old (14.4 per million). The 2-year overall survival (OS) in NSAA, SAA, and VSAA were 65.5%, 49.3%, and 20.1%, respectively (P P P = 0.037), respectively. The incidence of adult AA in Thailand is higher than those in Western countries, and the peak incidence is in the elderly. rATG ± CsA provided a better response than anabolic steroids, translating to the superior survival in SAA/VSAA treated with rATG ± CsA.

Systemic reports on the descriptive epidemiology of non-Hodgkin lymphoma (NHL) from Southeast Asia are scarce. A nationwide multi-institutional registry was conducted to compare the histopathology, clinical features, and survival of Thai adult patients with NHL using large registries, especially those from Far East Asia (FEA). Using a web-based registry system, 13 major medical centers from the 4 geographic regions of Thailand prospectively collected, from 2007 to 2014, the diagnostic pathology, according to the World Health Organization classification, 2008, clinical features and survival of 4056 patients who were newly diagnosed with NHL. The median age of the patients was 56 years (range, 16-99 years). The male-to-female ratio was 1.3:1. From the total of 4056 patients, T/NK-cell lymphoma (TNKCL) accounted for 12.6% of cases, and 5.1% had human immunodeficiency virus-associated lymphoma. The four leading histological subtypes were diffuse large B-cell lymphoma, not otherwise specified (58.1%); follicular lymphoma (5.6%); extranodal mucosa-associated lymphoid tissue lymphoma (5.2%); and peripheral T-cell lymphoma, not otherwise specified (4.0%). With a median follow-up duration of 46.1 months, the median overall survival of B-cell NHL was significantly longer than that of patients with TNKCL (76.5 vs 28.8 months, P = .0001). Compared to FEA, the Thai registry had an approximately one-half lower relative frequency of TNKCL; the prevalence of extranodal mucosa-associated lymphoid tissue lymphoma was much lower than in Korea, and the frequency of extranodal TNKCL, nasal type, was strikingly low compared to China. It is concluded that while the median age of Thai patients with NHL was approximately a decade younger than for Caucasians, the long-term survival rates for most histological subtypes were comparable. While the histological distribution generally complied with the characteristic Asian features, some differences from FEA were observed.

Background: Incidence of Aplastic Anemia (AA) in Asia tends to be higher than in western countries, but contemporary real-world incidence and outcomes of AA in Asia remain limited. This study aimed to explore the incidence across the country regions and to evaluate the patient outcomes according to age, the severity of disease, and treatment modalities. Method: This is a prospective multicenter nationwide population-based observational study of patients with AA aged over 15 years old, diagnosed between August 1st, 2014 to July 31st, 2016, with a longitudinal follow-up period over 2 years, from 30 medical centers. Patients with suspected hypocellular MDS and congenital bone marrow failure syndrome were excluded. Results: During the study period of 2 years, there were 348 newly diagnosed patients with aplastic anemia, giving the annual incidence of 4.6 per million inhabitants. There was a higher annual incidence of severe (SAA) and very severe aplastic anemia (VSAA) (3.8 per million) than non-severe aplastic anemia (NSAA) (0.8 per million). The incidence was greater among older patients with a peak incidence in patients aged 60-89 years old. (Figure 1) There was a high variation in the geographic incidences across country regions, ranging from 2.6 to 6.6 per million per year. (Figure 2) The 2-year overall survival (OS) for NSAA, SAA, and VSAA were 65.5%, 49.3%, and 20.1%, respectively (P < 0.001). Patients aged older than 60 years had the worst OS (42.6% as compared with 47.7% for the age 41-60 years and 64.5% for the age 15-40 years, P = 0.002). Among patients with SAA and VSAA (n = 280), the overall response rate (ORR) among patients treated with rabbit anti-thymocyte globulin and/or cyclosporin A (rATG±CsA) was significantly superior than those treated with CsA-based therapy and those treated with anabolic steroid (44.4% vs. 36.4% and 31.2%, respectively, P < 0.001). Among evaluable patients, ORR after the 1st treatment with rATG±CsA at 3, 6, 12 and 24 months were 23.9%, 43.8%, 68.4% and 89.2%, respectively. The 2-year OS among SAA/VSAA patients treated with rATG±CsA, CsA-based therapy, and anabolic steroid were 54.8%, 54.5%, and 37.6% (P = 0.037), respectively (Figure 3). From multivariate analysis, age > 60 years (HR 1.63, 95%CI, 1.14-2.33, P = 0.007), VSAA (HR 2.24, 95% CI, 1.45-3.46, P < 0.001) and not receiving immunosuppressive therapy or anabolic steroid (HR 4.96, 95%CI, 2.88-8.54, P Conclusion: The incidence rate of AA in Thailand from this contemporary nationwide population-based study is high, especially in the elderly. Patients treated with rATG±CsA had superior survival than those receiving anabolic steroid. The real-world outcome of patients with SAA/VSAA, especially in those aged over 60 years, is substantially poor. Figure 1 Disclosures No relevant conflicts of interest to declare.

