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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 (

Summary In the phase 3 study RERISE, patients with newly diagnosed chronic myeloid leukaemia in chronic phase demonstrated significantly faster and higher rates of major molecular response (MMR) with twice‐daily radotinib 300 mg (n = 79) or 400 mg (n = 81) than with once‐daily imatinib 400 mg (n = 81) after 12 months. With ≥48 months’ follow‐up, MMR was higher with radotinib 300 mg (86%) or 400 mg (83%) than with imatinib (75%). Among patients with BCR‐ABL1 ≤ 10% at three months, MMR and molecular response 4·5 (MR4·5) were achieved within 48 months by more radotinib‐treated patients (300 mg: 84% and 52%, respectively; 400 mg: 74% and 44%, respectively) than imatinib‐treated patients (71% and 44%, respectively). Estimated overall and progression‐free survival rates at 48 months were not significantly different between imatinib (94% and 94%, respectively) and radotinib 300 mg (99% and 97%, respectively) or 400 mg (95% and 93%, respectively). The treatment failure rate was significantly higher with imatinib (19%) than with radotinib 300 mg (6%; P = 0·0197) or 400 mg (5%; P = 0·0072). Safety profiles were consistent with previous reports; most adverse events occurred within 12 months. Radotinib continues to demonstrate robust, deep molecular responses, suggesting that treatment‐free remission may be attainable.

Purpose: The clinical role of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) in performing upfront high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains unclear in peripheral T cell lymphomas (PTCLs). This study investigated the prognostic relevance of interim and final FDG-PET/CT in predicting the outcome of upfront ASCT for the treatment of PTCLs. Method: The study conducted newly diagnosed 96 patients with PTCLs who aged under 65 years between January 2005 and December 2016 from two independent institutions. For making a comparison of clinical outcome between transplant and non-transplant patients according to interim or final FDG- PET/CT, 37 transplanted and 59 non-transplanted patients with the same populations were evaluated as a comparative group (non-ASCT). The enrolled patients were treated with mainly anthracycline-based chemotherapy except patients with NK/T cell lymphoma who were treated with non-anthracycline-based. If achieved complete or partial remission after primary treatment, patients proceeded to upfront ASCT. FDG-PET/CT was performed at the time of diagnosis, interim, and after primary treatment. The response of interim or final FDG-PET/CT was analyzed by visual assessment using Deauville five-point scale (5-PS). Results: The characteristics of transplant patients were similar to non-transplant patients except two features (IPI score, CT response). Final FDG-PET/CT response (P Conclusion: Final FDG-PET/CT response based on Deauville 5-PS had prognostic significance on the treatment outcome of PTCLs regardless of upfront ASCT. However, patients with ≥ 3 of Deauville score assessed by interim or final FDG-PET/CT had poor prognosis even though performing upfront ASCT. Disclosures No relevant conflicts of interest to declare.

The aim of this study was to evaluate the prognostic relevance of early risk stratification in diffuse large B-cell lymphoma (DLBCL) using interim Deauville score on positron emission tomography-computed tomography (PET-CT) scan and baseline International Prognostic Index (IPI). This retrospective study included 220 patients (median age, 64 years; men, 60%) diagnosed with DLBCL between 2007 and 2016 at our institution, treated with rituximab-based chemotherapy. Interim PET-CT was performed after three cycles of immuno-chemotherapy. Interim Deauville score was assessed as 4 or 5 in 49 patients (22.3%), and 94 patients (42.7%) had high-intermediate or high-risk IPI scores. In multivariate analysis, interim Deauville score (1-3 and 4-5) and baseline IPI (low/low-intermediate and high-intermediate/high) were independently associated with progression-free survival (for Deauville score, hazard ratio [HR], 1.00 vs. 2.96 [95% confidence interval (CI), 1.83-4.78], P < 0.001; for IPI, HR, 1.00 vs. 4.84 [95% CI, 2.84-8.24], P < 0.001). We stratified patients into three groups: low-risk (interim Deauville scores 1-3 and low/low-intermediate IPI), intermediate-risk (Deauville scores 1-3 with high-intermediate/high IPI or Deauville scores 4-5 with low/low-intermediate IPI), and high-risk (Deauville scores 4-5 and high-intermediate/high IPI). This early risk stratification showed a strong association with progression-free survival (HR, 1.00 vs. 3.98 [95% CI 2.10-7.54] vs. 13.97 [95% CI 7.02-27.83], P < 0.001). Early risk stratification using interim Deauville score and baseline IPI predicts the risk of disease progression or death in patients with DLBCL. Our results provide guidance with interim PET-driven treatment intensification strategies.

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.

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0–122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3–4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.

Introduction BCR-ABL1 mutations require consideration during second-line tyrosine kinase inhibitor selection for patients with chronic myeloid leukemia (CML). The present retrospective analysis compared the frequency of BCR-ABL1 mutations in Asian and white patients in whom imatinib therapy had failed. Patients and Methods A nonstudy cohort (76 Asian patients from community clinical practices) and 2 study cohorts (29 Asian and 352 white patients from dasatinib phase II and III clinical trials) were identified. Results In the nonstudy cohort, 80 mutations were identified; the most frequent was T315I (15%), followed by phosphate-binding loop mutations E255K (11%), G250E (10%), and Y253H (10%). Asian patients had a greater proportion of T315I and phosphate-binding loop mutations compared with the white patients. The nonstudy cohort was less likely to have multiple mutations compared with either study cohort. Single mutations highly resistant to dasatinib, nilotinib, and bosutinib were more frequent in the Asian than in the white cohorts. Conclusion These results suggest that mutational analysis findings will be invaluable for choosing an appropriate second-line tyrosine kinase inhibitor in Asia.

Background: The neutrophil-to-lymphocyte ratio (NLR) is an independent prognostic marker in solid and hematological cancers. While the derived NLR (dNLR) was shown to be non-inferior to the NLR in large cohorts of patients with different cancer types, it has not been validated as a prognostic marker for multiple myeloma (MM) to date. Methods: Between May 22, 2011 and May 29, 2014, 176 patients with MM from 38 centers who were ineligible for autologous stem cell transplantation were analyzed. The dNLR was calculated using complete blood count differential data. The optimal dNLR cut-off value according to receiver operating characteristic analysis of overall survival (OS) was 1.51. All patients were treated with melphalan and prednisone combined with bortezomib. Results: The complete response rate was lower in the high dNLR group compared to the low dNLR group (7 vs. 26.1%, respectively; p = 0.0148); the corresponding 2-year OS rates were 72.2 and 84.7%, respectively (p = 0.0354). A high dNLR was an independent poor prognostic factor for OS (hazard ratio 2.217, 95% CI 1.015–4.842; p = 0.0458). Conclusion: The dNLR is a readily available and cheaply obtained parameter in clinical studies, and shows considerable potential as a new prognostic marker for transplantation-ineligible patients with MM.

