Publications by authors named "Won Sik Lee"

150 Publications

Clinical impact of lymphatic spread in patients with limited-stage upper aerodigestive tract NK/T cell lymphoma.

Blood Res 2021 May 25. Epub 2021 May 25.

Department of Hematology-Oncology, Pusan National University Hospital Medical Research Institute, Busan, Korea.

Background: We investigated whether distance, that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL).

Methods: A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled.

Results: In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS): hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606-5.404; <0.001; overall survival (OS): HR, 2.619; 95% CI, 1.594-4.822; =0.003], short distance (PFS: HR, 0.170; 95% CI, 0.071-0.410; <0.001; OS: HR, 0.142; 95% CI, 0.050-0.402; <0.001), and CTx combined with RTx (HR, 0.168; 95%CI, 0.079-0.380; <0.001; OS: HR, 0.193; 95% CI, 0.087-0.429; <0.001) had an independent predictive value for PFS and OS.

Conclusion: The evaluation of the degree of lymphatic spread and local control by CTx combined with RTx is essential in patients with limited-stage UAT NKTCL.
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http://dx.doi.org/10.5045/br.2021.2020328DOI Listing
May 2021

Age and remission induction therapy for acute myeloid leukemia: An analysis of data from the Korean acute myeloid leukemia registry.

PLoS One 2021 7;16(5):e0251011. Epub 2021 May 7.

Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.

Objective: The clinical characteristics and therapeutic strategy in acute myeloid leukemia (AML) are influenced by patients' age. We evaluated the impact of age on remission induction therapy for AML.

Methods: We retrospectively analyzed 3,011 adult AML patients identified from a nationwide database between January 2007 and December 2011.

Results: Three hundred twenty-nine (10.9%) acute promyelocytic leukemia (APL) and 2,682 (89.1%) non-APL patients were analyzed. The median age was 51 years and 55% of patients were male. Six hundred twenty-three patients (21%) were at favorable risk, 1522 (51%) were at intermediate risk, and 743 (25%) were at poor risk. As the age increased, the proportion of those at favorable risk and who received induction chemotherapy decreased. After induction therapy, complete response (CR) was achieved in 81.5% (243/298) of APL and 62.4% (1,409/2,258) of non-APL patients; these rates decreased as the age increased, with an obvious decrement in those older than 60 years. The median overall survival of non-APL patients was 18.7 months, while that of APL patients was not reached, with a 75% five-year survival rate.

Conclusions: Age impacts both the biology and clinical outcomes of AML patients. Further studies should confirm the role of induction remission chemotherapy by age group.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251011PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104390PMC
May 2021

Clinical Impact of Extranodal Metabolic Tumor Volume in 240 Diffuse Large B cell Lymphoma Patients with Extranodal Involvement.

Ann Hematol 2021 May 25;100(5):1221-1229. Epub 2021 Mar 25.

Department of Nuclear Medicine, Busan Paik Hospital, Busan, Korea.

The present study is to investigate whether extranodal (EN) metabolic tumor volume (MTV) would have a specific clinical meaning for survival in EN diffuse large B cell lymphoma (DLBCL) patients. Two hundred forty DLBCL patients with EN involvement received 18F-fluorodeoxygenase (FDG) positron emission tomography/computed tomography (PET/CT) were enrolled. Survival analysis revealed that low EN MTV (PFS [progression-free survival], HR = 0.278, 95% CI = 0.127-0.807, p = 0.001; OS [overall survival], HR = 0.320, 95% CI = 0.145-0.703, p = 0.003), low total MTV (PFS, HR = 0.194, 95% CI = 0.085-0.445, p < 0.001; OS, HR = 0.213, 95% CI = 0.092-0.491, p < 0.007), and high National Cancer Center Network-International Prognostic Index score (PFS, HR = 3.152, 95% CI = 1.732-5.734, p < 0.001; OS, HR = 2.457, 95% CI = 1.363-4.430, p = 0.003) were independently associated with survivals in the patients. Our data showed that EN MTV is a useful and novel prognostic parameter for predicting survival in DLBCL patients with EN involvement.
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http://dx.doi.org/10.1007/s00277-021-04498-9DOI Listing
May 2021

Pegteograstim prophylaxis for chemotherapy-induced neutropenia and febrile neutropenia: a prospective, observational, postmarketing surveillance study in Korea.

