Publications by authors named "Sang Kyun Sohn"

188 Publications

Prognostic impact of F-FDG PET/CT in patients with multiple myeloma presenting with renal impairment.

Int J Hematol 2021 Jan 21. Epub 2021 Jan 21.

Departments of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.

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 F-fluorodeoxyglucose (F-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 < 0.001; overall survival (OS), 42.2 months vs. not reached, P = 0.001]. On multivariate analysis, PET/CT positivity was significantly associated with PFS and OS in patients with RI. In conclusion, PET/CT is a reliable imaging technique for predicting survival outcomes in patients with MM with RI.
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http://dx.doi.org/10.1007/s12185-021-03079-wDOI Listing
January 2021

RNA sequencing as an alternative tool for detecting measurable residual disease in core-binding factor acute myeloid leukemia.

Sci Rep 2020 11 18;10(1):20119. Epub 2020 Nov 18.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.

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 < 6.3e-05 and P < 2.2e-13). The level of reduction of RUNX1-RUNX1T1 as measured by RNA-seq and qPCR were highly correlated (R = 0.74, P < 5.4e-05). A decision tree analysis, based on 3-log reduction of RUNX1-RUNX1T1 and cKIT-D816 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 < 0.08) and 2-year relapse incidence rates at 13%, 42%, and 67% (P < 0.05). On the other hand, although low residual allelic burden was common, it was not associated with long-term outcome, indicating that mutation clearance alone cannot be interpreted as MRD-negative. Overall, our study demonstrates that the clinical utility of RNA sequencing as a potential tool for MRD monitoring in fusion gene-driven AML such as RUNX1-RUNX1T1 AML.
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http://dx.doi.org/10.1038/s41598-020-76933-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674449PMC
November 2020

Hypomethylating agent-based post-transplant strategies to maximize the outcome of high-risk acute myeloid leukemia after allogeneic stem cell transplantation.

Expert Rev Hematol 2020 09 14;13(9):959-969. Epub 2020 Aug 14.

Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University , Daegu, South Korea.

Introduction: 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.

Areas Covered: 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.

Expert Opinion: 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.
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http://dx.doi.org/10.1080/17474086.2020.1804355DOI Listing
September 2020

Quantitative Assessment of Interim PET/CT Could Have More Prognostic Relevance than Visual Assessment for Predicting Clinical Outcome of Extranodal Diffuse Large B Cell Lymphoma.

In Vivo 2020 Jul-Aug;34(4):2127-2134

Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, School of Medicine, Chonnam National University, Hwasun, Republic of Korea

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<0.001). Visual assessment using the Deauville 5-PS did not predict survival outcomes in patients with one or more EN involvements in terms of OS and PFS.

Conclusion: The quantitative SUV-based assessment with iPET/CT was a significant prognosticator for long-term survival outcomes, especially in patients with one EN involvement.
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http://dx.doi.org/10.21873/invivo.12018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439899PMC
March 2020

Intravenous busulfan and melphalan versus high-dose melphalan as a conditioning regimen for early autologous stem cell transplantation in patients with multiple myeloma: a propensity score-matched analysis.

Leuk Lymphoma 2020 11 25;61(11):2714-2721. Epub 2020 Jun 25.

Seoul National University Hospital, Seoul, Republic of Korea.

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 ( = 0.995). With respect to non-hematologic toxicities, infections were more frequently reported in the BUMEL group ( < 0.001). Three patients who received BUMEL developed veno-occlusive disease (VOD), and all of them recovered without administration of defibrotide. In conclusion, BUMEL is an effective alternative conditioning regimen in terms of efficacy, but attention should be paid to toxicities.
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http://dx.doi.org/10.1080/10428194.2020.1783448DOI Listing
November 2020

Apparent diffusion coefficient as a valuable quantitative parameter for predicting clinical outcomes in patients with newly diagnosed primary CNS lymphoma.

Blood Res 2020 Jun;55(2):99-106

Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.

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; =0.001], Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (HR, 10.429; < 0.001), higher lactate dehydrogenase (LDH) levels (HR, 7.408; =0.001), and low ADC (HR, 0.273; =0.009) were associated with lower OS. We modified the conventional prognostic scoring system using low ADC, old age (>60 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.
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http://dx.doi.org/10.5045/br.2020.2020032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343555PMC
June 2020

COVID-19 transmission and blood transfusion: A case report.

