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Background 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a useful tool for identifying high-risk features in patients with newly diagnosed multiple myeloma (NDMM). This study evaluated the role of autologous stem cell transplantation (ASCT) in patients presenting with positive results on PET/CT scans. Materials and Methods The medical records of 210 patients who underwent PET/CT at diagnosis were retrospectively reviewed. Eligible patients for transplantation proceeded to upfront ASCT with high-dose chemotherapy (HDT) after induction therapy with novel agents. Results The presence of a number of focal lesions (FL) >3 and extramedullary disease (EMD) occurred in 111 and 35 patients, respectively. ASCT was performed in 54 patients. Among patients with FL > 3, those treated with ASCT showed a prolonged 2-year progression-free survival (PFS) and overall survival (OS) rates compared to those not treated with ASCT (PFS, 60.2% vs. 23.5%, P 3, Revised International Staging System (R-ISS), and upfront ASCT were independent prognostic factors for PFS and OS. Conclusion Presenting FL > 3 on baseline PET/CT represents a high-risk feature in patients with NDMM. Frontline ASCT with HDT prolonged the survival of patients with FL > 3.

Background/Aims: The objective of this study was to evaluate the efficacy and feasibility of the pediatric-inspired regimen of the adult acute lymphoblastic leukemia (ALL) Working Party, the Korean Society of Hematology.Methods: Data of 99 patients with newly diagnosed ALL, who were treated with the KALLA 1406/1407 protocol, were retrospectively analyzed. All patients equally received age-adjusted daunorubicin, vincristine, and prednisolone. L-asparaginase was additionally administered to Philadelphia (Ph)-negative patients according to age, whereas Ph-positive patients received 600 mg/day of imatinib.Results: A total of 99 patients were enrolled in this study, of whom 62 (62.6%) were diagnosed with Ph-negative ALL and 37 (37.3%) were diagnosed with Ph-positive ALL. The median age of patients in the Ph-negative ALL group was 46 years, and that of patients in the Ph-positive ALL group was 49 years. In patients with Ph-negative ALL, 57 (92%) patients achieved complete remission (CR) and CR with incomplete hematologic recovery (CRi). Disease-free survival (DFS) and overall survival (OS) rates at 2 years were estimated to be 42% and 63%, respectively. In patients with Ph-positive ALL, 32 (86%) patients achieved CR/CRi, and 2-year DFS and OS were 31.2% and 49.1%, respectively. Patients who were able to proceed to the allogeneic hematopoietic cell transplantation and younger patients showed significantly superior survival in both Ph-negative ALL and Ph-positive ALL. Neutropenic fever and bacterial infection were the most common and severe adverse events.Conclusions: The KALLA 1406/1407 protocol showed tolerable toxicities in adult ALL patients. Especially, younger patients had more survival benefits with KALLA 1406/1407 protocol.

Introduction Ibrutinib is a highly effective drug for patients with chronic lymphocytic leukemia (CLL), and is well tolerated even by older patients and those unfit to receive conventional immuno-chemotherapy. Areas covered The occurrence of adverse events was revealed as a major cause of ibrutinib failure in the real-world. Ibrutinib-induced lymphocytosis carries the risk of an untimely interruption of therapy because it may be misinterpreted as disease progression. In addition, drug interactions can worsen ibrutinib-associated toxicities by increasing the plasma concentration of ibrutinib. In this review, we present a case of major hemorrhage and atrial fibrillation (AF) during ibrutinib use and summarize the adverse events associated with ibrutinib. Furthermore, the practical management of ibrutinib-associated toxicities was covered with reference to a drug interaction mechanism. Expert opinion Clinicians should examine the prescribed drugs prior to ibrutinib initiation and carefully monitor toxicities while taking ibrutinib. A reduced dose of ibrutinib with the concurrent use of CYP3A inhibitors such as antifungal agents could be an attractive strategy to reduce toxicities and may confer financial benefits. Reducing unexpected toxicities is as significant as achieving treatment response in the era of life-long therapy with ibrutinib in patients with CLL.

INTRODUCTION The long-term survival of relapsed/refractory (R/R) adult T-cell acute lymphoblastic leukemia (T-ALL) is quite poor, and early T-cell precursor (ETP) ALL has recently been described as a high-risk T-ALL subgroup. However, the optimal therapeutic approach to R/R adult T-ALL remains poorly established. AREAS COVERED At present, cytoreductive therapy followed by allogeneic stem cell transplantation (allo-SCT) is considered to be the most clinically relevant and curative modality for R/R T-ALL. Above all, achieving minimal residual disease (MRD) is a key factor for successful allo-SCT and maintaining long-term remission for R/R patients. As a salvage regimen, nelarabine is the only therapy that was specifically approved for use in patients with R/R T-ALL. A combination of conventional chemotherapeutic agents and novel agents, such as venetoclax, can be used as alternatives for cytoreduction and bridging to transplantation. Relevant literatures published in the last 30 years were searched from PubMed to review the topic of T-ALL, and allo-SCT. EXPERT OPINION An effective salvage regimen, to achieve negative MRD, followed by allo-SCT is currently the best way to improve the clinical outcomes of adult R/R T-ALL. Moreover, posttransplant therapies, such as prophylactic or preemptive donor leukocyte infusion and hypomethylating agents, need to be considered as sequential therapy.

Background Most older patients with acute myeloid leukemia (AML) who attain morphologic remission with intensive chemotherapy (IC) will eventually relapse and post-relapse prognosis is dismal. In the pivotal QUAZAR AML-001 trial, oral azacitidine maintenance therapy significantly prolonged overall survival by 9.9 months (P P Methods QUAZAR AML-001 is an international, placebo-controlled randomized phase 3 study. Patients aged ≥ 55 years with AML and intermediate- or poor-risk cytogenetics at diagnosis, who had attained first complete remission (CR) or CR with incomplete blood count recovery (CRi) within 4 months before study entry, were randomized 1:1 to receive oral azacitidine 300 mg or placebo once-daily for 14 days in repeated 28-day cycles. Safety was assessed in all patients who received ≥ 1 dose of study drug. Results A total of 469 patients received oral azacitidine (n = 236) or placebo (n = 233). Median age was 68 years. Patients received a median of 12 (range 1–80) oral azacitidine treatment cycles or 6 (1–73) placebo cycles. Gastrointestinal AEs were common and typically low-grade. The most frequent grade 3–4 AEs during oral azacitidine therapy were hematologic events. AEs infrequently required permanent discontinuation of oral azacitidine (13%), suggesting they were effectively managed with use of concomitant medications and oral azacitidine dosing modifications. Conclusion Oral azacitidine maintenance had a generally favorable safety profile. Prophylaxis with antiemetic agents, and blood count monitoring every other week, are recommended for at least the first 2 oral azacitidine treatment cycles, and as needed thereafter. Awareness of the type, onset, and duration of common AEs, and implementation of effective AE management, may maximize treatment adherence and optimize the survival benefits of oral azacitidine AML remission maintenance therapy. Trial registration This trial is registered on clinicaltrials.gov: NCT01757535 as of December 2012.

Chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cell accumulation and highly variable clinical manifestations that range from an indolent to an aggressive course, is rare in Korea. Asymptomatic patients with early stage CLL can be followed up without treatment; however, those with active or advanced disease require treatment immediately after diagnosis, for symptom alleviation and prolonging survival. Previously, chemotherapy using cytotoxic agents was the only therapeutic option available for patients with CLL. Research has provided a deeper understanding of the pathophysiology of the disease, and novel agents such as monoclonal antibodies and small-molecule inhibitors that target specific sites on leukemic cells have been introduced. The advent of these new drugs has led to improved clinical outcomes in patients with CLL. Currently, Bruton’s tyrosine kinase inhibitors or B-cell lymphoma-2 inhibitors are recommended as frontline therapy, prior to the administration of cytotoxic agents or combination therapy with monoclonal antibodies. In this article, we review the diagnosis and prognosis of CLL, in addition to the clinical implications of the various therapeutic options. (Korean J Med 2021;96:195-208)

Background We analyzed cell-free serum Epstein-Barr virus (EBV) DNA to identify its prognostic role in patients with newly diagnosed lymphoma. Patients and methods We retrospectively reviewed patients diagnosed with lymphoma between January 2014 and July 2020. Patients were enrolled according to the following criteria: i) pathologically confirmed lymphomas according to the World Health Organization criteria, ii) age over 18 years, iii) serum EBV DNA measurement using polymerase chain reaction prior to first-line therapy, and iv) receipt of curative standard chemotherapy. In total, 263 patients met these criteria and were included in this study. Results Serum EBV DNA was detected in 79 patients (30.0%). Patients with positive serum EBV tended to be older (P=0.090), and the proportion of T-cell lineage lymphomas was higher than that of B-cell lymphomas (P=0.003). EBV positivity was significantly associated with more advanced disease based on the Ann Arbor staging system (P=0.008) and the International Prognostic Index (P=0.009). EBV positivity was also associated with higher disease relapse (P=0.038) and death rates (P=0.005). EBV-positive lymphomas further showed inferior long-term survival outcomes in terms of progression-free survival (PFS) (P=0.053) and overall survival (OS) (P=0.014). In the subgroup analyses, serum EBV positivity was a significant prognostic factor for patients with B-cell lineage lymphomas in terms of PFS (P=0.003) and OS (P=0.033). Conclusion We demonstrated that cell-free serum EBV DNA status at the time of diagnosis has potential as a prognostic biomarker for patients with newly diagnosed malignant lymphomas.

