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Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with

In a prospective, explorative study, the donor-source difference of haploidentical family (HF), matched sibling (MS), and unrelated donors (UD) was evaluated for the outcome of haematopoietic cell transplantations (HCT) in 101 patients with acute myeloid leukaemia (AML) in complete remission (CR). To eliminate compounding effects, a uniform conditioning regimen containing antithymocyte globulin (ATG) was used. After transplantation, there was a significantly higher cumulative incidence of acute graft-versus-host disease (GVHD) in HF-HCT patients (49%, 7%, and 16% for HF-, MS- and UD-HCT respectively; p 0.001). A quarter of acute GVHD cases observed in HF-HCT patients occurred within three days of engraftment and were characterized by diffuse skin rash, fever, weight gain, and hypoalbuminaemia. This peri-engraftment acute GVHD was not observed in MS-HCT or UD-HCT patients. Additionally, a significantly higher proportion of HF-HCT patients achieved complete donor chimaerism in the peripheral mononuclear cells at one month (88%, 46%, and 69% for HF-, MS- and UD-HCT respectively; p = 0.001). There was no significant difference in engraftment, chronic GVHD, leukaemia recurrence, non-relapse mortality, and patient survival. In patients with AML in CR who received HCT using ATG-containing conditioning, stronger donor-patient alloreactivity was observed in HF-HCT, in terms of increased acute GVHD and higher likelihood of complete donor chimaerism.

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.

Clonal cytopenia of undetermined significance (CCUS) is characterized by persistent cytopenias with genetic aberrations, which do not meet the diagnostic criteria for myelodysplastic syndrome (MDS). We aimed to compare the clinical and genetic characteristics of CCUS with lower-risk MDS and identify patients with CCUS with a high risk of progression. We performed targeted sequencing of bone marrow (BM) samples from patients with idiopathic cytopenia of undetermined significance (ICUS) (n = 139) and MDS (n = 226). Overall survival (OS) of patients with CCUS (n = 78) was worse than non-clonal ICUS (n = 61) and superior to lower-risk MDS (n = 99). Patients with CCUS showed similar characteristics to those with lower-risk MDS, except for higher haemoglobin, lower BM cellularity, and less frequent SF3B1 mutations. Lower haemoglobin, DDX41 (biallelic germline and somatic), ETV6, and RUNX1 mutations were independent prognostic factors for worse OS. Lower haemoglobin and DDX41 mutations were also associated with lower progression-free survival. Patients with CCUS with high-risk features showed similar or worse OS than patients with lower-risk MDS. Our findings suggest that patients with CCUS having certain clinical or genetic features should be regarded and treated as lower-risk MDS despite lacking significant dysplasia or MDS-associated chromosomal abnormalities.

Acute lymphoblastic leukemia (ALL) is an aggressive hematological disease. The incorporation of tyrosine kinase inhibitors (TKIs) into the standard treatment regimen for Philadelphia (Ph)-positive ALL significantly improved clinical outcomes. TKI-based induction chemotherapy, followed by allogeneic hematopoietic cell transplantation (HCT) during the first complete remission (CR), is the standard of care for ALL patients. However, treatment with TKIs alone or TKIs plus low-intensity chemotherapy can achieve CR in some patients. Although this strategy is not enough to induce a deeper molecular response, it can reduce the incidence of treatment-related mortality. Despite promising results from pediatric trials, allogeneic HCT remains an important component of the treatment strategy for Ph-positive adult ALL. However, improving the highly sensitive BCR-ABL1 assays and introducing immunotherapy may decrease the demand for allogeneic HCT. Nevertheless, the treatment of Ph-positive ALL is still challenging, especially in cases with relapsed and refractory disease. Potent TKIs and monoclonal antibodies, such as blinatumomab and inotuzumab, have improved patient outcomes in relapse and refractory cases of ALL. The introduction of effective agents, such as potent TKIs and monoclonal antibodies, may improve the possibility of remission in Ph-positive ALL patients and hopefully cure this disease.

OBJECTIVES We evaluated the prognostic impact of MK on postremission outcomes of AML patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) in the first complete remission (CR1). METHODS We retrospectively analyzed 465 adult patients with AML who had received HSCT in the first CR between 2000 and 2016. RESULTS In MK + AML, the median leukocyte count was significantly lower (P

