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Background: Hepatitis B virus reactivation (HBVr) is a well-known complication of systemic chemotherapy for particularly hematologic malignancies in HBV carriers. We performed a multicenter retrospective study to investigate the incidence and risk factors of HBVr in patients with hepatitis B surface antigen (HBsAg)-positive multiple myeloma (MM)., Methods: We included 123 patients with HBsAg-positive MM who had received systemic therapy. The primary objective of the study was to evaluate the incidence of HBVr in patients with HBsAg-positive MM., Results: The median age was 59 years, and 72 patients were male. With a median follow-up duration of 41.4 months, there were 43 instances of HBVr in 35 patients (28.5%): 29 treatment-related HBVr occurred during 424 treatments. Treatments containing antiviral prophylaxis were associated with a significantly lower incidence of HBVr compared to those without (14.4% vs. 1.9%, P < 0.001). Moreover, treatment with cyclophosphamide (P = 0.002) and doxorubicin (P = 0.053) were risk factors for HBVr; stem cell transplantation was not associated with HBVr. There was no significant difference in overall survival between patients with and without HBVr (P = 0.753) and myeloma progression was the major cause of death., Conclusion: Considering the low incidence of HBVr in patients who had received antiviral prophylaxis, HBsAg-positivity should not impede patients from receiving optimal antimyeloma treatment or participating in clinical trials., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background/aims: Little attention is paid to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in Korea due to the rarity of the disease. With its rising incidence, we aimed to evaluate recent changes in treatment patterns and survival outcomes of patients with CLL/SLL., Methods: A total of 141 patients diagnosed with CLL/SLL between January 2010 and March 2020 who received systemic therapy were analyzed in this multicenter retrospective study., Results: The median patient age was 66 years at diagnosis, and 68.1% were male. The median interval from diagnosis to initial treatment was 0.9 months (range: 0-77.6 months), and the most common treatment indication was progressive marrow failure (50.4%). Regarding first-line therapy, 46.8% received fludarabine, cyclophosphamide, plus rituximab (FCR), followed by chlorambucil (19.9%), and obinutuzumab plus chlorambucil (GC) (12.1%). The median progression-free survival (PFS) was 49.3 months (95% confidence interval [CI], 32.7-61.4), and median overall survival was not reached (95% CI, 98.4 mo- not reached). Multivariable analysis revealed younger age (≤ 65 yr) (hazard ratio [HR], 0.46; p < 0.001) and first-line therapy with FCR (HR, 0.64; p = 0.019) were independently associated with improved PFS. TP53 aberrations were observed in 7.0% (4/57) of evaluable patients. Following reimbursement, GC became the most common therapy among patients over 65 years and second in the overall population after 2017., Conclusion: Age and reimbursement mainly influenced treatment strategies. Greater effort to apply risk stratifications into practice and clinical trials for novel agents could help improve treatment outcomes in Korean patients.

As the discussion of first-line anagrelide treatment is ongoing, we aimed to prospectively examine the efficacy and safety of anagrelide in cytoreduction therapy-naïve high risk essential thrombocythemia (ET) patients in Korea. Seventy patients from 12 centers were treated with anagrelide monotherapy for up to 8 weeks, followed up until 24 months. At week 8, 50.0% of the patients were able to achieve platelet < 600 x 10 9 /L, and by 12 months, 55/70 (78.6%) patients stayed on anagrelide, and 40.0% patients showed platelet normalization. 14 patients required additional hydroxyurea (HU) for cytoreduction. The median daily dose of needed HU was 500mg (range 250mg - 1500mg). The efficacy was independent of the somatic mutation status. There were 4 thromboembolic events and 7 bleeding events during the follow-up period. The most common adverse events associated with anagrelide use were headache, followed by palpitation/chest discomfort, edema and generalized weakness/fatigue. 7 patients wished to discontinue anagrelide treatment due to adverse events (3 due to headache; 2 due to edema; 1 due to palpitation and 1 due to skin eruption). All in all, first-line anagrelide treatment showed a favorable response with tolerable safety profiles regardless of somatic mutation status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Byun, Kim, Nam, Shin, Song, Park, Han, Park, Yuh, Mun, Do, Sohn, Bae, Shin and Yoon.)

