Jong Wook Lee’s research while affiliated with Hanyang University Seoul Hospital and other places

In patients with paroxysmal nocturnal hemoglobinuria (PNH), complement component 5 (C5) inhibitors ravulizumab and eculizumab control terminal complement activity and intravascular hemolysis, drivers of morbidity and mortality. During C5 inhibitor treatment, ongoing C3 fragment deposition on surviving PNH red blood cells may cause clinically significant extravascular hemolysis (csEVH) in some patients. csEVH is not thought to be life-threatening but may cause symptomatic anemia and need for transfusion. This post-hoc analysis of studies 301 (NCT02946463) and 302 (NCT03056040) evaluated the prevalence of csEVH (symptomatic anemia [hemoglobin levels < 9.5 g/dL] with absolute reticulocyte count ≥ 120 × 109/L) in adult patients with PNH treated with ravulizumab or eculizumab for 6 months (183 days). The association between csEVH and fatigue (measured using the Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] scale) was also evaluated in study 302 patients with stable disease. On Day 183 of studies 301 and 302, respectively, csEVH prevalence was 23.2% (29/125) and 20.2% (19/94) with ravulizumab, and 24.8% (30/121) and 21.3% (20/94) with eculizumab. All patients in study 302 with csEVH experienced fatigue, which was mostly mild (ravulizumab: 79%, eculizumab: 65%) or moderate (ravulizumab: 21%, eculizumab: 30%). FACIT-F scores remained stable from baseline (ravulizumab: 42.2; eculizumab: 38.3) to Day 183 (ravulizumab: 44.3; eculizumab: 38.3); close to general population normative values. This analysis demonstrated that csEVH affected 20-25% of patients with PNH, most of whom experienced mild fatigue, with fatigue remaining stable during treatment. Ravulizumab and eculizumab continue to provide benefit to adults with PNH with csEVH.

In patients with paroxysmal nocturnal hemoglobinuria (PNH), complement component 5 (C5) inhibitors ravulizumab and eculizumab control terminal complement activity and intravascular hemolysis, drivers of morbidity and mortality. During C5 inhibitor treatment, ongoing C3 fragment deposition on surviving PNH red blood cells may cause clinically significant extravascular hemolysis (csEVH) in some patients. csEVH is not thought to be life-threatening but may cause symptomatic anemia and need for transfusion. This post-hoc analysis of studies 301 (NCT02946463) and 302 (NCT03056040) evaluated the prevalence of csEVH (symptomatic anemia [hemoglobin levels < 9.5 g/dL] with absolute reticulocyte count ≥ 120 × 109/L) in adult patients with PNH treated with ravulizumab or eculizumab for 6 months (183 days). The association between csEVH and fatigue (measured using the Functional Assessment of Chronic Illness Therapy - Fatigue [FACIT-F] scale) was also evaluated in study 302 patients with stable disease. On Day 183 of studies 301 and 302, respectively, csEVH prevalence was 23.2% (29/125) and 20.2% (19/94) with ravulizumab, and 24.8% (30/121) and 21.3% (20/94) with eculizumab. All patients in study 302 with csEVH experienced fatigue, which was mostly mild (ravulizumab: 79%, eculizumab: 65%) or moderate (ravulizumab: 21%, eculizumab: 30%). FACIT-F scores remained stable from baseline (ravulizumab: 42.2; eculizumab: 38.3) to Day 183 (ravulizumab: 44.3; eculizumab: 38.3); close to general population normative values. This analysis demonstrated that csEVH affected 20-25% of patients with PNH, most of whom experienced mild fatigue, with fatigue remaining stable during treatment. Ravulizumab and eculizumab continue to provide benefit to adults with PNH with csEVH.