Renal insufficiency (RI) is a frequent manifestation of multiple myeloma (MM) at time of diagnosis but there is no reliable prognostic factor for patients with MM presenting with RI. This study investigated the prognostic impact of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in patients with MM with RI at diagnosis. The records of 209 patients with MM between June 2011 and November 2018 were retrospectively analyzed. PET/CT positivity was defined as the presence of more than three focal lesions or the presence of extramedullary disease. Of 209 patients, 90 (43.1%) had RI and showed similar survival outcomes to patients who had normal renal function. In total, 113 patients (54.0%) were PET/CT-positive, and 46.6% of patients with RI were PET/CT-positive at baseline. In patients with RI, those who were PET/CT-positive showed significantly inferior survival outcomes to those who were PET/CT-negative [progression-free survival (PFS), 12.7 vs. 34.0 months, P

Clinical outcomes of patients diagnosed with high-risk acute myeloid leukemia (AML) are poor, and relapse or refractoriness is main cause of treatment failure, even in those who underwent standard allogeneic stem cell transplantation (allo-SCT). Therefore, innovative or additional approaches are necessary to overcome refractoriness to the graft-versus-leukemia (GVL) effect immediately after allo-SCT.Hypomethylating agents (HMA) present a feasible option that can be adopted during the post-transplant phase. Moreover, combination strategies based on HMA may induce a synergistic effect by promoting anti-leukemic effects that overcome residual leukemic burden, and it is a well-tolerated therapeutic option for high-risk disease. Relevant literatures published in the last 30 years were searched from PubMed to review the topic of AML, allo-SCT, and HMAs.Post-transplant therapy is strongly needed to improve the outcomes of allogeneic transplantation for certain AML patients classified with high-risk disease. In that sense, prophylactic and preemptive HMAs are a promising additive therapy for allogeneic recipients.

Background This study attempted to identify novel prognostic factors in patients with newly diagnosed primary central nervous system lymphoma (PCNSL) using magnetic resonance imaging (MRI). Methods We retrospectively evaluated 67 patients diagnosed with central nervous system (CNS) tumors. The enrollment criteria were as follows: i) pathologic diagnosis of CNS lymphoma, ii) no evidence of systemic involvement, iii) no evidence of human immunodeficiency virus-1 infection or other immunodeficiencies, and iv) MRI scans available at diagnosis. Fifty-two patients met these criteria and were enrolled. Results The 3-year overall survival (OS) and failure-free survival rates were 69.7% and 45.6%, respectively, with a median follow-up duration of 36.2 months. OS of patients with low apparent diffusion coefficient (ADC) was lower than those with higher ADC. Multivariate analysis revealed that old age (>60 yr) [hazard ratio (HR), 20.372; P=0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR, 10.429; P60 yr), ECOG PS ≥2, and higher LDH. The risk of death was categorized as high (score 3-4), intermediate-2 (score 2), intermediate-1 (score 1), and low (score 0), with three-year OS rates of 33.5%, 55.4%, 88.9%, and 100%, respectively. Conclusion ADC demonstrated significant prognostic value for long-term survival in patients with newly diagnosed PCNSL. Low ADC was an independent unfavorable prognostic factor, suggesting that ADC obtained from MRI can improve the current prognostic scoring system.

We compared the efficacy and toxicity of busulfan and melphalan (BUMEL) and those of high-dose melphalan (HDMEL) as conditioning regimens for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) through a propensity score-matched analysis. No significant difference in the complete response and overall response rate after ASCT was observed between BUMEL and HDMEL. After a median follow-up of 37.3 months in the BUMEL group and 50.8 months in the HDMEL group, the median progression-free survival was calculated to be 32.9 months and 25.2 months (

Background A high number of focal lesions (FL) detected using PET/CT at diagnosis were found to be associated with adverse prognosis along with Revised International Staging System (R-ISS). In present study, we combined R-ISS with FL using PET/CT to design a reliable and easily applicable risk stratification system in patients with newly diagnosed MM (NDMM). Methods In training cohort, the data of 380 patients with NDMM who underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT upon diagnosis from 10 hospitals of the Korean Multiple Myeloma Working Party were retrospectively analyzed. All patients were classified by R-ISS and were treated by frontline therapy with proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD). The K-adaptive partitioning algorithm was adopted to develop the new risk groups with homogeneous survival. Sixty-seven patients in external validation cohort were additionally collected to confirm reproducibility of the new risk groups. Results In the training cohort, 199 patients (52.4%) showed FL > 3 using PET/CT at diagnosis. R-ISS stages I, II, and III were 78 patients (20.5%), 230 (60.5%), and 72 (18.9%), respectively. The combined R-ISS with PET/CT newly allocated NDMM patients into four groups: R-ISS/PET stage I (n=30; R-ISS I with FL≤3), stage II (n=149; R-ISS I with FL>3 and R-ISS II with FL≤3), stage III (n=166; R-ISS II with FL>3 and R-ISS III with FL≤3), and stage IV (n=35; R-ISS III with FL>3). The new R-ISS/PET showed significantly pronounced survival differences according to stages. Two-year overall survival (OS) rates were 96.6%, 89.5%, 75.0%, and 57.9% (p < 0.001), and 2-year progression-free survival (PFS) rates were 86.9%, 65.1%, 41.9%, and 15.2% (p < 0.001) in stages I, II, III, and IV, respectively. The prognostic role of the R-ISS/PET for survival outcomes was also confirmed in different subgroups classified by transplant eligibility and by types of treatments. In the external validation cohort, the new R-ISS/PET was successfully implemented. Two-year OS rates for were 100%, 89.9%, 82.6%, and 42.0% for R-ISS/PET I, II, III, and IV, respectively (p = 0.001). PFS rates at 2 years for each R-ISS/PET were 100%, 74.5%, 57.9%, and 25.6%, respectively (p = 0.004). In the multivariate Cox analysis for survival outcome, R-ISS/PET was a significant factor and could predict long-term outcomes with regard to OS: stage II vs. I (HR 2.50, p = 0.215), (ii) stage III vs. I (HR 5.11, p = 0.025), and (iii) stage IV vs. I (HR 10.3, p = 0.003) and PFS: (i) stage II vs. I (HR 2.21, p = 0.005), (ii) stage III vs. I (HR 4.57, p < 0.001), and (iii) stage IV vs. I (HR 9.48, p < 0.001). Conclusion The new R-ISS/PET had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely. Thus, R-ISS/PET is applicable for identifying heterogeneous manifestation of clinical MM. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The cumulative risk of therapy-related myelodysplastic syndrome (t-MDS) in breast cancer patients exposed to chemotherapy and/or radiotherapy is significantly high compared to that in other cancer patients. This report reviews the use of hypomethylating agents (HMAs) to treat a 57-year-old woman newly diagnosed with MDS during palliative chemotherapy for metastatic breast cancer. Over a period of 6 years, the patient received several DNA-damaging chemotherapeutics including doxorubicin, cyclophosphamide, and paclitaxel. Repeated thrombocytopenia was the main reason for suspecting secondary hematologic malignancy. She was diagnosed with t-MDS based on bone marrow examination and her treatment history for breast cancer. While azacitidine was originally administered to stabilize MDS, it also stabilized the patient's lung and lymph node metastases without any major toxicity. Therefore, the current case highlights the promising effects of HMAs for treating t-MDS following heavily pretreated breast cancer.

