1.Long-term Psychiatric and Endocrine Complications Following Hematopoietic Stem Cell Transplantation in Hematologic Disease in Korea: A Nation-Wide Cohort Study
Min Ji JEON ; Eunjin NOH ; Seok Joo MOON ; Eun Sang YU ; Chul Won CHOI ; Dae Sik KIM ; Eun Joo KANG
Cancer Research and Treatment 2024;56(4):1262-1269
Purpose:
Numerous patients experience long-term complications after hematopoietic stem cell transplantation (HSCT). This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications following HSCT through big data analyses.
Materials and Methods:
We established a cohort of patients with hematologic disease who underwent HSCT in Korea between 2010 and 2012 using the Health Insurance Review & Assessment Service data. A total of 3,636 patients were identified, and insurance claims were tracked using psychiatric and endocrine diagnostic International Classification of Diseases, 10th Revision codes for the ensuing decade. We identified the incidence rates of long-term complications based on the baseline disease and HSCT type. Prognostic factors for each complication were scrutinized using logistic regression analysis.
Results:
A total of 1,879 patients underwent allogeneic HSCT and 1,757 patients received autologous HSCT. Post-HSCT, 506 patients were diagnosed with depression, 465 with anxiety disorders, and 659 with diabetes. The highest incidence of long-term complications occurred within the first year post-HSCT (12.2%), subsequently decreasing over time. Risk factors for depressive disorders after allogeneic HSCT included female sex, a total body irradiation–based conditioning regimen, and cyclosporine. Identified risk factors for diabetes mellitus comprised old age, total body irradiation–based conditioning regimen, and non-antithymocyte globulin protocol. Regarding autologous HSCT, only female sex was identified as a risk factor for depressive disorders, whereas elderly patients and those with multiple myeloma were identified as poor prognostic factors for diabetes mellitus.
Conclusion
The incidence of long-term psychiatric and endocrine complications post-HSCT remains high, and patients with risk factors for these complications require vigilant follow-up.
2.First-Pass Recanalization with EmboTrap II in Acute Ischemic Stroke (FREE-AIS): A Multicenter Prospective Study
Jang-Hyun BAEK ; Byung Moon KIM ; Sang Hyun SUH ; Hong-Jun JEON ; Eun Hyun IHM ; Hyungjong PARK ; Chang-Hyun KIM ; Sang-Hoon CHA ; Chi-Hoon CHOI ; Kyung Sik YI ; Jun-Hwee KIM ; Sangil SUH ; Byungjun KIM ; Yoonkyung CHANG ; So Yeon KIM ; Jae Sang OH ; Ji Hoe HEO ; Dong Joon KIM ; Hyo Suk NAM ; Young Dae KIM
Korean Journal of Radiology 2023;24(2):145-154
Objective:
We aimed to evaluate the efficacy of EmboTrap II in terms of first-pass recanalization and to determine whether it could yield favorable outcomes.
Materials and Methods:
In this multicenter, prospective study, we consecutively enrolled patients who underwent mechanical thrombectomy using EmboTrap II as a front-line device. The primary outcome was the first pass effect (FPE) rate defined by modified Thrombolysis In Cerebral Infarction (mTICI) grade 2c or 3 by the first pass of EmboTrap II. In addition, modified FPE (mFPE; mTICI grade 2b–3 by the first pass of EmboTrap II), successful recanalization (final mTICI grade 2b–3), and clinical outcomes were assessed. We also analyzed the effect of FPE on a modified Rankin Scale (mRS) score of 0–2 at 3 months.
Results:
Two hundred-ten patients (mean age ± standard deviation, 73.3 ± 11.4 years; male, 55.7%) were included. Ninetynine patients (47.1%) had FPE, and mFPE was achieved in 150 (71.4%) patients. Successful recanalization was achieved in 191 (91.0%) patients. Among them, 164 (85.9%) patients underwent successful recanalization by exclusively using EmboTrap II. The time from groin puncture to FPE was 25.0 minutes (interquartile range, 17.0–35.0 minutes). Procedure-related complications were observed in seven (3.3%) patients. Symptomatic intracranial hemorrhage developed in 14 (6.7%) patients. One hundred twenty-three (58.9% of 209 completely followed) patients had an mRS score of 0–2. Sixteen (7.7% of 209) patients died during the follow-up period. Patients who had successful recanalization with FPE were four times more likely to have an mRS score of 0–2 than those who had successful recanalization without FPE (adjusted odds ratio, 4.13;95% confidence interval, 1.59–10.8; p = 0.004).
Conclusion
Mechanical thrombectomy using the front-line EmboTrap II is effective and safe. In particular, FPE rates were high. Achieving FPE was important for an mRS score of 0–2, even in patients with successful recanalization.