T lymphocytes are critical players in graft-versus-host disease (GVHD); however, their specific roles and mechanisms in GVHD have not been clearly defined. Co-inhibitory receptors including PD1, TIM3, TIGIT, and LAG3 play a key role in regulating T cell responses and maintaining immune homeostasis. TIM3 expression on lymphocytes was identified to induce immune tolerance in a mouse GVHD model; in addition, PD1 +TIM3 + double-positive T cells displayed more potent immunosuppression compared to PD1 + T cells. However, despite the strong immunosuppression exerted by PD1 +TIM3 + double-positive T cells, their clinical potential is greatly limited by their low cell number in peripheral blood. In this study, we introduce a novel method to isolate CD3 + cells from G-CSF mobilized peripheral blood stem cells (G-PBSCs), and culture CD3 +PD1 +TIM3 + lymphocytes to treat GVHD. Methods. The donors were subcutaneously injected with G-CSF (10μg/kg) for five days. G-PBSCs were collected from the donors using a COBE spectra cell separator. Then, the highly purified CD3 + cells were isolated by positive selection with magnetic-activated cell sorting (MACS) from G-PBSCs using CD3 Dynabeads™. Isolated CD3 + cells were cultured with a low concentration of IL-2 (50U/mL), and PD1, TIM3, LAG3, and TIGIT expressions were assessed using flow cytometry (FACS). CD3 +PD1 +TIM3 +, CD3 +PD1 +TIM3 +LAG3 +TIGIT - and CD3 +PD1 +TIM3 +LAG3 +TIGIT +cells are sorted and cultured with irradiated allo-MNCs for 4 days (Mixed Lymphocyte Reaction; MLR). We used 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) as an intracellular fluorescent dye in MLR (CFSE-MLR) to measure of T cells proliferation. Results. In normal, untreated G-PBSCs, very low percentages of cells are CD3 +PD1 +TIM3 +, CD3 +PD1 +LAG3 + and CD3 +PD1 +TIGIT + (0.6±0.4, 0.3±0.2 and 1.3±0.5% in G-PBSC, respectively). However, after treating G-PBSC cells with a low concentration of IL-2 (50 U/mL), we discovered the percentages of CD3 +PD1 +TIM3 +, CD3 +PD1 +LAG3 +, and CD3 +PD1 +TIGT + lymphocytes in G-PBSCs markedly increased by 19.6±5.9, 18.5±4.3, 17.7±6.5%, respectively. Of note, there was a very small change (~1.2 fold increase) in the total number of CD3 + lymphocytes, which indicates that the low dose IL-2 therapy alters subpopulations of T lymphocytes, rather than increasing the proliferation rate. Next, we tested the immunosuppressive capacity of the cultured CD3 +PD1 +TIM3 +cells. To do this, we used CSFE-MLR to measure T cell proliferation. CD3 +PD1 +TIM3 + lymphocytes were depleted in CD3 + G-PBSCs by flow cytometry-based cell sorting. Then we cultured the CD3 + G-PBSCs with allo-MNCs and discovered that the CD3 + G-PBSCs that lacked CD3 +PD1 +TIM3 + lymphocytes demonstrated a significantly increased level of T-cell proliferation compared to CD3 + G-PBSCs, and thereby confirming the immunosuppressive function of CD3 +PD1 +TIM3 + lymphocytes in inhibiting T cell proliferation (% of unstimulated T cells in CD3 + G-PBSCs vs. in CD3 +PD1 +TIM3 + depleted G-PBSC CD3 + cells; 33.5±7.5% vs. 6.3±4.2%). After confirming the immunosuppressive function of the IL-2 treated CD3 +PD1 +TIM3 + lymphocytes, we investigated expressions of other co-inhibitory surface markers such as LAG3 and TIGIT. Amongst the cultured CD3 +PD1 +TIM3 + lymphocytes, 96.2±3.3% of the CD3 +PD1 +TIM3 + lymphocytes were LAG3 +, 28.9±5.4% of the CD3 +PD1 +TIM3 + lymphocytes were TIGIT +, and 63.7±7.8% of the cells were TIGIT -. Interestingly, CD3 +PD1 +TIM3 +LAG3 +TIGIT - lymphocytes demonstrated significantly enhanced levels of immunosuppression compared to CD3 +PD1 +TIM3 +LAG3 +TIGIT + lymphocytes (% of unstimulated T cells in CD3 +PD1 +TIM3 +LAG3 +TIGIT - lymphocytes vs. in CD3 +PD1 +TIM3 +LAG3 +TIGIT + lymphocytes, 53.8±5.5% vs. 23.2±7.4%). Conclusion. We demonstrate that treating CD3 + G-PBSCs with low-dose IL-2 markedly increases the percentage of CD3 +PD1 +TIM3 + lymphocytes, which is known to exert strong immunosuppression. Also, we suggest that CD3 +PD1 +TIM3 +LAG3 +TIGIT - lymphocytes are the subpopulation within CD3 +PD1 +TIM3 + cells that demonstrate the most potent immunosuppression compared to other subpopulations of CD3 +PD1 +TIM3 + lymphocytes. Taken together, such findings suggest that the low-dose IL-2 therapy has therapeutic potential to treat patients with GVHD. Disclosures No relevant conflicts of interest to declare.

Background Plasmacytoma at the time of relapse of multiple myeloma is associated with poor response and survival. However, data on the activity of the recently available new drug or drug combinations in RRMM with plasmacytoma in the real-world clinical practice is limited. Pomalidomide and dexamethasone (Pd) with or without cyclophosphamide is an active therapeutic combination in relapsed and refractory multiple myeloma (RRMM) after 2 lines of previous line of therapy Method This study aimed to analyze the clinical outcome of the pomalidomide-based regimen in RRMM with plasmacytoma. Clinical data of 221 patients who were treated with Pd with or without cyclophosphamide from 7 hospitals participating in the Korean multiple myeloma working party were retrospectively analyzed by electronic medical chart review. All the of patients were previously treated with at least 2 lines of therapies including bortezomib and lenalidomide in most of the patients. Plasmacytoma was diagnosed by the computed tomography, magnetic resonance imaging or FDG-PET scan Result Twenty-nine patients among the 221 patients analyzed (13.1%) had plasmacytoma at the time of pomalidomide-based chemotherapy. Patients were previously treated with a median 4 lines of therapy (range, 2-14), including bortezomib, lenalidomide, autologous stem cell transplantation in 97%,100%, and 52% of the patients, respectively. 14 patients were treated with Pd and 15 patients had been treated with Pd and cyclophosphamide (PCd). Median number of sites of plasmacytoma involvement was 2 (range, 1-9), including paraskeletal and soft tissue involvement in 83% and 52% of the patients. Sites of soft tissue involvement were: 5 pleura, 4 lymph nodes, 4 subcutaneous, 3 liver, 3 muscle, 2 pancreas, 1 kidney, 1 pericardium, 1 peritoneum, 1 adrenal gland, and 1 stomach. 50% patients (13 among the 26 response evaluable patients) had responded to Pd with or without Cy: 2 complete response, 2 very good partial response, 9 partial response, 1 stable disease, 2 minimal response, and 10 progressive disease. Patients who were treated with PCd showed a better response compared with Pd therapy (53% versus 29%, P=0.264). After a median follow-up of 9.33 months (range, 0.30-52months), patients with plasmacytoma versus no plasmacytoma showed a progression-free survival of 3.57 (95% CI, 0.35-6.78 months) versus 8.40 months (95% CI, 7.00-9.80 months) (P=0.002) and an overall survival of 3.33 (95% CI, 0.00-7.82 months) versus 19.67 months (95% CI, 13.39-25.95 months) (P=0.001). Conclusion RRMM patients with plasmacytoma was responsive after pomalidomide-based chemotherapies. The addition of cyclophosphamide to Pd seemed to result in a better response compared with Pd only. However, RRMM patients with plasmacytoma had poorer survival compared with patients without plasmacytoma even after Pd with or without cyclophosphamide.

Backgroud: Although multiple trials have shown that stopping tyrosine kinase inhibitor (TKI) treatment can be employed in CP CML patients with sustained deep molecular response (DMR) after enough TKI therapy, they emphasized the need for close monitoring because about 50-70% of patients experienced molecular relapse. However, most patients with molecular recurrence regain their initial molecular level after restarting TKI therapy. Aims: In this study, we analyzed second imatinib (IM) discontinuation outcomes in patients regaining durable DMR in the Korean multicenter prospective study (Korean Imatinib Discontinuation Study; KID Study) Methods: CP CML patients who were treated with IM for more than 3 years and maintained DMR for at least 2 years were eligible for the Korean multicenter prospective study and in cases of MMR loss on 2 consecutive assessments, IM treatment was re-introduced. After IM resumption, the molecular response was evaluated every month until re-achievement of MMR and every 3 months thereafter. The second stop was permitted in the patients who were in second DMR for at least 2 years. Results: Among the patients who maintained a second DMR for at least 2 years after IM resumption, 23 patients entered into a second IM stop. Prior to first discontinuation, the median duration of IM therapy was 73.2 months (range, 38.4-133.2 months) and the duration of sustained UMRD was 38.4 months (range, 24-102 months). After first attempt of IM discontinuation, they relapsed after a median duration of 3.7 months (range, 1.8-20.8 months) and re-achieved UMRD at a median of 5.8 months (range, 1.7-12.1 months) after IM resumption. After sustaining a second DMR for a median of 26.3 months, IM therapy discontinued for a second time. With a median follow-up of 29.5 months (range, 9-63 months) since second IM stop, 15/23 patients (65%) lost MMR after a median 2.9 months (range, 1.8-30.7 months), which was similar to those of the first IM discontinuation [median 3.7 (range, 1.8-20.8 months)]. The patients who lost MMR were retreated with IM for a median of 24.5 months (range, 1.2-49.7 months); 14 patients re-achieved MMR and one patient was in therapy for 1.2 months. Conclusion: Our data demonstrated that a second attempt might be possible and the median time to MMR loss after second discontinuation was similar to those of the first discontinuation. Further studies on the predictors to select patients for a trial of second TFR and novel strategies will be warranted. Disclosures Kim: Takeda: Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; ILYANG: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sun Pharma.: Research Funding.

