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DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). Germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients in whom germline-based testing was performed. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, patients with a DDX41 mutation were more frequently male, older, had a normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the four ICUS patients with germline DDX41 mutations progressed to MDS. The incidence of DDX41 mutations in Korean patients was high and there was a distinct mutation pattern, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating patients with myeloid malignancies.

Parainfluenza virus (PIV) infection is a significant cause of morbidity and mortality, especially in hematologic malignancy patients including hematopoietic stem cell transplantation (HCT) recipients. However, limited information is available for risk stratification in PIV-infected patients with hematologic malignancy with or without HCT. Patients with hematologic malignancy diagnosed with PIV from January 2009 to December 2018 were retrospectively included in a tertiary care hospital in Seoul, South Korea. Upper respiratory tract infection (URTI) was defined as the detection of PIV in a nasopharyngeal sample with URTI symptoms without new pulmonary infiltrates. Lower respiratory tract infection (LRTI) was defined as detection of PIV in either upper or lower respiratory tract samples with new pulmonary infiltrates, with or without hypoxia. PIV-associated mortality was defined as death with respiratory failure and persistent LRTI within 90 days after diagnosis. The study included 143 adult patients. Of these, 55 (38%) progressed to or initially presented with LRTI. Among these, 22 (40%) died from PIV-associated mortality. An immunodeficiency risk score was developed from associated risk factors using a multivariable Cox regression model. Patients were stratified into low (0–2), moderate (3–5), and high risk (6–8) groups with PIV-associated mortalities of 0%, 9%, and 67%, respectively (p

In hematopoietic stem cell transplant recipients, the incidence of tuberculosis in positive interferon-γ release assay (IGRA) without isoniazid prophylaxis (3.58/100 person-years) was higher than in negative or indeterminate IGRA (1.15/100 person-years; P = .01) and in positive IGRA with isoniazid prophylaxis (0/100 person-years; P = .09). The number needed to treat was 22 (95% confidence interval, 12–99) with positive IGRA results.

Our previous research indicated that a reduced-intensity conditioning regimen (fludarabine and melphalan at 100 mg/m2) was useful in allogeneic hematopoietic cell transplantation (HCT) for patients with lymphoma. This retrospective study evaluated the reduced-intensity conditioning regimen in allogeneic HCT for adult patients with hemophagocytic lymphohistiocytosis (HLH). Sixteen patients with HLH were evaluated, including 6 patients who were enrolled in a prospective clinical trial (NCT00772811) and 10 patients who received the same conditioning regimen (fludarabine at 30 mg/m2/day on days –6 to –2 and melphalan at 100 mg/m2 on day –2). The median age was 42 years (range, 18 to 64), and 12 patients had Epstein-Barr virus (EBV)-associated HLH. Donors were an HLA matched sibling for 10 patients, an unrelated matched volunteer for 4 patients, and a mismatched family member for 2 patients. After excluding 3 patients who died soon after HCT, 12 patients achieved an engraftment (neutrophil median, day 12; platelet median, day 16). Five patients experienced acute graft-versus-host disease (GVHD), including 1 case of grade II and 4 cases of grades III to IV. Chronic GVHD occurred in 3 patients (moderate, 1 case; severe, 2 cases). After a median follow-up of 33.8 months 1 patient progressed, 3 patients relapsed, and 9 patients died. Five deaths were unrelated to relapse or progression and were caused by infection (n = 3), bleeding (n = 1), and GVHD (n = 1). No deaths or relapses were observed at >124 days post-transplant. The overall survival rate was 48.6%, and significant differences were observed according to pretransplant ferritin level (P = .007) and cytopenia lineage (P = .021). Before allogeneic HCT 10 of 12 patients still tested positive for EBV DNA: 6 patients tested negative for EBV DNA after HCT, 2 patients had persistent EBV DNA, and 2 patients were unassessable because of early death. Conditioning therapy using a lower dose of melphalan combined with fludarabine appears to be promising in allogeneic HCT for adults with HLH. However, strategies are needed to reduce the risk of early death.

Background This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). Methods We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000–September 2017) at our center. Results Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34+ cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. Conclusion Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis., Graphical Abstract

Background and objectives There are limited data in real clinical practice on the diagnostic value of a bronchoalveolar lavage (BAL) fluid galactomannan (GM) assay in patients with suspected invasive pulmonary aspergillosis (IPA) who had negative serum GM results. Thus, we investigated the diagnostic performance of a BAL GM assay in patients with negative serum GM assay results who were suspected to have IPA. Methods This retrospective study was performed between May 2008 and April 2019 at a tertiary care hospital in Seoul, South Korea. All patients with suspected IPA whose serum GM assays revealed negative results who sequentially underwent BAL were enrolled in this study. Results A total of 341 patients with suspected IPA including 4 cases of proven IPA, 38 case of probable IPA, 107 cases of possible IPA, and 192 patients without IPA were enrolled. Of these 341 patients, 107 (31%) with possible IPA were excluded from the final analysis. Of 42 patients with proven and probable IPA who had initial negative serum GM results, 24 (57%) had positive BAL GM results (n = 24) or BAL fungal culture results (n = 8). In addition, BAL revealed evidence of other opportunistic infections including Pneumocystis jirovecii pneumonia (14% [26/190]), cytomegalovirus (CMV) pneumonia (5% [9/188]), and respiratory viral pneumonia (6% [12/193]). Conclusion Sequential BAL in patients with suspected IPA who had initial negative serum GM results provided additional diagnostic yield in approximately half of patients with evidence of another co-infection.

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by platelet destruction through antibody-mediated mechanism. ITP is one of the manifestations of a coronavirus disease, as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several cases of ITP have been described after vaccination with two mRNA-based vaccines—BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)—against SARS-CoV-2. Herein, we report a case of ITP occurring after vaccination with ChAdOx1 adenovirus vector nCoV-19 (AstraZeneca) vaccine in Korea. A 66-year-old woman presented with multiple ecchymoses on both upper and lower extremities and gingival bleeding, appearing 3 days after receiving the first dose of ChAdOx1 nCoV-19. Her laboratory results showed isolated severe thrombocytopenia without evidence of combined coagulopathy. She was diagnosed with ITP and successfully treated with high-dose dexamethasone and intravenous immunoglobulin. Clinical suspicion to identify vaccine-related ITP is important to promptly initiate appropriate treatment., Graphical Abstract

The prognosis of patients with acute leukemia relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) is dismal. We aimed to evaluate the outcomes and prognostic factors of the second HSCT (HSCT2) in acute leukemia patients relapsed after the first HSCT (HSCT1). We analyzed 80 patients who received HSCT2 for relapsed acute leukemia in two Korean institutes. All but four patients received HSCT2 from a donor other than matched sibling donor: an unrelated donor (URD) in 30 and a familial haploidentical donor (FHD) in 46. Forty-four patients (55.0%) were in complete remission (CR) or CR with incomplete count recovery (CRi) at HSCT2, and the median time from HSCT1 to relapse was nine months. The two-year overall survival (OS) and event-free survival (EFS) were 21.0% and 17.5%, respectively. The outcomes were similar between URD and FHD. Multivariate analysis demonstrated that disease status (active disease vs. CR/CRi) at HSCT2 and remission duration after HSCT1 were independent prognostic factors for OS and EFS after HSCT2. HSCT2 from URD or FHD was feasible in patients with acute leukemia relapsed after allogeneic HSCT. Also, our study confirmed two critical prognostic factors; disease status at HSCT2 and remission duration after HSCT1.

