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Background Cytomegalovirus (CMV) establishes lifelong latency after primary infection under the control of the immune system because of the numerous virus evasion strategies that interfere with the host immune response at many levels. Human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) are involved in the early immune response and are an important defense mechanism in CMV infections, reactivation, and related diseases. Furthermore, an assessment of the clonal diversity of T cell responses against CMV infection provides important insight into the molecular basis of T cell immunodominance. In this single-center study, we tried to demonstrate a specific correlation between the donor HLA genotype and cumulative incidence of CMV reactivation and disease. Patients and methods We retrospectively analyzed 613 donors and recipients diagnosed with acute myeloid leukemia (AML) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched siblings (n=260), matched unrelated donors (n=167), or haploidentical family donors (n=186) from 2012 to 2017. The CMV-related disease was diagnosed with aggressive procedures in suspicious tissues such as the eyes, gastrointestinal tract, or respiratory tract. The cumulative incidence of overall CMV-related diseases was 12.3% (n=71; range, 9.8 - 15.2), and in each matched sibling, matched unrelated, and haploidentical family donor allo-HSCT group were 6.1% (range, 3.6-9.6), 14.4% (9.2-20.7), and 19.4% (14.0-25.5), respectively. Except for seven patients, all 64 patients developed CMV disease in the CMV reactivation state. We determined the genotypes of the HLA-A, B, C, and DRB1 alleles in 613 donors and recipients by sequencing method and further selected 560 (91.4%) CMV IgG seropositive donors to identify the genetic influence of donor HLA according to CMV infection. Results We first analyzed the relationship between entire donor HLA allotypes and the cumulative incidence of CMV-related disease, then subdivided the donor groups by CMV IgG seropositivity. In the CMV IgG seropositive donor group, we conducted subgroup analysis to identify any difference in CMV-related disease incidence according to types of allo-HSCT. As a result, an entire donor CMV serostatus, three genotype alleles, HLA A*3004 (OR 2.8; p-value 0.044), B*5101 (OR 2.3; p-value 0.003), and DRB1*0901 (OR 2.3; p-value 0.004), demonstrated a statistically significant odds ratio (OR) value with the proper number of patients. However, in the donor CMV IgG seropositive subgroup, two allotypes, HLA B*5101 (OR 2.0; p-value 0.003) and DRB1*0901 (OR 2.7; p-value 0.002), remained. Interestingly, the HLA DRB1*0901 allele showed a concrete association (OR 6.0; p-value HLA-DRB1*1302 showed a promising value as the protective marker (OR 0.2; p-value 0.041) only in the IgG seropositive donor subgroup with the matched unrelated allo-HSCT recipient category. HLA-A*2402 (OR 3.6; p-value 0.048) was only significant in the IgG seropositive donor subgroup with the matched sibling and haploidentical allo-HSCT recipient category. HLA-DR*1501 (OR 2.6; p-value 0.039) was only significant in the IgG seropositive donor subgroup with the matched sibling allo-HSCT recipient category. Conclusion This study demonstrated that certain donor alleles, donor CMV IgG serostatus, and types of allo-HSCT, especially the seropositive donor HLA-DR*0901 allele in the haploidentical allo-HSCT setting, significantly correlated with high CMV-related disease incidence and might be considered risk markers for suitable donor selection. Additionally, the specific donor HLA allele showed either protective or aggravated CMV-related disease incidence in a different allo-HSCT setting. For patients receiving various types of allo-HSCT, a strategic approach to donor selection with careful consideration of donor HLA allotype is important and intensive CMV reactivation monitoring may be required, especially in acute GVHD under active steroid pulse treatment. Disclosures Kim: BMS: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Ilyang: Research Funding. Lee:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

Background Overexpression of WT1 is a surrogate marker of abnormal myelopoiesis and has been evaluated as a potential tool to assess measurable residual disease (MRD) in myeloid malignancies. Given that lack of consensus on clinically relevant WT1 thresholds and time points in the allogeneic hematopoietic cells transplantation (allo-HSCT) setting, WT1 quantification has not yet gained widespread use despite several pieces of evidence demonstrating the possible role for MRD assessment with the limited numbers of patients. To investigate optimal threshold, time points, and candidates of WT1 quantification in AML, we retrospectively analyzed a large cohort of consecutive patients who underwent allo-HSCT at Catholic Hematology Hospital. Patients and methods This study included 425 consecutive patients with AML who underwent allo-HSCT at CR state from either a matched siblings (n=199), matched unrelated (n=117) or haploidentical family donors (n=109) from 2012 to 2016. Patients were in the first (n=400) or second (n=25) complete remission with