1.Decitabine as a First-Line Treatment for Older Adults Newly Diagnosed with Acute Myeloid Leukemia.
Hyunsung PARK ; Haerim CHUNG ; Jungyeon LEE ; Jieun JANG ; Yundeok KIM ; Soo Jeong KIM ; Jin Seok KIM ; Yoo Hong MIN ; June Won CHEONG
Yonsei Medical Journal 2017;58(1):35-42
PURPOSE: Decitabine, a DNA hypomethylating agent, was recently approved for use in Korea for older adults with acute myeloid leukemia (AML) who are not candidates for standard chemotherapy. This study aimed to evaluate the role of decitabine as a first-line treatment for older adults with AML. MATERIALS AND METHODS: Twenty-four patients with AML who received at least one course of decitabine (20 mg/m²/d intravenously for 5 days every 4 weeks) as a first-line therapy at Severance Hospital were evaluated retrospectively. RESULTS: The median age of the patients was 73.5 years. The longest follow-up duration was 502 days. A total of 113 cycles of treatment were given to 24 patients, and the median number of cycles was four (range, 1–14). Thirteen patients dropped out because of death, no or loss of response, patient refusal, or transfer to another hospital. Twenty-one (87.5%) and 12 (50%) patients completed the second and fourth cycles, respectively, and responses to treatment were evaluated in 17. A complete response (CR) or CR with incomplete blood-count recovery was achieved in six (35.3%) patients, and the estimated median overall survival was 502 days. Ten patients developed grade >2 hematologic or non-hematologic toxicities. In univariate analysis, bone marrow blasts, lactate dehydrogenase, serum ferritin level, and bone marrow iron were significantly associated with response to decitabine. CONCLUSION: Five-day decitabine treatment showed acceptable efficacy in older patients with AML who are unfit for conventional chemotherapy, with a CR rate 35.3% and about a median overall survival of 18 months.
Aged
;
Antimetabolites, Antineoplastic/administration & dosage/*therapeutic use
;
Azacitidine/*analogs & derivatives/therapeutic use
;
DNA Methylation
;
Female
;
Humans
;
Leukemia, Myeloid, Acute/*drug therapy/mortality
;
Male
;
Middle Aged
;
Remission Induction
;
Republic of Korea
;
Retrospective Studies
;
Treatment Outcome
2.Clinical characteristics and treatment outcomes of isolated myeloid sarcoma without bone marrow involvement: a single-institution experience.
Jung Yeon LEE ; Haerim CHUNG ; Hyunsoo CHO ; Ji Eun JANG ; Yundeok KIM ; Soo Jeong KIM ; Jin Seok KIM ; Shin Young HYUN ; Yoo Hong MIN ; June Won CHEONG
Blood Research 2017;52(3):184-192
BACKGROUND: Isolated myeloid sarcoma (MS) is a rare extramedullary tumor mass composed of malignant myeloid precursor cells without any evidence of leukemia in the peripheral blood and bone marrow. We describe the clinical characteristics and outcomes of patients diagnosed with isolated MS at our institution. METHODS: We retrospectively reviewed 9 of 497 acute myeloid leukemia (AML) patients (1.8%) with isolated MS. Isolated MS patients were divided into 2 groups according to the first-line treatment strategy: systemic treatment only (S) or local treatment with or without systemic treatment (LS). RESULTS: The most common site of MS occurrence was the head and neck area (N=4, 44.4%), followed by the anterior mediastinum (N=2, 22.2%) and the gastrointestinal tract (N=2, 22.2%). The tumors of 4 patients (44.4%) eventually evolved to AML, in a median time of 13.4 months (range, 2.4–20.1 mo). The number of patients achieving complete remission after first-line treatment was higher in the LS group (N=5, 83.3%) than in the S group (N=1, 33.3%) (P =0.226). All patients in the LS group survived, but those in the S group died (P=0.012). CONCLUSION: Accurate and rapid diagnosis using various modalities and the early initiation of intensive combined treatment may be the optimal strategies to reduce the risk of isolated MS subsequently evolving to AML. To fully understand the characteristics of isolated MS, a larger number of patients from a multinational study is necessary.
Bone Marrow*
;
Diagnosis
;
Gastrointestinal Tract
;
Head
;
Humans
;
Leukemia
;
Leukemia, Myeloid, Acute
;
Mediastinum
;
Neck
;
Retrospective Studies
;
Sarcoma, Myeloid*
3.Karyotypic change between diagnosis and relapse as a predictor of salvage therapy outcome in AML patients.
