ALBERT

Description: Introduction Various prognostic factors for multiple myeloma (MM) have been identified, and combinations of these factors were suggested for staging classification of MM patients. The international staging system (ISS) is a widely accepted prognostic system for MM patients. However, since ISS was established using data collected from 1981 through 2002, only a small portion of patients who received the novel agents (e.g., thalidomide, bortezomib, and lenalidomide) were included. Therefore its validity is being challenged in the era of novel agents. We aimed to develop an alternative prognostic index for MM patients based on easily obtained laboratory measures in the era of novel agents. Patients and methods Data were collected from February 2001 through June 2012 at Asan Medical Center. 470 patients were newly diagnosed as symptomatic MM and 156 of them were treated with novel agents including thalidomide, lenalidomide and bortezomib. We analyzed these 156 patients who received novel agent therapy at least once, using prospectively collected data. A new prognostic model was developed based on significant potential prognostic factors in univariate and multivariate analysis, which was validated in external validation data set from two tertiary hospitals in Korea. Results With a median follow-up duration of 27.9 months (range, 0.2-122 months), the median overall survival in the whole population was 28.7 months. The median overall survival (OS) of patients according to ISS stage 1, 2 and 3 were 122.2, 43.9 and 30.0 months, respectively. There were no significant differences in median OS between ISS stage 1 and 2 patients and 2 and 3 patients (Figure 1). Furthermore, ISS was not statistically significant in the multivariate analysis. We incorporated serum beta2-microglobulin (Sβ2M), serum albumin and serum lactate dehydrogenase (LDH) as independent risk factors to develop a new prognostic model. Using these three factors, we stratified the patients into three groups; Group 1, Sβ2M 〈 5.5 mg/L plus serum albumin 〉= 3.5 g/dL plus serum LDH normal; Group 2, neither group 1 nor 3; Group 3, Sβ2M 〉= 5.5 mg/L plus serum albumin 〈 3.5 g/dL plus serum LDH 〉 normal. We found that there were significant differences in median OS among these three groups (122.2, 41.6 and 5.6 months for group 1, 2 and 3, respectively) (Figure 2). This new prognostic index was further validated in the external cohorts (Median OS was 75.2, 36.3 and 23.1 months for group 1, 2 and 3, respectively) (Figure 3). Conclusion Our study suggests that this new prognostic index based on easily obtainable variables (Sβ2M, serum albumin, serum LDH) might be a simple and useful tool to predict prognosis for patients with MM in the era of novel agents, which warrants further validation. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 5084 Background & Aims 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) scan has been increasingly used for initial staging and response evaluation in patients with lymphomas, and its clinical utility is well established in diffuse large B-cell lymphoma as well as Hodgkin lymphoma. However, its role remains undetermined in marginal zone lymphomas (MZL), most common type of indolent lymphoma in Korea, due to its relatively low FDG avidity. Thus, we aimed to assess the prognostic significance of PET-CT scan in patients with MZL. Patients & methods We retrospectively reviewed the medical records of a total of 194 patients with pathologically confirmed MZL in the Asan Medical Center between February 2003 and February 2011. Post-treatment FDG PET-CT scan was defined as which performed during the periods of 2 to 4 weeks after the completion of induction chemotherapy or 7 to 9 weeks after radiotherapy. [a4] Among them, both baseline and post-treatment FDG PET-CT scans were performed in 64 patients. We investigated the prognostic significance of maximum standardized uptake value (SUVmax) at baseline PET-CT and metabolic complete response. Metabolic compete response (mCR) was defined as no pathologic FDG uptake at any site in post-treatment PET-CT scan. The log-rank test was used to assess the correlation of progression-free survival (PFS) and overall survival (OS) with baseline SUVmax or the presence of mCR. Results In a total of analyzable 64 patients, histopathologic subtypes of them were as follow: extranodal marginal zone lymphoma (ENMZL=38, 59. 4%) including mucosa-associated lymphoid tissue (MALT) (n=35, 54. 7%) and bronchus-associated lymphoid tissue (BALT) (n=3, 4. 7%) lymphoma, nodal MZL (n=25, 39. 0%), splenic MZL (n=1, 1. 6%). The median SUVmax in baseline PET-CT was 4. 9 (range, 1. 3 – 18. 8). There were no significant associations of baseline SUVmax (cutoff: 5) to mCR at post-treatment PET-CT scan or survival outcomes. Patients group with high SUVmax (SUVmax 〉5. 0) showed mCR rate of 72. 7 %, and patients low SUVmax (SUVmax ° Â 5) showed mCR rate of 67. 7%, respectively. (p=0. 786). With a median follow-up duration of 46 monthss (range, 13 to 109 months), 5-year OS and PFS rate were 91% and 71%, respectively. 5-year PFS rate (76% vs. 62%, p=0. 27) did not differ between complete metabolic responders and incomplete responders. However, complete metabolic responders showed higher 5 year OS rate compared with incomplete responders (93% vs. 86%, p=0. 43) although statistical significance was not secured. Conclusion In the study cohort, baseline SUVmax was not a significant predictor of mCR, PFS nor OS. However, the patients achieved mCR at the end of induction treatment seemed to have superior survival rates than incomplete responders, which warrants further investigation. Disclosures: No relevant conflicts of interest to declare.