Thromboembolism (TE) is a major cause of morbidity and mortality in patients with paroxysmal nocturnal hemoglobinuria (PNH). This narrative review summarizes available evidence on TE in Asian patients with PNH and discusses practical considerations and challenges for preventing and managing PNH-associated TE in Asian populations. Evidence suggests that, compared with non-Asians, fewer Asian patients have a history of TE (3.6% vs. 8.9%, p < 0.01), receive anticoagulants (8.5% vs. 16.2%, p = 0.002), or die from TE (6.9% vs. 43.7%, p = 0.000). Independent predictors of TE include lactate dehydrogenase ≥ 1.5 × upper limit of normal, pain, and male sex. Clone size alone does not appear to be a reliable estimate of TE risk. D-dimer levels are a useful marker of hemostatic activation, although they are not specific to PNH. Complement inhibition reduces the incidence of TE, although it does not wholly eliminate TE risk. Eligibility criteria and access to complement inhibitors vary across Asia, with limited availability in some countries. Anticoagulation is required to treat acute TE events and for primary or secondary prophylaxis in selected patients. Physicians and patients must stay alert to the signs and symptoms of TE to ensure prompt and appropriate treatment.

Ravulizumab is a second-generation complement component 5 (C5) inhibitor (C5i) approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) following positive results from two pivotal trials in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH. In both trials, after the 26week primary evaluation period, all patients received ravulizumab for up to 6 years. To report ravulizumab treatment outcomes in patients with PNH originally naive to C5i treatment and eculizumab-experienced patients with PNH treated for up to 6 years. Originally C5i-naive (N = 244) and eculizumab-experienced (N = 191) patients with PNH continued ravulizumab treatment for up to 6 years. Major adverse vascular events (MAVEs; including thrombotic events [TEs]) and survival are reported, including a comparison of survival with untreated patients from the International PNH Registry. Laboratory parameters for intravascular hemolysis (IVH) are also described. For up to 6 years (1468.0 patient-years of exposure), ravulizumab provided durable control of terminal complement activity and IVH, resulting in a low incidence of MAVEs (including TEs) reported (MAVE rate: 0.7–1.4 per 100 patient-years) and, compared with untreated patients from the International PNH Registry, reduced the risk of mortality by five-fold. The few breakthrough IVH events reported (N = 122) were commonly associated with complement-amplifying conditions, and only two events (1.8%) were associated with suboptimal inhibition of C5 (i.e. serum free C5 ≥ 0.5 µg/mL). These results support the long-term use of ravulizumab as the first-line treatment of choice for patients with PNH. Trial registration details: NCT01374360; registered: October 29, 2004; NCT02946463; registered: October 27, 2016; NCT03056040; registered: June 05, 2017.

Incidence of visual impairment (VI) and dyslipidemia is increasing with aging. Although good medication adherence (MA) is a crucial factor in achieving therapeutic goals for dyslipidemia, there is a paucity of studies measuring MA in the visually impaired with dyslipidemia. We investigated whether patients with VI had worse MA to dyslipidemia drugs than non-disabled people and determined the factors affecting MA among patients with VI. Data on dyslipidemia patients with VI were extracted in 2017 from the sample cohort database of the National Health Insurance Service. MA to dyslipidemia drugs was measured for two years based on the proportion of days covered (PDC). Conditional logistic regression analysis was performed to analyze the effect of VI on good MA (PDC ≥0.8). The VI group (0.860) had a larger PDC than the non-disabled group (0.850). The adjusted odds ratio (aOR) for good MA among VI vs. non-disabled individuals was statistically insignificant (1.137, 95% confidence interval:0.958–1.350). Significant factors for poor MA in the VI group were younger age (aOR for 20–39 vs. ≥75 years old: 0.124), lower income (aOR for 9-10th decile (rich) vs. 1-4th decile (poor): 1.771), shorter duration of dyslipidemia (aOR for 1–4 vs. 15 years: 0.416), having lower-level providers sas their main providers (aOR for clinics vs. general/tertiary-care hospitals: 0.545), and having mental diseases (aOR: 0.679). Patients with VI did not have worse MA than non-disabled patients taking dyslipidemia medication.