Event free survival at 24 months (EFS24) has been described as a powerful predictor for outcome in several subtypes of B cell lymphoma. However, it was limitedly described in T cell lymphoma. We explored the implication of EFS24 as a predictor marker for peripheral T cell lymphoma (PTCL). We reviewed 293 systemic PTCL patients at 13 nationwide major university hospitals in Thailand from 2007 to 2014. The median event free survival (EFS) and overall survival (OS) of PTCL patients in our cohort was 16.3 and 27.7 months with corresponding 2-year EFS and 2-year OS of 45.8% and 51.9%, respectively. A total of 118 patients achieved EFS24 (no events during the first 24 mo). Patients who achieved EFS24 had better OS than patients who did not (2-y OS 92% vs 18.8%; HR, 0.1; P < .001). The standardized mortality ratio of patients achieving EFS24 was 18.7 (95% CI, 14.6-22.8). Multivariable analysis demonstrated performance status, histologic subtype, remission status, and EFS24 achievement as independent predictors for OS. Our study affirmed the value of EFS24 as a powerful prognostic factor for PTCL. Further validation in prospective study setting is warranted.

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Secondary central nervous system (CNS) relapse is a serious and fatal complication of diffuse large B cell lymphoma (DLBCL). Data on secondary CNS (SCNS) relapse were mostly obtained from western countries with limited data from developing countries. We analyzed the data of 2034 newly diagnosed DLBCL patients enrolled into the multi-center registry under Thai Lymphoma Study Group from setting. The incidence, September 2006 to December 2013 to represent outcome from a resource limited pattern, management, and outcome of SCNS relapse were described. The 2-year cumulative incidence (CI) of SCNS relapse was 2.7 %. A total of 729, 1024, and 281 patients were classified as low-, intermediate-, and high-risk CNS international prognostic index (CNS-IPI) with corresponding 2-year CI of SCNS relapse of 1.5, 3.1, and 4.6 %, respectively (p

Background: Deep vein thrombosis (DVT) is a silent killer in hospitalized patients. Its prevalence in Thai population may be different from Western countries. Objective: To evaluate recognized risk factors for DVT in high-risk Thai patients according to the American College of Chest Physicians (ACCP). Methods: Hospitalized patients were prospectively enrolled at the Department of Medicine, Khon Kean Hospital. The study period was January 2010 to March 2011. Inclusion criteria were patients who were admitted with either (1) heart or respiratory failure or (2) one of the following conditions: cancer, sepsis, acute stroke, or inflammatory bowel disease. The admission length was at least four days. Patients were excluded if the hospitalization was because of venous thromboembolism or if there was a requirement for heparin therapy. Results: One hundred patients met the study criteria during the study. Of those, 5 patients (5%) had evidence of DVT by ultrasonography. None of these patients had pulmonary embolisms by computed tomographic angiography. In the multiple logistic regression analysis, only acute stroke was significantly associated with DVT. The adjusted odds ratio (OR) was 19.72; (95% confidence interval (CI) 1.37, 284.37). DVT was the only significant factor associated with death during admission with adjusted OR of 30.76 (95% CI: 2.02, 469.03). Conclusions: The prevalence of DVT in hospitalized high-risk patients by ACCP criteria was low. Admission because of acute stroke may increase the risk of DVT and having DVT may result in high mortality.

Introduction: Stage I disease represents a minor subset of aggressive Non-Hodgkin Lymphoma (NHL) accounting around 10%. Overall prognosis is generally good but varied upon different histologic subtypes and topographic presentation. Herein, we describe an implication of event free survival at 12 months (EFS12) as a predictor for outcomes of stage I aggressive NHL including real-world data on clinical characteristics and treatment patterns of stage I aggressive NHL in a resource-limited country. Patients and methods: Thai lymphoma study group conducted the lymphoma registry which prospectively enrolled and systematically followed newly diagnosed lymphoma patients between 2007 and 2014 from 13 nationwide major University hospitals. We abstracted data of stage I aggressive NHL patients from the registry and obtained additional information from medical record. Clinical characteristics, treatment patterns and survival outcomes were described. EFS12 was a binary endpoint defined as whether patients developed events at 12 months after treatment initiation. Overall survival (OS) was defined as duration from a specific time-point either at the time of diagnosis, at EFS12 time-point to or at the event to death from any causes. Logistic regression model was used to evaluate the association between clinical characteristics and EFS12. Cox regression with EFS12 as a time-dependent co-variate and other clinical parameters were applied to evaluate association between EFS12 and OS. Results: Of 4,371 newly diagnosed lymphomas, there was a total of 636 stage I lymphoma patients (6.86%) including 590 NHL (519 B cell, 71 T/NK cell) and 46 HL. Among 590 stage 1 NHL, 435 were considered patients (356 diffuse large B cell lymphoma (DLBCL) and 8 Burkitt lymphoma (BL), 19 peripheral T cell lymphoma not otherwise specified (PTCL-NOS), 7 angioimmunoblastic T cell lymphoma (AITL), 11 anaplastic large cell lymphoma (ALCL), 1 other PTCL subtypes and 33 extranodal NK T cell lymphoma (ENKTL)). Table 1 summarizes baseline characteristics and treatment data of stage I aggressive NHL. At the time of analysis 61 patients relapsed and 146 patients had died. Major causes of death included infection related events (n=37, 25.3%), non-infectious related complication (n=21, 14.4%) and disease progression (n=60, 41.1%) respectively. With a median follow up of 47.3 months, both median event free survival (EFS) and overall survival (OS) were not reached with corresponding 4 years EFS and 4 years OS of 79.0% and 68.9% respectively (Figure 1A). Four-years OS of patients with aggressive B cell NHL, PTCL and ENKTL was 70.2%, 75.5% and 48.0% respectively. A total of 328 patients achieved EFS12 (No event within the first 12 months after first line treatment initiation). Patients who achieved EFS12 had significant better OS than patients who failed to achieve EFS12 (4-years OS 89.1% vs 7.1%, Hazard ratio 25.9, 95% Confidence Interval 17.7-37.9, P Conclusion: Stage I disease represented a small proportion of aggressive NHL. Natural history and prognosis were highly varied depending upon histology. EFS12 was a power prognostic factor for stage I aggressive NHL and could be used as a clinical tool to stratify patients. Optimal treatment is to be defined to improve outcome and meanwhile minimize toxicities for stage I aggressive NHL patients. Disclosures No relevant conflicts of interest to declare.