Support Care Cancer 2021 Mar 8. Epub 2021 Mar 8.

Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, 877 Bangeojinsunwhandoro, Dong-gu, Ulsan, 44033, Republic of Korea.

Purpose: This observational study aimed to evaluate the safety and efficacy of pegteograstim prophylaxis in patients with lymphoma and solid malignancies.

Methods: This study was conducted at 18 sites in Korea between November 2015 and August 2018.

Results: In total, 611 patients (female, 61.2%) with a median age of 58 (range, 18-88) years were included. Most patients had lymphomas (n = 371, 60.7%) and breast cancer (n = 230, 37.6%) and were administered R-CHOP21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone per 21 days) (n = 284, 46.5%) and AC (doxorubicin and cyclophosphamide) (n = 177, 29.0%). The total pegteograstim dose in the 611 patients was 14,970 mg (2495 doses), with each patient receiving an average daily dose of 6.0 mg. Neutropenia grade 4 occurred in 97 patients (15.9%), and febrile neutropenia (FN) occurred in 31 patients (5.1%). Among the 611 patients, 267 patients (43.7%) developed 882 adverse events (AEs), and 11 patients (1.8%) experienced 18 adverse drug reactions (ADRs). There were 62 patients (10.2%) who experienced 81 cases of serious adverse events (SAEs), with FN and pneumonia being the most frequent at 14 and 13 episodes, respectively, in 13 patients (2.1%). Meanwhile, 1 patient (0.2%) developed 2 episodes of serious ADRs (grade 1 and grade 2 hypotension). No safety concerns in the elderly and patients with liver and/or renal disease were identified.

Conclusion: The prophylactic use of pegteograstim might have good overall safety and efficacy in patients with lymphomas and solid malignancies in routine clinical practice, even in those who are elderly and have liver and renal diseases.
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http://dx.doi.org/10.1007/s00520-021-06127-7DOI Listing
March 2021

Autologous hematopoietic cell transplantation following high-dose cytarabine consolidation for core-binding factor-acute myeloid leukemia in first complete remission: a phase 2 prospective trial.

Int J Hematol 2021 Jun 2;113(6):851-860. Epub 2021 Mar 2.

Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.

Core-binding factor (CBF)-acute myeloid leukemia (AML) generally have a favorable prognosis. However, approximately 50% of patients experience disease relapse during or after post-remission therapy. Retrospective studies on autologous hematopoietic cell transplantation (AHCT) have shown improved survival with decreased relapse rate in CBF-AML. In this prospective study, we evaluate the outcomes of AHCT following high-dose cytarabine (HiDAC) consolidation in patients with CBF-AML in first complete remission (CR). Adult patients with CBF-AML achieving first CR after induction chemotherapy were eligible for the study. High-dose chemotherapy before AHCT included intravenous busulfan (3.2 mg/kg/day, days - 7 to - 5) and etoposide (400 mg/m/day, days - 3 to - 2). Twenty-nine patients, 17 with t(8;21) and 12 with inv(16), underwent AHCT following 2 or 3 courses of HiDAC consolidation. The estimated 5-year overall and disease-free survival rates were between 89.0% and 82.5%, respectively. The cumulative incidences of relapse and non-relapse mortality were between 17.5% and 0%, respectively. Presence of measurable residual disease (MRD) before AHCT and KIT mutation were significantly associated with relapse after transplantation. In conclusion, the post-remission strategy of AHCT following HiDAC consolidation in CBF-AML was feasible and efficacious. Assays for MRD and KIT mutation may guide selection of patients who will benefit from AHCT in CBF-AML in first CR.
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http://dx.doi.org/10.1007/s12185-021-03099-6DOI Listing
June 2021

Appropriate Starting Dose of Dasatinib Based on Analyses of Dose-Limiting Toxicities and Molecular Responses in Asian Patients With Chronic Myeloid Leukemia.

Clin Lymphoma Myeloma Leuk 2021 Jun 2;21(6):e521-e529. Epub 2021 Feb 2.

Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea; Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea. Electronic address:

Background: Dasatinib is administered at a fixed starting dosage of 100 mg once daily regardless of patient-specific factors. However, such fixed dosing may not be optimal for the treatment of Asian patients with chronic myeloid leukemia in chronic phase (CP-CML).