Background: Peripheral T-Cell Lymphoma (PTCL) is an aggressive malignancy which lacks effective treatment. Emerging data suggests that the JAK-STAT pathway may play an important role in mediating pathogenesis of PTCL. DZD4205 (AZD4205) is an orally available, potent and highly selective JAK1 inhibitor. In T-cell lymphoma cell lines, DZD4205 modulates pSTAT3 pathway and suppresses cell proliferation, and in tumor xenograft models, DZD4205 exhibits dose-dependent anti-tumor activities, with good correlation with drug exposure and modulations of pSTAT3 in tumor tissues. A phase I/II study (JACKPOT8) was initiated to assess the safety, tolerability, pharmacokinetics and anti-tumor efficacy of DZD4205 in patients with refractory/relapsed (r/r) PTCL. Methods: The JACKPOT8 study (ClinicalTrials.gov Identifier: NCT04105010) included two parts: Part A, dose escalation and Part B, dose expansion. In Part A, patients with r/r PTCL who have progressed on or were refractory to systemic therapy will be enrolled and treated with DZD4205 at two different dose levels, 150 mg or 250 mg once daily. In Part B, patients will receive DZD4205 treatment at a defined dose. The primary objective is to assess the safety and tolerability of DZD4205, and the secondary objectives include anti-tumor efficacy and pharmacokinetics. Evaluation of safety/tolerability and tumor response will be based on the CTCAE version 5.0 and 2014 Lugano classification, respectively. Patients will be treated until disease progression, intolerance to adverse events, or withdrawal of consent. Results: As of June 30, 2020, a total of 23 patients with r/r PTCL were enrolled and received DZD4205 at 150 mg (n = 19) or 250 mg (n = 4) once daily. Patient characteristics: median age (range): 65.0 years (34-79); median prior systemic therapies (range): 2 lines (1-8). Four patients had undergone prior hematopoietic stem cell transplantation (HSCT). Six patients had bone marrow involvement at the study entry. Histological subtypes included peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) (n = 10, 43.5%), angioimmunoblastic T-cell lymphoma (AITL) (n = 10, 43.5%), ALK-negative anaplastic large cell lymphoma (ALCL ALK-) (n = 2, 8.7%) and extra-nodal nasal NK/T-cell lymphoma (NKTCL) (n = 1, 4.3%) . Preliminary data showed that 20 patients experienced treatment emergent adverse events (TEAEs), among whom 13 (56.5%) had ≥ grade 3 TEAEs. Based on local investigators' assessment, eight patients (34.8%) had ≥ grade 3 TEAEs which were considered to be related to DZD4205. The most common (> 5% incidence) DZD4205-related TEAEs (any grade) included thrombocytopenia (n = 6, 26.1%), neutropenia (n = 4, 17.3%), decreased appetite (n = 3, 13.0%), nausea (n = 2, 8.7%), interstitial lung disease (n = 2, 8.7%) and pneumonia (n = 2, 8.7%). Most TEAEs were manageable with dose interruption and reduction. Preliminary PK data is available in 20 patients (n = 19 at 150 mg, n = 1 at 250 mg). Exposure at 250 mg is higher than 150 mg following a single and multiple dose. As expected from long t1/2 of DZD4205, accumulation of about 3 folds in AUC was observed. DZD4205 had flat PK profile with small difference between Css,max and Css,min after 22 days of once daily dosing, which is an optimal PK profile to maintain DZD4205 concentrations above effective levels throughout the dosing interval. As of June 30, 2020, 22 patients (n = 19 at 150 mg, n = 3 at 250 mg) had at least one post-treatment Lugano assessment. In 150 mg cohort, 8 out of 19 patients showed tumor response, with objective response rate (ORR) of 42%, among whom 4 (21%) had complete response (CR) and another 4 (21%) partial response (PR). In 250 mg cohort, 1 out of 3 patients showed tumor response, with ORR of 33%. Tumor response was observed in subtypes including AITL, PTCL-NOS, ALCL (ALK-) and NKTCL. At the data cut-off date, the longest duration on treatment was > 8 months. Patient enrolment is ongoing. Updated clinical data will be shared at the meeting. Conclusion: DZD4205 shows good tolerability, pharmacokinetic profiles and promising anti-tumor efficacy in patients with r/r PTCL, indicating its potential as a therapeutic option for this unmet medical need. Disclosures Kim: Donga: Research Funding; Kyowa-Kirin: Research Funding; Roche: Research Funding; Johnson&Johnson: Research Funding; Celltrion: Research Funding; Mundipharma: Research Funding. Yoon:Celltrion: Honoraria; Samyang: Research Funding; Amgen, Chongkundang, Celgene, Astrazeneca: Consultancy. Wang:Dizal Pharmaceuticals: Current Employment. Li:Dizal Pharmaceuticals: Current Employment. Huang:Dizal Pharmaceuticals: Current Employment. Deng:Dizal Pharmaceuticals: Current Employment. Chen:Dizal Pharmaceuticals: Current Employment. Yang:Dizal Pharmaceuticals: Current Employment.

// Ho-Young Yhim 1, 2, * , Jeong-A Kim 3, 4, * , Sun-Hye Ko 3 , Youngrok Park 5 , Eunjung Yim 3 , Hee Sun Kim 6 and Jae-Yong Kwak 1 1 Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea 2 Research Institute of Clinical Medicine, Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea 3 Division of Hematology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea 4 Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea 5 Tumor Biology Training Program, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC, USA 6 College of Nursing, Chonbuk National University, Jeonju, Republic of Korea * These authors have contributed equally to this work Correspondence to: Jae-Yong Kwak, email: jykwak@jbnu.ac.kr Keywords: angiogenesis, CD11b, CX3CR1, diffuse large B-cell lymphoma, immunosuppression Received: May 14, 2017 Accepted: August 17, 2017 Published: September 23, 2017 ABSTRACT Despite their critical roles in angiogenesis and host immunosuppression within the tumor microenvironment, the prognostic significance of myeloid-lineage cells expressing CD11b and CX3CR1 in diffuse large B-cell lymphoma (DLBCL) has not been well studied. We prospectively enrolled newly-diagnosed DLBCL patients at two Korean institutions between May 2011 and Aug 2015. CD11b + CX3CR1 + cells were analyzed by flow cytometry using peripheral blood (PB) and bone marrow (BM) aspirate samples before treatments. Eighty-nine patients (52 males) were enrolled. The median age was 65 years (range, 19–88 years). Thirty-seven patients (42%) were classified as high-intermediate or high risk according to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI). Patients were categorized into either high or low PB-/BM-CD11b + CX3CR1 + monocyte group according to the cutoffs identified by the receiver-operating-characteristics analysis (PB, 3.68%; BM, 3.45%). The high PB-CD11b + CX3CR1 + monocyte group was significantly associated with high-intermediate and high risk NCCN-IPI group ( P = 0.004). With a median follow-up of 27.7 months (range, 1.7-60.4 months), the low PB-CD11b + CX3CR1 + monocyte group showed significantly better overall survival (OS) than the high PB-CD11b + CX3CR1 + monocyte group (3-year, 92.3% vs. 51.2%, respectively; P < 0.001). In contrast, no significant difference was observed between the high and low BM-CD11b + CX3CR1 + monocyte groups. Among patients with high-intermediate to high risk NCCN-IPI, the high PB-CD11b + CX3CR1 + monocyte group showed significantly worse OS than the low PB-CD11b + CX3CR1 + monocyte group (3-year, 29.3% vs. 80.2%, respectively; P = 0.008). Taken together, PB-CD11b + CX3CR1 + monocyte percentage correlates with the NCCN-IPI risk stratification, which enables identification of subgroups with extremely poor clinical outcomes.

Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) has been shown to improve the rates of successful peripheral blood stem cell (PBSC) mobilization in patients with malignant lymphoma or multiple myeloma (MM) who experienced prior failure of PBSC mobilization. We evaluated the mobilization results of re-mobilization using plerixafor and G-CSF in insufficiently mobilizing patients. Forty-four patients with lymphoma (n = 29) or MM (n = 15) were included in the study. The median age was 50 (range, 24-64) years. Previous mobilization regimens were chemotherapy with G-CSF (n = 28), including cyclophosphamide with G-CSF (n = 15), and G-CSF only (n = 16). All patients with lymphoma achieved at least partial response (PR) before the mobilization, including 13 complete responses (CRs). Eleven patients with MM achieved at least PR and four patients with MM were in stable disease before mobilization. The median number of apheresis was 3 (range, 1-6). The median yield of PBSC collections was 3.41 (0.13-38.11) × 10(6) CD34(+) cells/kg. Thirty-four (77.3 %) patients had successful collections defined as at least 2 × 10(6) CD34(+) cells/kg. The rate of successful collections was not different between the two underlying diseases (79.3 % in lymphoma and 73.3 % in MM). Of the entire cohort, 38 (86.4 %) of patients went on to receive an autologous transplant. Previous long-term use of high-risk drugs (4 cycles use of alkylating agents, platinum-containing agents, or thalidomide) (HR 10.8, 95 % CI 1.1-110.0, P = 0.043) and low platelet count (100 × 10(9)/L) 1 day before the first apheresis (HR 27.9, 95 % CI 2.9-273.7, P = 0.004) were independent prognostic factors for predicting failure of PBSC re-mobilization using plerixafor and G-CSF. In conclusion, re-mobilization using plerixafor and G-CSF showed a success rate of 77.3 % in patients with lymphoma or MM who experienced prior failure of PBSC mobilization, and the majority of them underwent autologous transplant. Therefore, plerixafor-based re-mobilization was an effective method in poor mobilizers.

Background: Imatinib mesylate (IM) discontinuation is under active investigation in chronic myeloid leukemia-chronic phase (CML-CP) patients with undetectable minimal residual disease (UMRD). However, limited data exist on the long-term outcomes following IM discontinuation in patients treated with frontline IM therapy. Methods: We consecutively enrolled patients with CML-CP who discontinued IM after achieving UMRD for ≥12 months between June 2009 and January 2013. Results: Nineteen patients (8 male, 11 female) were included. After IM discontinuation, 14 patients (74%) lost UMRD after a median of 4.0 months. Of the 14 patients with molecular relapses, 12 (86%) relapsed within the first 9 months after IM discontinuation and 2 (14%) relapsed at 20.5 and 22.8 months, respectively. No molecular relapse was observed after 2 years of IM discontinuation. With a median follow-up of 58.1 months (range 23.0-66.5), the estimated UMRD persistence rate at 5 years was 23.7%. IM was readministered in all patients with molecular relapse, and 12 patients (86%) reachieved UMRD at a median of 5.3 months. A high-risk Sokal score, delayed UMRD achievement and short-term IM therapy were significantly associated with molecular relapse. Conclusion: These findings suggest that IM discontinuation in patients who achieved UMRD after frontline IM therapy resulted in favorable long-term outcomes in terms of safety and feasibility.