Purpose This study investigated the occurrence of subsequent malignancies (SM) in adult patients with severe aplastic anemia (SAA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to address the lack of large-scale, long-term data on this complication. Methods A retrospective cohort analysis of 376 adult patients with SAA who underwent allo-HSCT between 2002 and 2021 at a single center was conducted. The incidence, risk factors, and survival impact of SM were also examined. Results During the follow-up period, 31 cases of SM (8.2%) were identified. Approximately one-third (32.3%) of SM cases were hematologic malignancies, including post-transplant lymphoproliferative disorder (16.1%), myelodysplastic neoplasm (6.5%), and acute myeloid leukemia (3.2%). Solid tumors accounted for 67.7% of cases, with thyroid cancer being the most prevalent (25.8%). The 15-year cumulative incidence of SM was 11.2%, and the hazard ratio for overall survival according to the development of SM was 16.25 ( p < 0.001). High-dose total body irradiation (TBI), anti-thymocyte globulin (ATG), and moderate-to-severe chronic graft-versus-host disease (GVHD) were identified as significant risk factors for subsequent malignancy. Post-transplant SAA patients exhibited a 3.54-fold higher observed cancer incidence than the expected incidence calculated from the age-, sex-, and calendar year-matched general population. Conclusion SM is a significant long-term complication in patients with posttransplant SAA and has a substantial survival impact. Patients receiving high-dose TBI or ATG, and those with moderate-to-severe chronic GVHD, require vigilant long-term monitoring.

Complement C5 inhibitor treatment with ravulizumab or eculizumab for paroxysmal nocturnal hemoglobinuria (PNH) improves outcomes and survival. Some patients remain anemic due to clinically significant extravascular hemolysis (cs-EVH: hemoglobin [Hgb] ≤9.5 g/dL and absolute reticulocyte count [ARC] ≥120×109/L). In the phase 3 ALPHA trial, participants received oral factor D inhibitor danicopan (150 mg 3 times daily) or placebo plus ravulizumab or eculizumab during the 12-week, double-blind treatment period (TP) 1; those receiving placebo switched to danicopan during the subsequent 12-week, open-label TP2 and continued during the 2-year long-term extension (LTE). There were 86 participants randomized in the study, of whom 82 entered TP2 and 80 entered LTE. The primary endpoint was met, with Hgb improvements from baseline at week 12 (Wk12) (LS mean change: 2.8 g/dL) with danicopan. For participants switching from placebo to danicopan at Wk12, improvements in mean Hgb were observed at Wk24. Similar trends were observed for the proportion of participants with ≥2 g/dL Hgb increase, ARC, proportion of participants achieving transfusion avoidance, and Functional Assessment of Chronic Illness Therapy-Fatigue scale scores. Improvements were maintained up to week 72. No new safety signals were observed. The breakthrough hemolysis rate was 6 events per 100 patient-years. These long-term data demonstrate sustained efficacy and safety of danicopan plus ravulizumab/eculizumab for continued control of terminal complement activity, intravascular hemolysis, and cs-EVH in PNH. Registration: Clinicaltrials.gov, NCT04469465.

COVID-19 became a global pandemic in 2020 and significantly affected the activity of hematopoietic cell transplants (HCT) worldwide. Despite these challenges, a total of 28,793 transplants, including 18,518 allogeneic and 10,275 autologous transplants, were performed in 719 facilities in 2020 in the Asia-Pacific (AP) region. This represented a 5.1% increase in allogeneic transplants and a 3.1% increase in autologous transplants, an overall increase of 4.4% compared to the numbers in 2019. With respect to the donor source, haploidentical transplants increased significantly by 18.6%, related transplants by 8.8%, and cord blood transplants (CBT) by 9.2%. However, the number of unrelated transplants, excluding CBT, decreased for the first time by 8.2%. As a result, COVID-19 facilitated the growth of haploidentical transplants due to cross-border restrictions. Regarding the changes in the total number of transplants by country/region in 2020, it increased by 2,048 transplants in China, followed by Japan (210 transplants) and Korea (230 transplants); however, 14 of the 22 countries and regions decreased their number of transplants in 2020 compared to the previous year. There was no correlation between the increase or decrease in the number of transplants in 2020 and the Gross National Income (GNI) per capita of each country/region in 2020, as well as Domestic General Government Health Expenditure as a percentage of General Government Expenditure (GGHE-D/GGE). In 2021, the total number of transplants in this region was 34,754. With the exception of a few countries/regions that decreased the number of transplants in 2020, most countries/regions have started to see a recovery in 2021. The COVID-19 pandemic significantly affected the supply chain and logistics involved in HCT rather than its numbers; however, we have found ways to overcome logistical challenges to carry out transplant medicine without delay, even under these circumstances.