Description: Background The International Prognostic Index (IPI) has been useful prognostic tool to predict prognosis of aggressive non-Hodgkin lymphoma in the last 20 years. Since the advent of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy for diffuse large B-cell lymphoma (DLBCL), its utility has been challenged and other prognostic index including revised IPI and National Comprehensive Cancer Network (NCCN)-IPI were proposed, which are not popularly used yet. We aimed to develop new prognostic model for DLBCL in rituximab era. Method Between March 2004 and June 2012, patients with DLBCL treated with R-CHOP were identified in the database of the Asan Medical Center (AMC) Lymphoma Registry. Primary end point was to devise a new prognostic index for DLBCL. Secondary end point was to validate the NCCN-IPI in our cohort. We tested new prognostic index model in the training set of AMC cohort consisted of randomly selected 80% of the sample (503 patients). The remaining 20% (118 patients) was used as an internal validations set. Results The AMC cohort consisted of 621 patients. Median follow-up duration was 43.3 months (6.2-122.5 months). Baseline characteristics of AMC cohort are presented in table 1. Median age was 57 years (range, 16-85 years). Median ϐ-2 microglobulin (ϐ-2 MG) was 2.10 mg/L (range, 1.0-66.0 mg/L). The univariate analysis of baseline characteristics revealed that age (≦60 vs. 〉60 years), LDH (within normal vs. increased), ECOG performance (0 or 1 vs. ≧2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal involvement (≦1 vs. 〉1), B symptoms (no vs. yes), and ϐ-2 MG (≦2.5 vs. 〉2.5) could predict overall survival (OS), whereas bulky disease and gender did not (p value 0.140, 0.621, respectively). In the multivariate analysis, age, LDH, ECOG performance status, and ϐ-2 MG were significantly associated with OS (p value 0.001, 60 years 57.0 377 244 16-85 60.7 39.3 57.0 300 203 16-84 59.6 40.4 57.0 77 41 17-85 65.3 34.7 Sex Male Female 343 278 55.2 44.8 273 230 54.3 45.7 70 48 59.3 40.7 ECOG PS 0 or 1 ≧ 2 569 52 91.6 8.4 462 41 91.8 8.2 107 11 90.7 9.3 Serum lactate dehydrogenase levels Normal Elevated 334 287 53.8 46.2 279 224 55.5 44.4 55 63 46.6 53.4 Ann Arbor stage I and II III and IV 293 328 47.2 52.8 236 267 46.9 53.1 57 61 48.3 51.7 Number of extranodal sites 2.5 mg/L 2.1 422 199 1.0-66.0 68.0 32.0 2.1 339 164 1.0-29.6 67.4 32.6 2.1 83 35 1.0-66.0 70.3 28.7 Table 2. Multivariate Analysis for Factors Associated with Overall Survival Factors HR 95% CI P value Score Age, years ≦ 60 years 〉 60 years 1.000 2.051 1.362-3.090 0.001 1 Serum lactate dehydrogenase levels Normal Elevated 1.000 3.165 1.951-5.135 2.5 mg/L 1.000 1.691 1.0391-2.622 0.019 1 Figure 1. IPI versus NCCN IPI versus new prognostic index model in Asan Medical Center training set (A) and internal validation set (B) Figure 1. IPI versus NCCN IPI versus new prognostic index model in Asan Medical Center training set (A) and internal validation set (B) Disclosures No relevant conflicts of interest to declare.