Patients And Methods: The dose-limiting toxicities (DLTs) and molecular responses (MRs) of dasatinib therapy were evaluated using clinical data obtained from 102 patients newly diagnosed with CP-CML at 17 hospitals in South Korea.

Results: By 36 months after the initiation of a fixed dose regimen of dasatinib 100 mg once daily as the first-line therapy, 55.9% of patients experienced at least one type of DLT. The 3 most frequent DLTs were thrombocytopenia (45.5%), pericardial or pleural effusion (30.9%), and anemia (7.3%). Patients with higher dasatinib dose adjusted for body weight (Dose/BW) had a greater rate of DLT occurrence (logit [P] = 1.58 × [Dose/BW] - 2.27, P = .03). As median Dose/BW increased from 1.23 to 2.00 mg/kg, the rate of DLT occurrence increased from 43.5% to 66.7% (P = .03). However, Dose/BW did not affect the achievement rate of major MR (60.9% to 69.6%, P = .92).

Conclusion: The starting dosage of dasatinib may need to be reduced (eg, 80 mg once daily or lower) for Asian patients with CP-CML, especially with lighter BW, to alleviate the risk of DLT occurrence without compromising the achievement of MR.
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http://dx.doi.org/10.1016/j.clml.2021.01.020DOI Listing
June 2021

Corona-Cov-2 (COVID-19) and ginseng: Comparison of possible use in COVID-19 and influenza.

J Ginseng Res 2021 Feb 18. Epub 2021 Feb 18.

School of Pharmacy, Sungkyunkwan University, Suwon 16419, South Korea.

In the 1918 influenza pandemic, more than 95% of mortalities were ascribed to bacterial pneumonia. After the primary influenza infection, the innate immune system is attenuated, and the susceptibility to bacteria is increased. Subsequent bacterial pneumonia exacerbates morbidity and increases the mortality rate. Similarly, COVID-19 infection attenuates innate immunity and results in pneumonia. In addition, the current pneumococcal conjugate vaccine may have limited defense against secondary pneumococcal infection after influenza infection. Therefore, until a fully protective vaccine is available, a method of increasing immunity may be helpful. Ginseng has been shown to increase the defense against influenza in clinical trials and animal experiments, as well as the defense against pneumococcal pneumonia in animal experiments. Based on these findings, ginseng is suspected to be helpful for providing immunity against COVID-19.
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http://dx.doi.org/10.1016/j.jgr.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891076PMC
February 2021

Carfilzomib in addition to lenalidomide and dexamethasone in Asian patients with RRMM outside of a clinical trial.

Ann Hematol 2021 Jan 15. Epub 2021 Jan 15.

Department of Hematology, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Carfilzomib, lenalidomide, and dexamethasone (KRd) effectively improve survival in patients with relapsed and refractory multiple myeloma (RRMM). However, the outcome of KRd treatment in Asian patients reflecting a general RRMM population outside of a clinical trial has not been reported. Fifty-five RRMM patients who were treated with carfilzomib in combination with Rd from the time of the first approval of KRd in the Republic of Korea were analyzed. The median age was 61 years. The percentage of patients with an ECOG performance status ≥ 3, creatinine clearance < 50 mL/min, high-risk cytogenetics, and ≥ 4 lines of prior treatment were 9%, 22%, 31%, and 27%, respectively. Forty-one patients started treatment with KRd, whereas the remaining 14 patients (25%) were added carfilzomib during the Rd treatment. In the whole cohort, the overall response rate was 73% and progression-free survival was 8.8 months. The addition of carfilzomib in patients who were refractory or had disease progression during Rd treatment reattained a response in half of the patients. The advantage of carfilzomib with Rd was significant in patients in the first relapse. Toxicity profile was acceptable, excluding severe infections. Carfilzomib in combination with Rd is effective and has a reasonable adverse event rate in Asian patients with RRMM.
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http://dx.doi.org/10.1007/s00277-021-04407-0DOI Listing
January 2021

Clinical features and outcomes of hypocellular acute myeloid leukemia in adults: A Korean AML registry data.

Medicine (Baltimore) 2021 Jan;100(1):e24185

Department of Hematology, Leukemia Research Institute, Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, South Korea.

