Chan Kyu Kim

Kim CK, et al. J Korean Med Sci. 2027 Feb;42:e29. https://doi.org/10.3346/jkms.2027.42.e29

To evaluate the prognostic value of integrated post-transplant monitoring of NGS-based measurable residual disease (MRD) and donor chimerism in older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), undergoing reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT). This retrospective study analyzed the clinical outcomes of 113 patients with AML or MDS, aged ≥ 60 years or ≥ 55 years if deemed unfit for standard-intensity conditioning, who underwent RIC allo-SCT. NGS-based MRD testing and donor chimerism were assessed at 3 months post-transplant. A total of 113 patients participated in the study (median age 63 years; 69.9% with AML); among the 105 patients evaluable at 3 months post-transplantation, MRD positivity occurred in 28 patients (26.7%) and predicted inferior overall survival (hazard ratio [HR] 6.373, 95% confidence interval [CI] 3.005-13.517; P < 0.001), while complete donor chimerism (CDC), achieved in 82 patients (78.1%), predicted improved survival (HR 0.356, 95% CI 0.195-0.916; P = 0.028). MRD positivity remained an independent predictor of survival on multivariate analysis (HR 3.315, 95% CI 1.423-7.230, P = 0.005), while CDC showed a trend toward improved survival that did not reach statistical significance (HR 0.494, 95% CI 0.306-1.009, P = 0.051). Two-year overall survival differed markedly across the four MRD/CDC subgroups, ranging from 85.6% [MRD(-)/CDC( +)] to 13.6% [MRD( +)/CDC(-)] (P < 0.001), with the MRD( +)/CDC(-) group showing the highest 2-year relapse incidence (69.7%). The combination of NGS-based MRD and chimerism monitoring is a critical prognostic strategy for older patients with AML/MDS undergoing RIC allo-SCT. Early identification of MRD positivity or mixed chimerism allows timely, risk-adapted interventions, including donor lymphocyte infusion, hypomethylating agents, and targeted therapies to reduce relapse and improve survival.

Background: Globally, the incidence rate of hepatocellular carcinoma (HCC) has increased among elderly patients. Elderly patients often present with multiple comorbidities that affect treatment tolerance and outcomes, and the optimal management strategy for this population has not yet been established. Therefore, we assessed comorbidities in elderly patients and investigated the treatment outcomes of radiotherapy (RT) to liver-confined HCC. Methods: We retrospectively reviewed 40 elderly patients aged ≥70 years with liver-confined HCC, who were treated with RT between 2015 and 2023. Comorbidity was assessed by using the Charlson Comorbidity Index (CCI). Survival outcomes were analyzed using the Kaplan–Meier method. Results: The median age was 75 years (range, 70–87 years). The Barcelona Clinic Liver Cancer stage was 0 in 7 patients, A in 10 patients, B in 9 patients, and C in 14 patients. Most patients (85%) had Child–Pugh class A hepatic function before RT. The CCI scores ranged from 2 to 9 (median, 5). Various RT techniques were applied according to patients’ condition, tumor burden, and treatment aim: three-dimensional conformal radiotherapy in four patients, intensity-modulated radiotherapy in 20 patients; and stereotactic body radiotherapy in 16 patients. RT was delivered with radical intent in 30 patients and with palliative intent in 10 patients. The median biological effective dose calculated with an α/β ratio of 10 was 53.7 Gy₁₀ (range, 39–134.4 Gy₁₀). The median follow-up period after RT was 18 months. The 1-year local progression-free survival and overall survival (OS) rates were 74% and 81%, respectively, and the 3-year rates were 44% and 52%, respectively. Patients with CCI < 5 had more favorable OS than those with CCI ≥ 5, but the difference was not statistically significant. Conclusions: RT for liver-confined HCC appears to be a feasible treatment option for elderly patients with multiple comorbidities.