Background The role of allogeneic hematopoietic cell transplantation (allo-HCT) compared with consolidation chemotherapy alone in intermediate-risk acute myeloid leukemia (AML) patients with wild-type nucleophosmin/negative or a low level of Fms related tyrosine kinase 3 internal tandem duplication (NPM1 wt/FLT3-ITDneg/low) has not yet been elucidated. Methods In this study, we retrospectively investigated 88 patients newly diagnosed with AML who received intensive induction chemotherapy at Kyungpook National University Hospital from March 2015 to July 2017. The selection criteria included the presence of results on genetic abnormalities including NPM1 and FLT3-ITD. Results According to the European LeukemiaNet (ELN) risk classification, 25 patients (28%) were categorized as favorable, 44 (50%) as intermediate, and 19 (22%) as adverse risk. Among the intermediate-risk patients, 40 were identified as NPM1 wt/FLT3-ITDneg/low. Among the patients with NPM1 wt/FLT3-ITDneg/low, complete remission (CR) was achieved in 26 patients out of 40 (65%). One-year overall survival (OS) rate was 100% in the favorable-risk group and 87.9% in the NPM1 wt/FLT3-ITDneg/low group (P=0.233). Among the intermediate-risk NPM1 wt/FLT3-ITDneg/low patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; P=0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; P=0.019] and the achievement of CR (HR, 2.95; P=0.017) were both identified as factors affecting OS of patients with newly diagnosed AML. Conclusion Among the AML patients, intermediate-risk NPM1 wt/FLT3-ITDneg/low patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk NPM1 wt/FLT3-ITDneg/low patients. Well controlled studies are needed to confirm the current results.

Objective: We aimed to evaluate the effect of stem cell source and dose on the survival of various donor subgroups, such as matched sibling donor (MSDs) and alternative donors (ADs), upon bone marrow (BM) or peripheral blood stem cell (PBSC) infusion in aplastic anemia (AA). Methods: We retrospectively investigated the effects of stem cell source and dose on allogeneic hematopoietic stem cell transplantation (alloHSCT) in AA. Results: A total of 267 patients were included in this analysis. The BM-treated group showed an association with low incidence of any-grade acute graft versus host disease (GvHD) (p < 0.001). A higher stem cell dose was related with a low incidence of extensive chronic GvHD in MSDs (p = 0.025). Multivariate analysis for overall survival (OS) revealed that only age at alloHSCT p = 0.010) and prior platelet transfusion p = 0.046) in MSDs and higher stem cell dose (hazard ratio = 2.596, p = 0.045) in ADs were favorable prognostic factors. Conclusion: PBSCs could be preferred in AD because high stem cell dose may be easily achieved to improve the OS at the expense of acute GvHD. However, BM stem cells are preferred in MSDs.

Bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapies for newly diagnosed multiple myeloma (NDMM). However, the appropriate depth of response to induction therapy and timing of upfront ASCT are still debated. We investigated if two additional cycles of VTD (VTD6) improved the responses and progression-free survival (PFS) compared with four cycles of VTD (VTD4). We retrospectively reviewed outcomes of 190 NDMM patients treated with at least four cycles of VTD followed by ASCT between September 2014 and August 2017 [VTD4, n = 129 (67.9%); VTD6, n = 61 (32.1%)]. The VTD6 group had a higher pre-ASCT complete response (CR) rate than the VTD4 group (31.1% versus 10.1%, P 2-microglobulin, and pre-ASCT CR as important factors for PFS. Two additional cycles of VTD prolonged PFS in patients with PR only after VTD4 [Hazard ratio (HR) = 0.29, P = 0.016] or those with Revised International Staging System stage I/II (HR = 0.36, P = 0.039). In conclusion, two additional VTD cycles may be helpful for patients with PR only after VTD4 but high risk MM needs the other treatment options.

Achieving a deep molecular response (DMR) to tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML) remains challenging and at present, there is no biomarker to predict DMR in this setting. Herein, we report that an HMGCLL1 genetic variant located in 6p12.1 can be used as a predictive genetic biomarker for intrinsic sensitivity to imatinib (IM) therapy. We measured DMR rate according to HMGCLL1 variant in a discovery set of CML patients (n = 201) and successfully replicated it in a validation set (n = 270). We also investigated the functional relevance of HMGCLL1 blockade with respect to response to TKI therapy and showed that small interfering RNA mediated blockade of HMGCLL1 isoform 3 results in significant decrease in viability of BCR-ABL1-positive cells including K562, CML-T1 or BaF3 cell lines with or without ABL1 kinase domain mutations such as T315I mutation. Decreased cell viability was also demonstrated in murine CML stem cells and human hematopoietic progenitor cells. RNA sequencing showed that blockade of HMGCLL1 was associated with G0/G1 arrest and the cell cycle. In summary, the HMGCLL1 gene polymorphism is a novel genetic biomarker for intrinsic sensitivity to IM therapy in CML patients that predicts DMR in this setting.

Ultra-deep sequencing detects low-frequency genetic mutations with high sensitivity. We used this approach to prospectively examine mutations in the BCR/ABL1 tyrosine kinase from patients with newly diagnosed, chronic-phase chronic myeloid leukemia (CML) treated with the tyrosine kinase inhibitor nilotinib. Between May 2013 and November 2014, 50 patients from 18 institutions were enrolled in the study. We screened 103 somatic mutations and found that mutations in the P-loop domain were the most frequent (173/454 mutations in the P-loop) and noted the presence of the V299 L mutation (dasatinib-resistant/nilotinib-sensitive) in 98 % of patients (49/50). No patients had Y253H, E255 V, or F359 V/C/I mutations, which would recommend dasatinib rather than nilotinib treatment. The S417Y mutation was associated with lower achievement of a major molecular response (MMR) at 6 months, and the V371A mutation was associated with reduced MMR and MR4.5 durations (MMR for 2 years: 100 % for no mutation vs. 75 % for mutation, P=0.039; MR4.5 for 15 months: 94.1 % vs. 25 %, P=0.002). Patients with known nilotinib-resistant mutations had lower rates of MR4.5 achievement. In conclusion, ultra-deep sequencing is a sensitive method for genetic-based treatment decisions. Based on the results of these mutational analyses, nilotinib treatment is a promising option for Korean patients with CML.

DNA sequencing-based measurable residual disease (MRD) detection has shown to be clinically relevant in AML. However, the same methodology cannot be applied to fusion gene-driven subtypes of AML such as core-binding factor AML (CBF-AML). Here in this study, we evaluated the effectiveness of using DNA and RNA sequencing in MRD detection and in tracking clonal dynamics in CBF-AML. Using RNA-seq, we were able to quantify expression levels of RUNX1-RUNX1T1 and CBFB-MYH11 at diagnosis and their levels of reduction during remission (P RUNX1-RUNX1T1 as measured by RNA-seq and qPCR were highly correlated (R2 = 0.74, P RUNX1-RUNX1T1 and cKIT-D816mut at diagnosis, stratified RUNX1-RUNX1T1 AML patients into three subgroups. These three subgroups had 2-year overall survival rates at 87%, 74%, and 33% (P RUNX1-RUNX1T1 AML.

The recent outbreak of the novel coronavirus disease 2019 (COVID-19) has been labelled as a pandemic by the World Health Organization. Although person-to-person transmission of the etiologic agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been confirmed, it is not known whether COVID-19 may be transmitted by blood transfusion. Notwithstanding the urgent requirement of blood, it is critical to know whether the SARS-CoV-2 virus can be transmitted by blood transfusion because many individuals may be asymptomatic carriers and may donate blood. Several cases in which specific viral RNA could be detected in the serum from patients with COVID-19 have already been reported; these findings suggest that blood donation may be an unexplored route of transmission. However, the American Association of Blood Banks and Centers for Disease Control and Prevention have not recommended any specific SARS-CoV-2-related actions to be taken at blood collection centres at this time. In this report, we describe a case of a 21-year-old man with very severe aplastic anaemia who received apheresis platelet transfusion from an individual who was subsequently diagnosed with COVID-19. Our patient tested negative for COVID-19 and is awaiting allogeneic stem cell transplantation.