This retrospective analysis compared anthracyclines (as part of an induction regimen) in 128 newly diagnosed FLT3-ITD-mutated AML patients. Induction regimens comprised high-dose daunorubicin (HD-DN; 90 mg/m2/d × 3d; n = 44), standard-dose daunorubicin (SD-DN; 45 mg/m2/d × 3d; n = 51), or idarubicin (IDA; 12 mg/m2/d × 3d; n = 33) in combination with cytarabine (100–200 mg/m2/d × 7d). Fifty-three patients showing persistent leukemia on interim bone marrow examination received a second course of induction chemotherapy comprising 2 days of daunorubicin (45 mg/m2/d) or IDA (8 or 12 mg/m2/d) in addition to 5 days of cytarabine. Complete remission (CR) rates were 77.3%, 56.9%, and 69.7% for HD-DN, SD-DN, and IDA, respectively (P = 0.101; HD-DN vs. SD-DN, P = 0.036; HD-DN vs. IDA, P = 0.453; IDA vs. SD-DN, P = 0.237). The HD-DN showed higher overall survival (OS) and event-free survival (EFS) than SD-DN and IDA: the differences between HD-DN and SD-DN (P = 0.009 for OS and P = 0.010 for EFS) were statistically significant. Results of in vitro studies using FLT3-ITD-mutated cell lines supported these findings. In conclusion, HD-DN improved the CR rate, OS, and EFS of FLT3-ITD-mutated AML patients. HD-DN also tended to yield better outcomes than IDA, though the difference was not significant. The superiority of HD-DN over IDA should be confirmed in future studies.

Introduction: Allogeneic hematopoietic cell transplantation is an only potentially curative option for patients with higher-risk myelodysplastic syndrome (MDS). Owing to the advances in treatment strategies including reduced intensity conditioning, graft-versus-host disease (GVHD) prevention and supportive care, more elderly patients or those with comorbidities can proceed to allogeneic HCT. However, the long-term survival rate following allogeneic HCT is reported to be less than 50%, and non-relapse mortality (NRM) rate is still high reaching upto 30%. In this study, we aimed to evaluate the feasibility of using post-transplantation cyclophosphamide (PTCy) as a GVHD prophylaxis in allogeneic HCT for higher-risk MDS patients. We also compared the post-transplantation outcomes of PTCy group and those of historical control who received HCT using anti-thymocyte globulin (ATG). Methods: Patients with higher-risk MDS or MDS/myeloproliferative neoplasm (MPN) with bone marrow blast ≥ 5% were included in this study. Higher-risk MDS was defined by MDS with International Prognostic Scoring System >1.0 or bone marrow blast ≥ 5% at any time points before HCT. Conditioning regimen consists of busulfan (4-days for patients aged Results: Ninety-two and 144 patients received allogeneic HCT using PTCy and ATG, respectively. The median overall survival were 47.9 and 44.0 months, respectively (P=.383). Cumulative incidence of total and grade II-IV acute GVHD in PTCy and ATG group were 19.6% vs. 37.5% (P=.002), and 2.6% vs. 21.7% (P Conclusion: Allogeneic HCT using PTCy as GVHD prophylaxis in higher-risk MDS seems feasible in terms of low rate of acute GVHD and relapse incidence. Disclosures Choi: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Korean Society of Hematology: Membership on an entity's Board of Directors or advisory committees; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board; AbbVie: Honoraria, Other: Advisory board.

Background Idiopathic cytopenia of undetermined significance (ICUS) is characterized by a persistent and clinically significant cytopenias which does not meet the diagnostic criteria for myelodysplastic syndrome (MDS). In some patients with ICUS, disease evolution to MDS or acute myeloid leukemia after variable periods of time was observed in several studies. However, the incidence and predictive factors of progression as well as management guidelines for ICUS patients are not well established. We aimed to identify the clinical and genetic characteristics of ICUS in comparison with lower-risk MDS for understanding the pathophysiologic features and providing guidance for treating physicians. Methods We performed targeted deep sequencing including 61 myeloid neoplasm-related genes with a MiSeqDx sequencer (Illumina) using bone marrow (BM) samples obtained from the patients with ICUS (n=139) and MDS (n=226) between May 2009 and December 2019. The cut-off level of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Cloncal cytopenia of undetermined significance (CCUS) was defined as ICUS with ≥ 2% VAF of mutations and lower-risk MDS was defined as MDS with revised international prognostic scoring system ≤3.5. Results When we compared the overall survival (OS) of the patients according to the disease subtypes, OS of CCUS (77.0% at 5-year) was significantly better than that of higher-risk MDS (41.0%, P Conclusion In our study, CCUS and lower-risk MDS showed similar OS which was significantly better than higher-risk MDS and worse than non-clonal ICUS. The clinical and mutational characteristics were also similar except for the degree of anemia and the SF3B1 and STAT3 mutation. Our findings suggest that the patients with CCUS may be regarded and treated as the lower-risk MDS despite a lack of significant dysplasia or MDS-associated definitive chromosomal abnormality. Disclosures Choi: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Ingenium Therapeutics, Daejeon, Korea: Consultancy, Current holder of individual stocks in a privately-held company. Lee: Korean Society of Hematology: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Other: Advisory board; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board.