Yundeok KIM ; Jieun JANG ; Shin Yong HYUN ; Dohyu HWANG ; Soo Jeong KIM ; Jin Seok KIM ; Jun Won CHEONG ; Yoo Hong MIN
Blood Research 2013;48(1):24-30
BACKGROUND: Only a few patients who experience AML relapse derive lasting benefit from re-induction therapy. The utility of reassessing the disease karyotype at relapse is unclear. The main goals of this study were to identify prognostic factors for AML relapse and to determine the prognostic utility of karyotypic change between diagnosis and relapse as a variable for predicting response to salvage therapy for relapsed AML. METHODS: This retrospective study included 58 patients with relapsed AML treated at the Yonsei University College of Medicine between 2005 and 2010. Karyotypes at both diagnosis and relapse were available for 45 patients (77%). A change in karyotype at relapse was observed in 17 of 45 cases (37%), and no change was noted in 28 of 45 cases (62%). RESULTS: Karyotypic changes between diagnosis and relapse were associated with the response rate (RR) to salvage therapy (P=0.016). Overall survival (OS) and event-free survival (EFS) in the group with karyotypic changes between diagnosis and relapse were significantly different from those with no karyotypic changes (P=0.004 and P=0.010, respectively). We applied multiple multivariate Cox regression analyses to identify independent prognostic factors for overall response (OR), OS, and EFS. A change in karyotype between diagnosis and relapse was significantly associated with OS (P=0.023; RR=2.655) and EFS (P=0.033; RR=2.831). CONCLUSION: Karyotypic changes between the diagnosis and relapse of AML could be used to predict outcomes and tailor clinical and biological therapeutic strategies for relapsed AML patients.
Disease-Free Survival
;
Humans
;
Karyotype
;
Leukemia, Myeloid, Acute
;
Prognosis
;
Recurrence
;
Retrospective Studies
;
Salvage Therapy
4.Karyotypic change between diagnosis and relapse as a predictor of salvage therapy outcome in AML patients.
Yundeok KIM ; Jieun JANG ; Shin Yong HYUN ; Dohyu HWANG ; Soo Jeong KIM ; Jin Seok KIM ; Jun Won CHEONG ; Yoo Hong MIN
Blood Research 2013;48(1):24-30
BACKGROUND: Only a few patients who experience AML relapse derive lasting benefit from re-induction therapy. The utility of reassessing the disease karyotype at relapse is unclear. The main goals of this study were to identify prognostic factors for AML relapse and to determine the prognostic utility of karyotypic change between diagnosis and relapse as a variable for predicting response to salvage therapy for relapsed AML. METHODS: This retrospective study included 58 patients with relapsed AML treated at the Yonsei University College of Medicine between 2005 and 2010. Karyotypes at both diagnosis and relapse were available for 45 patients (77%). A change in karyotype at relapse was observed in 17 of 45 cases (37%), and no change was noted in 28 of 45 cases (62%). RESULTS: Karyotypic changes between diagnosis and relapse were associated with the response rate (RR) to salvage therapy (P=0.016). Overall survival (OS) and event-free survival (EFS) in the group with karyotypic changes between diagnosis and relapse were significantly different from those with no karyotypic changes (P=0.004 and P=0.010, respectively). We applied multiple multivariate Cox regression analyses to identify independent prognostic factors for overall response (OR), OS, and EFS. A change in karyotype between diagnosis and relapse was significantly associated with OS (P=0.023; RR=2.655) and EFS (P=0.033; RR=2.831). CONCLUSION: Karyotypic changes between the diagnosis and relapse of AML could be used to predict outcomes and tailor clinical and biological therapeutic strategies for relapsed AML patients.
Disease-Free Survival
;
Humans
;
Karyotype
;
Leukemia, Myeloid, Acute
;
Prognosis
;
Recurrence
;
Retrospective Studies
;
Salvage Therapy
5.The Modified Glasgow Prognostic Scores as a Predictor in Diffuse Large B Cell Lymphoma Treated with R-CHOP Regimen.