Background/Aim: The present study retrospectively investigated the predictive accuracy of interim positron emission tomography/computed tomography (iPET/CT) based on the Deauville 5-point scale (5-PS) and a quantitative SUV-based assessment in patients with extranodal (EN) diffuse large B cell lymphoma (DLBCL). Patients and Methods: The Deauville 5-PS and the SUVmax reduction (ΔSUVmax) assessment for interpreting the response to iPET/CT were used. Results: A total of 163 patients were enrolled in this study. With a median follow-up of 52.5 months, ΔSUVmax successfully predicted the survival outcomes of patients with one extranodal (EN) involvement in terms of overall survival (OS) (p=0.012) and progression-free survival (PFS) (p

Background/Aims This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. Methods A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. Results HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. Conclusions For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

Next-generation sequencing (NGS) has been applied to define clinically relevant somatic mutations and classify subtypes in acute myeloid leukemia (AML). Persistent allelic burden after chemotherapy is associated with higher relapse incidence, but presence of allelic burden in AML patients after receiving allogeneic hematopoietic cell transplantation (HCT) has not been examined longitudinally. As such, we aimed to assess the feasibility of NGS in monitoring AML patients receiving HCT. Using a targeted gene panel, we performed NGS in 104 AML patients receiving HCT using samples collected at diagnosis, pre-HCT, and post-HCT at day 21 (post-HCTD21). NGS detected 256 mutations in 90 of 104 patients at diagnosis, which showed stepwise clearances after chemotherapy and HCT. In a subset of patients, mutations were still detectable pre-HCT and post-HCT. Most post-HCT mutations originate from mutations initially detected at diagnosis. Post-HCTD21 allelic burdens in relapsed patients were higher than in nonrelapsed patients. Post-HCTD21 mutations in relapsed patients all expanded at relapse. Assessment of variant allele frequency (VAF) revealed that overall VAF post-HCTD21 (VAF0.2%-post-HCTD21) is associated with an increased risk of relapse (56.2% vs 16.0% at 3 years; P < .001) and worse overall survival (OS; 36.5% vs 67.0% at 3 years; P = .006). Multivariate analyses confirmed that VAF0.2%-post-HCTD21 is an adverse prognostic factor for OS (hazard ratio [HR], 3.07; P = .003) and relapse incidence (HR, 4.75; P < .001), independent of the revised European LeukemiaNet risk groups. Overall, current study demonstrates that NGS-based posttransplant monitoring in AML patients is feasible and can distinguish high-risk patients for relapse.

Predictive factors for initiating hypomethylating agents’ (HMAs) treatment and the survival benefit of HMAs for lower-risk myelodysplastic syndrome (LR-MDS) are still unknown. This study evaluated the factors affecting the use of HMAs and compared long-term outcomes between best supportive care (BSC) and HMA groups after matching baseline clinical factors. Data of 353 patients diagnosed with LR-MDS by International Prognostic Scoring System between October 1992 and July 2013 were retrospectively analyzed. HMAs were administered continuously until a clinical response or progression. HMAs were administered to 243 patients with median 45 days (range 0–7078 days) after diagnosis, while 110 patients were treated with BSC. HMAs were administered over a median of 5 cycles and overall response was achieved in 104 patients (42.8%). The cumulative incidence of HMA treatment increased in higher-risk groups by other risk scoring systems. Three-year overall survival (OS) rate was higher in BSC group (69.1%) than HMA responders (47.4%, p = 0.065) or HMA non-responders (46.3%, p = 0.005). Among 162 case-matched cohorts, 3-year OS rates were comparable between the BSC group (67.1%) and HMA responders (58.1%, p = 0.914), while that of HMA non-responder was low (32.2%, p

The aim of this study was to investigate the efficacy of nilotinib (NIL) versus high-dose imatinib (IM) versus sustained standard-dose IM for patients with chronic myeloid leukemia (CML) with suboptimal molecular response to first-line IM therapy. Patients with CML who achieved complete cytogenetic response (CCyR) but not major molecular response (MMR) after 18–24 months on first-line IM therapy were enrolled and divided into three treatment cohorts: NIL 800 mg/day (Cohort 1, n = 28) and IM 800 mg/day (Cohort 2, n = 28) in the RE-NICE study, and sustained IM 400 mg/day (Cohort 3, n = 52) in clinical practice. The primary efficacy variable of cumulative rate of MMR by 12 months was not different among the three cohorts. However, the cumulative incidence of MMR by 36 months was significantly higher in Cohort 1 than Cohort 3 (83.1% vs. 57.1%, P = 0.021), but there were no significant differences in Cohort 1 vs. 2 (P = 0.195) and Cohort 2 vs. 3 (P = 0.297). Different profile for adverse events was observed between NIL and high-dose IM therapy. In conclusion, our data suggested that switching to NIL may provide more effective long-term response than sustaining standard-dose IM for patients with suboptimal molecular response to first-line IM.

Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML‐CP). We investigated the 2‐year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open‐label, multi‐institutional phase 4 study, 110 Philadelphia chromosome‐positive CML‐CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24‐month cumulative MR 4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per‐patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow‐up of 22.2 months, the 24‐month cumulative MR 4.5 rate was 56.2% (95% confidence interval, 44.0%–8.3%), and the median time to MR 4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR 4, and MR 4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML‐CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511.

This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10.7% (n = 42) with AML with mutated chromatin or RNA-splicing genes or both, 1.5% (n = 6) with AML with TP53 mutations, 13.5% (n = 53) with AML with biallelic CEBPA mutations, 2.0% (n = 8) with AML with IDH2-R172 mutations and no other class-defining lesion, 29.5% (n = 116) with AML with driver mutations but no detected class-defining lesion, 4.3% (n = 17) with AML with no detected driver mutation, and 3.8% (n = 15) patients with AML who met the criteria for ≥2 genomic subgroups. The 5-year overall survival and relapse rate of subgroup in AML with mutated chromatin, RNA-splicing genes, or both was 11.6% (95% CI = 1.4–21.8%) and 71.4% (95% CI = 45.7–86.5%), respectively. This study suggests that the recently recommended genomic classification is an appropriate and replicable categorization system in the NK AML population. The subgroup of AML with mutated chromatin, RNA-splicing genes, or both showed extremely poor survival in NK-AML; thus, a novel approach is needed to improve their prognosis.

Background Graft-versus-host disease (GVHD), where T- and B-cells derived from the graft attack host, is still a vital hurdle to overcome for successful allogeneic stem cell transplantation (allo-SCT). In particular, chronic GVHD (cGVHD) occurs approximately 30-70% of the patients and it is the most relevant cause of non-relapse morbidity (NRM) after allo-SCT. This multicenter, phase II study evaluated the safety and efficacy of imatinib mesylate in patients with steroid-resistant cGVHD. In addition, we scored the quality of life of the enrolled patients using Short Form Health Survey Questionnaire (SF-36). Patients and methods A total of 36 patients who diagnosed with steroid-refractory cGVHD participated in this study and treated with imatinib from March 2013 to February 2019. Enrolled patients received 100mg of imatinib daily for 2 weeks. Every 2 weeks, imatinib dosage was increased up to 400 mg/day if the patients did not have any grade 3-4 adverse event. Patients who showed stable disease (SD), partial remission (PR) and complete remission (CR) in the 3-month response evaluation continued the imatinib up to 6 months. Treatment response was evaluated every 2 weeks for 6 months according to the NIH global scoring system. Survival outcomes of the enrolled patients were followed up to 2 years. Quality of life was also evaluated using SF-36 at 1, 3, and 6 months after starting imatinib treatment. Response of cGVHD was evaluated based on the NIH response criteria by scoring each involved organ sites with four-point scale (0-3). CR was defined as resolution of all reversible manifestations related to cGVHD. Partial response (PR) of cGVHD was defined clinical score reduction of at least one point in one or more affected organs. Disease progression or treatment failure was defined as increased score at least one point in one or more organs or occurrence of any new symptoms or signs of c GVHD. Failure-free survival (FFS) and overall survival (OS) were calculated from the day of starting imatinib. Result Median age was 47.5 years (23-63). Majority of the patients were diagnosed with acute leukemia (75%) and myelodysplastic syndrome (16.9%), and underwent allo-SCT in CR disease status (69.5%). Twenty-five (69.4%) patients experienced acute GVHD. Most of the patients presented overlap symptoms. Skin GVHD was identified in 23 (63.9%) patients. Lung, mouth, and eye involvement were found in 16 (44.4%), 14 (38.9%), and 14 (38.9%) patients, respectively. All of the enrolled patients had been treated with steroid due to moderate (55.6%), and severe (44.4%) grade cGVHD. Overall, median duration of imatinib therapy was 5.4 months and no severe adverse effect over grade 3 was reported. The last therapeutic mean dosage of imatinib was 305.6 mg/day. Three patients (8.3%) achieved CR, and 18 (50%) and 12 patients (33.3%) were reported as PR and SD. Treatment failure was identified in three patients (8.3%). Overall response rate (ORR) of imatinib was 58.3% and 25 patients (69.4%) could reduce the steroid. According to the each involved organ site, ORR of the gastrointestinal (GI) and liver cGHVD were 70.5% and 66.7%, while skin and lung were 34.8% and 25.0%, respectively. The efficacy of imatinib was better in GI, liver, and mouth than skin and lung in the current clinical study. With the median follow-up duration of 28.5 months, two-year FFS and OS rate were 76% and 88.5%. Responders to the imatinib therapy showed a superior tendency in OS than non-responders (p = 0.066). In the patients-reported QOL evaluation with SF-36, both physical and mental component score were improved. Particularly, a factor representing emotional well-being was significantly improved (p = 0.002). Conclusion This multicenter clinical study showed that imatinib is an effective option not only for skin GVHD but also for GI and liver involvement. Moreover, QOL of the patients tended to improve during imatinib treatment with steroid dose reduction. Figure 1 Figure 1. Disclosures Lee: Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board; AbbVie: Honoraria, Other: Advisory board; Korean Society of Hematology: Membership on an entity's Board of Directors or advisory committees.