To investigate the role of antithymocyte globulin (ATG)-containing reduced-intensity conditioning (RIC) in hematopoietic cell transplantation (HCT) from unrelated (UD) or haploidentical family donors (HFD), we conducted a phase 2 trial of 237 patients (age range, 16 to 69 years) with acute myeloid leukemia (AML) in remission. Patients undergoing UD-HCT (n = 93) or HFD-HCT (n = 59) received RIC comprising busulfan, fludarabine, and ATG, 9 mg/kg, whereas those undergoing HCT from matched sibling donors (MSD, n = 85) received myeloablative busulfan and cyclophosphamide conditioning or aforementioned RIC with ATG, 4.5 mg/kg. For graft-versus-host disease (GVHD) prophylaxis, cyclosporine and methotrexate were administered. The median follow-up period was 44.7 months after HCT for 161 survivors. For UD-HCT versus HFD-HCT, there were no significant differences in leukemia recurrence, nonrelapse mortality, relapse-free survival, grades 2 to 4 acute GVHD, and moderate-to-severe chronic GVHD. Furthermore, when the outcomes of UD-HCT and HFD-HCT were combined and compared with those of MSD-HCT, there were no significant differences in leukemia recurrence (3-year cumulative incidence, 30% versus 29%), nonrelapse mortality (3-year cumulative incidence, 7% versus 8%), relapse-free survival (3-year estimate, 63% versus 63%), and grades 2 to 4 acute GVHD (120-day cumulative incidence, 16% versus 13%). Moderate-to-severe chronic GVHD, however, occurred less frequently in UD/HFD-HCT (2-year cumulative incidence, 22% versus 40%; P = .006). The addition of ATG to conditioning regimen was a significant predictor for less chronic GVHD (subdistribution hazard ratio, .59). In AML in remission, UD/HFD-HCT after ATG-containing RIC achieved leukemia control equivalent to that of MSD-HCT. Despite HLA disparity in UD/HFD-HCT, chronic GVHD occurred less frequently after ATG-containing RIC, suggesting a strong GVHD-modulating effect of ATG.

Background Allogeneic hematopoietic cell transplantation (HCT) has been more widely applicable to the patients with hematologic malignancies owing to the increased donor availability, advances in conditioning regimen, prevention of transplantation-related toxicities, and general supportive care. However, there is no comprehensive and uniform approach for decision making which incorporates transplantation-related factors including patients and donor selection, conditioning intensity, or prevention of graft-versus-host disease (GVHD). In this regard, we aimed to establish and validate a machine learning-based predictive model for survival after allogeneic HCT in hematologic malignancies. Method Data from 2,011 patients with hematologic malignancies (1,464 acute leukemia, 296 myelodysplastic syndrome, 100 chronic myeloid leukemia, 45 myeloproliferative neoplasm, 85 lymphoma, and 21 multiple myeloma) who received allogeneic HCT between December 1993 and December 2019 at the Asan Medical Center were retrospectively analyzed. Results The median overall and event-free survival of total patients were 4.2 year (95% confidence interval [CI], 2.9-5.4) and 1.5 year (95% CI, 1.1-1.8), respectively. To predict post-transplantation survival, the patients were classified into "survived more than 5 years" and "died before 5 years". Among four major machine learning models (random forest [RF], support vector machine, logistic regression, and feed forward neural network), we selected RF method according to the predictive power of each algorithm. Using the RF machine learning algorithm, we developed a post-transplantation survival predicting model with the training cohort of 1,408 patients (70%) and tested it with the validation cohort of 603 patients (30%). Of >200 variables, 33 were selected using recursive feature elimination, and the estimated area under the receiver operator characteristic curve and accuracy of the model was 0.812 and 0.73, respectively. We then evaluated the robustness of predictive power of the model using 10-fold cross-validation in validation cohort. In addition, risk scores were calculated from each patient in the validation cohort, and there was an agreement between the estimated predicted risk and observed risk. Conclusion In conclusion, the machine learning-based prediction model seems feasible assuming post-transplantation survival outcomes in hematologic malignancies. Our findings could be helpful for clinicians to select more appropriate donor in terms of age or type of human leukocyte antigen mismatch, conditioning regimen, and GVHD prophylaxis. Disclosures Lee: Astellas: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Lee:Hanmi: Research Funding.

Background Elderly patients with acute myeloid leukemia (AML) has generally poor prognosis prognosis in accordance with their unfavorable clinical and biologic features. Hypomethylating agents have shown potential in the treatment of AML as well as myelodysplastic syndrome (MDS). In this retrospective study, we compared the outcomes of elderly AML patients according to induction treatment options: decitabine versus intensive chemotherapy. We also tried to identify specific subsets of patients who are most likely to benefit from decitabine or intensive chemotherapy. Methods This study included elderly patients aged 65 years or older who received induction treatment with decitabine or intensive chemotherapy for newly diagnosed AML at a single institute. The endpoints for this study were overall survival (OS), response, and event-free survival (EFS). Response included complete remission (CR), CR with incomplete hematologic recovery (CRi), and CR with partial hematologic recovery (CRh). Results A total of 107 patients, decitabine for 75 and intensive chemotherapy for 32, were analyzed. Decitabine was given as 20 mg/m2/day for 5 days every 4 weeks. Median 5 courses (range, 1-43) were delivered to the patients and 16 patients were still on decitabine treatment at the time of analysis. Intensive chemotherapy regimens included cytarabine plus daunoruribin (n=21) or idarubicin (n=10), and hyper-CVAD (n=1): 25 patients received one course and 7 received two courses for induction treatment. The rate for CR + CRi + CRh (CRR) was 38.6% (39 of 101 assessable patients). With a median follow-up duration of 14.8 months (95% confidence interval [CI], 12.0-22.8) among surviving patients, 79 patients died and 22 relapsed. The median OS and EFS were 12.3 months (95% CI, 10.0-14.7) and 4.1 months (95% CI, 2.5-5.7), respectively. Decitabine showed lower CRR (26.1% vs. 65.6, P Conclusion Decitabine showed similar OS to intensive chemotherapy despite of lower response rate in elderly AML patients. Clinical outcomes of specific subgroups seemed to be different according to induction treatment options. Further studies are warranted for selection of optimal treatment options for elderly AML patients. Disclosures No relevant conflicts of interest to declare.

The present study aimed to investigate baseline and posttransplant prognostic factors for allogeneic hematopoietic cell transplantation (HCT) in 61 lymphoma patients. The 5-year probabilities of overall survival (OS), non-relapse mortality (NRM), progression-free survival (PFS), and event-free survival (EFS) were 31.1%, 28.8%, 38.8%, and 23.2%, respectively. Multivariate analysis demonstrated that the International Prognostic Index risk at HCT was a significantly independent prognostic factor for OS, NRM, PFS, and EFS, and chemosensitivity was a prognostic factor for OS, NRM, and EFS. The occurrence of chronic graft-versus-host disease (GVHD) was significantly associated with higher OS, but it was not with PFS or EFS. Various parameters of immune reconstitution at 1 month after transplantation were associated with clinical outcomes in different ways. Our study results might be helpful in selecting appropriate patients or adopting effective posttransplant treatment strategies, eventually leading to an improvement in outcomes after allogeneic HCT for lymphoma.