Introduction T-cell lymphoma is a group of heterogeneous diseases with various clinical behaviors and treatment outcomes, representing 10-15% of non-Hodgkin lymphomas. Owing to its rarity and heterogeneity, the standard treatment approach for T-cell lymphoma is still not established. Accordingly, conventional chemotherapy regimens adapted from B-cell lymphoma treatment has been used for T-cell lymphoma. However, their outcome is still not satisfactory, and there are limited data representing the real-world situation in terms of clinical features and treatment outcomes. Given the incidence of T-cell lymphoma is relatively higher in Asian than Western countries; a comprehensive registry study focusing on Asian patients with T-cell lymphoma could be helpful for better understanding of T-cell lymphoma as well as the development of more effective treatment strategy. Methods We performed a multi-national, multi-center, prospective registry study for patients with T-cell lymphoma and enrolled patients between 01-March-2016 and 31-January-2019. All patients received chemotherapy with curative intent after diagnosis, and were pathologically diagnosed with T-cell lymphoma according to the 2008 World Health Organization classification of lymphoid neoplasms. Patients belonged to any one of following clinical situations could be enrolled: (1) newly diagnosed, treatment-naïve patients; (2) patients who started treatment or completed treatment; (3) relapsed or refractory patients. After we enrolled the planned number of patients (n = 500), we analyzed clinical features and treatment outcomes. Results Out of 500 patients enrolled from nine Asian countries (Korea, China, Taiwan, Singapore, Indonesia, Bangladeshi, Vietnam, Malaysia, and Philippines), 490 patients were analyzed because 10 patients with insufficient information were excluded. The median age was 59 years (range, 20-85), male patients (59%) were predominant compared to female patients (41%). Extranodal NK/T-cell lymphoma (ENKTL) was the most common (28%) and angioimmunoblastic T-cell lymphoma (AITL) was the second common (24%). Peripheral T-cell lymphoma, not-otherwise specified (PTCL-NOS, 20%) and ALK+/- anaplastic large cell lymphoma (ALCL, 16%) were also major subtypes of T-cell lymphoma. The proportion of stage IV was 40%, however, the distribution of stage was different between ENKTL and nodal T-cell lymphomas such as PTCL-NOS. The CHOP (Cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens accounted for the mainstay of primary treatment for nodal T-cell lymphoma whereas non-anthracycline-based chemotherapy regimens such as SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) and GemOx-L (gemcitabine, oxaliplatin, and L-asparagainase) were mainly used for ENKTL. The overall survival of ENKTL was not significantly different from that of PTCL-NOS, AITL and ALK+/- ALCL. Conclusions Our study showed the distribution of T-cell lymphoma subtypes and tumor burdens at the time of diagnosis in Asian countries. Although clinical features of ENKTL are different from that of nodal T-cell lymphomas consisting of PTCL-NOS, AITL and ALK+/- ALCL, and the different types of treatment were used, survival outcome of patients were not significantly different. This finding might be associated with improved treatment outcomes of ENKTL compared to the past. However, considering a substantial number of patients experienced treatment failure in patients with PTCL-NOS as well as ENKTL, more effective treatment strategy should be warranted. Figure Disclosures Kim: F. Hoffmann-La Roche Ltd: Research Funding; Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding.

Background The recent discontinuation clinical trials have demonstrated that IM discontinuation can be employed based on clinical study in patients who had enough IM therapy and undetectable molecular residual disease (UMRD) durations prior to IM discontinuation. Moreover, treatment rechallenge in patients with molecular recurrence lead a second deep molecular response, suggesting that IM discontinuation is safe. However, the issues on the definition of molecular relapse requiring treatment resumption and the occurrence of late relapse with a long-term follow-up after IM discontinuation are important. Therefore, here we analyzed the long-term follow-up results of the patients who lost UMRD after IM discontinuation Methods CP CML patients who were treated with IM for more than 3 years and had undetectable levels of BCR-ABL1 transcripts determined by quantitative reverse transcriptase polymerase chain reaction (PCR) for at least 2 years were eligible for KID study and in cases of MMR loss after 2 consecutive assessments, IM treatment was re-introduced. After IM resumption for MMR loss, the molecular response was evaluated every month until MMR was re-achieved and every 3 months thereafter. The second stop was permitted in the patients who were in second UMRD for at least 2 years. Results Between October 2010 and June 2015, a total of 126 patients (70 females, 56 males) were enrolled on KID Study, with a median age of 47 years (range, 18-82), the percentages of patients with low, intermediate and high Sokal risk scores were 33%, 25% and 15%, respectively with unknown Sokal risk scores in 27%. And the median time on IM therapy and the median duration of sustained UMRD prior to discontinuation were 83 months (range, 32-141) and 41 months (range, 22-131), respectively. After a median follow-up of 62.6 months (range, 4.9-100.8 months) after IM discontinuation, 83 patients (65.9%) lost UMRD. Among them, 56 (67.5%) patients lost MMR in 2 consecutive analyses. The other 27 (32.5%) patients who lost UMRD but not MMR exhibited different patterns of BCR-ABL1 kinetics: 8 patients spontaneously re-achieved UMRD after a median time of 2.8 months (range, 0.9-3.0 months), and 19 patient showed fluctuation of BCR-ABL1 transcript under the level of 0.1% on IS for a median 19 months (range, 3-34), and then spontaneously returned and maintained UMRD for a median 31 months (range, 2-64). Of 73 patients who lost MR4.0, the rate of MMR loss was 76.7%. Out of 56 patients with molecular relapse, 54 patients (except two patients who restart radotinib) were re-treated with IM, all patients (except one patient lost follow-up) re-achieved MMR at a median of 1.9 months (range, 0.0 - 5.4 months) after resuming treatment. Among them, two patients who re-achieving of MMR after resuming IM therapy lost MMR again; One patient who relapsed at 53.2 months after IM discontinuation, despite re-achieving MMR 1.4 later after IM restarting, suddenly progressed to blast crisis at 6 months after restarting IM and in spite of switching to dasatinib and ponatinib, she died. Another patient lost MMR at 7.4 months after IM discontinuation and re-achieved MMR 1.7 later after IM restarting, but progressed to AP on the assessment 32 months later. The patient switched to dasatinib and lost follow-up. Among the patients who maintained a second UMRD for at least 2 years after IM resumption, 23 patients entered into a second IM stop. With a median follow-up of 29.5 months (range, 9-63 months) since second IM stop, 15/23 patients (65%) lost MMR after a median 2.9 months (range, 1.8-30.7 months), which was similar to those of the first IM discontinuation [median 3.7 (range, 1.8-20.8 months)]. The patients who lost MMR were retreated with IM for a median of 24.5 months (range, 1.2-49.7 months); 14 patients re-achieved MMR and one patient was in therapy for 1.2 months. Conclusions Our results showed that 67.5% and 76.7% of patients who lost UMRD and MR4.0, respectively resulted in MMR loss, and the other patients were below MMR without re-treatment, suggesting loss of MMR can be chosen for treatment re-challenge. Overall, IM discontinuation could be applied with approximately 55% of probability of sustained MMR in the long term. In addition, we demonstrated that a second attempt might be possible. Further studies on the predictors to select patients for a trial of second stop are warranted. Disclosures Kim: Il-Yang co.: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; BMS: Research Funding; Novartis: Research Funding.