Introduction : Chronic anemia impairs quality of life and adversely affects survival in patients with MDS. Recombinant erythropoietin (EPO) has been proven in maintaining hemoglobin (Hb) level and reducing red blood cell (RBC) transfusion in this group of patients. However, there were limited reports of EPO-β in MDS patients especially in Asian populations. Method: We have conducted a phase IV, multicenter, prospective, open labelled study in patients with low/intermediate-1 risk MDS to evaluate safety and efficacy of EPO-β 30,000 or 60,000 IU/week up to 12 weeks (NCT02145026). Patients with baseline Hb < 10g/dL were eligible if they required RBC transfusion < 4 unit/ 8 weeks and serum erythropoietin < 500 mU/ml. All enrolled patients will start EPO-β 30,000 IU weekly and their erythroid response will be assessed at week 4 and every 4 weeks thereafter until the end of study. If hemoglobin level reaches ≥ 12 g/dL at any time, EPO-β should be discontinued until Hb levels are ≤ 10 g/dL. While patients with Hb level is less than 12 g/dL and increased less than 1 g/dL from baseline level, a 60,000 IU weekly of EPO-β will be administered subcutaneously until week 12. Up to the clinical cut-off date for this interim analysis, 58 patients were screened, 27 of which were eligible for safety analysis whereas 25 patients were eligible for primary efficacy analysis to evaluate response according to International Working Group (IWG 2006) response criteria in MDS. Results: The median age of patients was 74.6 (range; 53.1-88.5), 18 (67%) were female. Three major subtypes of MDS were refractory cytopenia with multi-lineage dysplasia (RCMD, 44%), refractory cytopenia with uni-lineage dysplasia (RCUD, 32%) and refractory anemia with ring sideroblasts (RARS, 16%). Baseline Hb, hematocrit (Hct) and serum EPO were 8.1±1.3 g/dL, 25.2±3.7% and 89.5±116.6 mU/ml respectively. Twenty-five patients (92%) had serum EPO ≤ 200 mU/ml. There were 16 patients (64.0%) achieved hematologic improvement on erythroid (HI-E), while 6 patients (24.0%) achieved hematologic improvement on platelet (HI-P). Eleven patients (44.0%) (68% of responding patients) achieved Hb≥12 g/dL. Sixteen of 23 patients (69.6%) with serum EPO ≤ 200mU/ml achieved HI-E. Proportion of patients who required at least one RBC transfusion was reduced from 37% (n=10) to 11% (n=3) at the end of the study. By univariate analysis, none of baseline characteristics, including age, gender, comorbidity and MDS subtype, predicted response to EPO-β. From 27 patients eligible for safety analysis, there were 14 adverse events (AEs) and one serious adverse event (SAE) were reported in 13 patients (48.1%). The most frequently reported AEs were increased blood pressure (28.6%; all grade1), infections (21.4%) and gastrointestinal disorders (14.3%). There was no major AEs or SAEs which considered to be related to study drug by the investigators including hypertension, pure red cell aplasia (PRCA), thromboembolism and seizure. Conclusions Preliminary results suggest efficacy and safety of EPO-β in the treatment of anemia in low/intermediate-1 risk MDS patients. Two-third of patients demonstrated HI-E. There were no new unknown AEs found in this study and no SAEs considered related to study drug. Disclosures Charnwiboonsri: Roche (Thailand) Ltd.: Employment.