Background Following the advances in genetic tests, including next-generation sequencing, there have been new insights into hereditary hematopoietic malignancies. The germline mutation in DDX41 was included in a new category, myeloid neoplasms with germline predisposition, of the updated 2016 WHO classification. Based on the reported data to date, there seem to be racial differences in the mutation variants of DDX41 gene, which were found in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Idiopathic cytopenia of undetermined significance (ICUS) is known to be a precursor lesion of MDS, but the DDX41 mutations have not been evaluated in patients with ICUS. In this study, we aimed to reveal the incidence, genetic characteristics, and clinical features of the DDX41 mutations in patients with ICUS, MDS, and AML. Methods We performed targeted deep sequencing of 141 genes with a MiSeqDx sequencer (Illumina) using bone marrow (BM) samples obtained from the patients with ICUS (n=77), MDS (n=175), and AML (n=148) between May 2009 and June 2019. ICUS was defined by the proposed criteria of 2007 Consensus Group. The cut-off level of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. We divided ICUS into clonal cytopenia of undetermined significance (CCUS), which was defined as ICUS with ≥ 2% VAF of somatic mutations of myeloid malignancy-associated genes and non-CCUS. Results Overall, DDX41 mutations were detected in 6 (7.8%) of 77 ICUS, 19 (10.9%) of 175 MDS, and 8 (5.4%) of 148 AML patients. Thirty-eight (49.4%) of 77 ICUS patients had CCUS. Of 6 DDX41 mutated patients with CCUS, 5 showed biallelic mutations with the median VAF of 44.7% (range, 29.3−50.0) and 10.2% (range, 3.3−25.4), indicating that one germline and one somatic mutation exists. Of 175 MDS patients, 78 were categorized into lower-risk MDS (revised international prognostic scoring system [IPSS-R] < 3.5) and 97 into higher-risk MDS (IPSS-R ≥ 3.5), and DDX41 mutations were identified in 6 (7.7%) of 78 lower-risk MDS and 13 (13.4%) of 97 higher-risk MDS patients. Interestingly, biallelic mutations were found in 16 of 18 DDX41-mutated MDS patients with the median VAF of 47.75% (range, 43.4−55.6) and 13.8% (range, 2.7−35.8). In contrast, only one of 8 DDX41-mutated AML patients had biallelic mutation. Patients with DDX41 mutations typically showed hypocellular marrow (median BM cellularity, 30%; range, 5−95) with significant neutropenia (median neutrophil counts, 607/μL; range, 142−1675), male predominance (29/33, 87.9%), and relatively older age (median age, 64 years; range, 41−79) at diagnosis. In addition, we found novel mutation locations, which were different between presumed germline and somatic variants: V152G in germline, and T227M in somatic (Table 2). During a median follow-up duration of 2.9 years, 1 of 6 ICUS patients progressed to MDS-EB-1 after 17.3 months and 1 to non-severe aplastic anemia after 51.3 months. Conclusion Our data show that a significant proportion of ICUS, MDS, and AML patients had DDX41 mutations, many of which are presumably germline. These findings suggest that careful consideration of the predisposing germline mutation is important when selecting a familial donor for allogeneic HCT. We also found novel mutation locations of DDX41 gene which were different between somatic and germline variants. Further studies are warranted to define the clinical and molecular characteristics of DDX41 mutations and therapeutic implications in myeloid neoplasms. Disclosures No relevant conflicts of interest to declare.

Background: Unexplained cytopenia comprises a spectrum of hematological diseases from idiopathic cytopenia of undetermined significance (ICUS) to myelodysplastic syndrome (MDS). Revised International Prognostic Scoring System (IPSS-R) is the standard tool to assess risk in MDS. Here, we investigated the occurrence, characteristics, and changing pattern of mutations in patients with ICUS and MDS stratified by IPSS-R score. Methods: A total of 211 patients were enrolled: 73 with ICUS and 138 with MDS. We analyzed the sequencing data of a targeted gene panel assay covering 141 genes using the MiSeqDx platform (Illumina). The lower limit of variant allele frequency (VAF) was set to 2.0% of mutant allele reads. Bone marrow components were assessed for the revised diagnosis according to the 2016 WHO classification. Lower-risk (LR) MDS was defined as those cases with very low- or low-risk MDS according to the IPSS-R. Higher-risk (HR) MDS was defined as those cases with high- or very high-risk MDS according to the IPSS-R. Results: Patients with ICUS were classified as very low-risk (39.7%), low-risk (54.8%), and intermediate-risk (5.5%) according to the IPSS-R. Patients with MDS were classified as LR (35.5%), intermediate-risk (30.4%), and HR (34.1%). In the ICUS, 28 (38.4%) patients carried at least one mutation in the recurrently mutated genes in MDS (MDS mutation). The most commonly mutated genes were DNMT3A (11.0%), followed by TET2 (9.6%), BCOR (4.1%), and U2AF1, SRSF2, IDH1 and ETV6 (2.7% for each). IPSS-R classification was not associated with mutational VAF and the number of mutations in ICUS. In the 49 LR MDS, 28 (57.1%) patients carried at least one MDS mutation. The most commonly mutated genes were SF3B1 (20.4%), followed by TET2 (12.2%), U2AF1 (10.2%), DNMT3A (10.2%), ASXL1 (10.2%), and BCOR (6.1%). Higher VAF and number of mutations were observed in LR MDS compared to ICUS patients. In the 42 intermediate-risk MDS, 27 (64.3%) patients carried at least one MDS mutation. The most commonly mutated genes were ASXL1 (23.8%), followed by TET2 (21.4%), RUNX1 (16.7%), U2AF1 (14.3%), DNMT3A (14.3%), SF3B1 (9.5%), and SRSF2, BCOR, STAG2 and CBL (7.1% for each). In the 47 HR MDS, 36 (76.6%) patients carried at least one MDS mutation. The most commonly mutated genes were TET2 (25.5%), followed by DNMT3A (14.9%), TP53 (14.9%), RUNX1 (12.8%), U2AF1 (10.6%), ASXL1 (10.6%), and SRSF2 and KRAS (6.4% for each). As the disease progressed, VAF and number of the MDS mutations gradually increased, and mutations involving RNA splicing, histone modification, transcription factor or p53 pathway had a trend for increasing frequency. Specifically, ASXL1, TP53, and RUNX1 mutations were the most striking features in patients with advanced stage of the disease. Cohesin mutations were not detected in ICUS, whereas these mutations were detected at a relatively high frequency in HR MDS. Our data were summarized in Table 1. Conclusions: We demonstrate that on disease progression, MDS mutations are increased in number as well as are expanded in size. Furthermore, a subset of mutations tends to be enriched for intermediate- to HR MDS. The results of this study can aid both diagnostic and prognostic stratification in patients with unexpected cytopenia. In particular, characterization of MDS mutations can be useful in refining bone marrow diagnosis in challenging situations such as distinguishing LR MDS from ICUS. Disclosures No relevant conflicts of interest to declare.