We retrospectively analyzed the results of hypomethylating therapy in 586 patients (azacitidine in 423 and decitabine in 163) with International Prognostic Scoring System (IPSS) lower-risk myelodysplastic syndrome (MDS). The patients were reclassified with newer scoring systems (revised IPSS [R-IPSS], revised WHO classification-based Prognostic Scoring System [R-WPSS], and Lower Risk Prognostic Scoring System [LR-PSS]), and 21.8-38.4% of patients had high or very high risk features by the newer scoring systems. Median overall survival (OS) was 27.3 months and newer scoring systems well stratified the patients in terms of OS (R-IPSS, P=0.001; R-WPSS, P

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell neoplasm, with rapidly progressing clinical course. We evaluated the treatment status and survival outcomes of 69 Korean patients with pPCL. Of them, 59 patients were treated; 15 (25.4%) were treated initially with novel agent-based regimens with upfront autologous stem cell transplantation (ASCT), 7 (11.9%) with conventional chemotherapy with upfront ASCT, 21 (35.6%) with novel agent-based regimens only, and 16 (27.1%) were treated with conventional chemotherapy alone. Overall response rates after initial therapy were significantly higher in patients treated with novel agent-based regimens compared with those treated with conventional chemotherapies (75% vs. 43.4%, P = 0.026). Median progression-free survival (PFS) and overall survival (OS) were 12.2 months and 16.1 months, respectively. The median PFS of the four treatment groups–conventional chemotherapy alone, novel agents alone, conventional chemotherapy with ASCT, and novel agents with ASCT–were 1.2, 9.0, 10.5, and 26.4 months, respectively (P < 0.001); the median OS of the four treatment groups were 2.9, 12.3, 14.1, and 31.1 months, respectively (P < 0.001). The median OS was also significantly better in the patients with novel agents with ASCT versus other patients. In a multivariate analysis, an increased lactate dehydrogenase level, low albumin (< 3.5 g/dL), and non-CR after front-line treatment were independently associated with poor PFS and OS. In conclusion, the use of novel agent-based therapy with ASCT and achieving a deep response to front-line treatment are important in expecting improved PFS and OS in patients with pPCL.

// Da Jung Kim 1 , Ho Sup Lee 1 , Joon-Ho Moon 2 , Sang Kyun Sohn 2 , Hyeoung Joon Kim 3 , June-Won Cheong 4 , Deog-Yeon Jo 5 , Hawk Kim 6 , Hyewon Lee 7 , Soo-Mee Bang 8 , Won Sik Lee 9 , Yong Park 10 , Mark Hong Lee 11 , Jae Hoon Lee 12 , Sung Hwa Bae 13 , Min Kyoung Kim 14 and The Korean Society of Hematology AML/MDS Working Party 1 Department of Internal Medicine, Kosin University College of Medicine, Kosin University Gospel Hospital, Busan, South Korea 2 Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, South Korea 3 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, South Korea 4 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea 5 Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University, Daejeon, South Korea 6 Division of Hematology and Cellular Therapy, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea 7 Department of Hematology-Oncology, Center for Hematologic Malignancy, National Cancer Center, Goyang, South Korea 8 Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul, South Korea 9 Department of Internal Medicine, Busan Paik Hospital, Busan, South Korea 10 Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea 11 Division of Hematology-Oncology, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea 12 Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea 13 Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, South Korea 14 Department of Hematology-Oncology, Yeungnam University Medical Center, Yeungnam University School of Medicine, Daegu, South Korea Correspondence to: Ho Sup Lee, email: hs52silver@gmail.com Keywords: myelodysplastic syndrome, discontinuation, survival, decitabine, azacitidine Received: March 17, 2017 Accepted: April 28, 2017 Published: May 29, 2017 ABSTRACT It is often difficult to continue treatment with hypomethylating agent(HMA) in clinical practice because of problems such as toxicities, poor economics, etc. We compared clinical outcomes of those patients who continued HMA and those who discontinued HMA because of other causes, and evaluated factors associated with survival in those patients who discontinued HMA. Patients were divided into two groups: treatment failure, those who stopped treatment due to disease progression; and discontinuation, those who discontinued treatment because of other causes. The median progression free survival(PFS) was 9.2 months (range 7.7 – 10.7 months) vs 28.9 months (range 22.6 – 35.2) in the treatment failure and discontinuation groups, respectively ( P < 0.001). In a multivariate analysis, a lower risk by WPSS was an independent predictive factor for a longer PFS, and a lower risk by WPSS and median number of HMA cycles greater than seven were independent predictive factors for longer overall survival(OS) only in the discontinuation group. Patients who discontinued HMA without disease progression showed a prolonged survival than those who failed HMA treatment. Especially, a lower risk by WPSS and longer duration of HMA treatment may be predictive factors for a longer PFS and OS in patients who discontinued HMA.