Introduction Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare, aggressive subtype of primary gastrointestinal T-cell lymphoma. Owing to the absence of symptoms characteristic of MEITL, diagnosis can be challenging, and the low response rate to conventional chemotherapy leads to an abysmal prognosis. This study aimed to define the clinicopathologic characteristics of MEITL in Korea, evaluate the clinical outcomes of intensive chemotherapy with and without hematopoietic stem cell transplantation (HSCT), and explore prognostic factors. Methods This single-center retrospective study examined the clinical data of 35 patients diagnosed with MEITL at Seoul St. Mary’s Hospital from May 2012 to May 2023. Results We included 22 men and 13 women (median age: 59 years; range: 37–79 years). Many patients exhibited acute abdominal pain (n=23, 65.7%) related to bowel perforation (n=21, 60.0%). Most patients (30/35, 85.7%) underwent surgical intervention to diagnose MEITL, whereas only five were diagnosed via endoscopic evaluation. Of the 32 patients receiving first-line therapy, 4 died before assessment, 10 achieved a complete response (CR), 6 had a relapse, and 18 exhibited progressive disease (PD). Seven of 10 patients received upfront HSCT, either autologous (auto-HSCT, n=4) or allogeneic (allo-HSCT, n=3). All four patients on auto-HSCT died after relapse. All three patients who received allo-HSCT maintained a CR by the final follow-up. Three of 6 patients who relapsed and 13 of 18 exhibiting PD received salvage therapy; one patient on salvage auto-HSCT with cytokine-induced killer cell infusion has survived progression free. Salvage allo-HSCT was performed on 6 of 16 patients; among them, 2 achieved a CR, 2 died after relapse, and 2 died owing to septic shock while maintaining a CR. The remaining patients, who received salvage therapy without HSCT, mostly died owing to PD. The median overall survival was 12.1 months, and the median follow-up was 33.2 months. The 1- and 5-year overall survival was 50.9% and 13.3%, respectively. Discussion MEITL is an aggressive disease resistant to conventional therapy. Therefore, intensive chemotherapy followed by upfront allo-HSCT should be considered upon diagnosis. These findings underscore the need for novel therapeutic strategies and further investigation into optimizing treatment protocols for MEITL.

Paroxysmal nocturnal hemoglobinuria (PNH) clones can be identified in a significant proportion of patients with aplastic anemia (AA). Screening for PNH clones at the time of an AA diagnosis is recommended by national and international guidelines. In this report, an expert panel of physicians discusses current best practices and provides recommendations for managing PNH in patients with AA in the Asia–Pacific region. Plasma/serum lactate dehydrogenase (LDH) levels and reticulocyte count should be measured with every blood test. PNH clone size should be monitored regularly by flow cytometry, with on-demand testing in the event of a rise in LDH level ± reticulocyte count or development of symptoms such as thrombosis. Monitoring for PNH clones can guide the choice of initial AA treatment, although flow cytometry has resource implications which may present a challenge in some Asia–Pacific countries. The treatment of patients with both PNH and AA depends on which condition predominates; following PNH treatment guidelines if hemolysis is the main symptom and AA treatment guidelines if bone marrow failure is severe (regardless of whether hemolysis is mild or moderate). The expert panel’s recommendations on the monitoring and treatment of PNH in patients with AA are practical for healthcare systems in the Asia–Pacific region.