The optimum method of donor natural killer cell infusion (DNKI) after allogeneic hematopoietic cell transplantation (HCT) remains unclear. Fifty-one patients (age range, 19 years to 67 years) with refractory acute leukemia underwent HLA-haploidentical HCT and underwent DNKI on days 6, 9, 13, and 20 of HCT. Median DNKI doses were .5, .5, 1.0, and 2.0 × 108/kg cells, respectively. During DNKI, 33 of the 45 evaluated patients (73%) developed fever (>38.3°C) along with weight gain (median, 13%; range, 2% to 31%) and/or hyperbilirubinemia (median, 6.2 mg/dL; range, 1.0 mg/dL to 35.1 mg/dL); the toxicity was reversible in 90% of patients. After transplantation, we observed cumulative incidences of neutrophil engraftment (≥500/µL), grade 2 to 4 acute graft-versus-host disease (GVHD), chronic GVHD, and nonrelapse mortality of 84%, 28%, 30%, and 16%, respectively. The leukemia complete remission rate was 57% at 1 month after HCT and 3-year cumulative incidence of leukemia progression was 75%. When analyzed together with our historical cohort of 40 patients with refractory acute leukemia who underwent haploidentical HCT and DNKI on days 14 and 21 only, higher expression of NKp30 (>90%) on donor NK cells was an independent predictor of higher complete remission (hazard ratio, 5.59) and less leukemia progression (hazard ratio, .57). Additional DNKI on days 6 and 9 was not associated with less leukemia progression (75% versus 55%).

Patients with liver cirrhosis (LC) have impaired immunity and thus are predisposed to infections. Few studies have attempted to evaluate Staphylococcus aureus bacteremia (SAB) in LC patients. Therefore, this study prospectively evaluated the clinical characteristics and outcomes of 642 episodes of SAB from August 1, 2008 to September 31, 2010. Of 642 patients with SAB, 109 (17.0 %) were classified as LC patients whereas the remaining 533 (83.0 %) were classified as non-LC patients. The 30-day mortality rate of LC patients was significantly higher than that of patients with other diseases (32 % vs. 22 %, respectively; P = 0.047). The 30-day mortality rates of patients with MSSA bacteremia and MRSA bacteremia were not significantly different among LC patients (35.1 % with MSSA vs. 26.9 % with MRSA; P = 0.41). A univariate analysis of the 30-day mortality rate of LC patients with SAB for survivors and non-survivors showed that rapidly fatal or ultimately fatal according to the criteria of McCabe and Jackson (OR 5.0; 95 % CI 1.60-15.65), septic shock at initial presentation (OR 3.5; 95 % CI 1.18-10.39) and Child-Pugh class C (OR 2.8; 95 % CI 1.20-6.59) were associated with increased mortality. In contrast, the removal of the eradicable focus was associated with decreased mortality (OR 0.14; 95 % CI 0.04-0.52). Disease severity and liver dysfunction may be useful for predicting the prognosis of SAB in LC patients.

Background Improvement of cytopenia is one of the primary treatment purposes for patients with the lower-risk myelodysplastic syndrome (MDS). Androgens have been used for the treatment of aplastic anemia, immune thrombocytopenia, and telomere diseases. In this retrospective study, we aimed to evaluate the efficacy of androgen therapy in lower-risk MDS. Methods We analyzed the data of 139 patients who received androgens (danazol or oxymetholone) for treatment of cytopenia between February 1997 and May 2018. All patients had the international prognostic scoring system low or intermediate-1 risk at the time of androgen therapy. The assessment of hematologic improvement (HI) was based on the international working group response criteria for MDS. Results Androgens (oxymetholone for 83 patients and danazol for 56) were given as first (n=108, 77.7%) or over second (n=31, 22.3%)-line treatment for MDS (Table 1). The time interval between diagnosis and androgen treatment was median 1.3 months (range, 0-240.6), and 75 patients (54.0%) were red blood cell (RBC) transfusion-dependent before treatment. The dose intensity of oxymetholone and danazol was 79 and 385 mg/day respectively, and the median treatment duration was 5.8 months (range, 0.9-92.2). Seventy-nine patients (56.8%) achieved HI at any lineage: 29.0% for erythroid (HI-E), 51.9% for platelet (HI-P), and 60.5% for neutrophil (HI-N). The median time to HI following androgen therapy was 4.1 months (range, 0.6-124.5) for HI-E, 1.7 (range, 0.4-40.4) for HI-P, and 1.8 (range, 0.2-8.4) for HI-N. In univariate analysis, presence of RBC transfusion-dependence (46.7% vs. 68.8%, P=.009), pre-treatment low hemoglobin (45.2% vs. 74.5%, P=.001), high platelet count (46.5% vs. 73.6%, P=.002), and high neutrophil count (4.94% vs. 67.2%, P=.036) were associated with lower HI rate (Table 2). In multivariate analysis, pre-treatment low hemoglobin, high platelet count, and high neutrophil count remained as significant factors for lower HI rate (Table 2). During the median follow-up duration of survivors of 40.8 months (95% confidence interval [CI], 38.0-67.5), the estimated 5-year overall survival (OS) and acute myeloid leukemia-free survival was 68.8% and 67.7%, respectively. Achievement of HI was associated with longer OS (hazard ratio, 0.346; 95% CI, 0.174-0.688). There were no significant differences in HI and OS rates between danazol and oxymetholone. Conclusion Our data suggest that androgen can be a reasonable treatment option for lower-risk MDS patients with significant cytopenia. Prospective studies are warranted to investigate the efficacy of androgen therapy in lower-risk MDS. Disclosures No relevant conflicts of interest to declare.

Background and study aims Incomplete pancreas divisum (PD) has been generally regarded as merely a normal anatomic variant, without clinical implications. This study compares the prevalence, symptom occurrence rate, clinical presentation, and outcomes of endoscopic treatment in patients with incomplete PD and those with complete PD. Patients and methods The study population consisted of 56 patients (27 with complete PD and 29 with incomplete PD), identified from 4473 newly performed endoscopic retrograde cholangiopancreatography examinations. Endoscopic treatment (minor papilla sphincterotomy with stents or nasopancreatic drainage tube insertion) was attempted in 25 symptomatic patients with PD, which was suspected to be causing the associated pancreatic diseases: acute recurrent pancreatitis (ARP) (n = 13; five patients with complete PD and eight with incomplete PD); chronic pancreatitis (CP) (n = 10: five patients with complete PD and five with incomplete PD); and pancreatic-type pain (PP) (n = 2; one patient with complete PD and one with incomplete PD). The mean follow-up period was 17 months (range 9 - 49 months). Results In 12 of the 27 patients with complete PD--six with ARP, five with CP, and one with PP--it was suspected that PD was the cause of pancreatic disease. Ten of the 11 symptomatic patients with complete PD underwent successful endoscopic treatment (five with endoscopic minor papilla sphincterotomy and stenting, and five with endoscopic minor papilla sphincterotomy and endoscopic nasopancreatic drainage), and seven of these ten patients benefited from the endoscopic treatment. In 14 of the 29 patients with incomplete PD--eight with ARP, five with CP, and one with PP--it was suspected that pancreas divisum was the cause of pancreatic disease. Thirteen of the 14 symptomatic patients with incomplete PD underwent successful endoscopic treatments (six with endoscopic minor papilla sphincterotomy and stenting, and seven with endoscopic minor papilla sphincterotomy and endoscopic nasopancreatic drainage), and eight of these 13 patients experienced clinical improvement. Conclusions The prevalence rate, symptom occurrence rate, clinical presentation, and outcomes of endoscopic treatment were similar in patients with complete PD and incomplete PD. Incomplete PD may therefore have similar clinical implications to those of complete PD.