BACKGROUND Nodal peripheral T-cell lymphomas (PTCLs), except ALK-positive anaplastic large cell lymphoma (ALCL) have inferior outcomes compared with their B-cell counterparts. CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone) is considered the standard therapy despite consistent results showing its ineffectiveness. The addition of etoposide (E) to chemotherapy showed encouraging results in selected subgroups of patients. We performed a matched-pair analysis comparing the efficacy of EPOCH to CHOP for untreated patients with nodal PTCLs, excluding ALK-positive ALCL. PATIENTS AND METHODS According to the Thai Lymphoma Study Group uniform treatment project, 58 patients with nodal PTCLs including angioimmunoblastic lymphoma, ALK-negative ALCL and PTCL, not otherwise specified received conventional EPOCH regimen as frontline therapy between January 2009 and December 2015. These patients were matched to 58 patients receiving CHOP (1:1) in multicenter registry of lymphoma in Thailand between 2007-2014 by center, International Prognostic Index (IPI) and age. Patients who underwent upfront autologous stem cell transplantation (ASCT) were censored at the time of transplantation. RESULTS The baseline characteristics were well balanced between the two groups except a higher proportion of patients with ALK-negative ALCL in EPOCH group (24.1% vs 5.2%) (Table 1). The median cycle of chemotherapy was 6 (range, 1-8) in both groups. Four patients (6.9%) underwent upfront ASCT after EPOCH induction. The overall response rate for evaluable patients were 75.4% (complete response [CR] 57%) and 58% (CR 39%) in EPOCH and CHOP groups, respectively (P CONCLUSION EPOCH provided superior outcomes than CHOP regimen as frontline therapy for patients with nodal PTCLS, excluding ALK-positive ALCL. The promising efficacy of EPOCH warrants further evaluation in prospective randomized controlled study. Table 1 Baseline characteristics of patients with nodal PTCLs treated with EPOCH or CHOP regimens Table 1. Baseline characteristics of patients with nodal PTCLs treated with EPOCH or CHOP regimens Figure 1 Kaplan Meier progression free survival of patients with untreated nodal PTCLs according to chemotherapy regimens Figure 1. Kaplan Meier progression free survival of patients with untreated nodal PTCLs according to chemotherapy regimens Figure 2 Kaplan Meier overall survival of patients with untreated nodal PTCLs according to chemotherapy regimens Figure 2. Kaplan Meier overall survival of patients with untreated nodal PTCLs according to chemotherapy regimens Disclosures No relevant conflicts of interest to declare.

The impact of health insurance with inequitable rituximab coverage on the survival of patients with diffuse large B-cell lymphoma (DLBCL) has never been reported. We conducted a nationwide multicenter analysis on the outcome of 553 adult patients consecutively diagnosed with DLBCL between July 2003 and June 2006, in whom treatment cost was reimbursed under the Civil Servant Medical Benefit Scheme (CSMBS) (n =201) or the Universal Coverage Scheme (UCS) (n =352). The international prognostic index was comparable between the two payment groups. Rituximab-based therapy was administered in 45.3% and 3.1% of CSMBS and UCS patients, respectively (p0.001). With a median follow-up of 24.6 months, the 6-year progression-free survival (PFS) was superior for CSMBS patients (34.2 vs. 23.2%, p =0.005). "Not treated with rituximab-based therapy" was the strongest adverse prognostic feature indicating a short PFS (hazard ratio 2.1, p0.001). It is concluded that lack of access to rituximab is the principal factor accounting for the inferior PFS observed in Thai patients with DLBCL who are treated under the UCS.

INTRODUCTION: Hodgkin lymphoma (HL) is curable if the patients are treated early and properly. Thailand is a country where public health care resources are limited and as such, dacarbazine was not listed in the national drug list, thus, cannot be reimbursed in patients under the Universal Coverage payment scheme which comprised 60-70% of all patients. This study was aimed to compare outcome differences between patients with HL who were treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), ABV (doxorubicin, bleomycin, vinblastine) and COP/ABV (cyclophosphamide, vincristine, prednisolone, procarbazine /ABV) as happened in the real world practice in Thailand. METHODS: From the nationwide multicenter registry of 4,371 newly diagnosed lymphoma patients in Thailand from 2007 to 2014, there were 316 patients with HL. The data is part of the Thai Lymphoma Study Group Registry performed at the thirteen major medical centers in Thailand. The patients' characteristics, treatment options and outcomes were analyzed. RESULTS: The median age was 42 years (range,13-89 years). Male: female was 1.3:1. Fifteen percent of the patients were older than 60 years. Histological subtypes were classical HL, nodular sclerosis, 45.3%, mixed cellularity, 28.6%, lymphocytic rich, 3.5%, lymphocytic depletion 5.1%, nodular lymphocytic predominant, 7.5% and unclassifiable, 10.5%. Fifty percent of patients were stage III/IV and 46% had B symptoms. Clinical characteristics were not significantly different between patients treated with ABVD, ABV and COP/ABV (Table 1). Treatment options were varied according to doctors' preference, hospital strategy and the reimbursement policy. ABVD was the most common prescribed regimen (32.7%); the other options included ABV (29.2 %), COP/ABV (13.1 %), CHOP (2.8 %) and radiotherapy only (1.6%). With a median follow-up of 32 months, patients treated with ABVD had superior 5 year overall survival rate over those treated with ABV (86.6% vs 47.7%, p < 0.001) and COP/ABV (86.6% vs 62.7%, p < 0.01)(Figure 1). Discrepancies in survivals could be demonstrated both in patients with limited as well as in advanced diseases (Figure 2). CONCLUSION: ABVD yielded superior survival compared to ABV and COP/ABV. Dacarbazine is therefore an essential drug for the treatment of HL in developing countries. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Khuhapinant: Roche: Honoraria.