J Infect Public Health 2020 Nov 13;13(11):1678-1679. Epub 2020 May 13.

Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jiph.2020.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218366PMC
November 2020

Clinical Effects of Hypomethylating Agents in Patients with Newly Diagnosed Myelodysplastic Syndrome Who Received DNA-Damaging Chemotherapy for Metastatic Breast Cancer.

J Breast Cancer 2019 Dec 5;22(4):647-652. Epub 2019 Nov 5.

Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, Kyungpook National University Cancer Research Institute, Kyungpook National University School of Medicine, Daegu, Korea.

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.
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http://dx.doi.org/10.4048/jbc.2019.22.e50DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933035PMC
December 2019

Favorable long-term survival using consolidation chemotherapy without allogeneic hematopoietic cell transplantation for acute myeloid leukemia with wild-type without -ITD.

Blood Res 2019 Sep 25;54(3):189-197. Epub 2019 Sep 25.

Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea.

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 (/-ITD) 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 and -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 /-ITD. Among the patients with /-ITD, 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 /-ITD group (=0.233). Among the intermediate-risk /-ITD patients, there was no survival benefit with allo-HCT (N=19) compared to consolidation chemotherapy (N=21; =0.372). In the multivariate analysis, the ELN risk group [hazard ratio (HR), 6.36; =0.019] and the achievement of CR (HR, 2.95; =0.017) were both identified as factors affecting OS of patients with newly diagnosed AML.

Conclusion: Among the AML patients, intermediate-risk /-ITD patients and favorable-risk patients showed similar OS rates. Our results suggested that allo-HCT might have limited clinical benefit for the intermediate-risk /-ITD patients. Well controlled studies are needed to confirm the current results.
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http://dx.doi.org/10.5045/br.2019.54.3.189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779939PMC
September 2019

Use of Droplet Digital Polymerase Chain Reaction for Detecting Minimal Residual Disease: A Prospective Multi-Institutional Study.

In Vivo 2019 Nov-Dec;33(6):2273-2280

Department of Internal Medicine, Chonnam National University, Hwasun Hospital, Hwasun, Republic of Korea.

Background/aim: Droplet digital polymerase chain reaction (ddPCR) is an exact method of measuring nucleic acids. The aim of this prospective study was to evaluate minimal residual disease (MRD) using ddPCR in chronic myeloid leukemia (CML) patients.

Patients And Methods: Between May 2013 and November 2014, CML patients treated with nilotinib were enrolled in our study. BCR/ABL1 transcripts levels were evaluated using ddPCR at the first time of complete molecular response (CMR). We enrolled 15 patients from 7 Institutions. The treatment period and median follow-up period were 45 months and 47 months, respectively.

Results: Patients with a high level of BCR/ABL1 transcript had a greater tendency to lose the CMR during the follow-up period (p=0.095). In addition, patients with a low level of BCR/ABL1 transcript showed a longer duration of CMR compared to those with a high level (p=0.032).

Conclusion: We found that ddPCR is a sensitive method for detecting MRD and that MRD could affect the duration of the treatment response.
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http://dx.doi.org/10.21873/invivo.11733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6899155PMC
March 2020

Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis.

Lancet Infect Dis 2019 09 6;19(9):988-1000. Epub 2019 Aug 6.

CureVac, Tübingen, Germany.

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<0·0001) in all patients, excluding those with non-Hodgkin B-cell lymphoma and chronic lymphocytic leukaemia. Humoral and cell-mediated immune responses persisted above baseline until month 13 in all strata and, as expected, vaccine was more reactogenic than placebo (within 7 days after vaccination pain was reported by 221 [79·5%] of 278 vaccine group participants and 45 [16·4%] of 274 placebo group participants; fatigue was reported by 162 [58·3%] of 278 vaccine group participants and 102 [37·2%] of 274 placebo group participants). Incidences of unsolicited or serious adverse events, potential immune-mediated diseases, disease-related events, and fatal serious adverse events were similar between the groups.

Interpretation: The immunocompromised adult population with haematological malignancies is at high risk for herpes zoster. The adjuvanted recombinant zoster vaccine, which is currently licensed in certain countries for adults aged 50 years and older, is likely to benefit this population.