Introduction Acute myeloid leukemia (AML) that develops from pre-existing hematologic diseases, rather than developing de novo, is known as secondary AML (sAML). A number of hematologic malignancies can progress to sAML. However, the molecular and genetic characteristics behind the progression of hematologic malignancies to sAML remain unclear. To address this question and dissect the order of mutation acquisition throughout the course of the disease, we performed whole-exome sequencing and targeted deep sequencing on serial samples. Patients and Methods This study examined several cohorts with a combined total of 124 patients. This study was approved by research ethics boards at relevant institutions and samples were taken after informed consent. The discovery cohort (C1) consisted of 31 patients diagnosed with myelodysplasia who all progressed to sAML. Whole-exome sequencing (WXS) was performed for each case on bone marrow samples taken at the diagnosis of the antecedent malignancy and after sAML progression, as well as fractionated T-cell samples (CD3+). WXS (Agilent SureSelect v4) was performed on the 93 samples as per the manufacturer's protocol using an Illumina HiSeq 2000. The other cohorts included 72 non-progressed MDS patients (C2a, median follow-up of 3.5 years) and an additional 21 sAML patients (C2b) progressed to sAML from MDS, for whom samples from the MDS stage were not available. Targeted sequencing was performed using an Agilent custom probe set of the selected 92 genes. We multiplexed and sequenced the samples using an Illumina Hiseq 2000. Targeted deep sequencing was performed on all cohorts. Genomon-ITD was used to detect FLT3-ITD. Results The mean read depth retrieved for target regions for WXS data was 73x. After calling and prioritizing variants, we found a mean and median of 7.7 and 6 significant variants per patient at the time of initial diagnosis, and 12.4 and 10 variants after sAML progression, respectively. We also detected that FLT3-ITD emerged in 2 patients after sAML progression. The presence of variants in T-cell samples in 5 C1 and 20 C2a patients provides evidence on the relative timing of early events for a subset of patients. Both cohorts notably lack activated signaling pathway variants at this stage (Figure A). The T-cell variants in 5 C1 patients with pathway associations were all in genes involved in DNA methylation (DNMT3A, IDH1/2, and TET2) or splicing machinery (SRSF2 and SF3B1). This pattern was verified in 20 C2a patients except for a single case that had an NRAS-G13D mutation. These patients showed evidence of having clonal hematopoiesis. At MDS, there were a significant number of cases with variants in genes involved in DNA methylation and/or splicing machinery (35.5% and 48.3%, respectively). However, the portion of cases with variants affecting these pathways increased significantly at the MDS stage, but did not change much by the sAML stage (Figure C-D). On the other hand, variants in genes involved in activated signaling pathways showed a distinctive pattern. The portion of cases with variants affecting activated signaling pathways noticeably increased at the sAML step (25.8% to 54.8%) (Figure B). The changes in VAF between stages within cases of these variants revealed a similar pattern. In summary, clonal evolution patterns can be postulated based on the acquisition/expansion of mutations related to the three signature pathways (Figure E). Forty-eight percent of patients showed growth or development of clones containing activated signaling pathway variants at the sAML stage. Sixteen percent of patients developed the MDS from preleukemic mutations associated with DNA methylation or splicing machinery, and 26% first developed clones of this category at the MDS stage (a total of 42%). Conclusion Mutations in DNA methylation and splicing machinery genes are early disease events, expanding at the MDS stage but not during progression. On the other hand, activated signaling pathway mutations expand during progression, demonstrating that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order. Figure Figure. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: About 50% of older patients with AML attain remission with intensive induction chemotherapy (IC) but the majority will eventually relapse. Effective, well tolerated maintenance treatments are needed to reduce the risk of relapse and prolong survival for older patients with AML in remission, who are less likely than younger patients to be candidates for hematopoietic stem cell transplant (HSCT). CC-486 is an oral hypomethylating agent that allows for extended dosing schedules to sustain therapeutic activity. In the randomized, phase III QUAZAR AML-001 Maintenance Trial, CC-486 significantly prolonged overall survival (OS) and relapse-free survival (RFS) vs. placebo in patients aged ≥55 years with AML in first remission after IC ± consolidation. Gastrointestinal (GI) events were the most common treatment-emergent adverse events (TEAEs) reported in patients who received CC-486. Here we assess the rates of GI TEAEs and associated management strategies over time with CC-486 treatment in QUAZAR AML-001. METHODS: Eligible patients were aged ≥55 years and had AML with intermediate- or poor-risk cytogenetics and Eastern Cooperative Oncology Group performance status (ECOG PS) scores ≤3. Patients had achieved complete remission (CR) or CR with incomplete blood count recovery (CRi) after IC ± consolidation and were not candidates for HSCT. Within 4 months of achieving CR/CRi, patients were randomized 1:1 to CC-486 300 mg or placebo, administered once-daily on days 1-14 of repeated 28-day treatment cycles. Safety was assessed among patients who received ≥1 dose of study drug, from the date of first dose through 28 days after the last dose. Prophylaxis and treatment of GI TEAEs were allowed but not mandatory. RESULTS: In all, 236 patients received CC-486 and were evaluated for safety. The median age at study entry was 68 years (range 55-86), 202 patients (85.6%) had intermediate-risk cytogenetics at diagnosis, 185 (78.4%) had achieved CR after induction, and 184 (78.0%) received ≥1 course of consolidation before randomization. Overall, nausea, vomiting, and diarrhea (any grade) were reported in 65%, 60%, and 50%, respectively, of patients treated with CC-486. Few patients experienced grade 3 TEAEs (nausea, 3%; vomiting, 3%; diarrhea, 5%) or serious events (0.4%, 0.8%, and 1.3%, respectively), and only 1 grade 4 event (diarrhea) was reported at any time on-study. Rates of GI TEAEs were highest during initial treatment and decreased thereafter. In cycles 1-2, 3-4, and 5-6, respectively, nausea was reported in 53%, 17%, and 15% of patients; vomiting in 49%, 15%, and 10% of patients; and diarrhea in 29%, 16%, and 11% of patients (Figure). The most commonly used concomitant GI medications were 5-HT3 antagonists, metoclopramide, lactulose, and loperamide; use of these agents was also highest during the first 2 treatment cycles and decreased over time (Figure). GI events required CC-486 treatment interruptions for 13% of patients, dose-reductions for 6% of patients, and treatment discontinuation for 5% of patients. DISCUSSION: Most GI-related TEAEs reported by patients treated with CC-486 were low-grade, and events decreased in frequency after initial treatment cycles, indicating these events were well managed. Use of GI medications decreased concurrently, suggesting progressive GI tolerance to CC-486 with continued therapy. Few patients discontinued CC-486 due to GI TEAEs. Prophylaxis and symptomatic intervention of GI events during early CC-486 therapy may facilitate treatment adherence to promote better outcomes. Disclosures Ravandi: Amgen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Orsenix: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; AstraZeneca: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria. Selleslag:Alexion: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Astellas: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen Cilag: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; Belgian College: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Sayar:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Safah:Amgen: Honoraria; Astellas: Speakers Bureau; Verastem: Honoraria; Janssen: Speakers Bureau. Hiwase:Novartis Australia: Research Funding. La Torre:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Skikne:Bristol Myers Squibb: Current Employment. Kumar:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Dong:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Beach:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Dombret:Otsuka: Consultancy; Abbvie: Consultancy; Servier: Consultancy, Research Funding; Sunesis: Consultancy; Amgen: Consultancy, Research Funding; Jazz Pharma: Consultancy, Research Funding; Celgene: Consultancy; Nova: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Menarini: Consultancy; Janssen: Consultancy; Cellectis: Consultancy; Shire-Baxalta: Consultancy; Immunogen: Consultancy.

Context In the phase III QUAZAR AML-001 Maintenance Trial, CC-486, an oral hypomethylating agent significantly prolonged overall and relapse-free survival vs. placebo among patients with AML in first remission after induction chemotherapy (IC). Gastrointestinal (GI) events were the most frequent adverse events (AEs) with CC-486. Objective Assess GI AE rates with CC-486 over time and associated management strategies. Methods Eligible patients were aged ≥55 years and had AML with intermediate- or poor-risk cytogenetics, and ECOG-PS scores ≤ 3. Patients achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) after IC ± consolidation and were not transplant candidates. Within 4 months of CR/CRi, patients were randomized 1:1 to once-daily CC-486 300-mg or placebo on days 1-14 of repeated 28-day cycles. Safety was assessed in patients who received ≥1 dose, through 28 days after the last dose. Prophylaxis and treatment of GI AEs was allowed but not mandatory. Results 236 patients received CC-486 and were evaluated for safety. Median age was 68 years (range, 55-86). Rates of any-grade nausea, vomiting, and diarrhea were 65%, 60%, and 50%, respectively; few patients experienced grade 3 (3%, 3%, and 5%) or serious (0.4%, 0.8%, and 1.3%) events, and only 1 grade 4 event (diarrhea) was reported. Rates were highest during initial treatment and decreased thereafter: in cycles 1-2, 3-4, and 5-6, nausea was reported in 53%, 17%, and 15% of patients, respectively; vomiting in 49%, 15%, and 10%; and diarrhea in 29%, 16%, and 11%. 5-HT3-antagonists, metoclopramide, lactulose, and loperamide were the most common concomitant medications; use of these agents also decreased over time. GI events required CC-486 dose-reductions for 6% of patients, treatment interruptions for 13%, and discontinuation for 5%. Conclusions Most GI AEs with CC-486 were low-grade, and events decreased in frequency after initial cycles. Use of GI medications decreased concurrently, suggesting progressive GI tolerance to CC-486. Few patients discontinued CC-486 due to GI AEs, indicating these events were easily managed. Clinicians and patients should be aware of possible GI events during early CC-486 treatment; prophylaxis and symptomatic intervention may facilitate treatment adherence to promote better outcomes.

// Jae-Sook Ahn 1, 2 , Hyeoung-Joon Kim 1, 2 , Yeo-Kyeoung Kim 1, 2 , Seung-Shin Lee 1 , Seo-Yeon Ahn 1 , Sung-Hoon Jung 1 , Deok-Hwan Yang 1 , Je-Jung Lee 1 , Hee Jeong Park 2 , Seung Hyun Choi 2 , Chul Won Jung 3 , Jun-Ho Jang 3 , Hee Je Kim 4 , Joon Ho Moon 5 , Sang Kyun Sohn 5 , Jong-Ho Won 6 , Sung-Hyun Kim 7 , Szardenings Michael 8 , Mark D. Minden 9 , Dennis Dong Hwan Kim 9 1 Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea 2 Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea 3 Division of Hematology-Oncology, Samsung Medical Center, Seoul, Republic of Korea 4 Department of Hematology, Cancer Research Institute, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea 5 Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, Republic of Korea 6 Department of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, Republic of Korea 7 Department of Hematology-Oncology, Dong-A University College of Medicine, Busan, Republic of Korea 8 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany 9 Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada Correspondence to: Hyeoung-Joon Kim, email: hjoonk@chonnam.ac.kr Keywords: TET2 , IDH1/2, 5hmC, normal karyotype, AML Received: July 25, 2016 Accepted: November 24, 2016 Published: December 26, 2016 ABSTRACT Stem cells display remarkably high levels of 5-hydroxymethylcytosine (5hmC). Both TET2 and IDH1/2 mutations can impair the production of 5hmC, thus decreasing 5hmC levels. TET2 or IDH1/2 mutations are commonly observed in acute myeloid leukemia (AML). However, the implications of 5hmC on survival in normal karyotype AML patients have not been fully evaluated. The 5hmC levels were analyzed in 375 patients using ELISA. The levels of 5hmC in DNA samples were converted to a log scale for the analysis and correlations with TET2 and/or IDH1/2 mutations were evaluated. The median 5hmC level was 0.065% (range 0.001–0.999). Mutation rates were 13.1% for TET2 mut , 6.7% for IDH1 mut , and 13.9% for IDH2 mut . The prevalence of TET2 and/or IDH1/2 was 33.1% (124/375). TET2 and IDH1 / 2 mutated patients had significantly lower levels of log(5hmC) compared with patients without TET2 or IDH1/2 mutations ( p 0.05). To identify its prognostic value, we sub-classified the levels of 5hmC into tertiles for 5hmC values. However, there was no significant association between the categories of 5hmC levels and survival or relapse risk (all p >0.05). Patients with TET2 or IDH1/2 mutations had lower levels of 5hmC. The 5hmC levels may not be predictive of survival in patients with normal karyotype AML.

