1.Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study
Dong Won BAEK ; Han-Seung PARK ; Sang Kyun SOHN ; Dae Young KIM ; Inho KIM ; Jae-Sook AHN ; Young Rok DO ; Se Ryeon LEE ; Hyeon-Seok EOM ; Won-Sik LEE ; Sung-Hyun KIM ; Ho Sup LEE ; Yoo Jin LEE ; Joon Ho MOON ; Je-Hwan LEE ;
The Korean Journal of Internal Medicine 2023;38(5):734-746
Background/Aims:
We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL).
Methods:
Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation.
Results:
In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles.
Conclusions
The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).
2.Osimertinib Combined with Systemic Chemotherapy for EGFR Mutant, T790M-Negative, Non–Small Cell Lung Cancer Patients Who Develop Leptomeningeal Metastases with Extracranial Progression to Prior EGFR TKI
Hye Ryeon KIM ; Hyunji JO ; Hongsik KIM ; Joohyun HONG ; Sehhoon PARK ; Hyun Ae JUNG ; Se-Hoon LEE ; Jin-Seok AHN ; Myung-Ju AHN
Cancer Research and Treatment 2023;55(1):344-349
Leptomeningeal metastasis (LM) is a rare but fatal clinical condition with a short survival time. The incidence of LM from epidermal growth factor receptor mutant (EGFRm) non–small cell lung cancer (NSCLC) has increased due to the limited efficacy of first- or second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the central nervous system (CNS). Osimertinib is a third-generation, irreversible, CNS penetrant, oral EGFR TKI that demonstrates promising efficacy in CNS metastases regardless of T790M. Herein, we report four cases of T790M-negative EGFRm NSCLC patients treated with osimertinib combined with systemic chemotherapy, who progressed on prior EGFR TKI and developed LM with extracranial lesions. The combination treatment was well tolerated, and the mean overall survival from LM diagnosis was 14.7 months (95% confidence interval, 10.4 to 19.0). These results suggest that osimertinib combined with systemic chemotherapy would be a reasonable treatment option for T790M-negative EGFRm NSCLC patients who develop LM with extracranial progression to prior EGFR TKI. A further prospective study is warranted.
3.The effect of the response to the coronavirus disease pandemic on treatment outcomes in patients with lymphoma and multiple myeloma
Ka-Won KANG ; Byung-Hyun LEE ; Min Ji JEON ; Eun Sang YU ; Dae Sik KIM ; Se Ryeon LEE ; Hwa Jung SUNG ; Chul Won CHOI ; Yong PARK ; Byung Soo KIM
The Korean Journal of Internal Medicine 2021;36(6):1459-1470
Background/Aims:
Relatively little data are available on how the response to the coronavirus disease 2019 (COVID-19) pandemic has affected treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. We aimed to determine the effect of COVID-19 countermeasures on treatment outcomes in this patient population.
Methods:
We retrospectively analyzed data on patients treated for lymphoma or multiple myeloma in two tertiary hospitals in Seoul. Patients were divided into two groups: group 1 included patients who received chemotherapy between September and December 2019 (the control period), and group 2 included patients who received chemotherapy between September and December 2020 (the study period). Countermeasures to COVID-19 were applied to the patients in group 2. The countermeasures implemented included mask wearing and regular handwashing at home and in hospital; COVID-19 risk assessments on all hospital visitors; and pre-emptive COVID-19 screening for all newly hospitalized patients and their resident guardians.
Results:
No differences in treatment outcomes, including treatment response, incidence and duration of neutropenia or neutropenic fever, delays in chemotherapy, or number of deaths during chemotherapy, were observed between the g roups. None of the patients in group 2 tested positive for COVID-19, and there were no COVID-19-related deaths during the study period.
Conclusions
Countermeasures to COVID-19 did not affect treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. Data on the effect of countermeasures to COVID-19 on treatment outcomes should continue to be analyzed to ensure that treatment outcomes are not adversely affected.
4.Immature platelet fraction based diagnostic predictive scoring model for immune thrombocytopenia
Min Ji JEON ; Eun Sang YU ; Ka-Won KANG ; Byung-Hyun LEE ; Yong PARK ; Se Ryeon LEE ; Hwa Jung SUNG ; Soo Yong YOON ; Chul Won CHOI ; Byung Soo KIM ; Dae Sik KIM
The Korean Journal of Internal Medicine 2020;35(4):970-978
Background/Aims:
The diagnosis of immune thrombocytopenia (ITP) is based on clinical manifestations and there is no gold standard. Thus, even hematologic malignancy is sometimes misdiagnosed as ITP and adequate treatment is delayed. Therefore, novel diagnostic parameters are needed to distinguish ITP from other causes of thrombocytopenia. Immature platelet fraction (IPF) has been proposed as one of new parameters. In this study, we assessed the usefulness of IPF and developed a diagnostic predictive scoring model for ITP.