Background: Primary breast diffuse large B-cell lymphoma (DLBCL) has poor outcomes with frequent extranodal failures, particularly in the central nervous system (CNS). To prevent CNS recurrence, we designed this phase II trial that addressed feasibility and activity of conventional immunochemotherapy and CNS prophylaxis. Methods: This prospective, multicenter, single-arm phase II study was conducted to evaluate efficacy and safety of 6 cycles of conventional rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP) with the addition of 4 doses of intrathecal methotrexate (IT MTX; 12mg) during the first 4 cycles of R-CHOP in patients with primary breast DLBCL. Primary breast lymphoma was defined as lymphoma involving one or both breasts as a sole extranodal site regardless of specific nodal involvement status. The primary end-point was 2-year progression-free survival (PFS). Secondary end-points included cumulative incidence of CNS recurrence, overall survival (OS), and safety. All patients provided written informed consents and the study was registered at www.clinicaltrials.gov as #NCT01448096. Results: Thirty-three patients with primary breast DLBCL were enrolled between Jan 2012 and Jul 2017 in the Consortium for Improving Survival of Lymphoma (CISL) member institutions. The median age was 50 years at diagnosis (range, 29-75) and all were female. Right breast involvement was more common than left (18 [55%] vs 14 [42%]) and bilateral breast involvement was found in one patient (3%). Nodal involvement was present in 16 patients (49%), primarily in regional nodes (14 patients). Thus, the Ann Arbor stage was IE in 17 (52%), IIE in 13 (39%), IIIE in 2 (6.1%), and IV in 1 (3.0%). ECOG performance status was ≥2 in 1 patient (3%) and serum LDH level was elevated in 9 (27%). Therefore, the IPI and the CNS-IPI risk were mainly low (28 patients, 85%; respectively). No patients had CNS involvement at diagnosis. 32 (97%) of the 33 patients completed R-CHOP as planned, and the remaining patient withdraw a consent after four cycles of R-CHOP because of poor tolerance. CNS prophylaxis using IT MTX was completed as planned in 31 patients (94%), but it was discontinued in 2 patients because of patient's refusal. These 2 patients received two and three IT MTX doses, respectively. 32 patients (97%) were evaluable for treatment response and all these patients achieved a complete response. At the cutoff date of this analysis (10 Jul 2019), all patients who entered a follow-up phase had at least 24.0 months of follow-up. With a median follow-up duration of 46.1 months (IQR 31.1-66.8), 6 patients had experienced treatment failure and 3 of these died. The 2-year PFS and OS were 81.3% (95% CI, 67.7-94.8) and 93.5% (95% CI, 84.9-100.0), respectively (fig 1A and B). Of the 6 patients with treatment failure, diseases involved CNS with or without lymph nodes in 4 patients and breasts in 2 patients (1 ipsilateral and 1 contralateral breast recurrence). 3 of the four patients with CNS recurrence had isolated CNS recurrences (2 brain parenchymal and 1 meningeal disease) and one had a concurrent meningeal and lymph nodal recurrence. All 4 patients with CNS recurrence had received prophylactic IT MTX as planned by protocol. The 2-year cumulative incidence of CNS recurrence, taking into account the competing risk of death, was 12.5% (95% CI, 0.3-23.2, fig 1C). Although the number of patients with intermediate CNS-IPI risk was small (5 patients, 15%), the cumulative incidence of CNS recurrence did not differ significantly according to the CNS-IPI risk group. All CNS recurrences occurred within the first 2 years after enrolment. Toxicities were generally manageable during the R-CHOP and IT MTX treatment. No deaths as a result of toxicity occurred during treatment. Conclusion: Our study shows that conventional R-CHOP with prophylactic IT MTX is feasible in patients with primary breast DLBCL. However, given a substantially high rate of CNS recurrence, further studies to properly define the best strategy for CNS prophylaxis should be needed in patients with primary breast DLBCL. Figure 1 Disclosures Yoon: F. Hoffmann-La Roche Ltd: Research Funding. Kim:Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

Limited data exist on up-front autologous stem cell transplantation (ASCT) in extranodal natural killer/T cell lymphoma (ENKTL). Sixty-two patients (43 men and 19 women) with newly diagnosed ENKTL who underwent up-front ASCT after primary therapy were identified. Poor-risk characteristics included advanced stage (50%), high-intermediate to high-risk International Prognostic Index (25.8%), and group 3 to 4 of NK/T Cell Lymphoma Prognostic Index (NKPI, 67.7%). Pretransplant responses included complete remission in 61.3% and partial remission in 38.7% of patients, and final post-transplantation response included complete remission in 78.3%. Early progression occurred in 12.9%. At a median follow-up of 43.3 months (range, 3.7 to 114.6), 3-year progression-free survival (PFS) was 52.4% and 3-year overall survival (OS) was 60.0%. Patients with limited disease had significantly better 3-year PFS (64.5% versus 40.1%, P = .017) and OS (67.6% versus 52.3%, P = .048) than those with advanced disease. Multivariate analysis showed NKPI and pretransplant response were independent prognostic factors influencing survival, particularly NKPI in limited disease and pretransplant response in advanced disease. Radiotherapy was an independent factor for reduced progression and survival in patients with limited disease, but anthracycline-based chemotherapy was a poor prognostic factor for progression in patients with advanced disease. Up-front ASCT is an active treatment in ENKTL patients responding to primary therapy.

The hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen has been widely used for lymphoblastic lymphoma (LBL) as a primary treatment. However, there is few data about its treatment outcome in Asian patients. Thus, we conducted this study to evaluate the efficacy of hyper-CVAD induction and stem cell transplantation (SCT) consolidation in LBL patients. The treatment responses of 49 patients treated with the hyper-CVAD regimen were retrospectively analyzed in 13 institutions. Given 24 patients who responded to hyper-CVAD underwent consolidation treatment with SCT, overall survival (OS) and progression-free survival (PFS) of patients who received SCT were compared with patients who did not. The overall response rate was 79 %: 73 % (36/49) complete responses, 6 % (3/49) partial responses, and 4 % (2/49) induction deaths. The major limitation for the delivery of the planned hyper-CVAD cycles was hematological toxicity. Among 39 responders, 24 patients underwent autologous (n = 16) and allogeneic SCT (n = 8) consolidation. Their 3-year OS and PFS rates were 76 and 78 %, respectively, and there was no difference in survival outcomes between autologous and allogeneic SCT. However, 15 patients without SCT consolidation showed poorer PFS even though they all achieved complete response. Thus, only seven patients maintained their response at the time of analysis. In conclusion, the hyper-CVAD regimen is effective for remission induction in LBL, and SCT consolidation after hyper-CVAD induction produced better clinical outcomes than did continuation of hyper-CVAD.

This prospective study evaluated the efficacy and toxicity of intravenous busulfan and melphalan as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A total of 99 patients with MM, enrolled between January 2013 and March 2016, received intravenous busulfan (9.6 mg/kg) and melphalan (140 mg/m2) before ASCT. The median time to transplant was 6.2 months, and 90 (90.9%) patients underwent ASCT within 12 months of the diagnosis. The overall response rate after ASCT was 94.0%, including 43.5% with a stringent complete response/complete response, 27.3% with very good partial response, and 23.2% with partial response. The most common severe nonhematologic toxicity (grade 3 to 4) was infection (26.3%) and stomatitis (15.2%). Three (3.2%) patients developed veno-occlusive disease. No treatment-related mortality was observed. After a median follow-up of 26.1 months, the median progression-free survival was 27.2 months (range, 13.0 to 41.4 months) and median overall survival was not reached. In conclusion, a conditioning regimen of intravenous busulfan and melphalan was effective and tolerable. ClinicalTrials.gov. number: NCT01923935

Background Rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) is one of the effective chemotherapeutic regimens for patients with advanced stage marginal zone lymphoma (MZL). However, prognostic factors that affect the outcome of treatment for MZL are not well understood. Methods Between August 2006 and June 2013, patients with newly diagnosed stage III and IV MZL treated with R-CVP as a first-line therapy from 15 institutions were retrospectively analyzed. Patients' clinical and laboratory data at diagnosis were collected by review of medical records. Results A total of 80 patients were analyzed. Bone marrow involvement was observed in 30% cases. Twelve patients (15%) had nodal MZL, and 41.3% patients exhibited multiple mucosa-associated lymphoma tissue sites. Overall response rate was 91.3%, including 73.8% achieving complete response. Advanced MZL patients treated with R-CVP showed a 3-year progression-free survival (PFS) rate of 69.6%. Prognostic markers significantly affecting PFS in univariate analysis were platelet to lymphocyte ratio (PLR, 3.9 g/dL, P=0.008), and the International Prognostic Index (IPI) score (1 vs. 2–4, P=0.032). In multivariate analysis, only PLR (

We conducted a phase II trial of concurrent chemoradiotherapy (CCRT) followed by 2 cycles of L-asparaginase-containing chemotherapy for patients who were newly diagnosed with stages IE and IIE nasal extranodal NK/T cell lymphoma (ENKTL). CCRT consisted of 40-44 Gy of radiotherapy with weekly administration of 30 mg/m(2) of cisplatin for 4 weeks. Two cycles of VIDL (etoposide (100 mg/m(2)), ifosfamide (1,200 mg/m(2)), and dexamethasone (40 mg) from days 1 to 3, and L-asparaginase (4,000 IU/m(2)) every other day from days 8 to 20) were administered sequentially. CCRT yielded a 90 % overall response rate without significant side effects in 30 patients, including 20 patients with complete response (CR); however, two patients showed distant disease progression. After CCRT, VIDL chemotherapy showed an 87 % final CR rate (26/30). Although grade III or IV hematologic toxicity was frequent during VIDL chemotherapy, no treatment-related mortality was observed, and L-asparaginase-associated toxicity was manageable. With a median follow-up of 44 months, 11 patients showed local (n = 4) and distant (n = 7) relapse or progression. The estimated 5-year progression-free and overall survival rates were 73 and 60 %, respectively. In conclusion, CCRT followed by L-asparaginase-containing chemotherapy is a feasible treatment for newly diagnosed stages IE/IIE nasal ENKTL.