Background Droplet digital polymerase chain reaction (ddPCR) is an exact method of measurement in cancer research. The aim of this prospective study was to evaluate minimal residual disease (MRD) using ddPCR in patients with chronic myeloid leukemia (CML). We also evaluated treatment outcome depending on BCR/ABL1 transcript level using ddPCR. Methods Between May 2013 and November 2014, CML patients treated with nilotinib as the first-line therapy were enrolled. BCR/ABL1 transcripts levels were evaluated using ddPCR at the first time of complete molecular response (CMR). CMR was verified by quantitative real-time polymerase chain reaction. Results We enrolled 15 patients from 7 institutions. The treatment period and median follow-up period were 45 months (range, 37–55 months) and 47 months (range, 39–61 months), respectively. The median value of BCR/ABL1 measured by ddPCR was 3.6 copies/20 μl (range, 1.2–6.8 copies/20 μl). Patients with a high level of BCR/ABL1 transcript had a greater tendency to lose the CMR during the follow-up period (0/10 (0%) for low levels vs. 2/5 (40%) for high levels, P = 0.095). In addition, patients with a low level of BCR/ABL1 transcript showed a longer duration of CMR than those with a high level (rate of sustained CMR at 2 years: 100% for low levels vs. 37.5% for high levels, P = 0.032). Conclusions We found that ddPCR is a sensitive method for detecting MRD and that MRD could affect the duration of the treatment response. Legal entity responsible for the study The authors. Funding Novartis Pharmaceuticals Corporation. Disclosure All authors have declared no conflicts of interest.

BACKGROUND: The adjuvanted recombinant zoster vaccine (Shingrix) can prevent herpes zoster in older adults and autologous haemopoietic stem cell transplant recipients. We evaluated the safety and immunogenicity of this vaccine in adults with haematological malignancies receiving immunosuppressive cancer treatments. METHODS: In this phase 3, randomised, observer-blind, placebo-controlled study, done at 77 centres worldwide, we randomly assigned (1:1) patients with haematological malignancies aged 18 years and older to receive two doses of the adjuvanted recombinant zoster vaccine or placebo 1-2 months apart during or after immunosuppressive cancer treatments, and stratified participants according to their underlying diseases. The co-primary objectives of the study were the evaluation of safety and reactogenicity of the adjuvanted recombinant zoster vaccine compared with placebo from the first vaccination up to 30 days after last vaccination in all participants; evaluation of the proportion of participants with a vaccine response in terms of anti-glycoprotein E humoral immune response to the adjuvanted recombinant zoster vaccine at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia; and evaluation of the anti-glycoprotein E humoral immune responses to the vaccine compared with placebo at month 2 in all participants, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. We assessed immunogenicity in the per-protocol cohort for immunogenicity and safety in the total vaccinated cohort. The study is registered with ClinicalTrials.gov, number NCT01767467, and with the EU Clinical Trials Register, number 2012-003438-18. FINDINGS: Between March 1, 2013, and Sept 10, 2015, we randomly assigned 286 participants to adjuvanted recombinant zoster vaccine and 283 to placebo. 283 in the vaccine group and 279 in the placebo group were vaccinated. At month 2, 119 (80·4%, 95% CI 73·1-86·5) of 148 participants had a humoral vaccine response to adjuvanted recombinant zoster vaccine, compared with one (0·8%, 0·0-4·2) of 130 participants in the placebo group, and the adjusted geometric mean anti-glycoprotein E antibody concentration was 23 132·9 mIU/mL (95% CI 16 642·8-32 153·9) in the vaccine group and 777·6 mIU/mL (702·8-860·3) in the placebo group (adjusted geometric mean ratio 29·75, 21·09-41·96; p

The prognostic significance of molecular mutations (FLT3-ITD, NPM1, and CEBPA mutations) was examined in patients with normal-karyotype acute myeloid leukaemia (NK-AML) after allogeneic haematopoietic cell transplantation (HCT). In total, 115 patients received allogeneic HCT for NK-AML and were evaluated for FLT3-ITD, NPM1, and CEBPA mutations in diagnostic samples and for long-term outcomes following HCT, retrospectively. The prevalences of FLT3-ITD(pos), NPM1 (mut), and CEBPA (dm) (double mutations) were 32.2, 43.5, and 24.6 %, respectively. The triple-negative group (NPM1 (wild)/FLT3-ITD(neg)/non-CEBPA (dm)) showed a similar transplant outcome to those in the favourable European LeukemiaNet (ELN) risk group for overall survival (OS) (60.9 vs. 63.7 %; p = 0.810), but a more favourable OS than others in the intermediate-I risk group (40.0 %; p = 0.034). Also, the triple-negative group showed a similar relapse rate at 5 years compared with those in the favourable risk group (9.7 vs. 15.5 %; p = 0.499), but a lower rate of relapse than the others in the intermediate-I risk group (15.5 vs. 48.6 %; p = 0.004). The 5-year relapse incidences were 4.0 % (NPM1 (mut)/FLT3-ITD(neg)), 14.7 % (CEBPA (dm)), 15.5 % (NPM1 (wild)/FLT3-ITD(neg)/non-CEBPA (dm)), 39.1 % (NPM1 (mut)/FLT3-ITD(pos)/non-CEBPA (dm)), and 66.7 % (NPM1 (wild)/FLT3-ITD(pos)/non-CEBPA (dm)). Thus, the triple-negative (NPM1 (wild)/FLT3-ITD(neg)/non-CEBPA (dm)) group showed favourable long-term outcomes after allogeneic HCT in NK-AML, similar to those of the favourable risk group by the ELN risk classification.

e14532 Background: Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma (NHL). Although, there are various treatment options for PCNSL which include methotrexate based chemotherapy and whole brain radiotherapy (WBRT), half of the patients who initially achieved complete response experience disease relapse. Accordingly, we attempted to identify novel prognostic factors using MRI in patients with newly diagnosed PCNSL. Methods: We retrospectively evaluated 672 patients who were diagnosed with central nervous system (CNS) cancers between January 2011 and May 2018. Enrollment criteria were i) pathologic diagnosis of CNS lymphoma, ii) no evidence of systemic involvement, iii) no evidence of human immunodeficiency virus-1 infection or other immunodeficiencies, and iv) available magnetic resonance imaging (MRI) examinations at diagnosis. Fifty-two patients met these criteria and were enrolled. Results: Patients with low apparent diffusion coefficient (ADC) showed inferior overall survival (OS) compared to those with high ADC. Patients with a hyperintense signal on T2-weighted image and homogenous enhancement showed better failure-free survival (FFS), while patients with low ADC and necrosis showed poor FFS. In the multivariate survival analysis, old age ( > 60) (hazard ratio (HR) 20.372, p= 0.001), Eastern Cooperative Oncology Group performance status ((ECOG PS) ≥ 2 (HR 10.429, p < 0.001), higher levels of lactate dehydrogenase (LDH) (HR 7.408, p= 0.001), and low ADC (HR 0.273, p= 0.009) were associated with inferior OS, while ECOG PS ≥ 2 (HR 10.319, p= 0.021), presence of necrosis (HR 6.372, p= 0.008), and low ADC (HR 0.226, p= 0.020) were unfavorable factors for FFS. Conclusions: We conclude that ADC, a characteristic MRI finding, had significant prognostic value for long-term survival in our study of patients with newly diagnosed PCNSL Specifically, low ADC was an independent unfavorable prognostic factor, suggesting that ADC measurements through non-invasive MRI can improve the current prognostic scoring system.