Methods:
We retrospectively studied 568 patients with thrombocytopenia. Blood samples were collected and IPF quantified using a fully-automated hematology analyzer. We also estimated other variables that could affect thrombocytopenia by logistic regression analysis.
Results:
The median IPF was significantly higher in the ITP group than in the non-ITP group (8.7% vs. 5.1%). The optimal cut-off value of IPF for differentiating ITP was 7.0%. We evaluated other laboratory variables via logistic regression analysis. IPF, hemoglobin, lactate dehydrogenase (LDH), and ferritin were statistically significant and comprised a diagnostic predictive scoring model. Our model gave points to each of variables: 1 to high hemoglobin (> 12 g/dL), low ferritin (≤ 177 ng/ mL), normal LDH (≤ upper limit of normal) and IPF ≥ 7 and < 10, 2 to IPF ≥ 10. The final score was obtained by summing the points. We defined that ITP could be predicted in patients with more than 3 points.
Conclusions
IPF could be a useful parameter to distinguish ITP from other causes of thrombocytopenia. We developed the predictive scoring model. This model could predict ITP with high probability.
5.Impact of subsequent chemotherapy on the survival of elderly patients with extensive stage small cell lung cancer
Eun Joo KANG ; Yoon Ji CHOI ; Se Ryeon LEE ; Hwa Jung SUNG ; Jung Sun KIM
The Korean Journal of Internal Medicine 2020;35(6):1468-1476
Background/Aims:
The prognosis of small cell lung cancer (SCLC) is still poor because of rapid recurrence, despite good response to initial chemotherapy. Additionally, patients’ old ages and comorbidities are often obstacles that make it difficult to apply subsequent treatment after initial treatment. This retrospective study analyzed the correlation of post-progression survival (PPS) with overall survival (OS), and prognostic factors including comorbidities to figure out impact of subsequent chemotherapy on OS in elderly extensive disease SCLC.
Methods:
We analyzed 101 patients of age 65 years or older who were recently diagnosed with extensive disease SCLC (ED-SCLC) in Korea University Medical Center between January 1995 and December 2015. The degree of comorbidity was scored using simplified comorbidity score (SCS). Correlation between PPS, progression-free survival (PFS) and OS was analyzed using a Pearson correlation coefficient. Cox proportional hazards regression was employed to examine the influence of clinical variables on survival.
Results:
Median age of patients was 71 years old (range, 65 to 83). Median OS was 8.7 months (range, 0.3 to 42.7). PPS was a reliable factor on OS than PFS (R2 = 0.852, p < 0.001). Prognostic factors associated with improved survival were SCS < 9, administration > 4 cycles of first line chemotherapy and subsequent second line chemotherapy.
Conclusions
PPS was more correlated with OS than PFS in elderly patients with ED-SCLC. The most important prognostic factors for PPS and OS included SCS and second line chemotherapy. Patients receiving subsequent treatment had increased OS regardless of degree of comorbidity.
6.The role of platelet function analyzer-200 in predicting perioperative bleeding risk
Eun Sang YU ; Min Ji JEON ; Ka-Won KANG ; Byung-Hyun LEE ; Eun Joo KANG ; Yong PARK ; Se Ryeon LEE ; Hwa Jung SUNG ; Chul Won CHOI ; Byung Soo KIM ; Dae Sik KIM
The Korean Journal of Internal Medicine 2020;35(5):1199-1209
Background/Aims:
Various preoperative screening tests, such as platelet count, prothrombin time, activated partial thromboplastin time, and bleeding time, have been widely used to evaluate the risk of bleeding during surgery. Use of platelet function analyzer (PFA)-100/200 for assessing platelet function instead of bleeding time is increasing. However, its role in predicting the perioperative risk of bleeding remains controversial.
Methods:
Data of 703 patients who underwent surgery under general anesthesia were retrospectively analyzed. Preoperative platelet function was measured using PFA-200 system and the association with intraoperative bleeding was assessed. Additionally, other variables that could affect PFA-200 results were assessed by logistic regression analysis.