Kim SH, et al. J Korean Med Sci. 2023 Aug;38(36):e281. https://doi.org/10.3346/jkms.2023.38.e281

Ji YS, et al. Yonsei Med J. 2023 Jan;64:e14. https://doi.org/10.3349/ymj.2022.0331

The COVID-19 pandemic is changing rapidly and requires different strategies to maintain immunization. In Korea, different COVID-19 vaccines are recommended and available for various populations, including healthcare workers (HCWs) at high risk of SARS-CoV-2 infection. We plan to evaluate the adverse events (AEs) and immunogenicity of the BNT162b2 and ChAdOx1 vaccines in HCWs at a single center. This cohort study included HCWs fully vaccinated with either BNT162b2 or ChAdOx1. Blood samples were taken eight weeks after the second vaccination with both COVID-19 vaccines and six months after the second vaccination from participants with the BNT162b2 vaccine. The primary endpoint for immunogenicity was the serum neutralizing antibody responses eight weeks after vaccination. The secondary endpoint was the incidence of various AEs within 28 days of each vaccination. Between 16 March and 23 June 2021, 115 participants were enrolled (65 in the ChAdOx1 group and 50 in the BNT162b2 group). Significantly higher surrogate virus neutralization test (sVNT) inhibition was observed in participants vaccinated with two doses of BNT162b2 (mean (SD) 91.4 (9.68)%) than in those vaccinated with ChAdOx1 (mean (SD) 73.3 (22.57)%). The effectiveness of the BNT162b2 vaccine was maintained across all age and gender categories. At six months after the second dose, serum antibody levels declined significantly in the BNT162b2 group. The main adverse events, including fever, myalgia, fatigue, and headache, were significantly higher in the ChAdOx1 group after the first dose, whereas, after the second dose, those AEs were significantly higher in the BNT162b2 group (p < 0.05). Two doses of either the ChAdOx1 or the BNT162b2 COVID-19 vaccine resulted in very high seropositivity among the HCWs at our center. The quality of the antibody response, measured by sVNT inhibition, was significantly better with the BNT162b2 vaccine than with the ChAdOx1 vaccine. There was no significant association between neutralizing antibody response and AE after each vaccination in our cohort.

Tet methylcytosine dioxygenase 2 (TET2) is one of the most frequently mutated genes in myelodysplastic syndrome (MDS). TET2 is known to involve a demethylation process, and the loss of TET2 is thought to cause DNA hypermethylation. Loss of TET2 function is known to be caused by genetic mutations and miRNA, such as miR-22. We analyzed 41 MDS patients receiving hypomethylating therapy (HMT) to assess whether TET2 mutation status and miR-22 expression status were associated with their clinical characteristics and treatment outcomes. Responsiveness to HMT was not affected by both TET2 mutation (odds ratio (OR) 0.900, p = 0.909) and high miR-22 expression (OR 1.548, p = 0.631). There was a tendency for TET2 mutation to be associated with lower-risk disease based on IPSS (Gamma = −0.674, p = 0.073), lower leukemic transformation (OR 0.170, p = 0.040) and longer survival (Hazard ratio 0.354, p = 0.059). Although high miR-22 expression also showed a similar tendency, this tendency was weaker than that of TET2 mutation. In summary, the loss of TET2 function, including both TET2 mutation and high miR-22 expression, was not a good biomarker for predicting the response to HMT but may be associated with lower-risk disease based on IPSS, lower leukemic transformation and longer survival.

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.Y

Lim SH, et al. Yonsei Med J. 2021 Aug;62(8):671-678. https://doi.org/10.3349/ymj.2021.62.8.671

Background/Aims: Immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT) is affected by multiple variables during the transplantation. Methods: We assessed the clinical factors contributing to immune function reconstitution at 100 days post-allogeneic HSCT in 114 patients receiving fludarabine-based conditioning. Immunophenotypic analysis using flow cytometry was performed to evaluate the percentage and the absolute numbers of T-cell subsets, natural killer cells, and B-cells as clinical outcomes. Results: Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, T-cell depletion, and acute GVHD were significantly associated with delayed immune reconstitution of T-cell subsets. The incidence of chronic GVHD was significantly increased in the normal recovery group compared to the abnormal group (p = 0.01). Epstein-Barr virus reactivation was more frequently observed in the abnormal group of T-cell subsets (p = 0.045). All viral reactivation events including cytomegalovirus reactivation appeared to be more frequent in the abnormal group of T-cell subsets. Conclusions: The immune recovery status post-allogeneic HSCT was affected by GVHD prophylactic regimens, especially in cases receiving tacrolimus-based GVHD prophylaxis, T-cell depletion, and possibly those manifesting acute GVHD. Delayed immune reconstitution might increase the morbidity due to viral reactivation. Treatment strategies are needed to prevent infectious complications and enhance immune reconstitution based on the immune recovery status following allogeneic HSCT with fludarabine-based conditioning.