Abstract: The hypocellular variant of acute myeloid leukemia (AML) is defined as bone marrow cellularity of <20% in a biopsy specimen at presentation. We performed a retrospective analysis of the clinical features and survival outcomes of hypocellular AML in a Korean population. We reviewed the medical records of all patients diagnosed with AML at nine hospitals participating in the Korean AML registry from 2006 to 2012. Overall survival (OS) and event-free survival (EFS) rates were calculated from the time of diagnosis until death or an event, respectively. In total, 2110 patients were enrolled and 102 (4.8%) were identified as having hypocellular AML. Patients with hypocellular AML were older than those with non-hypocellular AML (median age: 59 vs 49 years; P < .001) and presented with leukopenia more frequently (mean white blood cell count: 5810/μL vs 40549/μL; P < .001). There was no difference between patients with and without hypocellular AML in terms of the presence of antecedent hematologic disorders (5.9% vs 5.3%; P  = .809). FLT3-ITD and NPM1 mutations were less common in hypocellular than non-hypocellular AML (FLT3-ITD mutations: 1.2% vs 14.3%, P < .001; NPM1 mutations: 0% vs 9.5%, P = .019). No differences were seen between the hypocellular and non-hypocellular AML groups in the complete remission rate (53.9% vs 61.3%, P = .139) or early death rate (defined as any death before 8 weeks; 14.7% vs 13.0%, P = .629). The OS and EFS did not differ between the hypocellular and non-hypocellular AML groups (median OS: 16 vs 23 months, P = .169; median EFS: 6 vs 9 months, P = .215). Hypocellular AML is more frequently observed in older-aged patients and have fewer FLT3-ITD and NPM1 mutation, but the clinical outcomes of hypocellular AML do not differ from those of non-hypocellular AML.
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http://dx.doi.org/10.1097/MD.0000000000024185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793401PMC
January 2021

Busulfan, etoposide, cytarabine, and melphalan as a high-dose regimen for autologous stem cell transplantation in peripheral T-cell lymphomas.

Ann Hematol 2021 Jan 17;100(1):189-196. Epub 2020 Nov 17.

Department of Hematology and Oncology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea.

Given the unsatisfactory survival in patients who received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) for peripheral T-cell lymphomas (PTCLs), we conducted a prospective trial of busulfan (Bu), etoposide (E), cytarabine (A), and melphalan (M) (BuEAM), including IV Bu instead of carmustine (BCNU) as in standard BEAM, as a high-dose regimen in such patients. This study evaluated the efficacy and toxicity of BuEAM as a high-dose regimen for ASCT in patients with T-cell lymphomas. The high-dose chemotherapy at seven centers in Korea included Bu (3.2 mg/kg IV qd from day 6 to day 5), E (200 mg/m IV bid on day 4 and day 3), A (1 g/m IV qd on day 4 and day 3), and M (140 mg/m IV qd on day 2). Eighty-one patients were enrolled in this study. The main subtypes were peripheral T-cell lymphoma, not other specified (n = 32, 39.5%), NK/T-cell lymphoma (n = 22, 27.5%), and angioimmunoblastic T-cell lymphoma (n = 12, 14.8%). Upfront and salvage ASCTs were performed in 65 (80.2%) and 16 (19.8%) patients, respectively. The disease status of the patients before ASCT was 54 patients (66.7%) with complete response and 27 patients (33.3%) with partial response. The common grade-III toxicities were anorexia (8.6%), diarrhea (7.4%), and stomatitis (4.9%). No veno-occlusive disorder was noted. Fifty-six (69.1%) and seven (8.6%) patients achieved complete and partial response, respectively, after ASCT, although 17 patients (21.0%) showed progressive disease. At a median follow-up duration of 49.3 months, the estimated 3-year progression-free survival and overall survival were 55.2% and 68.2% in all patients. The BuEAM high-dose regimen for ASCT was well tolerated and seemed to be effective in patients with T-cell lymphomas.
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http://dx.doi.org/10.1007/s00277-020-04309-7DOI Listing
January 2021

Long-term follow-up of abbreviated R-CHOP chemoimmunotherapy for completely resected limited-stage diffuse large B cell lymphoma (CISL 12-09).