This study was designed to evaluate the prevalence of chromosomal abnormalities and to identify the specific abnormalities associated with poor prognosis. A total of 2,474 patients whose conventional cytogenetics were available at the time of diagnosis were evaluated via a nationwide registry. Normal metaphase cytogenetics was observed in 2,012 patients (81.3%). Among the 462 patients with chromosomal abnormalities, there were 161 (34.8%) patients with hyperdiploidy, 197 (42.6%) with pseudodiploidy, 79 (17.1%) with hypodiploidy, and 25 (5.5%) with near-tetraploidy. Deletion 13 (Δ13) in metaphase was observed in 167 patients (6.8%). Fluorescent in situ hybridization (FISH) was carried out in 967 patients (39.1%), and 66 (13.7%) out of 482 and 63 (10.3%) out of 611 patients were positive for t(4;14) and del(17p), respectively. With a median follow-up duration of 25.1 months, the median overall survival (OS) was 51.2 months (95% confidence interval, 46.5-55.9 months). In univariate analysis, the following four chromosomal abnormalities were significantly associated with a poor survival outcome: Δ13, hypodiploidy, del(13q) in FISH, and del(17p) in FISH. In the subsequent multivariate analysis, in which del(13q) and del(17p) in FISH were excluded due to a relatively low number of patients, Δ13 and hypodiploid status were independently associated with a poor survival outcome after adjusting for important clinical factors, including age, sex, performance, beta2-microglobulin, albumin, and lactate dehydrogenase (LDH). Using conventional metaphase cytogenetics, we confirmed that both Δ13 and hypodiploid status were robust poor prognostic factors. The metaphase karyotyping should remain the primary cytogenetic tool and an essential investigation for risk stratification in newly diagnosed multiple myeloma patients.

Background We investigated the clinical features and treatment outcomes of patients with mantle cell lymphoma (MCL) in Korea. Methods We retrospectively analyzed the clinical characteristics and prognosis of 131 patients diagnosed with MCL between January 2004 and December 2009 at 15 medical centers in Korea; all patients received at least 1 chemotherapeutic regimen for MCL. Results The median age for the patients was 63 years (range, 26-78 years), and 77.9% were men. A total of 105 patients (80.1%) had stage III or IV MCL at diagnosis. Fifty-two patients (39.7%) were categorized with high- or high-intermediate risk MCL according to the International Prognostic Index (IPI). Eighteen patients (13.7%) were in the high-risk group according to the simplified MCL-IPI (MIPI). The overall incidence of extranodal involvement was 69.5%. The overall incidence of bone marrow and gastrointestinal involvements at diagnosis was 41.2% and 35.1%, respectively. Cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab were used frequently as the first-line treatment (41.2%). With a median follow-up duration of 20.0 months (range, 0.2-77.0 months), the overall survival (OS) at 2 years was 64.7%, while the event-free survival (EFS) was 39.7%. Multivariate analysis showed that the simplified MIPI was significantly associated with OS. However, the use of a rituximab-containing regimen was not associated with OS and EFS. Conclusion Similar to results from Western countries, the current study found that simplified MIPI was an important prognostic factor in Korean patients with MCL.

Purpose To identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies. Materials and Methods Three hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled. Results The overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) ≥2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (≥4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity. Conclusion We concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole.

Background Interim 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan may predict outcomes in patients with diffuse large B-cell lymphoma (DLBCL). However, overall accuracy in predicting treatment outcomes on adopting 5-point Deauville score (DS) was considerably low in DLBCL because of mainly low positive predictive value of interim PET-CT scans. This suggested that additional tool might be needed to more accurately predict treatment outcomes. International prognostic index (IPI) was greatly associated with outcomes for DLBCL and considered to reflect biologic aggressiveness of DLBCL. Thus, we hypothesized that combined assessments using DS on interim PET-CT scan and baseline IPI might improve the prediction of treatment outcomes in DLBCL patients. In this study, we aimed to establish the risk predicting model integrating DS on interim PET-CT as an estimate of early metabolic response and baseline IPI as a predictor of biologic aggressiveness in patients with newly diagnosed DLBCL. Methods In this retrospective cohort study, we consecutively enrolled patients with newly diagnosed DLBCL. Patients were eligible if they were histologically confirmed with DLBCL from Jan 2007 to June 2016, received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), and had PET-CT scan data at baseline and at interim after 3 cycles of R-CHOP. Primary CNS or transformed DLBCLs were excluded. Interim PET-CT was assessed using 5-point DS and four point or higher was regarded as positive. All PET-CT scans were assessed by 2 experienced nuclear medicine physicians, who were masked to treatment outcomes of the patients. Discrepant interpretations between 2 nuclear medicine physicians were resolved by consensus through mutual discussion. Results A total of 316 patients were screened for eligibility. Ninety-six patients were excluded from the analysis due to following reasons: unavailable baseline (n=9) or interim PET-CT scans (n=48), early death before interim PET-CT (n=16), Primary CNS or transformed DLBCLs (n=15), and insufficient medical records (n=8). Thus, 220 patients were analyzed. Median age was 64 years (range, 19-87) and 132 (60%) were male. Based on the IPI risk, patients were classified as the low or low-intermediate (LI; N=126, 57%), and high-intermediate (HI) or high (N=94, 43%) groups. Interim DS was determined as 1 (n=67, 30.5%), 2 (n=65, 29.5%), 3 (n=39, 17.7%), 4 (n=36, 16.4%), and 5 (n=13, 5.9%). With a median follow-up of 56.6 months (IQR 36.0-71.8), 5-year progression-free survival (PFS) rate was 65.2% (95% CI, 58.1-72.3) and overall survival (OS) rate was 69.9% (95% CI, 63.2-76.6). Interim DS (1-3 vs 4-5) and the IPI (low-LI vs HI-high) were independently associated with PFS (for interim DS of 4-5, hazard ratio [HR], 2.96 [95% CI, 1.83-4.78], P < 0.001; for HI-high IPI, HR, 4.84 [2.84-8.24], P < 0.001) and OS (for interim DS of 4-5, HR, 2.98 [1.79-4.98], P < 0.001; for HI-high IPI, HR, 5.75 [3.14-10.51], P < 0.001) in the multivariate analysis. We stratified patients into 3 groups based on the risk of progression: Low (low-LI IPI and interim DS 1-3), Intermediate (low-LI IPI with interim DS 4-5, or HI-high IPI with interim DS 1-3), and High (HI-high IPI and interim DS 4-5) risk groups. The risk stratification model showed a significant association with PFS (for low risk vs intermediate risk, HR 3.98 [95% CI, 2.10-7.54], P Conclusion Combining interim DS with baseline IPI can improve risk stratification in patients with newly diagnosed DLBCL. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: We successfully identified a subset of CD11b+ monocytes expressing CX3CR1, the only receptor of fractalkine (Fkn; CX3CL1), in G-CSF mobilized peripheral blood stem cell collection (PBSC). We found that Fkn-treated CD11b+CX3CR1+ monocytes express pigment epithelium-derived factor (PEDF) once Fkn activates Fkn/CX3CR1 signaling. PEDF is a glycoprotein, which belongs to the serpin family and involves various physiologic processes such as angiogenesis, cell proliferation, and survival. In this study, we investigate the role of PEDF and its mechanism of action in promoting angiogenesis. Materials andmethods: To mobilize mononuclear cells (MNCs) including CD11b+CX3CR1+ monocytes into peripheral blood (PB), heathy donors were subcutaneously injected with G-CSF (10μg/kg) for 5 days. Apheresis MNCs were collected from donor PB using a COBE spectra cell separator (COBE, Lakewood, CO) 5 days after daily G-CSF injection. Then, CD11b+CX3CR1+ cells were isolated with a MoFlo™ XDP Cell Sorter (Beckman Coulter, Brea, CA). Human umbilical vein endothelial cells (HUVECs) were isolated from human cords and cultured at 37 °C in 5% CO2 on top of collagen in four different settings: (1) untreated (HUVECs alone) (2) VEGF (1ng/mL) treated HUVECs; (3) PEDF (3,30 and 300 ng/mL) treated HUVECs; (4) VEGF (1ng/mL)+PEDF (3,30 and 300 ng/mL) treated HUVECs. To assess dose-dependency, PEDF was administered at different dosages (0, 3, 30 and 300 ng/mL) for 7 days in either the presence or absence of VEGF (1ng/mL). HUVEC growth areas were measured by image J. Results: CD11b+CX3CR1+ monocytes were found at 19.6±3.58% of total MNCs in human G-CSF mobilized PBSC. Fractalkine treatment (50ng/mL for 30 minutes) of these monocytes promoted endothelial cell proliferation of HUVECs and increased PEDF expression according to the angiogenic protein array results. Administration of PEDF inhibitor significantly decreased HUVEC proliferation and vascular structure formation compared to the control group (p Disclosures No relevant conflicts of interest to declare.