Background Patients with FLT3-ITD mutated acute myeloid leukemia (AML) have generally poor survival. Recent update of ECOG trial comparing standard- vs. high-dose daunorubicin showed that daunorubicin dose intensification improved survival in AML with FLT3-ITD mutants (Blood 2016;127:1551). In subgroup analysis of our previous randomized trial, high-dose daunorubicin seemed to be more effective than idarubicin in AML patients with FLT3-ITD mutants (ASH abstract No. 2535, 2015). In this retrospective investigation, we aimed to evaluate the role of daunorubicin dose intensification for induction therapy in AML patients with FLT3-ITD mutants who were treated at a single institute. Methods We analyzed data from 120 patients of newly diagnosed FLT3-ITD mutated AML patients who received induction chemotherapy between January 2002 and March 2016. The regimens consisted of high-dose daunorubicin (HD-DN, 90 mg/m2/d x 3d, n=39), standard-dose daunorubicin (SD-DN, 45 mg/m2/d x 3d, n=48), or idarubicin (IDA, 12 mg/m2/d x 3d, n=33) in combination with cytarabine (200 mg/m2/d x 7d). Patients with acute promyelocytic leukemia were not included. Results After the first round of induction chemotherapy, 53 patients had persistent leukemia; 50 received the second round of induction chemotherapy consisting of daunorubicin (45 mg/m2/d x 2d) or idarubicin (8 mg/ m2/d x 2d) in addition to cytarabine (200 mg/m2/d x 5d) and 3 received other regimens. A total of 81 patients achieved CR, and the CR rates were 76.9%, 58.3%, and 69.7% in HD-DN, SD-DN, and IDA, respectively (P=0.175). The 4-year cumulative incidence of relapse (CIR) of these 81 patients was 48.8%. With the median follow-up duration of survivors of 59.9 months (range, 4.6-170.7), 4-year overall survival (OS) and event-free survival (EFS) were 57.1%/27.7%/35.7% (P=0.025) and 45.2%/23.9%/36.0% (P=0.042) in HD-DN, SD-DN, and IDA, respectively. HD-DN showed statistically higher OS (hazard ration [HR], 0.424; P=0.005) and EFS (HR, 0.497; P=0.01), and lower CIR (P=0.036) than SD-DN, while OS and EFS differences between HD-DN and IDA were not statistically significant. Conclusion Daunorubicin dose intensification for induction therapy seemed to be effective in AML patients with FLT3-ITD mutants. Further studies are needed to investigate whether HD-DN is superior to IDA in this population. Considering high relapse rate, combination strategies of daunorubicin dose intensification and targeted agents such as FLT3 inhibitors should be developed. Disclosures No relevant conflicts of interest to declare.

Background: Allogeneic hematopoietic cell transplantation (HCT) has been increasingly used for the treatment of lymphoma. The outcomes of HCT in lymphoma depend on baseline patient characteristics including chemosensitivity and International Prognostic Index (IPI). Several studies have shown that post-transplant occurrence of acute or chronic graft-versus-host disease (GVHD) and immune recovery might be associated with the outcomes. In this retrospective study, we investigated baseline and post-transplant prognostic factors in lymphoma patients receiving allogeneic HCT. Patients and methods: Between May 1998 and December 2015, a total of 61 patients underwent allogeneic HCT for lymphoma and the median age was 39 years (range, 16-62 years). Thirty four patients (55.7%) had chemo-sensitive disease and 24 patients had received autologous HCT. Fifty-six of 61 patients received reduced-intensity conditioning regimens. We evaluated tumor response, overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), and event-free survival (EFS) after allogeneic HCT along with potential prognostic factors including GVHD and immune reconstitution. Results: Objective tumor response after HCT was observed in 41 (67.2%; complete 30 and partial 11). The 5-year probabilities of OS, NRM, PFS, and EFS were 30.7%, 23.5%, 41.3%, and 24.0%, respectively. Among the baseline characteristics, chemosensitivity had a significant impact on OS, NRM, and EFS. Persistent disease status at allogeneic HCT had an adverse effect on OS and low IPI risk category at HCT was associated with longer OS and EFS. HCT co-morbidity index ≥1 was an independent prognostic factor for higher NRM. Grade III-IV acute GVHD was associated with lower OS and higher NRM. Severe chronic GVHD had higher OS (60.0% vs. 19.8%, P=0.002), PFS (68.8% vs.35.9%, P Conclusion: Chemosensitivity was the most important prognostic factor in allogeneic HCT for lymphoma. Acute GVHD had unfavorable impact, whereas, chronic GVHD had favorable impact on post allogeneic HCT outcomes. Early immune recovery could predict allogeneic HCT outcomes. Disclosures No relevant conflicts of interest to declare.

Introduction: The IPSS has been widely used for risk stratification in myelodysplastic syndromes (MDS), and patients with IPSS low and intermediate-1 scores are designated as having lower-risk (LR) MDS. Despite its utility, the outcomes of patients with LR disease defined by IPSS are variable and a subset of patients experience inferior than expected outcomes. Treatment with hypomethylating agents is the standard of care in higher-risk MDS, but there have been little data for hypomethylating therapy in LR MDS. We retrospectively collected and analyzed the data related to hypomethylating therapy in IPSS LR MDS from 12 Korean institutes. Patients and Methods: A total of 610 patients, who were treated with azacitidine or decitabine for IPSS LR MDS, were included in this retrospective case series study. All patients received azacitidine (7-day) or decitabine (5-day). Both regimens were repeated every 4 weeks. The overall response rate (ORR) included rates for complete response (CR), partial response (PR), marrow CR (mCR), and stable disease (SD) with hematologic improvements (HI). For 139 patients who underwent allogeneic hematopoietic cell transplantation (HCT), all survival data were censored at the time of HCT. Results: Median age was 63 (19-84) years. IPSS category was low in 44 and intermediate-1 in 566. The patients were reclassified with other scoring systems including revised IPSS (R-IPSS), WPSS, and LR-PSS, and between 21.8% and 37.7% of patients were identified as having high or very high risk features by the other prognostic indices. Patients received azacitidine (n=436) or decitabine (n=174) for a median of 5 (1-46) courses. ORR was 51.3% (CR 78, PR 12, mCR with HI 27, mCR without HI 20, and SD with HI 176). 294 patients (48.2%) showed any HI. Median OS was 2.35 years and patients with HI had significantly longer OS than those without HI (P=0.001). Our case series patients were well stratified in terms of OS by R-IPSS (P=0.001), WPSS (P Conclusion: IPSS LR MDS included a broad range of prognostic implications. Hypomethylating therapy brought varying degrees of response in about half of the patients with IPSS LR MDS. The patients who had high risk features with other prognostic indices showed poor OS and allogeneic HCT should be considered during the course of hypomethylating therapy in these patients. Disclosures No relevant conflicts of interest to declare.