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

Background Scoring systems developed for predicting survival after allogeneic hematopoietic cell transplantation (HCT) show suboptimal prediction power, and various factors affect posttransplantation outcomes. Objective A prediction model using a machine learning–based algorithm can be an alternative for concurrently applying multiple variables and can reduce potential biases. In this regard, the aim of this study is to establish and validate a machine learning–based predictive model for survival after allogeneic HCT in patients with hematologic malignancies. Methods Data from 1470 patients with hematologic malignancies who underwent allogeneic HCT between December 1993 and June 2020 at Asan Medical Center, Seoul, South Korea, were retrospectively analyzed. Using the gradient boosting machine algorithm, we evaluated a model predicting the 5-year posttransplantation survival through 10-fold cross-validation. Results The prediction model showed good performance with a mean area under the receiver operating characteristic curve of 0.788 (SD 0.03). Furthermore, we developed a risk score predicting probabilities of posttransplantation survival in 294 randomly selected patients, and an agreement between the estimated predicted and observed risks of overall death, nonrelapse mortality, and relapse incidence was observed according to the risk score. Additionally, the calculated score demonstrated the possibility of predicting survival according to the different transplantation-related factors, with the visualization of the importance of each variable. Conclusions We developed a machine learning–based model for predicting long-term survival after allogeneic HCT in patients with hematologic malignancies. Our model provides a method for making decisions regarding patient and donor candidates or selecting transplantation-related resources, such as conditioning regimens.

BACKGROUND Scoring systems developed for predicting survival after allogeneic hematopoietic cell transplantation (HCT) show suboptimal prediction power, and various factors affect posttransplantation outcomes. OBJECTIVE A prediction model using a machine learning–based algorithm can be an alternative for concurrently applying multiple variables and can reduce potential biases. In this regard, the aim of this study is to establish and validate a machine learning–based predictive model for survival after allogeneic HCT in patients with hematologic malignancies. METHODS Data from 1470 patients with hematologic malignancies who underwent allogeneic HCT between December 1993 and June 2020 at Asan Medical Center, Seoul, South Korea, were retrospectively analyzed. Using the gradient boosting machine algorithm, we evaluated a model predicting the 5-year posttransplantation survival through 10-fold cross-validation. RESULTS The prediction model showed good performance with a mean area under the receiver operating characteristic curve of 0.788 (SD 0.03). Furthermore, we developed a risk score predicting probabilities of posttransplantation survival in 294 randomly selected patients, and an agreement between the estimated predicted and observed risks of overall death, nonrelapse mortality, and relapse incidence was observed according to the risk score. Additionally, the calculated score demonstrated the possibility of predicting survival according to the different transplantation-related factors, with the visualization of the importance of each variable. CONCLUSIONS We developed a machine learning–based model for predicting long-term survival after allogeneic HCT in patients with hematologic malignancies. Our model provides a method for making decisions regarding patient and donor candidates or selecting transplantation-related resources, such as conditioning regimens.

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.

Core-binding factor (CBF)-acute myeloid leukemia (AML) generally have a favorable prognosis. However, approximately 50% of patients experience disease relapse during or after post-remission therapy. Retrospective studies on autologous hematopoietic cell transplantation (AHCT) have shown improved survival with decreased relapse rate in CBF-AML. In this prospective study, we evaluate the outcomes of AHCT following high-dose cytarabine (HiDAC) consolidation in patients with CBF-AML in first complete remission (CR). Adult patients with CBF-AML achieving first CR after induction chemotherapy were eligible for the study. High-dose chemotherapy before AHCT included intravenous busulfan (3.2 mg/kg/day, days − 7 to − 5) and etoposide (400 mg/m2/day, days − 3 to − 2). Twenty-nine patients, 17 with t(8;21) and 12 with inv(16), underwent AHCT following 2 or 3 courses of HiDAC consolidation. The estimated 5-year overall and disease-free survival rates were between 89.0% and 82.5%, respectively. The cumulative incidences of relapse and non-relapse mortality were between 17.5% and 0%, respectively. Presence of measurable residual disease (MRD) before AHCT and KIT mutation were significantly associated with relapse after transplantation. In conclusion, the post-remission strategy of AHCT following HiDAC consolidation in CBF-AML was feasible and efficacious. Assays for MRD and KIT mutation may guide selection of patients who will benefit from AHCT in CBF-AML in first CR.

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.

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.

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.

The prognosis of adult acute lymphoblastic leukemia is much worse than that of pediatric acute lymphoblastic leukemia, even when patients achieve complete remission. Early response to treatment can be an important alternative indicator of treatment outcomes. The purpose of our current study was to identify the prognostic value of the blast percentage of the induction interim bone marrow, which might predict relapse-free survival and overall survival in patients with adult acute lymphoblastic leukemia. A retrospective analysis was performed on 80 adult patients diagnosed with Philadelphia chromosome-negative acute lymphoblastic leukemia from 1994 to 2011. Complete remission was observed in 75 (93.8%) patients after induction chemotherapy. On multivariate analysis, a reduction of blasts to a level of 5% or less in the induction interim bone marrow and CD20 positivity were significant prognostic predictors of relapse-free survival (hazard ratio, HR = 2.88, p = 0.006, and HR = 2.67, p = 0.010) and overall survival (HR = 2.10, p = 0.033, and HR = 2.39, p = 0.013). The blast percentage of the induction interim bone marrow may be a useful prognostic factor to predict outcome.

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.