3.Implications of the 5th Edition of the World Health Organization Classification and International Consensus Classification of Myeloid Neoplasm in Myelodysplastic Syndrome With Excess Blasts and Acute Myeloid Leukemia
Cheonghwa LEE ; Ha Nui KIM ; Jung Ah KWON ; Soo-Young YOON ; Min Ji JEON ; Eun Sang YU ; Dae Sik KIM ; Chul Won CHOI ; Jung YOON
Annals of Laboratory Medicine 2023;43(5):503-507
The fifth edition of the WHO classification (2022 WHO) and the International Consensus Classification (2022 ICC) of myeloid neoplasms have been recently published. We reviewed the changes in the diagnosis distribution in patients with MDS with excess blasts (MDS-EB) or AML using both classifications. Forty-seven patients previously diagnosed as having AML or MDS-EB with available mutation analysis data, including targeted next-generation and RNA-sequencing data, were included. We reclassified 15 (31.9%) and 27 (57.4%) patients based on the 2022 WHO and 2022 ICC, respectively. One patient was reclassified as having a translocation categorized as a rare recurring translocation in both classifications. Reclassification was mostly due to the addition of mutation-based diagnostic criteria (i.e., AML, myelodysplasia-related) or a new entity associated with TP53 mutation. In both classifications, MDS diagnosis required the confirmation of multi-hit TP53 alterations. Among 14 patients with TP53 mutations, 11 harbored multi-hit TP53 alterations, including four with TP53 mutations and loss of heterozygosity. Adverse prognosis was associated with multi-hit TP53 alterations (P=0.009) in patients with MDS-EB, emphasizing the importance of detecting the mutations at diagnosis. The implementation of these classifications may lead to the identification of different subtypes from previously heterogeneous diagnostic categories based on genetic characteristics.
4.Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing
Min Ji JEON ; Eun Sang YU ; Chul Won CHOI ; Dae Sik KIM
The Korean Journal of Internal Medicine 2023;38(6):893-902
Background/Aims:
Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge.
Methods:
We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing.
Results:
In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations.
Conclusions
We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.
5.Prediction of Stent Failure for Malignant Ureteral Obstruction in Non-Urological Cancer
Ji Eun HEO ; Dae Young JEON ; Jongsoo LEE ; Hyun Ho HAN ; Won Sik JANG
Yonsei Medical Journal 2023;64(11):665-669
Purpose:
To analyze prognostic factors associated with ureteral stent failure and to develop a prediction model for malignant ureteral obstruction (MUO) in patients with non-urological cancers.
Materials and Methods:
We retrospectively reviewed patients with non-urological cancers who underwent ureteral stenting or percutaneous nephrostomy (PCN) for MUO between 2006 and 2014. Variables predicting stent failure were identified using Cox regression analysis.
Results:
Of the 743 patients, 468 (63.0%) underwent ureteral stenting only, and 275 (37.0%) underwent PCN owing to technical (n=215) or functional (n=60) stent failure. The median overall survival was 4 [interquartile range (IQR) 1–11] months, and the median interval duration to stent failure was 2 (IQR 0–7) months. In univariate analysis, lower gastrointestinal cancer, previous radiotherapy to the pelvis, bladder invasion, lower ureteral obstruction, and low previous estimated glomerular filtration rate (eGFR) (<30 mL/min/1.73 m2 ) were significantly associated with a decreased survival rate. In multivariate analysis, bladder invasion and previous eGFR were significant predictors. With these two predictors, we divided patients into three groups based on their presence: low-risk (neither factor; n=516), intermediate-risk (one factor; n=206), and high-risk (both factors; n=21). The median stent failure-free survival rates of patients in the low-, intermediate-, and high-risk groups were 26 (8-unreached), 1 (0–18), and 0 (0–0) months, respectively (p<0.001).
Conclusion
In cases of ureteral obstruction caused by non-urological cancers, patients with bladder invasion and a low eGFR showed poor stent failure-free survival. Therefore, PCN should be considered the primary procedure for these patients.
6.Composite follicular lymphoma and classic Hodgkin lymphoma
Han-Na KIM ; Min Ji JEON ; Eun Sang YU ; Dae Sik KIM ; Chul-Won CHOI ; Young Hyeh KO
Journal of Pathology and Translational Medicine 2022;56(1):57-60
Composite lymphoma is very rare and a combination of Hodgkin lymphoma and non-Hodgkin lymphoma and even histiocytic tumors can occur. Because of the unfamiliarity, not only can this cause diagnostic problems, but can also affect treatment plan. We report a case of composite lymphoma in a 40-year-old male. Initial biopsy showed a composite lymphoma of follicular lymphoma grade 1 and classic Hodgkin lymphoma. After chemotherapy, another lymph node was taken because of disease progression, which revealed follicular lymphoma, grade 3a without Hodgkin lymphoma component.
7.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.
8.Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity
Junshik HONG ; Yoo Jin LEE ; Sung Hwa BAE ; Jun Ho YI ; Sungwoo PARK ; Myung Hee CHANG ; Young Hoon PARK ; Shin Young HYUN ; Joo-Seop CHUNG ; Ji Eun JANG ; Joo Young JUNG ; So-Yeon JEON ; Seo-Young SONG ; Hawk KIM ; Dae Sik KIM ; Sung-Hyun KIM ; Min Kyoung KIM ; Sang Hoon HAN ; Seonyang PARK ; Yoo-Jin KIM ; Je-Hwan LEE ;
Blood Research 2021;56(2):102-108
Background:
To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea.
Methods:
Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed.
Results:
A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%).
Conclusion
Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.
9.Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity
Junshik HONG ; Yoo Jin LEE ; Sung Hwa BAE ; Jun Ho YI ; Sungwoo PARK ; Myung Hee CHANG ; Young Hoon PARK ; Shin Young HYUN ; Joo-Seop CHUNG ; Ji Eun JANG ; Joo Young JUNG ; So-Yeon JEON ; Seo-Young SONG ; Hawk KIM ; Dae Sik KIM ; Sung-Hyun KIM ; Min Kyoung KIM ; Sang Hoon HAN ; Seonyang PARK ; Yoo-Jin KIM ; Je-Hwan LEE ;
Blood Research 2021;56(2):102-108
Background:
To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea.
Methods:
Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed.
Results:
A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%).
Conclusion
Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.
10.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.

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