Although hemophagocytic syndrome (HS) featuring secondary hemophagocytic lymphohistiocytosis (HLH) has a grave prognosis, little is known about the natural course of the disease. Patients who showed the clinical features of HLH as well as tissue-proven hemophagocytosis when seen at Asan Medical Center between 1999 and 2010 were included in this analysis. Patients with proven lymphoma were excluded. The median age of our 23 study patients was 49 years. Epstein–Barr virus was suspected to have caused HS in 16 (70%) patients and hepatitis A virus in one patient. Twenty-two patients were treated, 13 according to the HLH protocol and nine using immunosuppressive agents such as corticosteroid and/or cyclosporine. Five patients undertook allogeneic hematopoietic cell transplantation (HCT) during their treatment-dependent relapse (n = 4) or responsive status (n = 1). After the median follow-up of 180 days, 17 (74%) died and six (26%) were alive. The median time from initial presentation until death was 41 days among those patients who died. The serum fibrinogen level ≥166 mg/dL determined at the initial visit was significantly associated with the survival time according to univariate analysis. The low histiocyte proportion in bone marrow and early initiation of treatment tended to correlate with a favorable outcome. On multivariate analysis, serum fibrinogen ≥166 mg/dL (hazard ratio, 0.175, P = 0.018) was an independent clinical factor for determining the patient survival time. Despite appropriate patient management, the outcome of HS featuring HLH was grave. The serum fibrinogen level at the initial presentation was significant, and selected patients obtained some benefit from allogeneic HCT.

Background: The JL1 antigen is a novel epitope of CD43, a cell surface glycoprotein of mucin family. JL1 is a differentiation antigen expressed on stage II double positive (CD4+CD8+) human cortical thymocytes. The antigen is not expressed on mature peripheral blood cells or other normal tissues. The anti-JL1 monoclonal antibody binds to human leukemia MOLT-4 cells with 5,100-9,600 binding sites per cell. Preclinical studies have shown the cytotoxic effects of anti-JL1-based immunotoxin against JL1-positive leukemic cells, sparing most normal tissues other than thymocytes and some bone marrow mononuclear cells. Phase I clinical trial of new anti-leukemic agent with an anti-JL1 antibody (Leukotuximab; DiNonA, Korea) is now underway. In this study, we prospectively investigated the JL1 expression in patients with acute leukemia and myelodysplastic syndrome (MDS). Patients & methods: Flow cytometric analysis for the JL1 expression on leukemic blasts was performed using a FACSCanto II (Becton-Dickinson, Sunnyvale, CA, USA). The percent expression of JL1 antigen among leukemic blasts was recorded. Positive JL1 expression was defined if 20% or more leukemic blasts expressed the antigen. Association of JL1 expression with clinical, pathologic, and genetic characteristics was analyzed. Influence of JL1 expression on clinical outcomes of patients was also explored. Results: Between March 2014 and June 2015, a total of 245 adult patients with acute myeloid leukemia (AML, n=170), acute lymphoblastic leukemia (ALL, n=52), and MDS (n=23) were enrolled in this study. Positive JL1 expression was observed in 96 (57.1%) patients with AML, 28 (51.9%) with ALL, and 5 (21.7%) with MDS (P =0.006), while three normal controls showed negative JL1 antigen expression. Interestingly, JL1 expression was positive in all 14 patients with AML M3 with a median expression of 94.3% (range, 60.3-97.8%). In contrast, only 13 (39.4%) of 33 patients with AML with myelodysplasia-related changes (MRC) had positive JL1 expression. In AML patients, positive JL1 expression was significantly associated with CD34- (P =0.003), HLA-DR- (P =0.019), PML-RARA + (P =0.001), FLT3-ITD + (P =0.026), mutated NPM1 (P =0.003), and complex karyotype (3 or more clonal chromosomal abnormalities) (P =0.020). Cytarabine plus anthracycline based chemotherapy was given to 117 patients with AML, and the complete remission (CR) rate was significantly different between 63 JL1 expression positive patients and 54 negative patients (84.1% vs. 59.3%, P =0.003). Positivity of JL1 expression was not significantly associated with overall survival in all patients with AML (median survival, JL1 positive vs. negative, 20.6 vs. 18.2 months, P =0.489). In ALL patients, positive JL1 expression was significantly associated with CD13- (P =0.032) and the CR rate was not significantly different by JL1 expression. JL1 expression was measured twice or more in 85 patients during their clinical courses and positivity of JL1 expression was not changed in 61 (71.8%) (P =0.307). Five MDS patients progressed to AML and JL1 expression was changed in only one patient (JL1 positive to JL1 negative). Conclusion: JL1 was expressed in around 50% of patients with AML or ALL while less frequent expression of JL1 was observed in MDS and AML with MRC. JL1 expression was significantly associated with some immunophenotypic and genetic features, especially PML-RARA +. JL1 expression was significantly associated with the CR rate of AML patients. Expression of JL1 seems to be stable during clinical courses. Our data suggest that immunotherapeutic approach targeting JL1 antigen may be feasible in significant proportion of patients with acute leukemia and MDS. Disclosures Kim: Dinona Institute, Dinona Inc.: Employment. Yoon:Dinona Institute, Dinona Inc.: Employment. Jung:Dinona Institute, Dinona Inc.: Employment.