The clinical significance of tumor burden reduction following administration of hypomethylating agents (HMAs) for transplant-eligible patients with higher risk myelodysplastic syndrome (MDS) was evaluated.Data of 79 transplant-eligible patients (65 years) diagnosed with higher-risk MDS between July 2002 and March 2013 were retrospectively analyzed. Among 79 patients, 30 (38%) underwent allogeneic hematopoietic cell transplantation (HCT group), and 49 (62%) were treated with HMA alone (non-HCT group).The median follow-up duration was 732 days (range, 28-1952 days), and the 3-year overall survival (OS) rate of all patients was 30.6%. In the HCT group, early HCT showed a better 3-year OS rate than late HCT (67.1% vs. 25.7%; P = .035). In multivariate analysis, time/performance of allogenic transplant (no HCT vs. early HCT, hazard ratio, 0.18; 95% confidence interval, 0.04-0.81; P = .026) and follow-up higher risk International Prognostic Scoring System (hazard ratio, 6.22; 95% confidence interval, 2.09-18.51; P = .001) were significantly correlated with OS.To predict the clinical outcomes of patients with higher risk MDS, the optimal time for tumor burden evaluation is prior to follow-up rather than at the time of initial diagnosis. Patients with lower International Prognostic Scoring System risk groups after HMA treatment or early HCT had favorable OS.

Background The optimal number of high-dose cytarabine (HDAC) consolidation cycles before allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia is not fully standardized. Patients and Methods This study evaluated the impact of HDAC consolidation cycles before allogeneic HCT in 194 patients with acute myeloid leukemia in first complete remission between 1998 and 2014. The patients were reclassified into 3 groups—no consolidation (C0, n = 20), 1 consolidation (C1, n = 115), and ≥ 2 consolidations (C2, n = 59)—by pre-HCT consolidation cycle. Results The 3-year relapse-free survival rates was 45.9%, 66.9%, and 73.3% for the C0, C1, and C2 groups, respectively (P = .064), while the 3-year overall survival rates were 35.0%, 55.2%, and 67.5%, respectively (P = .106). The cumulative incidence of acute graft-versus-host disease (GVHD) was higher in the C2 group (38.7%) than in the C0 (22.2%) or C1 (17.7%) group (P = .018). However, the incidence of chronic GVHD showed no difference between the groups. Multivariate analysis for overall survival revealed the following independent factors: adverse cytogenetic risk (hazard ratio [HR] = 1.84, P = .046), C2 versus C0 (HR = 0.41, P = .037), pre-HCT status beyond CR1 versus CR1 (HR = 5.78, P Conclusion One or two cycles of HDAC consolidation therapy led to better subsequent HCT outcomes compared to the no–consolidation therapy group.

Background Elderly patients with multiple myeloma (MM) are vulnerable to adverse events (AEs). This study evaluated adherence to chemotherapy and treatment outcomes in elderly patients treated with a frontline bortezomib (BTZ), melphalan, and prednisone (VMP) regimen and regimens without BTZ. Methods One-hundred and forty elderly patients who were diagnosed with MM from March 2007 to March 2015 were included in this retrospective study. To evaluate regimen adherence, patients who were treated with more than 4 cycles were assigned to the good adherence group. Results Among the 140 patients, 71 were treated with a frontline VMP and 69 with non-BTZ regimens. The median age was 71 years (range, 65-90 years). The VMP group showed a higher complete response rate than the non-BTZ group: 26.8% vs. 7.2%. More patients in the VMP group achieved ≥very good partial response (VGPR) and ≥PR. In the VMP group, 27 patients (38.0%) received less than 4 cycles. The VMP good adherence group showed a higher 3-year overall survival (OS) rate (70.9%) than the poor adherence group (60.2%, p=0.059). In the multivariate analysis, treatment with ≥4 cycles of VMP was a favorable factor for OS. Conclusion A good adherence to a frontline VMP regimen resulted in favorable long-term survival. Adequate management of AEs will be needed to achieve favorable outcomes in elderly patients with MM.

Blinatumomab, a bispecific T cell-engaging antibody, has demonstrated efficacy for relapsed or refractory acute lymphoblastic leukemia (ALL). In this study, we evaluated the efficacy and toxicity of blinatumomab in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL. A total of 50 patients received blinatumomab treatment between June 2016 and August 2017 in Korea. The median number of prior therapy was one (range, 1–4). Among the 49 evaluable patients, 22 (44.9%) achieved complete response (CR) or CR with incomplete blood count recovery, and 16 of whom subsequently underwent allogenic stem cell transplantation. Although no statistically significant differences were observed, patients with extramedullary disease and poor performance status had lower responses to blinatumomab treatment. In addition, the use of high-dose dexamethasone prior to blinatumomab treatment did not affect the response to blinatumomab. The median event-free survival and overall survival of the responders were 7.5 and 8.1 months, respectively. For non-hematologic toxicities, the most common toxicity was infection. The incidences of severe cytokine release syndrome and neurologic toxicity each was 4%. In conclusion, blinatumomab was an effective and tolerable therapy in adult Korean patients with relapsed or refractory Philadelphia-negative B cell precursor ALL.

The effects of imatinib plus chemotherapy were assessed in 87 patients with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). Imatinib was administered continuously, starting from the eighth day of remission induction chemotherapy, then through five courses of consolidation or until allogeneic hematopoietic cell transplantation (HCT). Patients who were not transplanted were maintained on imatinib for 2 years. Eighty-two patients (94.3%) achieved complete remission (CR). Among these 82 CR patients, 40 experienced recurrence of leukemia. The 5-year relapse free survival (RFS) rate and overall survival (OS) rates were 39.0% and 33.4%, respectively. In total, 56 patients underwent allogeneic HCT in first CR. The 5-year cumulative incidence of relapse and OS rate of them were 59.1% and 52.6%, respectively. Six of seven patients who were maintained on imatinib after completion of consolidation relapsed and the median time of RFS was 40.7 months. In total patient, cumulative molecular CR rate was 88.5% and median time of molecular CR duration was 13 months. Initial imatinib dose intensity was significantly associated with median CR duration (P

We retrospectively assessed the clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria (PNH) according to severity of cytopenia. A total of 282 patients with hematological parameters assessed at the time of diagnosis of PNH were included. There were 24 patients with PNH/severe aplastic anemia (SAA) (at least two of the three criteria; hemoglobin ≤8 g/dL; absolute neutrophil count (ANC)0.5 × 10(9)/L; platelet count20 × 10(9)/L), 96 patients with PNH/aplastic anemia (AA) (at least two of the three criteria; hemoglobin ≤10 g/dL; ANC 0.5-1.5 × 10(9)/L; platelet count 20-100 × 10(9)/L), and 162 classic PNH patients. Compared with the classic PNH subgroup, the PNH/SAA subgroup had a significantly lower median granulocyte PNH clone size (26.7 vs. 51.0 %, P = 0.021) and lower incidence of lactate dehydrogenase ≥1.5 times the upper limit of normal (52.9 vs. 80.0 %, P = 0.049). The incidence of thromboembolism was similar in both subgroups. Overall survival was significantly lower in the PNH/SAA subgroup than in the classic PNH subgroup (P = 0.033). Our findings suggest that identification of patients with PNH/SAA at the time of diagnosis is important because of different clinical manifestations and poorer outcome compared with patients with classic PNH (clinicaltrials.gov identifier: #NCT01224483).

We investigated the effects of nilotinib plus multiagent chemotherapy, followed by consolidation/maintenance or allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with newly diagnosed Philadelphia-positive (Ph-pos) acute lymphoblastic leukemia (ALL). Study subjects received induction treatment that comprised concurrent vincristine, daunorubicin, prednisolone, and nilotinib. After achieving complete hematologic remission (HCR), subjects received either 5 courses of consolidation, followed by 2-year maintenance with nilotinib, or allo-HCT. Minimal residual disease (MRD) was assessed at HCR, and every 3 months thereafter. The molecular responses (MRs) were defined as MR3 for BCR-ABL1/G6PDH ratios ≤10(-3) and MR5 for ratios

According to current guidelines on therapeutic strategies for myelodysplastic syndrome (MDS), cytoreductive therapies before allogeneic stem cell transplantation (SCT) are not widely recommended for patients with high-risk MDS or refractory anemia with excess blasts (RAEB) who are eligible for allogeneic SCT because of controversial evidence on the role of such therapies. Yet, while treatment with hypomethylating agents (HMAs) has a critical limitation in eradicating MDS clones, the use of HMA treatment as a bridge to allogeneic SCT has become a focus with the hope of improving the SCT outcome based on the chance of achieving complete remission or reducing the blast percentage safely and effectively before allogeneic SCT. However, a consensus needs to be established on the use of HMAs as a bridging therapy for high-risk MDS or RAEB. Thus, the Korean AML/MDS working party group surveyed 34 Korean MDS experts on their bridging therapies for high-risk MDS. Accordingly, this paper presents the survey questionnaire and resulting data, along with a summary of the consensus and related recommendations regarding strategies using HMA treatment and allogeneic SCT based on reported studies and the current survey results.