Funding: GlaxoSmithKline Biologicals SA.
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http://dx.doi.org/10.1016/S1473-3099(19)30163-XDOI Listing
September 2019

Effect of Stem Cell Source and Dose on Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Idiopathic Aplastic Anemia: Data from the Korean Aplastic Anemia Trials.

Acta Haematol 2020 7;143(3):232-243. Epub 2019 Aug 7.

Division of Hematology and Cellular Therapy, Ulsan University Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea.

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 <31 years (p = 0.010) and prior platelet transfusion <86 U (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.
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http://dx.doi.org/10.1159/000501496DOI Listing
August 2020

Benefits of additional cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy compared to four cycles of VTD for newly diagnosed multiple myeloma.

Bone Marrow Transplant 2019 12 29;54(12):2051-2059. Epub 2019 Jul 29.

Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

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 < 0.001), but, the pre- and post-ASCT ≥ very good partial response (VGPR), and 2-year PFS were similar. Multivariate analysis revealed age, β-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.
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http://dx.doi.org/10.1038/s41409-019-0629-7DOI Listing
December 2019

Favorable Outcomes With Tumor Burden Reduction Following Administration of Hypomethylating Agents Before Allogeneic Hematopoietic Cell Transplantation in Patients With Higher Risk Myelodysplastic Syndrome.

Clin Lymphoma Myeloma Leuk 2019 07 11;19(7):e367-e373. Epub 2019 Apr 11.

Department of Hematology/Oncology, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address:

Introduction: 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.

Patients And Methods: 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).

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.clml.2019.03.016DOI Listing
July 2019

HMGCLL1 is a predictive biomarker for deep molecular response to imatinib therapy in chronic myeloid leukemia.

Leukemia 2019 06 16;33(6):1439-1450. Epub 2018 Dec 16.

Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.

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.
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http://dx.doi.org/10.1038/s41375-018-0321-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756062PMC
June 2019

Impact of Consolidation Cycles Before Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First Complete Remission.

Clin Lymphoma Myeloma Leuk 2018 12 29;18(12):e529-e535. Epub 2018 Aug 29.

Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea; School of Medicine, Kyungpook National University Hospital, Daegu, Korea. Electronic address:

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 < .001), and presence of chronic GVHD (HR = 0.45, P = .004).

Conclusion: One or two cycles of HDAC consolidation therapy led to better subsequent HCT outcomes compared to the no-consolidation therapy group.
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http://dx.doi.org/10.1016/j.clml.2018.08.010DOI Listing
December 2018

Efficacy and safety of blinatumomab treatment in adult Korean patients with relapsed/refractory acute lymphoblastic leukemia on behalf of the Korean Society of Hematology ALL Working Party.

Ann Hematol 2019 Jan 26;98(1):151-158. Epub 2018 Sep 26.

Pusan National University School of Medicine, Medical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea.

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.
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http://dx.doi.org/10.1007/s00277-018-3495-2DOI Listing
January 2019

Next-generation sequencing-based posttransplant monitoring of acute myeloid leukemia identifies patients at high risk of relapse.

Blood 2018 10 14;132(15):1604-1613. Epub 2018 Aug 14.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

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-HCT). 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-HCT allelic burdens in relapsed patients were higher than in nonrelapsed patients. Post-HCT mutations in relapsed patients all expanded at relapse. Assessment of variant allele frequency (VAF) revealed that overall VAF post-HCT (VAF-post-HCT) is associated with an increased risk of relapse (56.2% vs 16.0% at 3 years; < .001) and worse overall survival (OS; 36.5% vs 67.0% at 3 years; = .006). Multivariate analyses confirmed that VAF-post-HCT is an adverse prognostic factor for OS (hazard ratio [HR], 3.07; = .003) and relapse incidence (HR, 4.75; < .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.
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http://dx.doi.org/10.1182/blood-2018-04-848028DOI Listing
October 2018

Response to hypomethylating agents improves long-term outcomes for lower-risk patients with myelodysplastic syndrome in case-matched cohorts.

Ann Hematol 2018 Dec 2;97(12):2309-2317. Epub 2018 Aug 2.

Department of Hematology/Oncology, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, South Korea.

