Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/ AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

Purpose: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide.National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. Materials and Methods: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the “before COVID” period, and the years 2020 and 2021 as the “during COVID” period. Results: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it.Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. Conclusions During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.

Background: This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). Methods: We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000– September 2017) at our center. Results: Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34 + cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. Conclusion Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.

Background: This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). Methods: We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000– September 2017) at our center. Results: Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34 + cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. Conclusion Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by platelet destruction through antibody-mediated mechanism. ITP is one of the manifestations of a coronavirus disease, as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several cases of ITP have been described after vaccination with two mRNA-based vaccines—BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)—against SARS-CoV-2. Herein, we report a case of ITP occurring after vaccination with ChAdOx1 adenovirus vector nCoV-19 (AstraZeneca) vaccine in Korea. A 66-year-old woman presented with multiple ecchymoses on both upper and lower extremities and gingival bleeding, appearing 3 days after receiving the first dose of ChAdOx1 nCoV-19. Her laboratory results showed isolated severe thrombocytopenia without evidence of combined coagulopathy. She was diagnosed with ITP and successfully treated with high-dose dexamethasone and intravenous immunoglobulin. Clinical suspicion to identify vaccinerelated ITP is important to promptly initiate appropriate treatment.

OBJECTIVE: To evaluate the value of airway computed tomography (CT) in patients with obstructive sleep apnea (OSA) as a predictor of cerebrocardiovascular disease (CCVD) clinically, by quantitatively analyzing carotid arterial calcification (CarAC). MATERIALS AND METHODS: This study included 287 patients aged 40–80 years, who had undergone both polysomnography (PSG) and airway CT between March 2011 and October 2015. The carotid arterial calcium score (CarACS) was quantified using the modified Agatston method on each upper airway CT. The OSA severity was categorized as normal, mild, moderate, and severe using the PSG results. Clinical characteristics, comorbid diseases, and lipid profiles of all patients were analyzed, and the prevalence of CCVDs was investigated during the follow up period (52.2 ± 16.0 months). RESULTS: CCVD occurred in 27 patients (9.3%) at the end of follow-up, and the CCVD-present groups showed a significantly older mean age (57.5 years vs. 54.2 years), higher prevalence of hypertension (59% vs. 34%) and CarAC (51.9% vs. 20.8%), whereas sex, other comorbid diseases, and severity of OSA were not significantly different from the CCVD-absent group. A univariate analysis showed that age, hypertension, incidence of CarAC, and CarACS were risk factors for the occurrence of CCVD events. In a multivariate analysis, the incidence of CarAC was the only independent risk factor for CCVD. CONCLUSION: CarAC is an independent risk factor for CCVD, whereas the severity of OSA is not a contributory risk factor in patients with OSA. Therefore, additional analysis of CarACS based on airway CT scans may be useful for predicting CCVD.
Calcium ; Carotid Arteries ; Fluorouracil ; Follow-Up Studies ; Humans ; Hypertension ; Incidence ; Methods ; Multivariate Analysis ; Polysomnography ; Prevalence ; Risk Factors ; Sleep Apnea, Obstructive ; Tomography, X-Ray Computed

No abstract available.
Humans ; Multiple Myeloma ; Plasma Cells ; Plasma ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

The detailed kinetics of the cytomegalovirus (CMV)-specific T cell response in hematopoietic stem cell transplant (HCT) recipients have not yet been fully assessed. We evaluated these kinetics of CMV-specific T cell response and factors associated with high CMV-specific T cell responses 1 year after HCT. In HCT recipients, CMV pp65 and IE1-specific ELISPOT assay were performed before HCT (D0), and at 30 (D30), 90 (D90), 180 (D180), and 360 (D360) days after HCT. Of the 51 HCT recipients with donor-positive (D+)/recipient-positive (R+) serology, 26 (51%) developed CMV infections after HCT. The patterns of post-transplantation reconstitution for CMV-specific T cell response were classified into 4 types: 1) an initial decrease at D30 followed by gradual T cell reconstitution without CMV infection (35%), 2) an initial decrease at D30 followed by gradual T cell reconstitution preceded by CMV infection (35%), 3) failure of gradual or constant T cell reconstitution (26%), and 4) no significant T cell reconstitution (4%). There was no significant difference between ELISPOT counts of D360 and those of D0. High CMV-specific T cell responses at D360 were not associated with high CMV-specific T cell response at D0, CMV infection, ganciclovir therapy, graft versus host disease (GVHD), and immunosuppressant use. In conclusion, there are 4 distinct patterns of reconstitution of the CMV-specific T cell response after HCT. In addition, reconstituted donor-origin CMV-specific T cell responses appeared to be constant until day 360 after HCT, regardless of the level of the pre-transplant CMV-specific T cell response, CMV infection, and immunosuppressant use.
Cytomegalovirus ; Enzyme-Linked Immunospot Assay ; Follow-Up Studies* ; Ganciclovir ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Kinetics* ; Theophylline

BACKGROUND: Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT. METHODS: Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis. RESULTS: The median time from HCT to relapse was 6.6 (range, 0.9–136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival. CONCLUSION: Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.
Cell Transplantation* ; Cytarabine ; Cytogenetics ; Drug Therapy ; Humans ; Lymphocytes ; Myelodysplastic Syndromes* ; Recurrence ; Retrospective Studies ; Tissue Donors ; Transplants*

A 37-year-old female presented to our hospital with a history of bleeding episodes (excessive bleeding after tooth extraction, gum bleeding, easy bruising, and excessive menstruation) and severe thrombocytopenia (2,000/µL). She had no family history of bleeding tendency or thrombocytopenia. No peripheral lymphadenopathy or splenomegaly was noted. The patient's white blood cell count was normal; hemoglobin was 9.7 g/dL. A peripheral blood smear showed markedly decreased platelets, with occasional giant or large platelets. Bone marrow examination found increased megakaryocytes. The patient also complained of hearing difficulty; a hearing test indicated sensory-neural hearing impairment. Her thrombocytopenia was refractory to treatment with glucocorticosteroids, intravenous gamma-globulin, and danazol. In the 13 years following her initial presentation, the patient required anti-hypertensive treatment, a hearing-aid for progressive hearing loss, and started maintenance kidney dialysis. Her clinical history of refractory thrombocytopenia, progressive hearing impairment, and renal failure suggested myosin heavy chain 9 gene-related congenital syndrome (Epstein syndrome), which was confirmed by the presence of a heterozygous deletion mutation, c.221_223del, (p.Lys74del) in peripheral leukocyte deoxyribonucleic acid.
Adult ; Bone Marrow Examination ; Danazol ; Dialysis ; DNA ; Female ; gamma-Globulins ; Gingiva ; Hearing ; Hearing Loss ; Hearing Loss, Sensorineural ; Hearing Tests ; Hemorrhage ; Humans ; Kidney ; Leukocyte Count ; Leukocytes ; Lymphatic Diseases ; Megakaryocytes ; Myosin Heavy Chains ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Sequence Deletion ; Splenomegaly ; Thrombocytopenia* ; Tooth Extraction