Introduction: Despite improved treatment outcome of DLBCL in the immunochemotherapy era, secondary CNS relapse remains a serious and fatal complication. Several prognostic models were reported in order to define high-risk patients for CNS relapse and provide proper prophylactic strategies. There is no standard approach for CNS prophylaxis in DLBCL with more data suggesting lack of efficacy of intrathecal chemoprophylaxis. In 2013, the DSHNHL introduced a prognostic model including each international prognostic index (IPI) factor (age, lactate dehydrogenase (LDH), stage, performance status (PS), extranodal involvement (EN) and kidney/adrenal involvement) to stratify patients into 3 groups. Herein, we applied and validated DSHNHL model to DLBCL patients treated at nationwide University hospitals in Thailand including analyzing an impact of rituximab and intrathecal chemoprophylaxis on CNS relapse. Method: From the nationwide multicenter registry of 4,371 newly diagnosed lymphoma patients in Thailand between 2007 and 2014, there were a total of 2,399 DLBCL patients. We looked at the incidence and clinical predictors of CNS relapse, the effect of immunotherapy and intrathecal chemoprophylaxis on CNS relapse in DLBCL who were treated with at least one cycle of CHOP-like or intensive chemotherapy regimens. Result: After excluding patients with CNS/ocular involvement at diagnosis, 2,034 DLBCL patients were included in the analysis. Table 1 summarizes baseline characteristics of DLBCL patients. The median follow up time for living patients was 51 months (interquartile range, 22-75 months). A total of 565 patients (27.8%) progressed or relapsed after first-line induction therapy and 61 patients (3.0%) developed CNS relapse. Median time to CNS relapse was relatively shorter than non-CNS relapse (8.4 vs 10.5 months, P=0.07). A total of 729 (35.8%), 1,024 (50.3%) and 281 (13.8%) patients were classified as low-, intermediate- and high-risk groups based on DSHNHL risk model for CNS relapse. Of high DSHNHL risk group, 45 patients (16%) received intrathecal chemotherapy for CNS prophylaxis along with induction treatments. Using the competing risk regression analysis, 2-year cumulative incidence of CNS relapse was 2.7% (1.5%, 3.1%, and 4.6% for low-, intermediate- and high-risk DSHNHL group respectively). Univariate analysis showed elevated LDH, poor PS, stage III/IV, presence of B symptoms, higher risk IPI and DSHNHL risk group as risk factors of CNS relapse (Table 2). Presence of concurrent EN involvement more than one site and elevated LDH was a significant predictor of CNS relapse (Hazard Ratio [HR] 2.39, P =0.004). Kidney/adrenal gland and gonadal involvement were not associated with higher risk of CNS relapse whereas breast involvement showed a trend toward higher incidence of CNS relapse (HR 2.46, P=0.07). Either immunochemotherapy or intrathecal chemoprophylaxis was not associated with lower risk of CNS relapse; in fact patients who received intrathecal chemotherapy had more CNS relapse though this could be due to selection bias. Median survival of patients with CNS relapse was 13.2 months which was significantly worse than patients without CNS relapse (81.8 months, P Conclusion: The 2-year cumulative incidence of CNS relapse in DLBCL in this analysis was 2.7% which was comparable to other series. Using the DSHNHL prognostic model was able to define DLBCL patients into low, intermediate and high risk for CNS relapse. The high-risk group in our series had lower incidence of CNS relapse compared to German and recently reported British Columbia cohorts. Our study confirms poor survival outcome of DLBCL patients with CNS relapse and no protective effect of immunochemotherapy or intrathecal chemoprophylaxis on the incidence of CNS relapse. Novel risk-adapted CNS prophylaxis strategies are warranted to be further investigated in prospective studies. Figure 1. Baseline characteristics of DLBCL patients based on pattern of CNS relapse IQR: Interquartile Range Figure 1. Baseline characteristics of DLBCL patients based on pattern of CNS relapse. / IQR: Interquartile Range Figure 2. Univariate analysis for factors associated with risk of CNS relapse DSHNHL: The German High Grade Non-Hodgkin's Lymphoma Study Group, R:Rituximab Figure 2. Univariate analysis for factors associated with risk of CNS relapse. / DSHNHL: The German High Grade Non-Hodgkin's Lymphoma Study Group, R:Rituximab Figure 3. 1A shows cumulative incidence (CI) of CNS relapse. 1B shows CI of CNS relapse stratified by the presence of > 1 extranodal involvement and elevated LDH. 1C shows CI of CNS relapse stratified by DSHNHL risk group. 1D shows overall survival based on relapse status. Figure 3. 1A shows cumulative incidence (CI) of CNS relapse. 1B shows CI of CNS relapse stratified by the presence of > 1 extranodal involvement and elevated LDH. 1C shows CI of CNS relapse stratified by DSHNHL risk group. 1D shows overall survival based on relapse status. Disclosures Khuhapinant: Roche: Honoraria.