Introduction/background: Ruxolitinib is an established treatment for myelofibrosis (MF) that has demonstrated clinical benefit by reducing spleen size and debilitating MF-related symptoms. However, despite the efficacy of ruxolitinib, anemia remains a major adverse event that causes dose modification or discontinuation in real-world practice. Additionally, dependence on red blood cell (RBC) transfusion (TF) is common during treatment; therefore, we explored the outcome of ruxolitinib therapy with a primary focus on RBC TF., Patients/methods: We retrospectively reviewed the medical records of 123 MF patients treated with ruxolitinib between January 2012 and April 2020 at eight academic centers in Korea., Results: At ruxolitinib initiation, 38 patients (30.9%) underwent ≥ 2 units of RBC TF over 8 weeks. The most common reason for permanent discontinuation was intolerant anemia (10/63, 15.9%). The most common reasons for temporary interruption were nonhematologic toxicity (26/55, 21.1%), anemia (23/55, 18.7%) and thrombocytopenia (13/55, 10.6%). Among the 123 patients in the study, 57 (46.3%), 42 (34.1%), and 40 patients (32.5%) who were receiving or stopped ruxolitinib therapy had a status of RBC TF dependence, long-term RBC TF dependence, or severe RBC TF dependence, respectively. The presence of ≥ 2 units of RBC transfusion over 8 weeks at ruxolitinib initiation was an independent risk factor for persistent RBC TF dependence., Conclusion: The requirement for RBC TF is commonly encountered during treatment of MF with ruxolitinib, particularly among those with pre-existing ≥ 2 units of RBC TF over 8 weeks. For those patients, overcoming the barrier of maintenance TF is demanding., Competing Interests: Disclosure No conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea., Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response., Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients)., Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

Objectives: Anti-angiogenic agents are reported to exert clinical activity on epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancers. We evaluated the clinical outcomes of nintedanib and docetaxel in refractory NSCLC according to EGFR mutation status during the Korean nintedanib named patient program., Methods: Docetaxel was administered either 75 or 37.5 mg/m2 on D1, D8 q every 3 weeks for 4-6 cycles plus nintedanib 200 mg orally twice daily until disease progression or unacceptable toxicity., Results: Sixty-two patients were enrolled for study. Twenty-eight patients with activating EGFR mutations progressed after EGFR-tyrosine kinase inhibitors (TKI) therapy and 25 out of 28 patients showing progression after platinum doublet chemotherapy were enrolled. The objective response rate was 29% and median PFS and OS were 3.9 months and 11.7 months. Based on the EGFR mutation status, the objective response rate was 39.3 vs. 21.9% (EGFR mut(+) vs. EGFR mut(-), p = 0.142) and median PFS was 6.5 vs. 3.3 months (EGFR mut(+) vs. EGFR mut(-), p = 0.009). No treatment-related deaths were reported. The most frequent drug-related adverse events (AE) were neutropenia (53.2%) and diarrhea (37.1%). Treatment in 12 patients (19.3%) was permanently discontinued due to AEs without disease progression., Conclusions: Our data indicated that nintedanib-docetaxel combination could be considered to be effective treatment in EGFR TKI-resistant EGFR mutant NSCLC., (© 2018 S. Karger AG, Basel.)

Purpose: The treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data., Materials and Methods: This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016., Results: A total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patientswas 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment., Conclusion: Age itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.

