Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Purpose: Inotuzumab ozogamicin (INO) has demonstrated a safe bridging role to allogeneic hematopoietic stem cell transplantation (HSCT) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). How‑ ever, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is frequently observed. This study aimed to identify significant features of INO-associated VOD/SOS. Methods: We reviewed seven cases of hepatic VOD/SOS that developed either during INO salvage or after alloge‑ neic HSCT following INO-induced complete remission (CR). Diagnosis and severity grading of VOD/SOS were based on the revised criteria from the European Society for Blood and Marrow Transplantation. Defibrotide was used to treat severe to very severe cases. Results: Four patients developed VOD/SOS during INO salvage therapy (at 21 and 36 days post-INO1, 77 days postINO3, and 21 days post-INO5), while three were diagnosed at 2, 5, and 10 days post-HSCT following INO-induced CR.Doppler ultrasonography revealed preserved portal vein flow (range 10.2–26.0 cm/sec) and normal hepatic artery resistive index (RI, range 0.56–0.74) in all but one patient (RI 0.83). Despite this, all patients presented with massive ascites and progressively elevated total bilirubin levels. All cases were classified as severe to very severe; six were treated with defibrotide and one underwent liver transplantation. Most patients ultimately died owing to VOD/SOS progression. Conclusion Post-INO VOD/SOS manifested as two different clinical settings and was characterized by preserved portal vein flow, which complicated diagnosis. Despite timely defibrotide administration, clinical outcomes were poor.These findings emphasize the need for vigilance and potential consideration of prophylactic strategies for prevention of INO-associated VOD/SOS.

Background: Arsenic trioxide (ATO) is the standard treatment for relapsed acute promyelocytic leukemia (APL). However, consensus on post-remission therapies is still lacking. Methods: We evaluated 52 patients who experienced relapse following initial treatment of APL between 2000 and 2019 at Catholic Hematology Hospital. Among them, 41 patients received reinduction treatment, 30 with ATO-based regimen, whereas 11 with conventional intensive chemotherapy (IC). Results: The ATO reinduction group showed a significantly higher second molecular complete remission (mCR2) rate, superior neutrophil and platelet recovery, and a lower infection rate than the IC reinduction group. No significant differences were observed in survival outcomes after post-remission treatment among the ATO-based (N=19), autologous (N=12), and allogeneic (N=6) hematopoietic stem cell transplantation (HSCT) groups. In the ATO-based and autologous HSCT groups, among patients with mCR2 after ATO reinduction, nine and five patients experienced a second relapse, respectively (50.7% vs. 41.7%, P =0.878). Among these patients, seven received salvage allogeneic HSCT; six remained alive. The other seven patients received ATO without HSCT. Five died from disease progression, and two survived and have been in mCR2 since. Conclusion Post-remission treatment outcomes of patients with relapsed APL were not significantly different, regardless of the treatment option, suggesting the feasibility of ATO-based treatment without HSCT in mCR2. Allogeneic HSCT may be an effective salvage treatment modality for patients with a second relapse. Owing to a few cases of relapsed APL, multicenter prospective studies may help elucidate the efficacy of each post-remission treatment.

Background/Aims: Idiopathic multicentric Castleman disease (iMCD) comprises approximately 30% of all cases of Castleman disease. It is characterized by constitutional symptoms, enlarged lymph nodes at multiple anatomical sites, and laboratory test abnormalities, which are primarily related to the overproduction of interleukin 6 (IL-6). Siltuximab is a human-mouse chimeric immunoglobulin G1κ monoclonal antibody against human IL-6. In view of the limited treatment options for iMCD, this study aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. Methods: In this real-world retrospective study, we administered siltuximab to 15 patients with iMCD who previously received conventional chemotherapy and/or steroid pulse therapy. The median time to a durable symptomatic response was 22 days (range, 17 to 56). The serum hemoglobin and albumin levels and erythrocyte sedimentation rates significantly normalized after the first 3 months of siltuximab treatment. Lymph node involution, assessed using imaging, was relatively gradual, demonstrating a complete or partial response at 6 months. Results: On an average, the improvements in clinical, laboratory, and radiologic parameters of iMCD in responders were observed after one, three, and eight cycles of siltuximab treatment, respectively. Siltuximab demonstrated a favorable safety profile, and prolonged treatment was well-tolerated. Conclusions Despite the small sample size of the present study, the results are encouraging and demonstrate the potential of siltuximab as the first-line treatment of iMCD. Further large multicenter studies are needed to evaluate the clinical outcomes and adverse events associated with siltuximab.

