Purpose: To identify the clinical usefulness of serum M protein and to establish a rationale for regular follow-up with serum protein electrophoresis in solitary plasmacytoma. Materials and Methods: Sixty-nine patients with solitary plasmacytoma and solitary plasmacytoma with minimal marrow involvement according to the International Myeloma Working Group criteria were retrospectively reviewed. Results: At a median follow-up of 6.2 years, 5-year local control (LC), 5-year multiple myeloma-free survival (MMFS), 5-year failure-free survival (FFS), and 5-year overall survival (OS) were 82.6%, 44.1%, 41.8%, and 85.1%, respectively. Among the patients whose initial serum M protein was present or not evaluated, 37.3% of patients showed disappearance of serum M protein after various treatment. MMFS of these patients were comparable to non-secretory plasmacytoma with undetectable levels of M protein, and significantly better than patients with persistent M protein. Increase of serum M protein ≥0.1 g/dL was most predictive of treatment failure with area under the curve of 0.731. Conclusion Patients who eventually showed persistence of serum M protein after treatment showed worse MMFS and FFS compared to those whose serum M protein disappeared or who had initially non-secretory disease. The increase of serum M protein level ≥0.1 g/dL from current nadir was predictive of treatment failure. Therefore, regular follow-up with serum M protein is highly recommended especially unless the patient had initially non-secretory disease.

Acute myeloid leukemia (AML) is a complicated disease characterized by genetic heterogeneity and simultaneous alterations in multiple genes. For decades, its only curative method has been intensive induction chemotherapy with or without allogeneic hematopoietic stem cell transplantation, and this approach cannot be applied to elderly patients, who make up more than 50% of AML patients. Recent advances in genomics facilitated the elucidation of various mutations related to AML, and the most frequent mutations were discovered in epigenetic regulators. Alterations to epigenetic modifications that are essential for normal cell biology, including DNA methylation and histone acetylation, have been identified. As epigenetic dysregulation is an important carcinogenic mechanism and some epigenetic changes are reversible, these epigenetic alterations have become targets for novel drug development against AML. This review summarizes the recent advances in epigenetic therapies for AML and discusses future research directions.

Acute myeloid leukemia (AML) is a complicated disease characterized by genetic heterogeneity and simultaneous alterations in multiple genes. For decades, its only curative method has been intensive induction chemotherapy with or without allogeneic hematopoietic stem cell transplantation, and this approach cannot be applied to elderly patients, who make up more than 50% of AML patients. Recent advances in genomics facilitated the elucidation of various mutations related to AML, and the most frequent mutations were discovered in epigenetic regulators. Alterations to epigenetic modifications that are essential for normal cell biology, including DNA methylation and histone acetylation, have been identified. As epigenetic dysregulation is an important carcinogenic mechanism and some epigenetic changes are reversible, these epigenetic alterations have become targets for novel drug development against AML. This review summarizes the recent advances in epigenetic therapies for AML and discusses future research directions.

PURPOSE: To assess the clinical outcomes of radiotherapy (RT) using two-dimensional (2D) and three-dimensional conformal RT (3D-CRT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma to evaluate the effectiveness of involved field RT with moderate-dose and to evaluate the benefit of 3D-CRT comparing with 2D-RT. MATERIALS AND METHODS: Between July 2003 and March 2015, 33 patients with stage IE and IIE gastric MALT lymphoma received RT were analyzed. Of 33 patients, 17 patients (51.5%) were Helicobacter pylori (HP) negative and 16 patients (48.5%) were HP positive but refractory to HP eradication (HPE). The 2D-RT (n = 14) and 3D-CRT (n = 19) were performed and total dose was 30.6 Gy/17 fractions. Of 11 patients who RT planning data were available, dose-volumetric parameters between 2D-RT and 3D-CRT plans was compared. RESULTS: All patients reached complete remission (CR) eventually and median time to CR was 3 months (range, 1 to 15 months). No local relapse occurred and one patient died with second primary malignancy. Tumor response, survival, and toxicity were not significantly different between 2D-RT and 3D-CRT (p > 0.05, each). In analysis for dose-volumetric parameters, D(max) and CI for PTV were significantly lower in 3D-CRT plans than 2D-RT plans (p < 0.05, each) and D(mean) and V₁₅ for right kidney and D(mean) for left kidney were significantly lower in 3D-CRT than 2D-RT (p < 0.05, each). CONCLUSION: Our data suggested that involved field RT with moderate-dose for gastric MALT lymphoma could be promising and 3D-CRT could be considered to improve the target coverage and reduce radiation dose to the both kidneys.
Helicobacter pylori ; Humans ; Kidney ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone* ; Radiotherapy ; Recurrence ; Stomach

No abstract available.
Hematopoietic Stem Cell Mobilization ; Heterocyclic Compounds ; Korea ; Stem Cells