Description: Abstract 3674 Introduction Chemotherapy with curative intent should be given to all patients with diffuse large B-cell lymphoma (DLBCL), however, elderly patients often have a variety of co-morbidities and poor functional status resulting in high rate of adverse events related to treatment such as anthracycline-related cardiotoxicity or hematologic toxicities. Although primary prophylactic granulocyte colony-stimulating factor (G-CSF) is often used to prevent severe neutropenia, pharmaco-economic arguments exist and it is not available for considerable populations worldwide. Therefore, we aimed to assess the efficacy and safety of the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (R-CHOP) with reduced doses of cyclophosphamide and doxorubicin by 25% in elderly patients with DLBCL. Patients and methods Medical records of a total of 118 patients aged ≥65 years with DLBCL, newly diagnosed between September 2007 and March 2012, were retrieved from the database. All patients received R-CHOP chemotherapy every 3 weeks with reduced doses of cyclophosphamide (562.5 mg/m2) and doxorubicin (37.5 mg/m2). No patient received primary prophylactic G-CSF, however, it was allowed to those who suffered from febrile neutropenia or grade 4 neutropenia (ANC

Description: Abstract 5111 Purpose We aimed to evaluate the clinicopathologic characteristics and clinical outcomes in patients with testicular non-Hodgkin lymphoma. Material and Methods We reviewed the medical records of 24 patients with testicular non-Hodgkin lymphoma diagnosed at the Asan Medical Center between November, 2000 and June, 2012. Results Median age of the patients was 52 years (23–79 years). Histopathologic subtypes were as follows: DLBCL (n=18, 75%), Burkitt's lymphoma (n=2, 8. 3%), extranodal natural killer/T-cell lymphoma (NKTCL) (n=2, 8. 3%), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n=1, 4. 2%) and T-cell lymphoblastic lymphoma (T-LBL) (n=1, 4. 2%). Ten patients (41. 7%) were in stage I, 1 patient (4. 2%) in stage II, and the other 13 patients (54. 2%) were in stage IV. Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 1 in 22 patients (87. 5%) and 〉1 in 5 patients (20. 8%). Serum LDH levels were elevated in 14 patients (58. 3%). International Prognostic index (IPI) score was low (0–1) in 6 patients (25%), low-intermediate (2) in 8 patients (33. 3%), high-intermediate (3) in 7 patients (29. 2%), high (4–5) in 3 patients (12. 5%). B-symptoms were present in 4 patients (16. 7%). Bilateral testicular involvement was observed in 5 patients (20. 8%). Fifteen patients (62. 5%) underwent orchiectomy as an initial therapeutic and diagnostic procedure. All the patients underwent chemotherapy: R-CHOP (n=16, 66. 6%), CHOP (n=2, 8. 3%), and other regimens (n=6, 25%). None received intrathecal prophylaxis just except a T-LBL patient. Prophylactic radiotherapy to contralateral testis was given in 12 patients (50%). Twenty-one patients (87. 5%) achieved complete response. At a median follow-up duration of 22 months (1–139 months), 2 patients (8. 3%) showed disease progression and 7 patients (29. 2%) experienced disease recurrence; in the central nervous system (n=2, 8. 3%), regional lymph nodes (n=3, 12. 5%), bone marrow (n=1, 4. 2%), nasopharynx (n=1), skin (n=1), and testicular bed (n=1). Five patients (20. 8%) died of sepsis (n=3, 12. 5%) or progression of disease (n=2, 8. 3%). Median progression free survival and overall survival were 20 months (1–139 months) and 22 months (1–139 months), respectively. ECOG PS 〉1 (p=0. 015) and bilateral testicular involvement (p=0. 000) were associated with a significantly short progression free survival (PFS). ECOG PS 〉1 (p=0. 001), high-intermediate or high risk of IPI (p=0. 010), presence of B symptoms (p=0. 035), and bilateral testicular involvement (p=0. 001) were associated with a significantly short overall survival. Conclusions Testicular lymphoma is a rare but aggressive extranodal lymphoma. High ECOG PS, high IPI, B symptom, and bilateral testicular involvement were associated with poor prognosis. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4980 Background: Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. However, immunoglobulin isotype switching (IS) has been reported during follow-up of patients with MM. Its clinical significance has not been established well. We aimed to evaluate the clinical characteristics of the patients with IS and outcomes in those patients in a single center cohort. Patients and Methods: A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and June 2012. We compared clinical characteristics and outcomes between those with and without IS. Results: Of the 377 patients, 34 (9%) demonstrated IS after a median 7. 9 months (range, 2. 2–95. 7 months) from diagnosis. These 34 patients with IS comprised 18. 2% (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3. 1% (7/229) of patients treated without ASCT (P

Description: Aims Primary or secondary central nervous system (CNS) lymphoma is a rare entity which often leads to unsatisfactory outcome. Autologous stem cell transplantation (ASCT) using thiotepa containing regimen as conditioning chemotherapy showed improved outcomes in patients with CNS lymphoma. However, there are insufficient data on response to treatments and safety profile of thiotepa containing regimen in Asian population. We, therefore, aimed to evaluate clinical outcomes including safety profile and response to thiotepa, busulfan and cyclophosphamide (TBC) chemotherapy compared with busulfan, cyclophosphamide and etoposide (BuCyE) as conditioning regimens in patients with CNS lymphoma. Methods From November 2005 to April 2014, patients with primary and secondary CNS lymphoma who underwent one of the two conditioning regimens (TBC or BuCyE) followed by ASCT were included in this retrospective analysis. All patients were less than 66 years of age at the time of ASCT. TBC consists of thiotepa 250 mg/ m2 on day -9 to day -7, busulfan 3.2 mg/kg on day -6 to day-4 and cyclophosphamide 60 mg/kg on day -3 to day -2. BuCyE consists of busulfan 3.2 mg/kg on day -7 to day -5, etoposide 200 mg/m2 twice a day on day -5 to day-4 and cyclophosphamide 50 mg/kg on day -3 and day -2. Patient demographics, ECOG performance status, baseline and follow-up CBC profile, adverse events and radiologic response for 2 years after ASCT were retrospectively reviewed. Response to treatment was assessed by IELSG criteria. Event free survival (EFS), overall survival (OS) and date of engraftment were calculated by Kaplan-Meier method and compared by log-rank test. Adverse events were scored according to National Cancer Institute Common Terminology Criteria of Adverse Event version 4.0. Engraftment was defined as absolute neutrophil count (ANC) 〉 500 /mm3, and platelet count 〉 20,000 /mm3. Results Sixty one patients with primary or secondary CNS lymphoma underwent with TBC (n=26) or BuCyE (n=35) as conditioning regimen followed by ASCT. In TBC group, 17 patients (diffuse large B cell lymphoma: 17) had primary CNS lymphoma and 9 patients (diffuse large B cell lymphoma: 7, angioimmunoblastic lymphoma: 1 and T-lymphoblastic lymphoma: 1) had secondary CNS lymphoma. In BuCyE group, 28 patients (diffuse large B cell lymphoma: 27 and peripheral T-cell lymphoma: 1) had primary CNS lymphoma and 7 patients (diffuse large B cell lymphoma: 5, NK-T cell lymphoma: 1 and mantle cell lymphoma: 1) had secondary CNS lymphoma. Median age of TBC group and BuCyE group at ASCT was 52.5 years (range, 18-64 years) and 54 years (range, 26-64 years), respectively. Median ECOG performance status of TBC group and BuCyE group was 1 (range 0-2) and 1 (range 0-1), respectively. After the induction chemotherapy, 11 patients (42.3%) in TBC group and 21 patients (60%) in BuCyE group had already achieved complete remission (CR). In TBC and BuCyE group, CR had been induced in 9 (64.2%) and 11 (78.5%) among patients in partial