Background: In RERISE phase 3 study, radotinib demonstrated significantly higher and faster rates of major molecular response (MMR) than imatinib in patients with newly diagnosed CML-CP. By 36 months follow up, MMR (BCR-ABL1IS ≤ 0.1%) and MR4.5 (BCR-ABL1IS ≤ 0.0032%) in radotinib 300 mg twice daily (bid) were higher than imatinib group. Also, early molecular response (EMR) at 3 months could predict better long term outcomes in both radotinib and imatinib groups. Here, authors updated 48 months long-term benefits and risks of 300mg bid and imatinib 400mg qd from RERISE phase 3 study (NCT01511289). Methods: RERISE study was randomized trial of radotinib 300 mg bid (n=79), radotinib 400 mg bid (n=81), or imatinib 400 mg once daily (qd) (n=81) in patients with newly diagnosed CML-CP. We evaluated long-term MMR and MR4.5, overall survival (OS), and progression-free survival (PFS) including safety data by 48 months. Results: At the study completion, 53% of patients with radotinib and 44% of patients with imatinib treated were remained. MMR and MR4.5 continued to be higher in patients receiving radotinib 300 mg bid compared with imatinib 400mg qd (Table). Especially, MMR rate by 48 months was significantly higher for radotinib compared to imatinib (76% vs 56%; P=0.0070, Figure). Also, early molecular response (EMR) at 3 months were observed in 86% of patients in the radotinib 300 mg bid group and 68% in the imatinib group (P = 0.0179). More patients treated with radotinib 300mg bid who had EMR at 3 months achieved MMR and MR4.5 by 48 months: 84% and 53% in the radotinib 300 mg bid group and 71% and 44% in the imatinib group, respectively. 48 months estimated OS and PFS rate were not significantly different in two groups (99% vs 94%; P=0.3224, 97% vs 94%; P=0.4328). Treatment failure was lower in radotinib group compared with imatinib group (Table). The safety profiles were consistent with those previously reported and most of adverse events (AEs) developed within 12 months. No new or unexpected safety events were reported in both arms by 48 months and no serious CVE related with radotinib reported. Conclusions: With a minimum 48 months follow-up, radotinib continued to demonstrate higher rates of MMR and MR4.5 than imatinib in newly diagnosed CML-CP. Also, these responses with radotinib were earlier and deeper compared with imatinib. Up to 48 months, no new and serious safety events related with radotinib reported. These results demonstrate that radotinib may have higher possibility of treatment- free remission (TFR) on frontline therapy as well as it can be one of the standards of care in newly diagnosed CML-CP. Figure. Figure. Disclosures Bunworasate: IL-YANG: Research Funding. Comia:IL-YANG: Research Funding. Mun:IL-YANG: Research Funding. Caguioa:IL-YANG: Research Funding. Kim:Pfizer: Research Funding; Novartis: Research Funding; BMS: Research Funding; Ilyang: Research Funding.

In contrast to the well known immunostimulatory roles of IL-12, little has been known about its immunosuppressive roles. In the present study, IL-12-activated lymphocyte-mediated macrophage apoptosis was investigated by employing murine lymphocyte/macrophage cocultures. IL-12-activated lymphocytes and their culture supernatants induced an inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) synthesis in macrophages. The NO synthesis was markedly inhibited by blocking antibodies to IFN-γ and TNF-α, suggesting the key role of these lymphocyte cytokines in mediating the NO synthesis. The endogenously produced NO inhibited macrophage proliferation, and induced apoptosis in concordance with the accumulation of p53, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and DR5, and the activation of caspase-3, processes that were inhibited by N(G)-monomethyl-l-arginine, aminoguanidine (NO synthase inhibitors) and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (an NO scavenger). These results were further supported by the findings obtained from the experiments employing IFN-γ-knockout and iNOS-knockout mice. Our study demonstrated a novel, non-contact-dependent mechanism of macrophage suppression by IL-12-activated lymphocytes: induction of growth inhibition and apoptosis of macrophages due to endogenous NO synthesis induced by cytokines secreted from IL-12-activated lymphocytes.

We conducted a retrospective analysis of lenalidomide with dexamethasone for patients with relapsed/refractory multiple myeloma (RRMM) who were treated within the Korean patient access program. Lenalidomide has been approved for RRMM for several years in Europe and North America, but has not been accessible to Asian patients in the past. Between 2008 and 2012, 110 patients from 20 hospitals were enrolled. The overall response rate (ORR) was 43.6 % with 15.4 % of very good partial response (VGPR) or better. The median time to progression (TTP) in this heavily pretreated patient population was 8.0 months, and median overall survival (OS) was 23 months. Hematologic toxicities, fatigue, anorexia, and constipation were the most common adverse events. The number of previous treatment lines, previous exposure to thalidomide, refractoriness to thalidomide and bortezomib, pretreatment white blood cell count (WBC), platelet count, t(14;16), and 17p deletion were significant prognostic factors for TTP, and creatinine clearance, refractoriness to thalidomide and bortezomib, performance status, platelet count, and 17p deletion were significant for OS in univariate analysis. In multivariate analysis, WBC and platelet count were significant prognostic factors for TTP and performance status for OS. For Korean myeloma patients, lenalidomide showed considerable efficacy, and toxicities were comparable to the data published in Europe and North America.

Several studies have suggested the possibility of a prognostic relationship between Epstein–Barr virus (EBV) and diffuse large B-cell lymphoma (DLBCL). The clinical outcome of EBV-associated DLBCL is not clear, especially since the introduction of rituximab. We retrospectively analyzed 222 elderly patients (≥50 years) with DLBCL who received R-CHOP chemotherapy and evaluated the state of EBV-encoded RNA-1 (EBER). Eighteen cases (8.1%) were EBER-positive (+). After a median of six cycles of R-CHOP chemotherapy, the response rate (≥partial response) was 72.2% (13/18) in the EBV (+) patients and 90.2% (184/204) in the EBV (−) DLBCL patients (P = 0.021). Four of 18 (22.2%) EBV (+) DLBCL patients received two or fewer cycles of R-CHOP chemotherapy. R-CHOP chemotherapy was also interrupted early more frequently compared with the EBV (−) group (2.5%) (P = 0.00). At a median follow-up of 32.8 months, there was no significant difference in the overall survival between the groups (P = 0.627). The EBV (+) DLBCL patients with early interruption of R-CHOP chemotherapy showed a trend toward a high EBV-DNA titer (≥1,000 copies/mL) (P = 0.091). The results suggest that the EBV (+) tumoral status of elderly DLBCL patients who undergo R-CHOP chemotherapy does not predict their survival but that their EBV status may contribute to the early interruption of R-CHOP chemotherapy. Am. J. Hematol. 88:774–779, 2013. © 2013 Wiley Periodicals, Inc.

Azacitidine is recommended for patients with higher-risk myelodysplastic syndromes (MDS) who are not eligible for intensive therapy or for patients with lower-risk MDS who have thrombocytopenia or neutropenia or have anemia that is unresponsive to other therapies. However, standard treatment with azacitidine has not been optimized and many issues about the use of azacitidine remain unresolved. The use of azacitidine is expanding rapidly, but limited comparative clinical trial data are available to (i) define the optimal use of azacitidine in patients with higher-risk MDS or around the time of allogeneic hematopoietic stem cell transplantation, (ii) identify those patients with lower-risk MDS who may benefit from treatment, and (iii) guide physicians on alternative therapies after treatment failure. Increasing evidence suggests that the clinical features, prognostic factors, and cytogenetic profiles of patients with MDS in Asia differ significantly from those of patients in Western countries, so the aim of this review is to summarize the evidence and provide practical recommendations on the use of azacitidine in patients with MDS in the Republic of Korea. Evidence considered in this review is based on published clinical data and on the clinical experience of an expert panel from the acute myeloid leukemia/MDS Working Party of the Korean Society of Hematology.

To examine the role of high-dose melphalan therapy with autologous stem cell transplantation (HDM/ASCT) in the final outcomes of multiple myeloma (MM) patients receiving bortezomib-containing induction therapy (IT), we analyzed relationships between quality of response after IT including bortezomib or HDM/ASCT and survival. In total, 92 MM patients who received IT with bortezomib followed by HDM/ASCT were enrolled. The median follow-up was 28.0 months. Three-year progression-free survival (PFS) and overall survival (OS) were 41.1 and 72.0 %, respectively. A complete response (CR) after HDM/ASCT was a strong prognostic factor for PFS and OS (p = 0.002 and 0.001, respectively). Additionally, out of 67 patients who failed to achieve CR after IT, 36 (53.7 %) patients achieved CR after HDM/ASCT. PFS and OS in patients with CR after additional HDM/ASCT were similar to those in patients who had already achieved CR after IT. However, achievement of at least very good partial response following IT with bortezomib failed to improve PFS and OS (p = 0.35 and 0.11, respectively). Thus, we conclude that post-HDM/ASCT CR is the best prognostic factor for both PFS and OS regardless of response to bortezomib. Therefore, HDM/ASCT remains an important therapy in MM patients even after introduction of bortezomib IT.