Allogeneic hematopoietic cell transplantation (HCT) from HLA-matched sibling (MS) or unrelated donors (MU) is a well-established treatment for patients with intermediate/high-risk acute myelogenous leukemia (AML) in remission. When HLA-matched donors are not available, however, use of haploidentical family (HF) donors for HCT remains controversial. Therefore, we performed a prospective study, where patients with AML in complete remission (CR) underwent allogeneic HCT according to the donor priority of MS, MU, or HF donors. Conditioning regimen for MS-HCT was busulfan (3.2 mg/kg • 4 days)-cyclophosphamide (60 mg/kg • 2 days) or, for patients >55 years or with co-morbidity, busulfan (3.2 mg/kg • 2 days)-fludarabine (30 mg/m2 • 6 days)-Thymoglobulin (1.5 mg/kg • 3 days). Patients undergoing MU- or HF-HCT received busulfan (3.2 mg/kg • 2 days)-fludarabine (30 mg/m2 • 6 days)-Thymoglobulin (3 mg/kg • 3 days) (Lee K-H et al; Blood 2011;118:2609-2617; Am J Hematol 2011;86:399-405). Ex-vivo T cell depletion was not performed. GVHD prophylaxis included cyclosporine plus a short course of methotrexate. Between January 2010 and December 2014, 244 patients enrolled. Of those, 16 patients were excluded from the analysis (12 patients relapsed before HCT; 3 with major protocol violation; and 1 with incomplete data). Of remaining 228 patients, 81 underwent HCT from MS donors, 90 from MU donors, and 57 from HF donors. The donors for MU-HCT were younger and more male-dominant than those for MS- or HF-HCT. The characteristics of patients and their donors were summarized in Table 1. Table 1. MS-HCT (n=81) UD-HCT (n=90) HF-HCT (n=57) P* Median age, yr (range) 48 (19-66) 43 (16-66) 46 (17-69) Sex, male/female 37/44 44/46 29/28 0.824 CR1/CR2 76/5 82/8 47/10 0.098 Chromosome risk,low**/intermediate/high/high-monosomal 6/57/10/5 4/65/16/3 2/40/7/5 0.751 Donor median age, yr (range) 45 (18-63) 28 (20-45) 29 (15-58) Donor age, yrup to 2526-45over 45 44136 29610 19326 0.000 Donor sex, male/female 46/35 76/14 36/21 0.000 Donor relation, parents/sibling/offspring 7/24/26 HLA allele mismatch/8 (GVH direction), 0/1/2/3/4 81/0/0/0 51/26/10/2/1 0/0/5/22/30 0.000 Graft, bone marrow/peripheral blood 28/53 0/90 0/57 0.000 Median nucleated cell count, •108/kg (range) 8.0 (0.9-19.0) 10.8 (4.1-31.4) 10.8 (5.1-19.3) Median CD34+ count, •106/kg (range) 4.9 (0.8-18.0) 8.0 (1.4-26.2) 6.4 (2.4-25.7) *by Chi-square test; **Twelve patients with AML of low-risk chromosomal abnormality included 6 patients in CR2, 3 with c-kit mutation, and 3 with persistent aml1-eto or cbf beta-myh11 after induction chemotherapy. The median follow-up duration of 164 survivors in the study was 34.7 months (range, 3.7-63.6) after HCT. The donor-group effect on the HCT outcomes was described in Table 2. Patients who underwent MS-HCT showed slightly slower neutrophil engraftment and higher incidence of chronic GVHD. Otherwise, in terms of disease recurrence, NRM, graft failure, EFS, and OS, there was no significant difference according to the donor-type. For AML recurrence, cytogenetic risk was an independent prognostic factors (P =0.003; hazard ratio of low-risk to; intermediate-risk, 1.42; high-risk, 2.53; high-risk with monosomal karyotype, 5.47). Table 1. MS-HCT (n=81) UD-HCT (n=90) HF-HCT (n=57) P Cumulative incidence ( 95% confidence interval)* AML recurrence 29% (19-40%) 26% (17-36%) 35% (20-51%) 0.785 Non-relapse mortality (NRM) 8% (3-16%) 7% (2%-16%) 11% (4-21%) 0.435 Graft failure 1% (0.1-6%) 6% (2-12%) 5% (1-13%) 0.293 ANC>500/uL median days (range) 100% 13 (9-20) 99%12 (10-45) 98% 12 (6-22) 0.049 Platelet>20,000/uL median days (range) 99% (86-100%) 14 (0-83) 97% (88-99%) 13 (0-77) 96% (83-99%) 14 (0-106) 0.352 Grades 2-4 acute graft-versus-host disease (GVHD) 12% (6-21%) 13% (7-21%) 23% (13-34%) 0.176 Moderate to severe chronic GVHD 39% (28-50%) 22% (13-30%) 23% (13-35%) 0.0452 4-year survival** Event-free (EFS) 63% 69% 54% 0.381 Overall (OS) 62% 74% 64% 0.077 *compared by Gray's method; **compared by log-rank test Our study showed that, despite heterogeneity of baseline donor characteristics (age and sex), conditioning regimen, and graft source (bone marrow vs. peripheral blood), overall post-transplant outcomes were similar among recipients from MS-, MU-, and HF-donors. Therefore, for patients with AML in CR but without an HLA-matched donor available, HCT from a haploidentical family member may be considered. Disclosures No relevant conflicts of interest to declare.

【Although advances in multi-detector computed tomography (CT) technique make it possible to evaluate peripheral subsegmental pulmonary arteries, several studies have reported that small peripheral embolisms may still be missed. Recently, some reports demonstrated that dual-energy CT improved the capability to detect peripheral pulmonary embolism. We report a case of lymphoma presenting as disseminated microvascular pulmonary tumor embolism, detected by perfusion images using dual energy CT.】

An inflammatory myofibroblastic tumor (IMT) is a rare disease entity, and the clinical characteristics range from indolent to aggressive forms. No established management for patients with unresectable or aggressive IMT is available. We report on a 62-year-old patient with aggressive IMT who achieved a durable partial response lasting 12 months after anthracycline-containing cytotoxic chemotherapy without corticosteroids. The patient was admitted for an evaluation of progressive weight loss and lower abdominal pain lasting for 2 weeks. Abdominopelvic computed tomography revealed a 10 cm sized heterogeneous mass in the mesentery that encased the superior mesenteric artery and a liver metastasis. The diagnosis of IMT was confirmed by percutaneous core needle biopsy of the mesenteric mass. Systemic chemotherapy was performed after confirming disease progression during a 1 month observation period. A partial response was obtained after two cycles of chemotherapy. Anthracycline-containing cytotoxic chemotherapy could be a treatment option for patients with aggressive IMT. (Korean J Med 2012;82:749-753)

Disseminated Mycobacterium avium complex (MAC) infection can occur in immunocompromised patients, and rarely in immunocompetent subjects. Due to the extensive distribution of the disease, clinical presentation of disseminated MAC may mimic malignancies, and thorough examinations are required in order to make accurate diagnosis. We report a case of disseminated Mycobacterium intracellulare disease in an immunocompetent patient, which involved the lung, lymph nodes, spleen, and multiple bones. F-18 fluorodeoxyglucose positron-emission tomography imaging showed multiple hypermetabolic lesions, which are suggestive of typical hematogenous metastasis. However, there was no evidence of malignancy in serial biopsies, and M. intracellulare was repeatedly cultured from respiratory specimens and bones. Herein, we should know that disseminated infection can occur in the immunocompetent subjects, and it can mimic malignancies.

Adult T-cell leukemia/lymphoma (ATLL) is a malignancy of mature T-cells caused by the human T-cell lymphotrophic virus type I (HTLV-D. HTLV-I is endemic in some areas in Japan, the Caribbean basin, and Africa but has low prevalence in South Korea. Patients with ATLL are susceptible to opportunistic infections such as cytomegalovirus (CMV) infection, but CMV infection in chronic ATLL is uncommon. Reported herein is a case involving a 44-year-old woman with chronic ATLL who presented the symptoms of fever and diarrhea. She was suspected to have acute-type ATLL but was later diagnosed with CMV colitis.