Introduction The difference in origin between nodal and extranodal DLBCL may contribute to the distinct clinical outcomes and prognoses. Previous studies including patients with both limited and advanced diseases showed various clinical results. The purpose is to study the clinical characteristics, and outcomes of patients with limited stage DLBCL according to the primary site of lymphoma. Methods From the 4,371 patients in a multi-institutional registry of newly diagnosed lymphoma in Thailand between 2007-2014, there were 920 patients with limited stage DLBCL, excluding those with primary central nervous system lymphoma. The baseline patient characteristics and clinical outcomes were analyzed according to the primary site of diseases. Results Majority of patients had extranodal diseases (n= 535, 58.2%) while the other 385 cases (41.8%) had nodal DLBCL. The five most common primary sites of extranodal disease were Waldeyer ring (12.2%), stomach (7.3%), intestine (6.8%), sinonasal cavity (6.7%) and breast (2.8%) (Figure 1). Baseline characteristics, treatment and responses were well balanced between the two groups except for a slightly higher proportion of stage I disease in extranodal DLBCL (36.8% vs 28.8%, P =0.01) (Table 1). Two-third of patients received CHOP chemotherapy while the others were treated with R-CHOP. Radiotherapy (RT) was delivered to one-fifth of the patients in each group. Overall response rates were comparable between patients with nodal and extranodal diseases (68.6% vs 66.7%). With a median follow up of 52 months, there were no significant differences of progression free (PFS) (57.6 vs. 60.8%, P =0.46) and overall survival (OS) (63.1% vs. 65.6%, P =0.20) between patients with extranodal and nodal diseases. Among patients with extranodal manifestations, those with primary lymphoma at pancreas & gall bladder, pleura & lung, adrenal gland & kidney and intestine had the worst 4-year OS (33.3%, 39.3%, 53.3%, and 53.7%, respectively) (Figure 2). RT improved PFS (71.7% vs. 54.5%, P =0.03) and OS (74.7% vs. 62.9%, P =0.02) only in primary nodal DLBCL. The two prognostic factors for survivals were being treated with R-CHOP (HR for PFS 0.84, 95%CI: 0.74-0.96; HR for OS 0.70, 95%CI: 0.55-0.91) and the IPI scores (HR for PFS 1.49, 95%CI: 1.24-1.80; HR for OS 1.86, 95%CI: 1.37-2.51). Conclusion Among limited stage DLBCL in Thailand, primary extranodal disease was more common than the nodal manifestations. Primary sites of origins did not affect baseline characteristics as well as the outcomes. Patients with unusual site lymphomas, however, had an inferior survivals warranted a further investigational therapy. Table 1. The clinical characteristics of limited stage DLBCL according to disease of origin Clinical characteristics Nodal DLBCL(n = 385) Extranodal DLBCL(n = 535) p-value Male 205 (53.2%) 294 (55%) 0.60 Median age (years) 54.9 56.2 0.23 Stage Stage I Stage II 111 (28.8%) 274 (71.2%) 197 (36.8%) 338 (63.2%) 0.01 HIV seropositivity 11 (3.4%) 19 (4.3%) 0.53 Age ≥ 60 164 (42.6%) 230 (43%) 0.90 High serum LDH 183 (47.5%) 230 (43%) 0.17 ECOG ≥ 2 46 (11.9%) 60 (11.2%) 0.73 IPI Low (IPI = 0-1) Low-intermediate (IPI =2) High-intermediate (IPI = 3) 285 (74.0%) 81 (21.0%) 19 (4.9%) 406 (75.9%) 108 (20.2%) 21 (3.9%) 0.82 Chemotherapy regimens R-CHOP CHOP 98 (29.0%) 227 (67.2%) 160 (33.7%) 286 (60.2%) 0.25 Radiotherapy 94 (24.9%) 120 (22.8%) 0.46 Response Overall response Complete response 261 (68.6%) 227 (59.7%) 352 (66.7%) 322 (61%) 0.24 *IPI: International prognostic index Figure 1. Sites of origin among limited stage DLBCL Figure 1. Sites of origin among limited stage DLBCL Figure 2. Overall survival of patients with limited stage DLBCL according to primary sites of lymphoma Figure 2. Overall survival of patients with limited stage DLBCL according to primary sites of lymphoma Disclosures Khuhapinant: Roche: Honoraria.