Patients with cancer have been associated with increased risk of recurrent venous thromboembolism (VTE). However, data on recurrent VTE in Asian patients with advanced solid cancers are limited. Methods This study was conducted using data from the Korean VTE registry, which is an ongoing, prospective database. Patients were eligible if they had diagnosed with recurrent/metastatic solid cancers and initiated anticoagulation therapy following index VTE diagnosis. A total of 449 patients were included in this analysis. The 6-month and 12-month cumulative incidences of recurrent VTE were 20.6% and 27.0%, respectively. Isolated pulmonary embolism (PE) (51%) was the most predominant recurrence type. Pancreas as the primary tumor site, poor Eastern Cooperative Oncology Group performance status at the time of index VTE diagnosis, and initial presentation with PE were independent risk factors for developing recurrent VTE. With a median follow-up of 29.1 months (range, 1.0-91.2), the median overall survival (OS) was 11.9 months. Patients with recurrent VTE had a significantly worse OS than those without recurrent VTE (median, 8.4 vs. 13.0 months, respectively; P = 0.001). In conclusion, the incidence of recurrent VTE in Korean patients with advanced solid cancers is comparable with Caucasian patients. Pancreas as the primary tumor site, poor performance status, and initial presentation with PE are independent recurrent VTE risk factors in advanced cancer VTE patients. Additionally, OS is adversely affected by recurrent VTE.

Although recent studies have suggested that cessation of imatinib (IM) in chronic myeloid leukemia patients can be associated with sustained response, further validation is needed to explore predictive factors. In a prospective, multicenter study, chronic phase patients were eligible for cessation of IM therapy after more than 3 years if they had no detectable BCR-ABL1 transcript for at least 2 years. A total of 48 patients with a median age of 47 years (19-74 years) were enrolled. Twenty patients received IM for post-transplant relapse. After a median follow-up of 15.8 months (1.4-28.2 months) after IM discontinuation, nine of the non-transplant group lost undetectable molecular residual disease (UMRD) and major molecular response (MMR), whereas none of the 20 patients in the transplant group experienced UMRD loss. Probabilities for sustained MMR and UMRD were 64.4% and 66.3% in the non-transplant group, respectively. Of nine patients re-treated with IM, eight patients re-achieved MMR at a median of 1.7 months (0.9-2.8 months). Seven of these patients re-achieved UMRD at a median of 5.6 months (2.8-12.1 months). Previous transplantation, IM duration, and UMRD duration were significantly associated with sustained molecular responses. Our data strongly suggest that immunological control contributes to sustained suppression of residual leukemia cell expansion and that IM can be safely discontinued in patients with post-transplant relapse.

The aim of the Korean Imatinib Discontinuation Study was to identify predictors for safe and successful imatinib discontinuation. A total of 90 patients with a follow-up of ≥12 months were analyzed. After a median follow-up of 26.6 months after imatinib discontinuation, 37 patients lost the major molecular response. The probability of sustained major molecular response at 12 months and 24 months was 62.2% and 58.5%, respectively. All 37 patients who lost major molecular response were retreated with imatinib therapy for a median of 16.9 months, and all achieved major molecular response again at a median of 3.9 months after resuming imatinib therapy. We observed newly developed or worsened musculoskeletal pain and pruritus in 27 (30%) patients after imatinib discontinuation. Imatinib withdrawal syndrome was associated with a higher probability of sustained major molecular response (P=0.003) and showed a trend for a longer time to major molecular response loss (P=0.098). Positivity (defined as ≥ 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before imatinib discontinuation were associated with a higher probability of sustained major molecular response. Our data demonstrated that the occurrence of imatinib withdrawal syndrome after imatinib discontinuation and longer duration of imatinib were associated with a lower rate of molecular relapse. In addition, minimal residual leukemia measured by digital polymerase chain reaction had a trend for a higher molecular relapse. (Trial registered at ClinicalTrials.gov: NCT01564836).

There has been controversy surrounding Waldeyer’s ring (WR), especially focused on the question of whether it should be regarded as a nodal or an extranodal site. We conducted retrospective analyses of marginal zone B cell lymphomas involving WR (WR-MZLs) to observe their clinical features and prognosis, with specific regard to the nodal-or-extranodal question. A total of 52 patients with histological diagnosis of WR-MZL were retrospectively analyzed. The most common involvement site was the tonsil (40.4 %). Ann Arbor stage III/VI disease was present in 48.1 % (25 of 52). The response rate of the 27 stage I/II patients was 88.9 %, with 21 complete remissions and three partial remissions. The median time to progression (TTP) was 3.7 years (95 % CI 2.5–4.9 years). The estimated 5-year TTP and overall survival rates were 39.4 and 90.5 %, respectively. In a comparison with the historical data regarding extra-WR MALT lymphoma and nodal MZL (N-MZL), MALT lymphoma showed better TTP results than did WR-MZL and N-MZL (P

Purpose: Primary thyroid marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type (pTY-MZL) is an extremely uncommon form of lymphoma. Due to its rarity, the natural history and optimal treatment modality for this disease have yet to be clearly established. Methods: A total of 27 patients with histologically confirmed pTY-MZL were retrospectively analyzed. Results: The median age of our subjects was 53 years (range 25–82). This study involved 17 females (63.0%) and 10 males (37.0%). Twenty-four out of 27 patients (88.9%) initially presented with localized disease, defined by Ann Arbor stage I/II. Bone marrow involvement was detected in 8.3% of the patients (2 patients), and 91.7% of the patients (25 of 27) were categorized into the low or low-intermediate risk group, according to the International Prognostic Index criteria. Accompanying Hashimoto’s thyroiditis was detected in 72% of the patients, whereas thyroglobulin antibody levels were elevated in 70% of the patients. Twenty-six patients were treated with surgery, radiotherapy or chemotherapy, and 25 patients achieved complete remission. During the follow-up period, only 2 patients evidenced progression, and no deaths occurred over the course of the study. Conclusion: pTY-MZL tends to be an indolent disease. However, unlike other mucosa-associated lymphoid tissue site MZLs, pTY-MZL was well controlled via several treatment modalities, and the patients’ responses were sustained for a prolonged period.

Ethnic and regional differences in the epidemiology and pathological aspects of Hodgkin’s lymphoma (HL) between Western and Asian patients may be associated with differences in clinical features and prognosis. We retrospectively analyzed the clinical and histopathological characteristics, therapeutic outcomes, and prognostic factors of 539 HL patients treated at 16 centers in Korea. We found that the incidence of histological subtypes of HL in Korea was similar to that in Western and other Asian countries. However, the incidence peaked between 16 and 30 years of age, unlike the bimodal age distribution seen in Western countries. In patients with stage I–IIA non-bulky disease, the complete response (CR) rate was similar between combined modality therapy and chemotherapy alone (93% vs. 84%, P = 0.44), and there was no difference in relapse-free survival (RFS) and overall survival (OS). Patients with stage I–II disease plus unfavorable factors and those with advanced-stage disease treated with combination chemotherapy regimens had an overall CR rate of 77%, with no difference between doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and non-ABVD regimens (77.2% vs. 76.8%, P = 0.95). Among those patients who achieved final CR, there was no significant difference in RFS or OS between those who achieved interim CR and PR. Only the presence of B symptoms was independently predictive of a shorter RFS. Age > 45 years, Eastern Cooperative Oncology Group 2–4, and B symptoms were independent risk factors for death. Although the incidence of HL was lower in Korea than in Western countries, the distribution of morphological subtypes, treatment outcomes, and patient prognosis were similar.

There are few treatment options for patients with non-Hodgkin lymphoma (NHL) who experienced progression after high-dose chemotherapy (HDC) with autologous stem cell transplantation (auto-SCT). The role of allogeneic stem cell transplantation (allo-SCT) in these patients has not been clarified yet. In this study, we report clinical outcomes of allo-SCT in patients with NHL who experienced progression after HDC with auto-SCT. Patients were enrolled from seven hospitals in Korea. A total of 38 patients were included: 18 patients (47.4%) underwent myeloablative conditioning and 20 patients (52.6%) reduced intensity conditioning. Overall response rate was 73.3%. Median event-free survival was 6.3 months. Median overall survival (OS) was 19.0 months. Estimated 5-year survival rate was 35.0%. Acute graft-versus-host disease developed in 13 patients (34.2%). Transplant-related mortality (TRM) was 21.1% (eight patients). Ann Arbor stage (p = 0.022), performance status (p

The current retrospective study investigated the incidence of lymphocytosis following second-line dasatinib therapy in chronic myeloid leukemia (CML) and analyzed the clinical factors predictive of the development of lymphocytosis, as well as association with treatment outcomes. Fifty CML patients who failed imatinib treatment and received dasatinib were included from nine centers in the Republic of Korea. The cumulative incidence of lymphocytosis was assessed, and cytogenetic and molecular response, treatment failure, loss of response, progression to advanced disease, and survival were evaluated and analyzed according to the development of lymphocytosis. After a median of 17 months of dasatinib therapy, 23 patients (46%) developed lymphocytosis (median onset 4 months). No clinical predictive factor for the development of lymphocytosis was found. The group presenting lymphocytosis showed a higher complete cytogenetic response (CCyR; 78.3 vs. 29.6%, P = 0.001) and major molecular response (MMR; 52.2 vs. 14.8%, P = 0.005), in comparison to the group without presenting lymphocytosis. The development of lymphocytosis after dasatinib was identified as a favorable independent marker for predicting a CCyR (P = 0.002) or MMR (P = 0.003). Further study is necessary to identify which subset of lymphocytes was expanded and to reveal the exact mechanism by which dasatinib induces lymphocyte expansion.