Yundeok KIM ; Soo Jeong KIM ; Dohyu HWANG ; Jieun JANG ; Shin Young HYUN ; Yu Ri KIM ; Jin Seok KIM ; Yoo Hong MIN ; June Won CHEONG
Yonsei Medical Journal 2014;55(6):1568-1575
PURPOSE: The modified Glasgow Prognostic Score (mGPS) consisting of serum C-reactive protein and albumin levels, shows significant prognostic value in several types of tumors. We evaluated the prognostic significance of mGPS in 285 patients with diffuse large B cell lymphoma (DLBCL), retrospectively. MATERIALS AND METHODS: According to mGPS classification, 204 patients (71.5%) had an mGPS of 0, 57 (20%) had an mGPS of 1, and 24 (8.5%) had an mGPS of 2. RESULTS: Our study found that high mGPS were associated with poor prognostic factors including older age, extranodal involvement, advanced disease stage, unfavorable International Prognostic Index scores, and the presence of B symptoms. The complete response (CR) rate after 3 cycles of R-CHOP chemotherapy was higher in patients with mGPS of 0 (53.8%) compared to those with mGPS of 1 (33.3%) or 2 (25.0%) (p=0.001). Patients with mGPS of 0 had significantly better overall survival (OS) than those with mGPS=1 and those with mGPS=2 (p=0.036). Multivariate analyses revealed that the GPS score was a prognostic factor for the CR rate of 3 cycle R-CHOP therapy (p=0.044) as well as OS (p=0.037). CONCLUSION: mGPS can be considered a potential prognostic factor that may predict early responses to R-CHOP therapy in DLBCL patients.
Adult
;
Aged
;
Antibodies, Monoclonal, Murine-Derived/therapeutic use
;
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
;
C-Reactive Protein/*metabolism
;
Cyclophosphamide/therapeutic use
;
Doxorubicin/therapeutic use
;
Female
;
Glasgow Outcome Scale
;
Humans
;
Lymphoma, Large B-Cell, Diffuse/blood/*diagnosis/*drug therapy/mortality
;
Male
;
Middle Aged
;
Multivariate Analysis
;
Prednisone/therapeutic use
;
Prognosis
;
Remission Induction
;
Retrospective Studies
;
Serum Albumin/*metabolism
;
Survival Rate
;
Treatment Outcome
;
Vincristine/therapeutic use
6.Survival impact of adherence to tyrosine kinase inhibitor in chronic myeloid leukemia
Yundeok KIM ; Tae-Hwa GO ; Jaeyeon JANG ; Jii Bum LEE ; Seung Taek LIM ; Kwang Yong SHIM ; Jong In LEE ; Jee Hyun KONG
The Korean Journal of Internal Medicine 2021;36(6):1450-1458
Background/Aims:
Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database.
Methods:
This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]).
Results:
The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS.
Conclusions
Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.
7.Aurora A kinase expression is increased in leukemia stem cells, and a selective Aurora A kinase inhibitor enhances Ara-C-induced apoptosis in acute myeloid leukemia stem cells.
Soo Jeong KIM ; Ji Eun JANG ; June Won CHEONG ; Ju In EOM ; Hoi Kyung JEUNG ; Yundeok KIM ; Doh Yu HWANG ; Yoo Hong MIN
Korean Journal of Hematology 2012;47(3):178-185
BACKGROUND: The overexpression of Aurora A kinase (AurA) has been reported in various malignancies, including acute myeloid leukemia (AML). However, the expression of AurA and the effects of AurA inhibition in cancer stem cells are not yet fully understood. We investigated the expression and inhibition of AurA in AML stem cells (CD34+/CD38-). METHODS: Expression of AurA was investigated in cell lines (NB4 and KG1) that express high levels of CD34 and low levels of CD38. Primary AML cells were harvested from 8 patients. The expression of AurA and cell death induced by inhibition of AurA were analyzed in CD34+/CD38- cells. RESULTS: AurA was shown to be overexpressed in both primary AML cells and leukemia stem cells (LSCs) compared to normal hematopoietic stem cells. Inhibition of AurA plus cytarabine treatment in LSCs resulted in increased cytotoxicity compared to cytarabine treatment alone. Additional stimulation with granulocyte-colony stimulating factor (G-CSF) increased the cell death caused by AurA inhibition plus cytarabine treatment. CONCLUSION: To our knowledge, this is the first report describing increased expression of AurA in LSCs. Our results suggest that selective AurA inhibition may be used to reduce LSCs, and this reduction may be enhanced by stimulation with G-CSF. Further exploration of relationship between nuclear factor kappa-B and AurA inhibition and the potential of AurA inhibition for use in leukemia treatment is needed.