remission (PR) after ASCT, respectively. With a median follow up period of 8.6 months (range, 0.2 to 18.5 months), 1-year OS rate did not significantly differ between two arms (76.4% in TBC group and 68.6% in BuCyE group, p=0.634). However, 1-year EFS rate was higher in TBC group (72.8%) compared with BuCyE group (45.7%, p=0.034). TBC group achieved ANC engraftment one day earlier compared to BuCyE group (day 8, range 7-12 days vs. day 9, range 7-12 days) (p= 0.011). However, there was no difference in time to engraftment of platelet between TBC group (median 8 days, range 6 to 34 days) and BuCyE group (median 8 days, range 6 to 22 days, p=0.582). Toxicity profiles are summarized in Table 1. Table 1. Toxicity above grade 2 TBC BuCyE p-value Mucositis 92% 14.3%

Description: Abstract 4412 Background High-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) has been adopted as the first-line treatment for young and/or fit patients with multiple myeloma, providing higher remission rates. However, only few factors have been identified affecting the outcome in such patients. One previous retrospective study suggest that high levels of mobilized peripheral CD34+ cells are associated with favorable outcome in myeloma patients undergoing HDC-ASCT. However, prognostic significance of hematopoietic progenitor cell (HPC) count (Suh C, Transfusion 2004), an estimate of immature cells used for timing stem cell harvest instead of CD34+ cell count, has not been investigated yet. Methods We measured peripheral HPC counts at the day 1 of autologous stem cell collection (ASCC) by Sysmex SE9000 in 112 myeloma patients at the Asan Medical Center between May 2000 and May 2012. Patients were divided into two groups (super vs normal mobilizers) with a cutoff of 50 HPC count per μL. Results Among 112 patients, 34 had more than 50 HPCs per μL (super mobilizers) and 76 had less than 50 HPCs per μL (normal mobilizers). The two groups showed no differences with regards to age, sex, subtype, light chain, ISS stage at diagnosis, performance, cytogenetics, BM plasma cells, the regimen used for induction chemotherapy and response to induction chemotherapy. However, more patients of super mobilisers received tandem ASCT comparing to normal mobilizers (35.3% vs 14.3%; p=0.052). In addition, all super mobilizers received chemotherapy combined with growth factor as mobilization, 15.6% of normal mobilizers received growth factor only (p=0.017). The mean number of HPCs in the super mobilizer group was 167.3 ± 25.7 per μL, and 16.5 ± 1.5 per μL in the normal mobilizer group (p

Description: Diet is a health-related factor that can modify lung function. This study hypothesized that the change in age-related dietary intake affects lung function. The subjects who undertook a dietary assessment and spirometry in 2012 and 2017, were retrospectively collected in a health screening center. Dietary intakes were directly evaluated using food frequency questionnaires (FFQ) administered by trained dietitians and were compared at the baseline (2012) and 5-year follow-up (2017). A forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) value below 0.70 was defined as airflow limitation. Logistic regression models were used to estimate the odds ratio (ORs) adjusted for potential confounders. A total of 1439 subjects with normal spirometry were enrolled. New airflow limitations were detected in 48 subjects (3.3%) at the 5-year follow-up, including 41 (85.4%) men and 11 (22.9%) current smokers. After adjusting for age, sex, smoking history, and baseline FEV1/FVC, the odd ratios (OR) for new airflow limitation in fiber, vitamin C, and folic acid per 10% decrease in daily recommended requirement were 2.714 (95% confidence interval (CI), 1.538–4.807; p = 0.001), 1.083 (95% CI: 1.020–1.149; p = 0.007), and 1.495 (95% CI: 1.172–1.913; p = 0.001), respectively. A decreased intake of dietary fiber, vitamin C, and folic acid is associated with a newly developed airflow limitation.