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 < 0.001). In the case-matched cohorts, HMA non-responder were associated with inferior OS rate in the multivariate analysis (hazard ratio 3.01, p = 0.001). Higher-risk groups by other clinical risk scoring systems among IPSS lower-risk patients showed an increased incidence of using HMAs. The OS rate of HMA responders among case-matched cohorts showed an improved OS rate similar to the BSC group.
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http://dx.doi.org/10.1007/s00277-018-3458-7DOI Listing
December 2018

Chemotherapy adherence is a favorable prognostic factor for elderly patients with multiple myeloma who are treated with a frontline bortezomib-containing regimen.

Yeungnam Univ J Med 2018 06 30;35(1):76-83. Epub 2018 Jun 30.

Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea.

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%, =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.
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http://dx.doi.org/10.12701/yujm.2018.35.1.76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784679PMC
June 2018

Comparative analyses of nilotinib versus high-dose imatinib versus sustained standard-dose imatinib in patients with chronic phase chronic myeloid leukemia following suboptimal molecular response to first-line imatinib.

Leuk Res 2018 07 7;70:100-105. Epub 2018 Jun 7.

Leukemia Research Institute, The Catholic University of Korea, Seoul, Republic of Korea; Department of Hematology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

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.
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http://dx.doi.org/10.1016/j.leukres.2018.06.002DOI Listing
July 2018

A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTKorea.

Cancer Med 2018 05 25;7(5):1814-1823. Epub 2018 Mar 25.

Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

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 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 rate was 56.2% (95% confidence interval, 44.0%-8.3%), and the median time to MR was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR , and MR 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.
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http://dx.doi.org/10.1002/cam4.1450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943463PMC
May 2018

Assessment of a new genomic classification system in acute myeloid leukemia with a normal karyotype.

Oncotarget 2018 Jan 22;9(4):4961-4968. Epub 2017 Dec 22.

Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

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 mutation, 10.7% (n = 42) with AML with mutated chromatin or RNA-splicing genes or both, 1.5% (n = 6) with AML with mutations, 13.5% (n = 53) with AML with biallelic mutations, 2.0% (n = 8) with AML with 72 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.
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http://dx.doi.org/10.18632/oncotarget.23575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797026PMC
January 2018

Phase 2 Study of an Intravenous Busulfan and Melphalan Conditioning Regimen for Autologous Stem Cell Transplantation in Patients with Multiple Myeloma (KMM150).

Biol Blood Marrow Transplant 2018 05 12;24(5):923-929. Epub 2018 Jan 12.

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

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/m) 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.
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http://dx.doi.org/10.1016/j.bbmt.2018.01.004DOI Listing
May 2018

No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome.

Korean J Intern Med 2018 Nov 15;33(6):1194-1202. Epub 2017 Dec 15.

Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea.

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.

Conclusion: 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.
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http://dx.doi.org/10.3904/kjim.2016.426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234402PMC
November 2018

The role of frontline autologous stem cell transplantation for primary plasma cell leukemia: a retrospective multicenter study (KMM160).

Oncotarget 2017 Oct 16;8(45):79517-79526. Epub 2017 Jun 16.

Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

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%, 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 ( < 0.001); the median OS of the four treatment groups were 2.9, 12.3, 14.1, and 31.1 months, respectively ( < 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.
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http://dx.doi.org/10.18632/oncotarget.18535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668064PMC
October 2017

Can we consider discontinuation of hypomethylating agents in patients with myelodysplastic syndrome : a retrospective study from The Korean Society of Hematology AML/MDS Working Party.

Oncotarget 2017 Oct 29;8(45):79414-79424. Epub 2017 May 29.

Department of Hematology-Oncology, Yeungnam University Medical Center, Yeungnam University School of Medicine, Daegu, South Korea.

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 ( < 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.
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http://dx.doi.org/10.18632/oncotarget.18258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668053PMC
October 2017

Benefits of hypomethylating therapy in IPSS lower-risk myelodysplastic syndrome patients: A retrospective multicenter case series study.

Leuk Res 2017 09 15;60:135-144. Epub 2017 Aug 15.

Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Republic of Korea. Electronic address:

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<0.001; LR-PSS, P<0.001). Hematologic improvement (HI) was observed in 279 patients (47.6%). OS differed by the achievement of HI (39.4% vs. 36.2%, P=0.067). The differences were significant only in patients of intermediate or high risk group by LR-PSS (P=0.034) or R-IPSS (P=0.018). In summary, IPSS lower-risk MDS included a broad range of prognosis, and hypomethylating therapy induced HI in approximately half of the patients. Achievement of HI was associated with longer survival, especially in patients with intermediate or high risk features by newer scoring systems. Hypomethylating therapy seems to have potential benefits in IPSS lower-risk MDS.
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http://dx.doi.org/10.1016/j.leukres.2017.08.004DOI Listing
September 2017

Distinctive clinical characteristics and favorable outcomes in patients with large granular lymphocytosis after allo-HCT: 12-year follow-up data.