Purpose: The aim of the study was to assess the clinical activity and toxicity of oxaliplatin and leucovorin in combination with bolus and continuous infusional 5-fluorouracil administered every 2 weeks (modified FOLFOX-6 regimen) to patients with adenocarcinoma of an unknown primary site (ACUP)., Methods: Previously untreated ACUP patients were treated with oxaliplatin (100 mg/m(2)) and leucovorin (200 mg/m(2)) as a 2-h infusion followed by bolus administration of 5-fluorouracil (400 mg/m(2)) and continuous infusion of 5-fluorouracil (2400 mg/m(2)) every 2 weeks., Results: A total of 23 patients were enrolled and treated with a modified FOLFOX-6 regimen between May 2009 and November 2014. This trial was terminated before the scheduled enrollment due to poor accrual. A total of 134 cycles of mFOLFOX-6 were administered to 23 patients. The median number of cycles of mFOLFOX-6 was 5 (range 1-12). Among 20 patients whose tumor responses were evaluable, seven patients showed a partial response (no complete response), with an objective response rate of 35.0%. The median duration of response was 3.9 months (range 3.0-19.8). The median progression-free survival and overall survival were 3.0 and 9.5 months, respectively (95% confidence interval 1.4-6.7 months and 4.8-26.4 months, respectively). Treatment-related toxicity was manageable., Conclusions: mFOLFOX-6 showed modest activity in treatment-naïve patients with ACUP. A future, prospective large-scale study incorporating a parallel molecular prediction marker study is warranted.

In advanced or relapsed pancreatic cancer, mono- or duo-therapy has shown modest efficacy at best. The present study evaluated the efficacy of a triplet combination in relapsed or advanced pancreatic cancer. A total of 37 patients with adenocarcinoma of the pancreas in stage III/IV or with relapsed disease were treated with a gemcitabine, 5-fluorouracil and cisplatin (GFP) regimen every 3 weeks. Only 29 out of 37 patients were evaluable for response due to early treatment interruption in 8 patients. The overall response rate was 24.1% and the disease control rate was 68.9%. The progression-free survival (PFS) rate was 61.5, 30.9 and 17.6% at 3, 6 and 9 months, respectively, and the overall survival (OS) rate was 46.5 and 30.6% at 6 and 12 months, respectively. Grade 3/4 leukopenia, neutropenia and thrombocytopenia occurred in 18.4, 29.9 and 24.5% of 147 cycles, respectively. Old age and a poor performance status (PS) were associated with the early discontinuation of chemotherapy (P=0.038 and P=0.036, respectively). In patients <65 years old and with a PS of <2, the median PFS and OS times were 5.3 months and 10.3 months, respectively. Overall, although GFP resulted in acceptable response and survival rates, it does not appear to have marked superiority to gemcitabine-based single or duplet chemotherapy.

Background: Combination chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone (IMEP) was active as first-line and second-line treatment for extranodal natural killer/T-cell lymphoma (NTCL)., Methods: Forty-four patients with chemo-naïve stage I/II NTCL were enrolled in a prospective, multicenter, phase II study and received six cycles of IMEP (ifosfamide 1.5 g/m(2) on days 1-3; methotrextate 30 mg/m(2) on days 3 and 10; etoposide 100 mg/m(2) on days 1-3; and prednisolone 60 mg/m(2) per day on days 1-5) followed by involved field radiotherapy (IFRT)., Results: Overall response rates were 73% (complete remission [CR] in 11 of 41 evaluable patients [27%]) after IMEP chemotherapy and 78% (CR 18 of 27 evaluable patients [67%]) after IMEP followed by IFRT. Neutropenia and thrombocytopenia were documented in 33 patients (75%) and 7 patients (16%), respectively. Only 8 patients (18%) experienced febrile neutropenia. Three-year progression-free survival (PFS) and overall survival (OS) were 66% and 56%, respectively. High Ki-67 (≥70%) and Ann Arbor stage II independently reduced PFS (p = .004) and OS (p = .001), respectively., Conclusion: Due to the high rate of progression during IMEP chemotherapy, IFRT needs to be introduced earlier. Moreover, active chemotherapy including an l-asparaginase-based regimen should be use to reduce systemic treatment failure in stage I/II NTCL., (©AlphaMed Press; the data published online to support this summary is the property of the authors.)