BACKGROUND: Standard remission induction chemotherapy consisting of anthracycline plus cytarabine (3+7) is administered for adult acute myeloid leukemia (AML). However, the effects of intensified regimen on complete remission (CR), relapse and overall survival (OS) remain unknown. METHODS: We analyzed 1195 patients treated with idarubicin plus cytarabine/BHAC (3+7) from 2002 to 2013. Among them, 731 received early intensification with 3-day cytarabine/BHAC (3+10, N=363) or 2-day idarubicin plus cytarabine/BHAC 3 days (5+10, N=368). The 3+10 and 5+10 strategies were applied to patients with bone marrow blast counts of 5–20% and >20% on day 7 of 3+7, respectively. RESULTS: Early intensification correlated with a younger age (median: 40 vs. 45 yr) and higher t(8;21) frequency (20.4% vs. 7.1%), compared to 3+7. After early intensification, the early death rates were higher among the elderly (3+10 [15.7%], 5+10 [21.7%] vs. 3+7 [6.3%], P=0.038), while the post-induction CR rate was higher in young patients (3+10 [79.8%], 5+10 [75.1%] vs. 3+7 [65.1%], P<0.001). Early relapse rate was also decreased (3+10 [11.8%], 5+10 [11.7%] vs. 3+7 [22.0%], P<0.001). In multivariate analysis, early intensification correlated with an inferior 5-year OS among elderly patients (19.2% vs. 22.8%; hazard ratio [HR]=1.84, 95% confidence interval [CI]; 1.11–3.06, P=0.018) and lower overall relapse rate among young patients (33.0% vs. 41.4%, P=0.023; HR=0.71, 95% CI; 0.55–0.93, P=0.012). CONCLUSION: Early intensification correlated with higher CR and lower relapse rates, but not OS in young AML patients. In elderly patients, early intensification correlated with a higher early death rate and poorer OS.
Adult* ; Aged ; Bone Marrow ; Cytarabine ; Drug Therapy* ; Humans ; Idarubicin ; Induction Chemotherapy* ; Leukemia, Myeloid, Acute* ; Mortality ; Multivariate Analysis ; Recurrence ; Remission Induction

This retrospective study aimed to compare the clinical features of paramedullary lesions (PLs) and extramedullary lesions (ELs) of plasmacytomas at diagnosis, using positron emission tomography integrated with computed tomography, using glucose labeled with the positron-emitting radionuclide ¹⁸F (¹⁸F-FDG-PET/CT) in newly diagnosed multiple myeloma (NDMM), and to address their prognostic impact. Sixty-four patients with NDMM presenting ELs (n=22) and/or PLs (n=42) were included. Patients with ELs at initial presentation had unfavorable laboratory parameters of calcium and lactate dehydrogenase, a higher percentage of bone marrow plasma cells, and showed a trend toward advanced international staging system (ISS), compared to patients with PLs. Using X-ray imaging, high bone disease (HBD) was observed in 50% and 71% of patients with ELs and PLs, respectively. After a median follow-up of 29.2 months (range, 3.4–76.5 months) in survivors, patients with ELs had a significantly lower overall survival (OS) (p=0.033) than patients with PLs did, whereas the progression-free survival (PFS) did not differ significantly (p=0.818). However, the PFS after 1(st) progression was significantly worse in patients with ELs than in those with PLs (p=0.017). In the multivariate analyses, the negative impact of initial ELs on OS (p=0.033) was sustained. Our results demonstrated the different clinical features and outcomes of ELs and PLs in NDMM. Patients with initial ELs showed a shorter PFS after 1(st) progression, which translated into poor OS, providing insight into the different biological effect of ELs.
Bone Diseases ; Bone Marrow ; Calcium ; Diagnosis ; Disease-Free Survival ; Follow-Up Studies ; Glucose ; Humans ; L-Lactate Dehydrogenase ; Multiple Myeloma* ; Multivariate Analysis ; Plasma Cells ; Plasmacytoma ; Positron-Emission Tomography ; Retrospective Studies ; Survivors