Eur J Haematol 2017 Aug 30;99(2):160-168. Epub 2017 May 30.

Department of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.

An increase in large granular lymphocytes (LGL) is frequently seen in patients following allogeneic hematopoietic cell transplantation (allo-HCT) and it has been associated with better outcomes in some reports. We assessed 826 consecutive patients at our institution with over 12 years of follow-up for the occurrence of LGL lymphocytosis after allo-HCT. The 3-year cumulative incidence of LGL lymphocytosis was 14.5% with a median duration of over 3.5 years. The development of LGL lymphocytosis was strongly correlated with CMV viremia and GVHD. The clinical course of patients with LGL lymphocytosis after allo-HCT was indolent, with the majority of these patients not displaying any clinical signs or symptoms related to the LGL proliferation. LGL lymphocytosis was associated with better outcomes, including higher overall survival (OS 86.6% vs 44.7% at 3 years), lower non-relapse mortality (NRM 5.5% vs 30.4% at 3 years), and lower risk of relapse (8.9% vs 22.9% at 3 years). A time-dependent multivariable analysis confirmed the favorable impact of LGL lymphocytosis on OS and NRM, but not on the risk of relapse. In multivariable analysis, a longer duration of LGL lymphocytosis was associated with better OS and NRM. Improved immunomodulatory properties of these cells, regulating GVHD and infections, may explain the observed favorable outcomes of patients who developed LGL lymphocytosis following allo-HCT.
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http://dx.doi.org/10.1111/ejh.12899DOI Listing
August 2017

Improved prognostic stratification power of CIBMTR risk score with the addition of absolute lymphocyte and eosinophil counts at the onset of chronic GVHD.

Ann Hematol 2017 May 18;96(5):805-815. Epub 2017 Feb 18.

Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Department of Medicine, University of Toronto, 610 University Ave, Toronto, ON, M5G2M9, Canada.

The CIBMTR chronic graft-versus-host disease (cGVHD) risk score can be refined and improved for better prognostic stratification. Three hundred and seven consecutive patients diagnosed with cGVHD by the NIH consensus criteria were retrospectively reviewed and had the CIBMTR risk score applied and analyzed. The CIBMTR risk score was successfully validated in our cohort (n = 307). The 3-year overall survival (OS) rates in each risk group (RG) were 82.5 ± 11.3% (RG1), 79.4 ± 3.0% (RG2), 71.8 ± 6.3% (RG3), and 27.3 ± 13.4% (RG4). A significantly lower OS rate and higher non-relapse mortality (NRM) were noted in RG4 compared to the other RGs. However, there were no differences in OS or NRM among RG1 to 3. To improve prognostic stratification power of the CIBMTR risk score, we incorporated the absolute lymphocyte (ALC) and eosinophil count (EC) at time of cGVHD into the CIBMTR risk score. Lower ALC (<1.0 × 10/L, HR 1.94, p = 0.014) and lower EC (<0.5 × 10/L, HR 3.27, p = 0.014) were confirmed as adverse risk factors for OS. Patients were stratified into four revised risk groups (rRG). The 3-year OS rates were 93.3 ± 6.4% (rRG1, score 0-3), 84.9 ± 3.4% (rRG2, score 4-6), 70.9 ± 4.4% (rRG3, score 7-9), and 32.0 ± 1.1% (rRG4, score ≥ 10) (p < 0.001). The 3-year NRM rates were 0.0% (rRG1), 6.7 ± 0.4% (rRG2), 18.4 ± 0.7% (rRG3), and 57.7 ± 5.1% (rRG4) (p < 0.001). The revised CIBMTR risk score was superior to the original CIBMTR risk score for OS (p < 0.001). The revised CIBMTR risk score including ALC and EC at the onset of cGVHD improved the prognostic stratification power of the CIBMTR risk score for long-term outcomes.
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http://dx.doi.org/10.1007/s00277-017-2939-4DOI Listing
May 2017