Results:
Collagen/epinephrine (COL/EPI) test was prolonged in 199/703 (28.3%) patients (EPI group), while 99/212 (46.7%) patients showed COL/adenosine diphosphate test abnormalities. Bleeding over 300 mL during surgery occurred in 14.3% and 20.1% of patients in the normal and EPI groups, respectively (p = 0.058). In addition, red blood cell transfusion within 72 hours after surgery rate was significantly higher in the EPI group than in the normal group (31.7% vs. 23.4%,p= 0.024). In multivariate logistic analysis, prolongation closure time with COL/EPI (p = 0.068) was marginally associated with risk of bleeding during surgery. Furthermore, PFA-200 results were influenced by various factors, such as nonsteroidalanti-inflammatory drug use, blood group, hematocrit, and time of blood collection.
Conclusions
Preoperative PFA-200 test may be helpful in predicting the risk of perioperative bleeding. However, its results should be carefully interpreted becausethey are affected by several factors.
7.Usefulness of Chromosomal Microarray in Hematologic Malignancies: A Case of Aggressive NK-cell Leukemia with 1q Abnormality
Yoo Na CHUNG ; Ha Nui KIM ; Se Ryeon LEE ; Hwa Jung SUNG ; Myung Hyun NAM
Laboratory Medicine Online 2019;9(3):189-193
A variety of clonal cytogenetic abnormalities have been reported in aggressive natural killer (NK)-cell lymphoma and leukemia. Recent chromosomal microarray studies have shown both gain and loss of 1q and loss of 7p as recurrent abnormalities in aggressive NK-cell leukemia. Here, we report a case of aggressive NK-cell leukemia with complex chromosomal gains and losses, as confirmed by chromosomal microarray analysis. The patient showed an aggressive clinical course, which was complicated by hemophagocytic lymphohistiocytosis. Conventional cytogenetic analysis revealed trisomy 3 and 1q gain only. However, chromosomal microarray analysis detected an additional gain of 1q21.1–q24.2 and a loss of 1q24.2–q31.3. These abnormal lesions might play a role in the pathogenesis of aggressive NK-cell leukemia by inactivating tumor suppressor genes or by activating oncogenes. These results suggest that chromosomal microarray analysis may be used to provide further genetic information for patients with hematological malignancies, including aggressive NK-cell leukemia.
Chromosome Aberrations
;
Cytogenetic Analysis
;
Genes, Tumor Suppressor
;
Hematologic Neoplasms
;
Humans
;
Leukemia
;
Lymphohistiocytosis, Hemophagocytic
;
Lymphoma
;
Microarray Analysis
;
Oncogenes
;
Trisomy
8.Analysis of Overall Survival According to Bone Marrow Aspiration Results in Non-Hodgkin's Lymphoma Patients
Jung Yoon CHOI ; Ka Won KANG ; Byung Hyun LEE ; Eun Sang YU ; Dae Sik KIM ; Se Ryeon LEE ; Hwa Jung SUNG ; Seok Jin KIM ; Chul Won CHOI ; Byung Soo KIM ; Yong PARK
Korean Journal of Medicine 2019;94(2):182-190
BACKGROUND/AIMS: The staging work-up for patients with non-Hodgkin's lymphoma includes bone marrow aspiration and biopsy. Consistent results of both procedures can clarify the diagnosis. However, no clear guidelines have been established regarding positive results for bone marrow aspiration alone. The aim of this study was, therefore, to analyze the overall survival (OS) for the clinical diagnoses of these patients using morphological methods. METHODS: We performed a retrospective analysis of patients who were consecutively enrolled in the Korea University Lymphoma Registry from 1991 to 2016. OS was compared according to the bone marrow group: without bone marrow involvement (BMA−/BMBx−), with positive results for aspiration and negative results for biopsy (BMA+/BMBx−), and with bone marrow involvement in biopsy (BMBx+). OS was assessed using the Kaplan-Meier method and multivariate analysis. RESULTS: Of 1,735 patients, 1,326 were analyzed and 409 were excluded. In the Kaplan-Meier survival analysis, OS was significantly worse for patients in the BMBx+ group compared with those in the BMA−/BMBx− group (p < 0.001). However, there was no significant difference in OS between patients in the BMA+/BMBx− group and those in other groups (vs. BMA−/BMBx−, p = 0.163; BMBx+, p = 0.292). In multivariate analysis, by adjusting survival-related variables, the BMA+/BMBx− group showed marginal significance compared to the BMA−/BMBx− group (p = 0.081), and showed significance in the subgroup of indolent non-Hodgkin's lymphoma patients (p = 0.003). CONCLUSIONS: This study suggested that even if there are positive results in bone marrow aspiration alone in patients with non-Hodgkin lymphoma, attention to patient characteristics, involving significance as a poor prognosis for OS, is required.