Ann Hematol 2020 Dec 28;99(12):2831-2836. Epub 2020 Sep 28.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

The standard of treatment for completely resected limited-stage diffuse large B cell lymphoma (DLBCL) in patients without residual lesions has not yet been established. Previously, we designed a phase II trial to evaluate the safety and efficacy of three cycles of abbreviated R-CHOP in patients with completely resected limited-stage DLBCL and reported favorable survival outcomes. We present the long-term follow-up results to taking into account the importance of delayed relapse in patients with limited-stage DLBCL. With a median follow-up duration of 62.7 months (range, 60.2-75.5 months), the 5-year OS and DFS rates were both 95.0% (95% confidence interval, 85.59-104.11%). Only one patient experienced disease progression which was confirmed at 12.3 months, and one patient with primary intestinal DLBCL developed non-small cell lung cancer 6 years after treatment. The long-term results of our data support the use of three cycles of abbreviated R-CHOP for patients with completely resected limited-stage DLBCL. The study was reviewed and approved by the review boards of the participating institutes and registered at ClinicalTrials.gov , number NCT01279902, in August 3, 2010.
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http://dx.doi.org/10.1007/s00277-020-04284-zDOI Listing
December 2020

Clinical impact of frailty on treatment outcomes of elderly patients with relapsed and/or refractory multiple myeloma treated with lenalidomide plus dexamethasone.

Int J Hematol 2021 Jan 5;113(1):81-91. Epub 2020 Sep 5.

Department of Internal Medicine, Seoul St. Mary's Hospital, Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea.

We compared efficacy and safety, according to frailty, of elderly patients with relapsed and refractory multiple myeloma (RRMM) treated with lenalidomide and dexamethasone (Rd), for whom bortezomib treatment had failed. Patients, 164 (52.9%) and 146 (47.1%), were classified as non-frail and frail using a simplified frailty scale. The overall response rates (ORR) and survival outcomes were lower in frail than in non-frail patients (ORR: 56.2% vs. 67.7%, P = 0.069; median progression free survival: 13.17 vs. 17.80 months, P = 0.033; median overall survival: 23.00 vs. 36.27 months, P = 0.002, respectively). The number of treatment emergent adverse events in grade 3 or worse was higher in frail than in non-frail patients (41.8% vs. 24.4%, P = 0.002, respectively). In frail patients, independent poor prognostic factors for survival were two or more Charlson comorbidity index (CCI) score, prior to exposure to both bortezomib and thalidomide, and achieved less than partial response In conclusion, frailty could predict clinical outcomes of Rd treatment in elderly patients with RRMM who had failed prior bortezomib. In frail patients, lower CCI in addition to less previous treatment exposure and deep response were associated with better survival.
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http://dx.doi.org/10.1007/s12185-020-02988-6DOI Listing
January 2021

Prognostic significance of interim PET/CT response for the treatment of advanced-stage marginal zone lymphoma in the post-rituximab era.

Sci Rep 2020 07 15;10(1):11649. Epub 2020 Jul 15.

Chonnam National University Hwasun Hospital, Hwasun, Jeollanam-do, Republic of Korea.

There are still controversies about the use of interim positron emission tomography/computed tomography (PET/CT) in indolent non-Hodgkin lymphoma due to the variable fluorodeoxyglucose (FDG) avidity. Therefore, this study aimed to evaluate the roles of interim PET/CT in marginal zone lymphoma (MZL), a representative indolent lymphoma. We analyzed the data of 146 MZL patients. All were treated with rituximab-containing immunochemotherapy. Interim PET/CT scan was performed after 2-3 cycles of therapy, and the response was assessed using the Deauville 5-point scales (5-PS) and a semi-quantitative assessment using the SUVmax reduction rate (ΔSUVmax). Progression-free survival (PFS) was well stratified according to a visual assessment of interim PET/CT using 5-PS (p < 0.001). Particularly, there was a significant difference in PFS between patients with interim score 1-2 and those with score 3. However, ΔSUVmax did not predict the survival outcome using 59.8% of the optimal cutoff value. In the multivariate analysis, failure to achievement of grade 1-2 in interim PET/CT was significantly associated with inferior PFS (HR, 2.154; 95% CI 1.071-4.332; p = 0.031). The interim PET/CT response based on the 5-PS is useful for predicting PFS of patients with MZL in the post-rituximab era.
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http://dx.doi.org/10.1038/s41598-020-68310-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363857PMC
July 2020

Reduced-Intensity Conditioning with Busulfan and Fludarabine for Allogeneic Hematopoietic Stem Cell Transplantation in Acute Lymphoblastic Leukemia.

