Se Hyung 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.

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

Lim SH, et al. J Korean Med Sci. 2023 Apr;38(18):e139. https://doi.org/10.3346/jkms.2023.38.e139

Lim SH, et al. J Korean Med Sci. 2023 Mar;38(13):e103. https://doi.org/10.3346/jkms.2023.38.e103

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

Inki Moon, M.D., M.S., Min Gyu Kong, M.D., M.S., Young Sok Ji, M.D., M.S., Se Hyung Kim, M.D., Ph.D., Seong Kyu Park, M.D., Ph.D., Jon Suh, M.D., Ph.D., and Mi-Ae Jang, M.D., Ph.D.. Ann Lab Med 2023;43:145-52. https://doi.org/10.3343/alm.2023.43.2.145

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

Background Side population (SP) cells are known as enriched source of cancer initiating cells with stem cell properties. The SP cells show a distinct low-staining pattern with the Hoechst 33342 dye. Our aim was to identify SP cells in multiple myeloma (MM) cell lines as well as characteristics of SP cells. Furthermore, we investigated drugs that are effective against SP cells of MM. Methods SP (side population), MP (main population) cells from human multiple myeloma cell line (RPMI8226) were sorted by flow cytometry based Hoechst 33342 staining. We performed proliferative capacity in vitro, colony-forming cell assay, cell cycle analysis, drug toxicity (doxorubicin, dexamethasone, bortezomib, melphalan). Expression of stem cell markers (ABCG2, Oct4, Sox2, and Nanog) was observed by western blotting assay. Results Several established studies have shown a clonogenic MM cell population with CD 138^-status. Therefore, we assessed whether there is correlation between CD 138 ^- subpopulations and SP cells. CD 138^- subpopulations of MM cell lines were not consistent with SP cells. And we have found no correlation between expression of CD 19, CD20, and CD 27 and the proportion of SP cells. No difference was observed for expression of stem cell marker between the SP cells and MP cells. We examined cell cycle analysis and proliferation ability of SP and MP cells. SP cells showed a capacity for higher proliferation abilities and clonogenecity than MP cells. (Fig1,2) We investigated target SP cells with several drugs (doxorubicin, dexamethasone, melphalan, bortezomib). Importantly, bortezomib was the most effective drug for SP cells.(Table1) Conclusion In our study, there was lack of evidence that SP cells was consistent with MM stem cells. No difference was observed for any other marker between SP cells and MP cells. However SP cells had higher proliferation index and clonogenicity compared with MP cells. We suggest that SP cells are rather related to resistance of drugs. Furthermore, bortezomib reduced the SP cells more effectively compared to other drugs.