Purpose: The objective of this study was to evaluate whether extended-release hydromorphone (osmotic-controlled release oral delivery system [OROS] hydromorphone) treatment provided pain relief in cancer patients whose pain was inadequately controlled by other analgesics., Methods: In this prospective, open-label, multicenter trial, patients who have sustained cancer pain with other analgesics were enrolled. After the baseline evaluation (visit 1), OROS hydromorphone was administered. Two evaluations (visits 2 and 3) were made: 29 ± 7 and 57 ± 7 days later, respectively. The primary end point was the pain intensity difference (PID) at visit 3 relative to visit 1 (expressed as percent PID)., Results: In total, 879 patients were screened and 432 completed all three visits. Of the 874 full analysis set patients, 343 (39.2 %) improved by more than 30 % PID. Of the 432 per-protocol patients, 282 (65.3 %) improved by more than 30 % PID. At visits 2 and 3, the degree of sleep disturbance, the number of awakenings, and the degree of sleep satisfaction were significantly better than at visit 1 (all P < 0.0001 for both visit 1-visit 2 and visit 1-visit 3). However, this pain relief was not associated with improved quality of life (P = 0.326 and P = 0.055 for visit 1-visit 2 and visit 1-visit 3, respectively)., Conclusions: This study suggested that active pain management using the strong opioid OROS hydromorphone was beneficial in the management of cancer pain that was not controlled by other analgesics.

Aims and Background: For advanced cancers of the bile duct, gallbladder and ampulla of Vater, there are only a few treatment options. We explored the efficacy of the combination of gemcitabine, 5-fluorouracil and cisplatin for advanced biliary cancers., Methods: From September 2003 to April 2010, 28 patients with recurrent or metastatic biliary tract cancer were enrolled. A treatment regimen consisting of gemcitabine (800 mg/m² at a fixed dose rate on days 1 and 8), 5-fluorouracil (1 g/m²/day continuous infusion for 4 days) and cisplatin (60 mg/m² on day 2) was repeated every 3 weeks., Results: One (3.6%) patient showed complete response, 8 (28.6%) partial response, 14 (50%) stable disease and 5 (17.9%) disease progression. Overall, the objective response rate was 32.1% (95% CI, 17.9-50.6%) and the disease control rate was 82.1% (95% CI, 64.4-92.1%). Median progression-free survival and overall survival were 7.6 months (95% CI, 5.5-9.7) and 11.2 months (95% CI, 6.8-15.5), respectively. G3/4 neutropenia was observed in 44 (24.3%) of 181 cycles and G3/4 thrombocytopenia in 48 (26.5%) of 181 cycles. There was no treatment-related mortality., Conclusions: The combined regimen of gemcitabine, 5-fluorouracil and cisplatin has comparable activity for patients with advanced cancer of the bile duct, gallbladder and ampulla of Vater. Toxicity was tolerable but substantial.

Thymomas are one of the most common neoplasms of the mediastinum derived from thymic epithelium. It is common that invasive thymoma invades the lung, pericardium, and great vessels. Airway compression by mass effect also occurs, but direct polypoid tumor growth into the airway is extremely rare. Only 20 cases of invasive thymoma with endobronchial polypoid growth have previously been reported globally. However, there is no case report of invasive thymoma with endotracheal growth. Herein, we report a rare case of invasive thymoma with endotracheal polypoid growth in a 28-year-old woman.