Yonsei Med J 2020 Jun;61(6):452-459

Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea.

Purpose: Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation.

Materials And Methods: Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m²/day of fludarabine for 5 or 6 days were analyzed.

Results: The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26-1.08; =0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II-IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively.

Conclusion: RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.
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http://dx.doi.org/10.3349/ymj.2020.61.6.452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256005PMC
June 2020

Autologous stem cell transplantation in elderly patients with multiple myeloma in Korea: the KMM1807 study.

Int J Hematol 2020 Jul 25;112(1):84-95. Epub 2020 May 25.

Center for Hematologic Malignancy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Geyonggi, 410-769, Republic of Korea.

Autologous stem cell transplantation (ASCT) is not frequently performed for elderly patients multiple myeloma (MM) in Korea, despite its being a standardized approach for young patients. Medical records of 150 patients from 15 Korean institutions who received ASCT at age ≥ 64 years were analyzed retrospectively. Patients included had symptomatic MM, and had received their first ASCT at age ≥ 64 following induction chemotherapy. The main outcome was the response after ASCT. Overall survival (OS) and progression-free survival (PFS) were also analyzed. Median time to ASCT was 6.3 months. Complete response plus stringent complete response rate increased from 36 (24.0%) to 105 (70.0%) after ASCT, and high-quality response (≥ very good partial response) increased from 96 (64.0%) to 125 (83.3%). With a median follow-up of 32.6 months after ASCT, 5-year OS and PFS were 59.7% and 22.8%, respectively. Febrile neutropenia occurred in 43.5%, and nausea (21.3%) and stomatitis (13.2%) were common grade 3-4 non-hematologic adverse events. Of 44 deaths, disease progression (n = 23) was the most common cause of mortality, followed by infection (n = 13). Treatment-related death occurred in four cases (2.7%). ASCT is an effective and safe option for elderly MM patients and is associated with superior clinical outcomes.
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http://dx.doi.org/10.1007/s12185-020-02869-yDOI Listing
July 2020

Long-term data from a phase 3 study of radotinib versus imatinib in patients with newly diagnosed, chronic myeloid leukaemia in the chronic phase (RERISE).

Br J Haematol 2020 04 3;189(2):303-312. Epub 2020 Feb 3.

Seoul St. Mary's Hematology Hospital, Leukemia Research Institute, The Catholic University of Korea, Seoul, South Korea.

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 (MR ) 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.
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http://dx.doi.org/10.1111/bjh.16381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187446PMC
April 2020

Poor prognostic impact of high serum ferritin levels in patients with a lower risk of diffuse large B cell lymphoma.

Int J Hematol 2020 Apr 6;111(4):559-566. Epub 2020 Jan 6.

Division of Hematology/Oncology, Department of Internal Medicine, Kosin University College of Medicine, Kosin University Gospel Hospital, 262 Gamcheon-ro, Seo-gu, Busan, 49267, South Korea.

The International Prognostic Index (IPI) and other prognostic models cannot accurately classify risks in patients with lower-risk diffuse large B cell lymphoma (DLBCL). This study retrospectively analyzed serum levels of ferritin (500 and ≥ 500 ng/mL) and other reported risk factors for survival in 312 patients. High and high-intermediate risk IPI scores (hazard ratio (HR) [95% confidence interval (CI)] 2.22 [1.33, 3.72], P = 0.002 and 2.29 [1.33, 3.93], P = 0.003, respectively) and ferritin concentration ≥ 500 ng/mL (HR [95% CI] 2.22 [1.37, 3.60], P = 0.001 and 2.18 [1.31, 3.63], P = 0.003, respectively) were independent poor prognostic factors for 5-year progression-free survival (PFS) and overall survival (OS) rates in all patients. Additionally, high ferritin level (≥ 500 ng/mL) was an independent poor prognostic factor for PFS and OS in patients with lower-risk IPI (HR [95% CI] 3.37 [1.36, 8.33], P = 0.009 and 3.29 [1.23, 8.83], P = 0.0018, respectively). In conclusion, serum ferritin levels may be helpful in predicting survival in patients with DLBCL, especially in those with lower-risk IPI scores.
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http://dx.doi.org/10.1007/s12185-019-02816-6DOI Listing
April 2020

A phase II study of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) for patients with refractory or relapsed Hodgkin's lymphoma.