Apoptosis
;
Cell Death
;
Cell Line
;
Cytarabine
;
Epilepsy
;
Granulocyte Colony-Stimulating Factor
;
Hematopoietic Stem Cells
;
Humans
;
Leukemia
;
Leukemia, Myeloid, Acute
;
Neoplastic Stem Cells
;
Phosphotransferases
;
Protein-Serine-Threonine Kinases
;
Stem Cells
8.Clinical significance of B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
Jin Seok KIM ; Soo Jeong KIM ; June Won CHEONG ; Yundeok KIM ; Doh Yu HWANG ; Sulhee YOON ; Jieun JANG ; Shin Young HYUN ; Yoo Hong MIN
Korean Journal of Hematology 2011;46(3):175-179
BACKGROUND: BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) are members of the tumor necrosis factor family and promote B cell survival and proliferation. We evaluated the correlation between serum concentration of BAFF or APRIL and severity of acute graft-versus-host disease (GVHD). METHODS: Fifteen patients who received allogeneic hematopoietic stem transplantation for leukemia and developed acute GVHD were enrolled. We determined serum concentrations of BAFF and APRIL at the onset of the first clinical manifestation of GVHD by enzyme-linked immunosorbent assay. RESULTS: Nine patients had grade 2 acute GVHD, and 6 had grade 3-4 acute GVHD. The BAFF serum concentration was higher in patients with grade 3-4 acute GVHD (1,093.42 in grade 2 vs. 2,171.99 pg/mL in grade 3-4), although the difference was not significant (P=0.077). However, the ratio of BAFF serum concentration to absolute lymphocyte count (ALC) (BAFF/ALC) was significantly higher in patients with grade 3-4 acute GVHD (P=0.045). The APRIL serum concentration and APRIL/ALC ratio showed similar results (P=0.077 and P=0.013, respectively). CONCLUSION: Patients with grade 3-4 acute GVHD had higher BAFF/ALC and APRIL/ALC ratios than patients with grade 2 acute GVHD. These findings suggest that B cells might play an important role in the development of acute GVHD, and that the BAFF and APRIL concentrations in serum might be significant predictive factors for estimating the severity of acute GVHD. Their clinical significance should be further evaluated in a larger patient population.
B-Lymphocytes
;
Cell Survival
;
Graft vs Host Disease
;
Hematopoietic Stem Cell Transplantation
;
Hematopoietic Stem Cells
;
Humans
;
Leukemia
;
Lymphocyte Count
;
Transplants
;
Tumor Necrosis Factor-alpha
10.Changes in deoxyhemoglobin and admission duration in carbon monoxide poisoning patients: a retrospective study
Jae Gu JI ; Yang Weon KIM ; Chul Ho PARK ; Yoo Sang YOON ; Yundeok JANG ; JI-Hun KANG ; Chang Min PARK ; Sang Hyeon PARK
Journal of The Korean Society of Clinical Toxicology 2023;21(1):32-38
Purpose:
The purpose of this study was to determine whether deoxyhemoglobin changes were associated with admission duration in carbon monoxide (CO)-poisoned patients.
Methods:
This retrospective study included 181 patients who were able to breathe by themselves after CO poisoning. Arterial blood gas analysis was performed to measure their deoxyhemoglobin levels. Their baseline characteristics and clinical outcomes during hospitalization in the emergency department (ED) were collected and compared. To assess changes in deoxyhemoglobin levels, blood samples were taken immediately after patients presented to the ED and then again after 6 hours. For statistical analysis, logistic regression was utilized to determine the effect of deoxyhemoglobin changes on admission duration.
Results:
The incidence rates of hypocapnia and hypoxemia at presentation after acute CO poisoning were 28.7% and 43.6%, respectively. Moreover, the magnitude of increasing deoxyhemoglobin levels in patients with hypoxemia (2.1 [1.7–3.1], p<0.001) and changes in deoxyhemoglobin levels appeared to have an impact on the length of hospitalization in the ED (odds ratio, 1.722; 95% confidence interval, 0.547–0.952; p<0.001).
Conclusion
In patients with acute CO poisoning, deoxyhemoglobin levels appeared to increase in those with hypoxemia, which in turn was associated with prolonged hospitalization.