a median age of 48 years (range, 18~70). Favorable, intermediate, poor risk groups by 2017 NCCN criteria were 28% (n=120), 49% (n=206), and 23% (n=99), respectively. Bone marrow WT1 levels before, and at 1 or 3 months after allo-HSCT were determined using real-time PCR using the ELN normalized method. We sought to clarify the prognostic relevance of the WT1 quantification regarding the cumulative incidence of relapse (CIR) and survival outcomes. Results With a median follow-up of 39 months (range, two days to 73 months), the 4-year overall survival, disease-free survival, CIR and non-relapse mortality were 63.6%±2.6%, 61.5%±2.6%, 17.9%±2.1% and 24.7%±2.5%, respectively. Analysis of dynamic changes of WT1 levels demonstrated decreased levels at 1 (n=333, mean 86 copies, range 0~1800) and three months (n=346, mean 101 copies, range 0~1670) after allo-HSCT compared to before allo-HSCT (n=425, mean 219 copies, range 0~9630). Relapsed patients had significantly higher WT1 levels before (P=0.018) and at three months (P=0.041) after allo-HSCT, whereas no difference at one month after allo-HSCT (P=0.167). Even the ROC curve analysis revealed that WT1 levels before allo-HSCT were significantly available to predict CIR after allo-HSCT (P In subgroup analyses in each risk group by 2017 NCCN criteria, the WT1-MRD positivity before allo-HSCT was significantly effective to predict CIR in the intermediate risk group (57% vs. 12%, P Conclusions These data suggest standardized bone marrow WT1 levels using the ELN threshold (250 copies) before and at three months after allo-HSCT provided relevant information to predict relapse in AML with intermediate and poor risk groups by 2017 NCCN criteria, respectively. The validated WT1 MRD assay by ELN was revealed to be particularly available in AML without specific MRD markers, such as NPM1 or CBF-AML, and different significance by times points should be considered for clinical applications to identify high-risk AML for relapse, potential candidates for various immunomodulatory approaches. Disclosures Kim: Pfizer: Research Funding; Ilyang: Research Funding; BMS: Research Funding; Novartis: Research Funding. Lee:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

Background: Recently, a high-risk subgroup of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) called Philadelphia chromosome (Ph)-like ALL was identified in adolescents and young adults. However, there are conflicting data regarding the incidence and prognosis of Ph-like ALL in adult patients, and no data have yet been introduced in Asian countries. Aim: We tried to identify the prevalence and genetic characteristics of Ph-like ALL in adult patients with newly diagnosed BCP-ALL. Furthermore, we analyzed the clinical characteristics, long-term outcomes, and prognostic impact of Ph-like ALL compared with non-Ph-like ALL (Ph-positive ALL or BCP-other ALL). Methods: Between December 2008 and March 2016, 334 adult patients with newly diagnosed BCP-ALL who received modified hyper-CVAD chemotherapy and had suitable material for genomic analysis were included in this analysis (median age, 43 years [range, 16-65 years]). Our post-remission therapy was based on allogeneic hematopoietic cell transplantation (HCT) if a donor is available. Ph-like ALL was determined by next generation sequencing using the Archer® FusionPlex® ALL Kit (ArcherDX Inc., CO) which can detect fusions, point mutations, and expression levels in 81 genes associated with ALL and additional FISH analysis was done. Results: Overall, 48 (14.4%) of the 334 patients were Ph-like ALL, and the cohort was divided into patients with ABL1-class rearrangements (n=4), CRLF2 rearrangements (n=11), JAK2 rearrangements (n=4), other JAK-STAT sequence mutations (n=12), and RAS mutations (n=17). The remaining 286 patients had Ph-positive ALL (n=197) and BCP-other ALL (n=89; including 19 patients with KMT2A [MLL] rearrangements). No significant differences in baseline characteristics were observed between the Ph-like ALL and BCP-other ALL subgroups, whereas patients with Ph-positive ALL were older (median age, 47 vs 37 years; p=0.003) and had higher presenting leukocyte counts (median, 33.1 vs 11.4´109/L; p=0.001) compared with Ph-like ALL. The complete remission rate was somewhat different between the 3 disease subgroups (Ph-like ALL, 97.9%; Ph-positive ALL, 95.9%; BCP-other ALL, 88.8%; p=0.027). A higher proportion of patients with Ph-like ALL actually received allogeneic HCT in CR1 than patients with non-Ph-like ALL (Ph-like ALL, 91.6%; Ph-positive ALL, 84.2%; BCP-other ALL, 71.9%; p=0.007). With a median follow-up of 58.1 months (range; 6.0-121.0), outcomes of patients with Ph-like ALL were not inferior compared with outcomes of patients with non-Ph-like ALL. Disease-free survival rates at 5 years were 56.0% for Ph-like ALL, 42.6% for Ph-positive ALL, and 40.6% for BCP-other ALL (p=0.138). The 5-year cumulative incidence of relapse were 19.2% for Ph-like ALL, 35.3% for Ph-positive ALL, and 33.5% for BCP-other ALL (p=0.076). These findings were maintained when only patients receiving HCT were considered. Within the Ph-like ALL subgroup, patients with ABL1-class and CRLF2-rearrangements had worse