Ann Hematol 2020 Feb 2;99(2):255-264. Epub 2020 Jan 2.

Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea.

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m on day 5, and i.v. oxaliplatin 130 mg/m on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156.
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http://dx.doi.org/10.1007/s00277-019-03891-9DOI Listing
February 2020

Pralatrexate in patients with recurrent or refractory peripheral T-cell lymphomas: a multicenter retrospective analysis.

Sci Rep 2019 12 30;9(1):20302. Epub 2019 Dec 30.

Department of Oncology, Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea.

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent or refractory PTCLs. The purpose or this study was to investigate the efficacy and safety of pralatrexate in relapsed or refractory PTCLs in real-world practice. This was an observational, multicenter, retrospective analysis. Between December 2012 and December 2016, a total of 38 patients with relapsed or refractory PTCLs were treated with pralatrexate at 10 tertiary hospitals in Korea. Patients received an intravenous infusion of pralatrexate at a dose of 30 mg/m/week for 6 weeks on a 7-week schedule. Modified dosing and/or scheduling was allowed according to institutional protocols. Median patient age was 58 years (range, 29-80 years) and the most common subtype was peripheral T-cell lymphoma, not otherwise specified (n = 23, 60.5%). The median dosage of pralatrexate per administration was 25.6 mg/m/wk (range, 15.0-33.0 mg/m/wk). In intention-to-treat analysis, 3 patients (7.9%) showed a complete response and 5 patients (13.2%) showed a partial response, resulting in an overall response rate (ORR) of 21.1%. The median duration of response was 7.6 months (range, 1.6-24.3 months). The median progression-free survival (PFS) was 1.8 months (95% confidence interval [CI], 1.7-1.8 months) and the median overall survival was 7.7 months (95% CI, 4.4-9.0 months). The most common grade 3/4 adverse events were thrombocytopenia (n = 13, 34.2%), neutropenia (n = 7, 23.7%), and anemia (n = 7, 18.4%). Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice. The toxicity profile was acceptable and manageable. We also observed significantly lower dose intensity of pralatrexate in real-world practice.
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http://dx.doi.org/10.1038/s41598-019-56891-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937326PMC
December 2019

The effectiveness and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma in real-world clinical practice: a study of the Korean Multiple Myeloma Working Party (KMMWP-151 study).

Ann Hematol 2020 Feb 23;99(2):309-319. Epub 2019 Dec 23.

Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea.

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes.
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http://dx.doi.org/10.1007/s00277-019-03904-7DOI Listing
February 2020

Correction to: Clinical outcomes in patients with diffuse large B cell lymphoma with a partial response to first-line R-CHOP chemotherapy: prognostic value of secondary International Prognostic Index scores and Deauville scores.

Ann Hematol 2020 01;99(1):213

Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50-1 Yonsei-ro, Seoul, Seodaemun-gu, 03722, South Korea.

An additional affiliation for the first author was not indicated. Hyewon Lee is also affiliated with: Department of Internal Medicine, Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, South Korea.
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http://dx.doi.org/10.1007/s00277-019-03868-8DOI Listing
January 2020

Phase II study of R-CVP followed by rituximab maintenance therapy for patients with advanced marginal zone lymphoma: consortium for improving survival of lymphoma (CISL) study.

Cancer Commun (Lond) 2019 10 16;39(1):58. Epub 2019 Oct 16.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, 05505, Republic of Korea.

Background: The response rate and survival improvement for rituximab, a CD20-targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single-arm, open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III-IV CD20-positive MZL who had responded to first-line R-CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R-CVP warrants further investigation.

Methods: Prior to rituximab-maintenance therapy, patients received 6-8 cycles of first-line R-CVP therapy for stage III-IV MZL. Rituximab (375 mg/m), cyclophosphamide (750 mg/m), and vincristine (1.4 mg/m; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3-week cycle, while oral prednisolone (100 mg) was given on days 1-5 of each 3-week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R-CVP treatment, were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m every 8 weeks for up to 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety.