We analyzed expression profiles of immune checkpoint receptors on T cell subsets and ligands on leukemic blasts in patients with B-lymphoblastic leukemia (B-ALL).Total 149 bone marrow (BM) samples obtained from 65 B-ALL patients with four different clinical status (41 at diagnosis, 54 in complete remission [CR], 34 in persistence, and 20 in relapse), and 32 BM control samples were prospectively enrolled. Expression of immune checkpoint receptor (programmed cell death protein-1 [PD-1]) on T cell subsets and ligands (PD-L1, PD-L2) on leukemic blasts was evaluated by flow cytometry, and was compared between patient subgroups.Relapsed patients demonstrated highest PD-1 expression proportion and intensity on CD3In BM aspirates from B-ALL patients, PD-1 expression on T-cell subsets is increased at diagnosis, and to a greater extent, at relapse. These data suggest the potential usefulness of PD-1 blockade in the treatment of B-ALL, particularly at relapse.

Posaconazole prophylaxis is effective in decreasing the incidence of invasive fungal diseases (IFDs) in patients with acute myeloid leukemia (AML). However, the use of antifungal prophylaxis varies in real-life practice, and only a small number of studies have compared the incidence of IFDs between those receiving posaconazole prophylaxis and those without prophylaxis. We compared the clinical characteristics and outcomes of IFDs between patients with AML who received posaconazole prophylaxis and those without antifungal prophylaxis.We reviewed the medical records of adult AML patients who underwent induction chemotherapy between June 2016 and October 2019 at Asan Medical Center (Seoul, South Korea), where posaconazole prophylaxis is not administered in patients with gastrointestinal symptoms that may hinder sufficient absorption of oral prophylactic agents, and in patients with abnormal liver functions considering the possible exacerbation of adverse events. Patients who received posaconazole prophylaxis for ≥7 days were included in the prophylaxis group. Clinical characteristics and outcomes including the incidence of IFDs were compared between the 2 groups.Of the 247 patients with AML who underwent induction chemotherapy, 162 (66%) received posaconazole prophylaxis and 85 (34%) did not receive any prophylaxis. The incidence of proven/probable IFD was significantly higher in the no prophylaxis group than in the prophylaxis group (9.4% [8/85] vs 2.5% [4/162], P = .03). Of the 8 cases of IFDs in the no prophylaxis group, 7 were mold infections and 1 was invasive candidiasis. Of the 4 cases of IFDs in the prophylaxis group, 3 were mold infections and 1 was invasive candidiasis. Patients with posaconazole prophylaxis less frequently received therapeutic antifungal therapy (2.5% vs 9.4%, P = .03) and had a longer median, duration from chemotherapy to antifungal therapy compared with the no prophylaxis group (18 vs 11 days, P .99).Patients with AML who received posaconazole prophylaxis had a lower incidence of breakthrough IFDs compared with those who did not receive any prophylaxis. Invasive mold infection was the most common IFD regardless of antifungal prophylaxis.

Reduced-intensity conditioning (RIC) regimens can cause decreased non-relapse mortality (NRM) but lead to higher relapse rates in higher-risk myelodysplastic syndrome (MDS). However, relapse is not the main problem after hematopoietic cell transplantation (HCT) in lower-risk MDS, and post-transplant outcomes may therefore improve with less intense non-myeloablative conditioning (NMC) regimens. We here report the results of a single-center feasibility study of NMC with cyclophosphamide-fludarabine-antithymocyte globulin (CyFluATG) in MDS patients with bone marrow blasts5 %. We compared post-transplant outcomes between CyFluATG and a RIC regimen, busulfan-fludarabine-antithymocyte globulin (BuFluATG). Fifteen MDS patients received allogeneic HCT after CyFluATG conditioning comprising cyclophosphamide (100 mg/kg), fludarabine (150 mg/m(2)), and ATG, and 30 MDS historical control patients received BuFluATG conditioning which contained busulfan (8 [oral] or 6.4 [i.v.] mg/kg), fludarabine, and ATG. The 4-year overall survival (OS) and NRM rates were 80.0 and 20.0 % for CyFluATG and 73.3 and 20.0 % for BuFluATG, respectively. Neutrophil and platelet engraftment was significantly faster with CyFluATG than BuFluATG (median 12 vs. 14 days, P = 0.005 for neutrophils; median 15 vs. 21 days, P = 0.032 for platelets). CyFluATG produced a faster immune reconstitution of T-cells at 1 month after HCT than BuFluATG. Fertility was maintained after HCT with CyFluATG. In conclusion, the CyFluATG regimen is feasible in lower-risk MDS patients in terms of adequate engraftment and low NRM.

Purpose Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation. Materials and methods Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m²/day of fludarabine for 5 or 6 days were analyzed. Results The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26-1.08; p=0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II-IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively. Conclusion RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.

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.

Our previous research indicated that a reduced-intensity conditioning regimen (fludarabine and melphalan at 100 mg/m

Background Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT. Methods Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis. Results The median time from HCT to relapse was 6.6 (range, 0.9-136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival. Conclusion Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.

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.