Aims and Background: Low-dose leucovorin is a well known potentiator of 5-fluorouracil activity in colorectal cancer but not in gastric cancer. To assess their efficacy on response rate and survival, 5-fluorouracil and low-dose leucovorin were combined with mitomycin C., Methods: Fifty patients with gastric cancer and metastatic disease, unresectable or relapsed disease were treated with the following regimen every 28 days: mitomycin C, 7 mg/m2 IV bolus on day 1, and leucovorin, 20 mg/m2 IV, followed immediately by 5-fluorouracil, 375 mg/m2 on days 1-5. All had measurable disease and were assessable for toxicity. Prognostic factors were analyzed to examine any association with response rate or overall survival., Results: Nineteen of the 48 assessable patients (39.6%; 95% confidence interval [CI], 25.8-53.4) responded, including 4 complete responses (8.3%). The median progression-free survival was 108 days (range, 18+ - 146), and the median duration of survival was 338 days (11.3 months; range, 18+ - 903 days). Response rate and overall survival were not significantly associated with CEA level, performance status, age, or primary and metastatic tumor sites. Toxicity associated with the chemotherapy was tolerable, and all patients were treated at the outpatient clinic. Leukopenia and thrombocytopenia WHO grade ≥3 occurred in 5% and 1% of the patients, respectively. Nausea and vomiting were the most frequent adverse effects (29%), all grade 1 or 2., Conclusions: Combination chemotherapy of 5-fluorouracil plus leucovorin with mitomycin C is effective for the treatment of advanced gastric cancer and is well tolerated.

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.

Primary cardiac lymphomas (PCL) are extremely rare. Clinical manifestations may be variable and are attributed to location. Here, we report on a case of PCL presenting with atrioventricular (AV) block. A 55 year-old male had experienced chest discomfort with unexplained dyspnea and night sweating. His initial electrocardiogram (ECG) revealed a first degree AV block. Along with worsening chest discomfort and dyspnea, his ECG changed to show second degree AV block (Mobitz type I). Computed tomography (CT) scan showed a cardiac mass (about 7 cm) and biopsy was performed. Pathologic finding confirmed diffuse large B-cell lymphoma. The patient was treated with multi-drug combination chemotherapy (R-CHOP: Rituximab, cyclophoshamide, anthracycline, vincristine, and prednisone). After treatment, ECG changed to show normal sinus rhythm with complete remission on follow-up CT scan.

Purpose: Although platinum based chemotherapy is known to improve the survival duration for the patients with non-small cell lung cancer, the role of platinum for elderly patient is not yet clear. We administered gemcitabine and carboplatin combination therapy to elderly patients with NSCLC. The aim of this study was to evaluate the efficacy and toxicities of this regimen for elderly patients., Materials and Methods: THE ELIGIBILITY CRITERIA WERE AS FOLLOWS: pathologically confirmed NSCLC, an age >or=65 years, advanced disease with stage IIIB or IV and the patients were chemotherapy-naive. The treatment regimen was as follows; gemcitabine 1,000 mg/m(2) was administered on days 1 and 8 and carboplatin AUC=5 was administered on day 1. This regimen was repeated every 3 weeks. The efficacy was evaluated in terms of the response rate, the time to progression and the overall survival duration., Results: From Dec 2001 to Feb 2005, a total of 20 patients were entered into this study. The median patient age was 68 years (range: 65 approximately 75). 19 patients were evaluable for their treatment response. A partial response was obtained in 8 patients (response rate: 42.1%, 95% CI: 19.4 approximately 64.8%). The median time to progression and the survival duration were 136 days and 453 days, respectively. Among a total of 65 cycles of treatment, grade 3 or 4 leukopenia and thrombocytopenia were observed in 7.7% and 13.9% of the cycles, respectively. Grade 3 or 4 vomiting was observed in 7.7% of the cycles. Grade 3 skin rash developed in 1.5% of the cycles. 1 patient died of septic shock after chemotherapy., Conclusions: Gemcitabine and carboplatin combination chemotherapy was relatively safe and effective for treating elderly patients with NSCLC.