OBJECTIVE: To analyze clinical features, outcome of treatment and prognosis of Thai patients with oropharyngeal diffuse large B cell lymphoma (DLBCL). METHODS: From the nationwide multicenter registry of 4,371 newly diagnosed lymphoma patients in Thailand between 2007 and 2014, there were a total of 2,399 DLBCL patients. The patients who have oropharyngeal lesions were collected. Clinical profiles and response to treatment and outcome were analyzed. RESULTS: Among 2,399 DLBCL patients, 1664 cases(69.4%) had extranodal lesions. The five most common site of extranodal involvement were oropharyngeal, stomach, intestine, sinonasal cavity and breast. There were 193 cases with oropharyngeal lesions accounted to 11.6% of DLBCL with extranodal lesions. The median age was 58 years (range17-91).Fifty percent of patients were male. B symptoms were presented in 39.9%. Most common sites of involvement were tonsils (81.8%) and base of tongue (15.0%) Majority of patients presented with stage I-II ( 21.2%, 43.0%) , 38.8% presented with advanced stage. Eighty three percent of the patients had ECOG score 0-1. Majority of the patients have IPI< 2 (74.6%). Ninety four percent of the patients received chemotherapy, the most common regimen was CHOP (96.0%), Rituximab was given in 29.1%. Intrathecal methotrexate was given in 8.9% Radiation therapy combine with chemotherapy was used in 16.0%, 2.7% received only local radiation therapy and 2.7% received only palliative care . Among those who received curative aim treatment,the overall response rate was 87.1% (CR 78.4 %). With a median follow-up time of 46 months (range 4-91 months) , median overall survival (OS) was 50.3 months and median progression free survival(PFS) was 31.5 months. The multivariate analysis revealed IPI>2, age>60 years and stage >2 associated with poor OS (HR 2.98, CI: 1.93-4.61, p=0.000, HR 2.79, CI:1.67-4.68, p=0.000 and HR 1.79,CI:1.09-2.97, p=0.002) but only age and IPI was significantly associated with PFS (HR 2.79,CI: 1.28-6.06, p=0.10, HR 2.86, CI:1.37-5.97, p=0.005). Advanced stage trended to associated with poor PFS but did not reach statistical significant (HR 1.90,CI:0.95-3.79, p=0.07). Rituximab significantly improved both OS and PFS (HR 0.58, CI;0.33-0.99, p=0.046 and HR 0.44, CI; 0.19-1.0, p=0.05) but radiotherapy did not improved outcomes(HR1.05,CI:0.56-1.99, p=0.87). The patient who received intrathecal methotrexate had poor outcome (HR 3.43,CI: 1.57-7.50, p=0.004) CONCLUSION: Comparing to other Thai patients with DLBCL , those with orpharyngeal lesion have similar prognosis. Receiving Rituximab improved outcomes. Different from international data, combination chemo-radiotherapy and intrathecal chemotherapy were not routinely practice and did not relate with good outcomes. This may be caused by limited resource of radiotherapy in Thailand so it was reserved for only patients with bulky mass or impending airway obstruction. Table 1. Clinical characteristics No. of patients % Median age in year (range)58 (17-91) < 60 >60 108 85 55.96 44.04 Male: female ratio 1:1Male Female 98 95 50.78 49.22 Stage1-2 3-4 124 69 64.25 35.75 ECOG0-1 2-4 159 34 82.3. 17.62 B symptom 77 39.9 LDHNormal High 111 82 57.51 42.49 IPI groupLow Intermediate-Low Intermediate high High 77 67 32 17 39.90 34.72 16.58 8.81 TreatmentPalliative Chemotherapy alone XRT alone Combine chemo-XRT 5 145 5 28 2.73 79.23 2.73 15.30 Response to treatment Overall response Complete response Partial response 121 109 12 87.1 78.4 8.7 Disclosures Khuhapinant: Roche: Honoraria.

OBJECTIVES: To analyze clinical features, treatment outcomes in Thai patients with angioimmunoblastic T cell lymphoma (AITL). PATIENTS AND METHODS: From a nationwide multicenter registry of 4,056 NHL patients in Thailand between 2007 and 2014, there were a total of 54 angioimmunoblastic T cell lymphoma (AITL) patients. The clinical features and treatment outcomes were analyzed. RESULTS: There were a total of 54 cases accounted to the prevalence of 1.2 % of NHL and 12% of peripheral T cell lymphoma. The median age was 59 years (range 35-81). Male: female was 1.5:1. Seventy-eight percent of patients had advanced disease (stage III, IV), 69% had B symptoms, 28% had poor performance status (ECOG > 2) and 61% had elevated serum LDH level. Extranodal involvement was 56 %; the most common sites of which were bone marrow (30%) and liver (19 %). Thirty-five percent of the patients had IPI score > 2 and 7% had PIT >2. Eighty-one percent of patients were treated with chemotherapy of which CHOP/CHOP-like was the main regimen. Of the 43 evaluable patients receiving chemotherapy, complete remission was achieved in 41.9%. Forty-four percent of patients with complete remission had disease progression. With the median follow-up time of 65 months, the 5-year overall survival was comparable to peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS), (28% vs. 37%, p=0.7). On multivariate analysis, response to treatment (at least PR) was associated with better outcome (HR 0.13, 95%CI 0.05-0.33, p= 0.000). Patients with PIT > 2 or B symptoms trended to have inferior survival outcome, although statistical significant was not achieve (HR 3.2, 95%CI 0.36-27.95, p=0.3; HR 2.3, 95%CI 0.78-7.31, p=0.13). CONCLUSIONS: The prevalence of Thai patients with AITL was much less than data reported from the international T-cell lymphoma project (18% of T-NHLs) (Vose et al, JCO2008;26:4124-30). The long-term survival was not inferior to patients with PTCL, NOS. Disclosures Khuhapinant: Roche: Honoraria.