outcomes than patients with other JAK-STAT sequence and RAS mutations. Also, patients with higher CRLF2 expression had inferior outcomes. Conclusion: Within the limitation of sample size, our data showed a different frequency of subtypes (e.g., lower incidence of CRLF2 rearrangements, higher RAS mutations) and treatment outcomes of adult patients with Ph-like ALL compared with other Western reports. Racial and ethnic differences in the patient population studied may have contributed to these differences. We also suggest that HCT-based post-remission therapy may overcome the poor prognosis of Ph-like ALL. Disclosures Kim: BMS: Research Funding; Ilyang: Research Funding; Pfizer: Research Funding; Novartis: Research Funding. Lee:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

Hematology, Catholic Hematology Hospital and Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea, 2Department of Biomedical Science, College of Medicine, The Catholic University of Korea, Seoul, Korea, 3Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea Background: Hemophagocytic lymphohistiocytosis (HLH) is a disease showing severe systemic inflammatory cascade which is life-threatening if not detected and treated appropriately. The diagnosis of HLH is confused due to other similar febrile diseases with cytopenia such as severe sepsis, autoimmune disease, and malignancies. Although decreased or absent natural-killer cell (NK) cytotoxicity is known as an important diagnostic parameter for pediatric HLH, the role for adult HLH is not elucidated well and also the significant level is not reported compared to other similar febrile diseases. Aim: We tried to identify the initial level of NK cytotoxicity in several febrile diseases and find out the role for diagnosis of HLH in adult patients in related with several cytokine levels. Methods: We prospectively enrolled 55 patients from 2015 to 2017. Adult patients older than 18 years with fever>38℃ presenting cytopenia in at least two lineages (neutrophil Results: HLH was diagnosed in 37 patients caused by viral infection (n=11), malignancies (n=7), autoimmune diseases (n=5), bacterial infection (n=2), malaria (n=1), anaplasmosis (n=1) and unknown origin (n=10). Febrile diseases other than HLH (n=18) were diagnosed with hematological diseases (n=8), infectious mononucleosis (n=2), rheumatologic disease associated macrophage activation syndromes (n=6), and unknown origin (n=2). The results of both K562 lysis and ADCC assay was well correlated (correlation coefficient = 0.684, 95%CI 0.512-0.804, P Conclusion: We identified that decreased NK cytotoxicity and elevated IL-2R are relevant diagnostic markers for diagnosis of secondary HLH also in adult patients. We also identified ADCC lower than 23.7% was predictable for severe HLH presenting poor treatment outcome. Disclosures Kim: BMS: Research Funding; Ilyang: Research Funding; Novartis: Research Funding; Pfizer: Research Funding. Lee:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

Background Venous thromboembolism (VTE) is a critical complication of malignant disease. Pancreatic cancer is one of the cancers most commonly associated VTE. In general, the VTE incidence rate of Asians is lower than that of Caucasians. In 2007, a Korean study reported that only four cases of VTE (5.3%) occurred in Seventy five patients with advanced pancreatic adenocarcinoma. We evaluated VTE incidence in pancreatic cancer and characteristics of pancreatic cancer patients with VTE. (We found out that VTE incidence rate among Asians was not lower, and the event of VTE was poor prognosis.) Method We retrospectively reviewed the medical records of patients with histopathologically proven pancreatic cancer from January 2006 to December 2012 at Soonchunhyang university hospital. We detected VTE through CT (chest CT, pulmonary embolism CT) and low extremity ultrasoundgraphy. Results Five hundred and fourteen patients with pancreatic adenocarcinoma were enrolled. (M: F, 300:214, localized: locally advanced: metastatic=31:230:253, mean age: 66.7 years). Ninety six of 514 patients (18.6%, symptomatic: aymptomatic=38:58, PE: DVT: PE+DVT: visceral thrombosis=20:19:19:38) were diagnosed as VTE. At the time of DVT diagnosis, cancer status of 50 patients cancer was progression, and that of 15 was stable. Thirty one patients were diagnosed with the pancreatic cancer and VTE, at the same time. They all had metastatic lesions. Fifty VTE patients were treated with antithrombotic therapy. Ninety three of 96 patients died, and three of them have probability that cause of death was VTE. The others died of pancreatic cancer progression. From pancreatic cancer diagnosis to VTE diagnosis, the period is 1.7month. (95%CI 1.1-2.3 month). Median overall survival (OS) was not significantly different between pancreatic cancer with VTE or without VTE. OS was significantly longer VTE patients after pancreatic cancer diagnosis than VTE patients with pancreatic cancer at the same time (10.73m vs. 1.7, p=0.00). Conclusion The incidence of VTE (18.6%) in Soonchunhyang university hospital with pancreatic cancer was not lower than that in western groups. Disclosures: No relevant conflicts of interest to declare.