Heparin is a well-known anticoagulant widely used in various clinical settings. Interestingly, recent studies have indicated that heparin also has anti-inflammatory effects on neuroinflammation-related diseases, such as Alzheimer's disease and meningitis. However, the underlying mechanism of its actions remains unclear. In the present study, we examined the anti-inflammatory mechanism of heparin in cultured cerebral endothelial cells (CECs), and found that heparin inhibited the tumor necrosis factor alpha(TNF alpha)-induced and nuclear factor kappa B (NF-kappa B)-dependent expression of adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), which are crucial for inflammatory responses. Heparin selectively interfered with NF-kappa B DNA-binding activity in the nucleus, which is stimulated by TNF alpha. In addition, non-anticoagulant 2,3-O desulfated heparin (ODS) prevented NF-kappa B activation by TNF alpha, suggesting that the anti-inflammatory mechanism of heparin action in CECs lies in heparin's ability to inhibit the expression of cell adhesion molecules, as opposed to its anticoagulant actions.
Alzheimer Disease ; Cell Adhesion Molecules ; Endothelial Cells ; Heparin ; Intercellular Adhesion Molecule-1 ; Meningitis ; NF-kappa B ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1

Arsenic trioxide is the most prevalent natural inorganic form of arsenic, which is a widely used heavy metal and is ubiquitously distributed in the environment. A 71-year-old man ingested about 10 g of arsenic trioxide powder in an attempted suicide. He developed severe vomiting, watery diarrhea and abdominal pain, and he presented to the emergency room 15 hours after the ingestion. On admission he was slightly drowsy, but shocked. He showed metabolic acidosis, acute renal failure and abnormal electrocardiogram suspecting myocardial infarction. The chest and abdominal X-rays revealed radiopaque materials in the stomach and small bowel. The stomach was irrigated via a nasogastric tube and activated charcoal was given to bind unabsorbed arsenic. The whole bowel irrigation was tried to remove the remained arsenic in the gastrointestinal tract and BAL (British anti-lewisite) was repeatedly administrated. Despite of intensive supporting management with supplemental oxygen, aggressive volume expansion, correction of metabolic disturbances and administration of cardiotonic agents, he developed progressive hypotension and died 42 hours after the ingestion. Random urine arsenic concentration, which was collected at the time of admission, but confirmed after death, was 3,564 microgram/L.
Abdominal Pain ; Acidosis ; Acute Kidney Injury ; Aged ; Arsenic Poisoning* ; Arsenic* ; Cardiotonic Agents ; Charcoal ; Diarrhea ; Eating ; Electrocardiography ; Emergency Service, Hospital ; Gastrointestinal Tract ; Humans ; Hypotension ; Myocardial Infarction ; Oxygen ; Poisoning ; Shock ; Stomach ; Suicide, Attempted ; Thorax ; Vomiting

PURPOSE: Gastric cancer is believed to be a disease of the elderly, and rarely occurs in young patients. The aim of this study was to analyze the clinicopathological and prognostic factors related to young gastric cancer patients. METHODS: A total of 877 patients with gastric cancer from 1995 to 2004 in a secondary referral center in Suwon City were enrolled in this study. The clinicopathological features of the young (aged<40 years) gastric cancer patients were compared with those of the older (aged > or =40 years) patients. The overall survival was the main outcome measure. The survival curves were constructed using the Kaplan-Meier method, Univariate analysis was performed using the log-rank test, and multivariate analysis was performed using with Cox regression. A P value<0.05 was considered significant. RESULTS: Of the 877 patients, 65(7.4%) were in the young age group. The mean age of this group was 34.9 years (range, 19~39 years). The male-to-female ratio of the patients younger than 40 was 1.24/1; whereas the ratio was 2.07/1 in those older than 40. 7.7 percent of the patients had a family history of gastric cancer. A significantly higher percentage of young patients had a poorly differentiated histology than the older patients (P=0.0001). Twenty-three patients (38.9%) were stage III or IV disease, whereas 36 patients (61.0%) presented with stage I or II disease. A resection with a curative intent was undertaken in 53 patients (81.5%), and a resection with a palliative intent was performed in 12 patients (18.4%). With a mean follow-up of 39 months, the disease-specific 5-year survival rates were similar to those observed in the older group of patients. The variables with a significant impact on survival were a curative resection, a lymph node metastasis, lymphatic invasion, peritoneal metastasis, and adjuvant chemotherapy. CONCLUSION: There were no significant differences in the clinicopathological characteristics and clinical outcome of a gastric adenocarcinoma between the younger and older patients. The important prognostic factors were curability, lymph node metastasis, lymphatic invasion, peritoneal metastasis, and adjuvant chemotherapy.
Adenocarcinoma ; Aged ; Chemotherapy, Adjuvant ; Follow-Up Studies ; Gyeonggi-do ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Multivariate Analysis ; Neoplasm Metastasis ; Outcome Assessment (Health Care) ; Secondary Care Centers ; Stomach Neoplasms* ; Survival Rate