Biopsy
;
Bone Marrow
;
Diagnosis
;
Humans
;
Korea
;
Lymphoma
;
Lymphoma, Non-Hodgkin
;
Methods
;
Multivariate Analysis
;
Prognosis
;
Retrospective Studies
9.Analysis of Overall Survival According to Bone Marrow Aspiration Results in Non-Hodgkin's Lymphoma Patients
Jung Yoon CHOI ; Ka Won KANG ; Byung Hyun LEE ; Eun Sang YU ; Dae Sik KIM ; Se Ryeon LEE ; Hwa Jung SUNG ; Seok Jin KIM ; Chul Won CHOI ; Byung Soo KIM ; Yong PARK
Korean Journal of Medicine 2019;94(2):182-190
BACKGROUND/AIMS:
The staging work-up for patients with non-Hodgkin's lymphoma includes bone marrow aspiration and biopsy. Consistent results of both procedures can clarify the diagnosis. However, no clear guidelines have been established regarding positive results for bone marrow aspiration alone. The aim of this study was, therefore, to analyze the overall survival (OS) for the clinical diagnoses of these patients using morphological methods.
METHODS:
We performed a retrospective analysis of patients who were consecutively enrolled in the Korea University Lymphoma Registry from 1991 to 2016. OS was compared according to the bone marrow group: without bone marrow involvement (BMA−/BMBx−), with positive results for aspiration and negative results for biopsy (BMA+/BMBx−), and with bone marrow involvement in biopsy (BMBx+). OS was assessed using the Kaplan-Meier method and multivariate analysis.
RESULTS:
Of 1,735 patients, 1,326 were analyzed and 409 were excluded. In the Kaplan-Meier survival analysis, OS was significantly worse for patients in the BMBx+ group compared with those in the BMA−/BMBx− group (p < 0.001). However, there was no significant difference in OS between patients in the BMA+/BMBx− group and those in other groups (vs. BMA−/BMBx−, p = 0.163; BMBx+, p = 0.292). In multivariate analysis, by adjusting survival-related variables, the BMA+/BMBx− group showed marginal significance compared to the BMA−/BMBx− group (p = 0.081), and showed significance in the subgroup of indolent non-Hodgkin's lymphoma patients (p = 0.003).
CONCLUSIONS
This study suggested that even if there are positive results in bone marrow aspiration alone in patients with non-Hodgkin lymphoma, attention to patient characteristics, involving significance as a poor prognosis for OS, is required.
10.Modified dose of melphalan-prednisone in multiple myeloma patients receiving bortezomib plus melphalan-prednisone treatment
Se Ryeon LEE ; Hojoon CHOI ; Byung Hyun LEE ; Ka Won KANG ; Eun Sang YU ; Dae Sik KIM ; Yong PARK ; Chul Won CHOI ; Byung Soo KIM ; Hwa Jung SUNG
The Korean Journal of Internal Medicine 2019;34(6):1333-1346
BACKGROUND/AIMS:
Bortezomib plus melphalan-prednisone (VMP) is a standard treatment for multiple myeloma, particularly for patients who are ineligible for high-dose therapy. However, early discontinuation or treatment modification is often needed owing to adverse events. The aim of this study was to investigate the clinical outcomes of modifying the dose of melphalan-prednisone (MP) in patients receiving VMP.
METHODS:
We examined 67 patients who received a modified dose of MP, and 38 patients who received the regularly planned dose of MP. We then analyzed clinical differences between the groups.
RESULTS:
Although there was no difference in the proportion of discontinuation due to adverse events between dose groups, more patients in the planned-dose group experienced earlier discontinuation in general. The overall response rate (ORR) was 81.0% and complete response (CR) rate was 30.5%. After a median 15.7 months of follow-up, the median progression-free survival (PFS) and overall survival (OS) were 25.0 and 47.8 months, respectively. There was no significant difference in the ORR, CR, PFS, and OS of the two dose groups. A median of four cycles were delivered, and the median cumulative bortezomib dose was 41.6 mg/m². The median PFS in patients with doses ≥ 41.6 mg/m² was longer than that in patients with doses < 41.6 mg/m² (35.1 months vs. 9.6 months). However, when MP was < 50% of the planned dose, PFS and OS were poor.
CONCLUSIONS
Modifying the dose of MP might be a feasible and effective therapeutic approach for multiple myeloma patients receiving VMP treatment.

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