BACKGROUND: Patients with transformed chronic myelogenous leukemia(CML) and advanced myelodysplastic syndrome(MDS) have poor prognosis. The aim of this study is to evaluate the feasibility of second chronic phase induction in accelerated phase(CML-AP) or blastic crisis of CML(CML-BC) and remission induction in advanced MDS by combining topoisomerase I inhibitor (topotecan) with topoisomerase II inhibitor(mitoxantrone). METHODS: Twenty-four evaluable patients were entered on this study with a median age of 34 years. Eighteen patients with transformed CML(7 CML-AP, 11 CML-BC) and 6 patients with advanced MDS were treated. Topotecan was administered as 1.5 mg/m2/day by continuous infusion over 24 hours daily for 5 days every 4 to 8 weeks until remission. To enhance the tumoricidal effects, mitoxantrone(12 mg/m2/day, Days 1-3) was added. RESULTS: Eight patients(33+ACU-) achieved a complete remission(CR). Four of 7 patients with CML-AP(57+ACU-), 2 of 4 patients with CML-lymphoid blastic crisis (-LBC)(50+ACU-) and 2 of 6 patients with advanced MDS(33+ACU-) had CR lasting more than 45 days(45 to 400 days). There was no CR in the patients with CML-myeloid blastic crisis(-MBC). The dose level of 1.5 mg/m2/day(7.5 mg/m2/course) of topotecan was well tolerated in all patients. Mucositis occurred in 69+ACU- of patients (severe in 5+ACU-) and diarrhea in 67+ACU-(severe in 8+ACU-). In addition, there were no new or unexpected toxicities in the patients who were treated at this dose(7.5 mg/m2/course). In patients who recovered their neutrophil count, the absolute neutrophil count(ANC) remained below 500/microL for a period of 13 to 58 days(median 21 days) and the time to ANC recovery was associated with pretreatment severity of bone marrow fibrosis(mainly CML patients). Likewise, in the patients who recovered unsupported platelets, the platelets remained below 20,000/microL for a period of 0 to 37 days (median 19 days). CONCLUSION: The combination of topotecan-mitoxantrone has shown modest activity in CML-AP, CML-LBC and advanced MDS with acceptable toxicities.
Adult ; Aged ; Antineoplastic Agents, Combined/therapeutic use+ACo- ; Antineoplastic Agents, Combined/adverse effects ; Female ; Human ; Leukemia, Myeloid, Chronic/drug therapy+ACo- ; Male ; Middle Age ; Myelodysplastic Syndromes/drug therapy+ACo- ; Topotecan/administration +ACY- dosage+ACo-

Although ionizing radiation is known to induce cellular senescence in vitro and in vivo, its long-term in vivo effects are not well defined. In this study, we examined the prolonged expression of senescence markers in mice irradiated with single or fractionated doses. C57BL/6 female mice were exposed to 5 Gy of gamma-rays in single or 5, 10, 25 fractions. At 2, 4, and 6 months after irradiation, senescence markers including mitochondrial DNA (mtDNA) common deletion, p21, and senescence-associated beta-galactosidase (SA beta-gal) were monitored in the lung, liver, and kidney. Increases of mtDNA deletion were detected in the lung, liver, and kidney of irradiated groups. p21 expression and SA beta-gal staining were also increased in the irradiated groups compared to the non-irradiated control group. Increases of senescence markers persisted up to 6 months after irradiation. Additionally, the extent of mtDNA deletion and the numbers of SA beta-gal positive cells were greater as the number of radiation fractions increased. In conclusion, our results showed that ionizing radiation, especially that delivered in fractions, can cause the persistent upregulation of senescence marker expression in vivo. This should be considered when dealing with chronic normal tissue injuries caused by radiation therapy or radiation accidents.
Aging ; Animals ; Cell Aging ; DNA, Mitochondrial ; Female ; Humans ; Kidney ; Liver ; Lung ; Mice ; Radiation, Ionizing ; Radioactive Hazard Release ; Up-Regulation ; beta-Galactosidase

BACKGROUND/AIMS: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. METHODS: In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. RESULTS: Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. CONCLUSIONS: Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall.
Bone Marrow Examination ; Bone Marrow* ; Diagnosis ; Follow-Up Studies ; Helicobacter pylori ; Humans ; Korea ; Lymph Nodes ; Lymphoid Tissue ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone* ; Male ; Prevalence* ; Prognosis ; Retrospective Studies ; Risk Factors ; Stomach

No abstract available.
Humans ; Idarubicin* ; Induction Chemotherapy* ; Leukemia, Myeloid, Acute*

Background/Aims: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most fatal complications of hematopoietic cell transplantation (HCT), and defibrotide is the only curative drug. We conducted this study to confirm the survival rate of VOD/SOS patients diagnosed in Korea and assess the efficacy of defibrotide. Methods: Patients diagnosed with VOD/SOS after allogenic HCT between 2003 and 2020 were enrolled. We investigated day +100 survival rates and associated risk factors in patients who satisfied the modified Seattle criteria within 50 days of HCT. Results: A total of 110 patients satisfied the modified Seattle criteria, of which 65.5% satisfied the Baltimore criteria. Thirty-seven patients were treated with defibrotide. The day +100 survival rate of the 110 patients was 65.3%. The survival rates in patients who did not meet the Baltimore criteria and in those who did were 86.8% and 53.7%, respectively (p = 0.001). The day +100 survival rate of patients treated with defibrotide was 50.5%. Among the patients receiving defibrotide, those whose creatinine levels were more than 1.2 times the baseline had a significantly lower survival rate at 26.7% (p = 0.014). On multivariate regression analysis, the hazard ratio of satisfaction of the Baltimore criteria was 4.54 (95% confidence interval [CI], 1.69 to 12.21; p = 0.003). In patients treated with defibrotide, the hazard ratio was 8.70 (95% CI, 2.26 to 33.45; p = 0.002), when creatinine was more than 1.2 times the baseline on administration. Conclusions The day +100 survival rate was significantly lower when the Baltimore criteria were satisfied, and when there was an increase in creatinine at the time of defibrotide administration.