Introduction The additional benefit of consolidation radiotherapy (RT) following chemotherapy in limited stage DLBCL remains controversial. Previous 5 randomized trials, 4 trials before rituximab era (SWOG 8736, ECOG 1484, GELA 93-1 and 93-4 studies) and 1 trial with R-CHOP combination (Lysa/Goelams 02-03), could not demonstrate a remarkable benefit of RT. The purpose of this study is to explore the benefit of combined modality treatment including the combination of RT and rituximab (R)-based chemotherapy in limited stage DLBCL. Methods From the 4,371 patients in a multi-institutional registry of newly diagnosed lymphoma in Thailand between 2007-2014, there were a total of 2,399 patients with DLBCL. We included patients with limited stage DLBCL receiving CHOP/CHOP-liked chemotherapy +/- R and +/- RT. The baseline patient characteristics and clinical outcomes were analyzed according to treatment modalities. Results A total of 816 patients with a median age of 56 years (range, 15-91) were included in the study. Male:female was 1:1.1. Majority of patients had primary extranodal diseases (58%), stage II (68%), good performance status (89%), normal LDH (55%) and no B-symptoms (59%). The IPI scores were 0 (30.6%), 1(45%), 2 (20%) and 3 (3.9%), respectively. The modalities of treatment were CHOP alone (48.5%), R-CHOP (26.5%), CHOP+RT (17.9%) and R-CHOP+RT (7.1%). Patients in R-CHOP group were older than in other groups ( P =0.001) (Table 1).There was a higher proportion of patients in stage II disease in R-CHOP (74.1%) and R-CHOP+RT (74.1%) groups than in CHOP (66.9%) and CHOP+RT (57.5%) groups ( P =0.007), whereas the patients were relatively equally distributed between the IPI scores. Complete response (CR) rate was higher in R-CHOP+RT group (82.8%) than in R-CHOP (75%), CHOP+RT (70%) and CHOP groups (58%) ( P

Introduction: Mantle cell lymphoma (MCL) is a relatively rare and aggressive mature B-cell non-Hodgkin lymphoma (NHL) entity, encounting for 3-10% of newly diagnosed patients. The purpose of the study is to analyse the incidence, clinical features and outcomes of Thai patients with MCL and compare data with those of Western countries. Patients and methods: From the nationwide multicenter registry of 4,056 newly diagnosed NHL patients in Thailand between 2007-2014, patients with MCL were identified according to the criteria of diagnosis by WHO classification of lymphoid disorders, 2008. The incidence, baseline clinical characteristics and outcomes were then analysed. Results: Ninety-nine patients (2.4%) were found to have MCL. The median age was 59.8 years (range 33-86). Seventy-nine percent of patients were men. The primary sites of disease were lymph nodes (60%), bone marrow (19%), GI tract (9%), Waldeyer's ring (4%), sinonasal area (2%) and miscellaneous (6%). (Figure 1). Eighty-three percent of the patients had stage III/IV. Eighty-one patients (82%) received chemotherapy (60.5% with CHOP or CHOP-like chemotherapy, 30.9% with HyperCVAD, and 26% with rituximab-based). Other received palliative chemotherapy or did not receive any. At a median follow-up time of 42 months, the median survival was 30 months (range, 1-94 months). By using Cox analysis, only Ann Arbor stage had impact on overall survival. Conclusion: MCL is less frequent in Thailand compare to the Western countries. The long-term survival is also much inferior reflecting the limited access to rituximab as well as the high intensity therapy in treating MCL in Thailand. Table 1. Comparison of MCL patients according to treatment modalities Clinical characteristics (Total 81 cases) CHOP-like (n=49 ) High intensity CMT (n = 25 ) CVP or palliative CMT (n = 7 ) p-value No R 33 19 4 - Age > 60 19 (67%) 6 (24%) 5 (71%) - Stage III-IV 42 (85.7%) 21 (84%) 7 (100%) - Response Overall response Complete response 26 (53.1%) 19 (38.8%) 17 (68%) 11 (44%) 6 (85.7%) 3 (42.8%) - Survival Mean OS (months) (Min-Max) 3yr-OS 5yr-OS 26.8 (0.1-83) 52.2% 52.2% 38.8 (0.8-93.9) 51% 38.1% 34.3 (10.7-70.5) 51% 30.2% 0.44 0.44 Figure 1. Biopsy sites Figure 1. Biopsy sites Figure 2. The Kaplan-Meier plots of OS according to treatment groups Figure 2. The Kaplan-Meier plots of OS according to treatment groups Figure 3. The Kaplan-Meier plots of OS according to tretment with rituximab Figure 3. The Kaplan-Meier plots of OS according to tretment with rituximab Disclosures Khuhapinant: Roche: Honoraria.