Purpose: We wanted to assess the effectiveness and safety of combination chemotherapy with paclitaxel, 5-fluorouracil (5-FU) and cisplatin for treating advanced gastric cancer., Materials and Methods: Patients with metastatic or recurrent gastric cancer were entered into this study. Paclitaxel at a dose of 135 mg/m(2) on day 1, 5-FU 1 g/m(2)/day in a 24 hour continuous infusion from day 1 to day 4 and cisplatin 60 mg/m(2) on day 1 were administered. This regimen was repeated every 3 weeks., Results: A total of 34 patients were enrolled in this study. Among them, 33 patients were finally evaluable for their response. 17 (51.5%) patients had a partial response (95% CI: 26.0 approximately 77.0%). The median duration of overall survival was 13.2 months. Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15.2% and 1.1% of all the cycles, respectively. Grade 3 stomatitis and neurotoxicity were observed in 20.6% and 1.1% of all patients, respectively. Grade 4 non-hematologic toxicity was not observed., Conclusions: The regimen of paclitaxel, 5-FU and cisplatin demonstrated activity and acceptable toxicity for treating metastatic gastric cancer.

Background: This national survey was undertaken to propose the classification of extranodal natural killer (NK)/T-cell lymphoma (NTCL) subtypes and to clarify a clinical heterogeneity., Patients and Methods: Two hundred and eighty patients newly diagnosed as NTCL were enrolled from 22 Korean medical centers. Two subsets were compared: one involving the upper aerodigestive tract (UAT) and another involving the non-upper aerodigestive tract (NUAT) region, which comprises the skin, gastrointestinal tract, and liver or soft tissues. Clinical prognostic factors, survival outcomes, and independent predictors for survival were compared between each subset., Results: NUAT-NTCL (59 patients) had significantly higher proportions of disseminated disease, aggressive biologic features, and unfavorable host reactions compared with UAT-NTCL (221 patients). NUAT-NTCL had shortened 5-year overall survival (OS) (22% versus 41%, P = 0.001). Ann Arbor staging, the International Prognostic Index, and the NTCL prognostic index failed to predict the OS of NUAT-NTCL, but did predict the OS in UAT-NTCL. Independent predictors for OS by multivariate analyses differed between each subset. In the NUAT subset, extranodal sites and regional nodes predicted the OS, while Ann Arbor staging, age, performance status, and lactate dehydrogenase level predicted the OS in the UAT subset., Conclusion: NUAT-NTCL may represent a distinctive disease entity in terms of clinical factors, independent predictors, and survival outcomes.

Purpose: The therapeutic strategy for relapsed or refractory patients with diffuse large B-cell lymphoma (DLBL) remains challenging yet. Salvage therapy has been tried for these patients according to their clinical status. We studied ICD (irinotecan, cisplatin and dexamethasone) regimen as salvage chemotherapy for DLBL patients previously treated with RCHOP., Methods: Between February 2005 and May 2006, 15 patients were treated prospectively with ICD chemotherapy; irinotecan 65 mg/m(2)/day on days 1 and 8, cisplatin 30 mg/m(2)/day on days 1 and 8, and dexamethasone 40 mg/day on days 1-2 and 8-9. This schedule was planned to repeat every 3 weeks until disease progression, severe toxicity or stem cell transplantation., Results: Of the 14 patients evaluable for response, 3 patients achieved CR, 7 patients PR, with 1 SD and 3 PD; overall response rate 71% (10/14; 95% confidence interval, 47-95%). The median progression free survival (PFS) and event free survival (EFS) were 113 (range 21-493+) and 77 (range 21-324+) days, respectively. The median overall survival was 267 (range 31-493+) days. Grade 3/4 neutropenia and grade 3 neutropenic fever were observed in 67% (22/33) and 18% (6/33) of cycles, respectively. There were 20% of grade 3/4 nausea and diarrhea observed., Conclusions: The ICD regimen with current schedule showed high response rate for DLBL patients previously treated with RCHOP. But the high incidence of neutropenia led to delay of subsequent cycles causing dose intensity reduced, which seems to be related with short PFS and EFS.