Results: 47 patients were enrolled, of whom, 45 (96%) received rituximab-maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R-CVP first-line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow-up of 38.2 months, their observed 3-year PFS rate was 81%. During the rituximab-maintenance, 6 PR and 1 SD patients achieved CR following the administration of R-CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P = 0.003) and demonstrated a 3-year OS rate of 90%. Rituximab-maintenance therapy was well tolerated, and the common treatment-emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%).

Conclusion: Rituximab-maintenance therapy following first-line R-CVP demonstrated good PFS in patients with stage III-IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov: NCT01213095.
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http://dx.doi.org/10.1186/s40880-019-0403-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796378PMC
October 2019

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

Lenalidomide as a second-line therapy after failure of hypomethylating agents in patients with myelodysplastic syndrome.

Br J Haematol 2019 09 9;186(5):e151-e155. Epub 2019 Jun 9.

Department of Haematology, Catholic Haematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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http://dx.doi.org/10.1111/bjh.15991DOI Listing
September 2019

A phase II trial of bendamustine, carboplatin, and dexamethasone for refractory or relapsed peripheral T-cell lymphoma (BENCART trial).

Leuk Lymphoma 2019 12 6;60(13):3251-3257. Epub 2019 Jun 6.

Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.

This trial was designed to investigate the efficacy and toxicity of bendamustine, carboplatin, and dexamethasone (BCD) for relapsed or refractory peripheral T-cell lymphomas (PTCLs), which would be expected to exhibit more promising clinical outcomes compared with bendamustine therapy alone. After treatments with BCD, eight patients exhibited a complete response (CR; 29%) and seven exhibited a partial response (PR; 25%). The overall response rate (ORR) was 54%. Five patients proceeded to ASCT and three patients finally achieved CR. The median progression-free survival (PFS) was 4.4 months (2.8-6.0, 95% CI). For a total of 85 cycles of BCD, grade 3 or 4 neutropenia, thrombocytopenia, and anemia occurred in 17.6, 38.8, and 16.5% of cycles, respectively. Only one patient experienced febrile neutropenia. BCD was a considerable salvage regimen for relapsed or refractory PTCLs with acceptable toxicity; AITL or ASCT eligible patients were more effective to BCD.NCT02424045.
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http://dx.doi.org/10.1080/10428194.2019.1622100DOI 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

The effects of erythropoiesis-stimulating agents on the management of chemotherapy-induced anemia and tumor growth in diffuse large B-cell lymphoma patients.

Int J Cancer 2019 11 6;145(9):2459-2467. Epub 2019 May 6.

Department of Internal Medicine, Kosin University College of Medicine, Busan, South Korea.

Erythropoiesis-stimulating agents (ESAs), such as erythropoietin (EPO) and darbepoetin, may alleviate anemia in diffuse large B-cell lymphoma (DLBCL) patients. However, many cancer cells express EPO receptors (EPOR), through which exogenously administered ESAs potentially promote cancer cell growth. We conducted preclinical/phase II studies to investigate the safety and efficacy of ESAs for managing chemotherapy-related anemia in DLBCL patients. We examined EPOR expression in germinal center B-cell (GCB)- and activated B-cell (ABC)-DLBCL cell lines, and investigated the effects of ESAs on cell proliferation, and rituximab-mediated complement-dependent cytotoxicity (CDC). The clinical study enrolled 50 histologically confirmed DLBCL patients receiving rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP) who had hemoglobin levels <10.0 g/dl after a maximum of three R-CHOP cycles and received ≥4 doses of fixed-dose darbepoetin (360 μg) once every 3 weeks. EPOR mRNA was detected in all GCB-DLBCL cell lines, but little/none was detected in ABC-DLBCL cell lines. GCB-DLBCL and ABC-DLBCL cell proliferation was unaffected by EPO or darbepoetin. Rituximab-mediated CDC of DLBCL cell lines with/without EPOR expression was not affected adversely by EPO. In the clinical study, baseline mean hemoglobin was 9.19 g/dl; the overall mean change in hemoglobin was 1.59 ± 1.3 g/dl (16 weeks). Forty-eight percent of enrolled patients achieved a hematopoietic response. Our study shows that ESAs do not affect the growth of DLBCL cells or rituximab-mediated CDC under the experimental conditions that we used, and the appropriate use of ESAs may be effective and safe for DLBCL patients with anemia after R-CHOP.
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http://dx.doi.org/10.1002/ijc.32328DOI Listing
November 2019