Purpose: We evaluated efficacy and safety of XELOX in previously untreated patients with AGC., Patients and Methods: Patients received intravenous oxaliplatin 130 mg/m(2) over 2 h on day 1 plus oral capecitabine 1,000 mg/m(2) twice daily on days 1-14, every 3 weeks (XELOX). Treatment was continued until disease progression, intolerable toxicities or eight cycles reached. All tumour evaluations were reviewed and confirmed centrally. Design was according to Ensign's three-stage method., Results: Fifty-four patients (37 men) were enrolled; median age 57 years (range 29-70). In total, 311 cycles of XELOX were delivered. Overall response rate was 63% (95% CI, 50-76%), with 3 complete and 31 partial responses. At 13 months' median follow-up, median progression-free and overall survival were 5.8 (95% CI, 4.4-7.2) and 11.9 months (95% CI, 8.8-15.1), respectively. The most common haematological adverse event was anaemia (70% of patients). Grade 3-4 neutropenia was observed in four patients, with neutropenic fever in only one patient. Most common non-haematological toxicities were neuropathy (70%), vomiting (50%), diarrhoea (33%), and hand-foot syndrome (HFS) (39%). Grade 3-4 toxicities were rare. Treatment was delayed or the dose reduced in 30 and 15% of cycles, respectively. There was one treatment-related death associated with grade 4 neutropenic sepsis., Conclusion: XELOX was active and well tolerated as a first-line therapy for AGC.

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder; thus far, only seven families have been reported with c-kit germline mutations. Presented herein is a case of multiple intestinal GIST in a 38-year-old man with a germline mutation of the c-kit gene. Operative specimens of the jejunal segment and multiple wedge resection specimens included approximately 30 masses, ranging in size from 1.0 to 6.0 cm. Microscopically, the tumors were composed of CD117-positive spindle/epitheloid cells with variable numbers of mitotic counts, a characteristic of GIST. The mitotic rate increased to more than 5/50 high-power fields. Interestingly, marked hypertrophy of the myenteric plexus with CD117-positive cells was identified in the intestinal segment. By polymerase chain reaction-single-strand conformation polymorphism analysis and direct DNA sequencing, a heterozygous c-kit missense mutation at nucleotide 1676 of codon 559 (T --> C, Val --> Ala), part of the juxtamembrane domain, was detected in the normal tissue. The same mutation was homozygous in the tumor samples. The present case is the first proven case of multiple GIST with a c-kit germline mutation in Korea and is distinguishable from other reported germ-line c-kit mutations because the same 1676 T --> C missense mutation occurs in the normal allele as well as the affected allele, although the significance of the identical mutations remains to be investigated.

Background/aims: Gemcitabine has been the standard regimen for advanced pancreatic cancer, but the effect on the response rate and survival is still disappointing, leading to many trials of combination chemotherapy. 5-FU and cisplatin were combined with gemcitabine in this trial, as they are synergistic with gemcitabine and each other as well. This study was aimed to assess the effectiveness and safety of combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer., Methods: Patients with advanced pancreatic cancer were entered into this study. Gemcitabine at a dose of 800 mg/m2 on day 1 and 8, 5-FU 1,000 mg/m2/day from day 1 to 3 for 72 hours, and cisplatin 60 mg/m2 on day 2, 24 hours after the start of gemcitabine were administered every 3 weeks., Results: From December 2001 to January 2004, twenty patients were enrolled in this study. Among 17 of these patients assessable, 3 patients had a partial remission with the response rate of 23.6% (95% confidence interval, 6.2-41.0%). The median time to disease progression was 230 days and median duration of survival was 322 days. Among total of 91 cycles, leukopenia, neutropenia, and thrombocytopenia of grade 3 or 4 occurred in 12 cycles (13.2%), 12 cycles (13.2%), and 23 cycles (24.4%), respectively. Grade 3 or 4 mucositis developed at 2 cycles (2.2%), and nausea and vomiting were encountered in 3 cycles (3.3%)., Conclusions: Combination chemotherapy with gemcitabine, 5-FU, and cisplatin for advanced pancreatic cancer is active and well-tolerated, warranting a phase III study.

Inflammation is a significant component of chronic neurodegenerative diseases. Cyclooxygenase-2 (COX-2) is expressed in activated microglial cells and appears to be an important source of prostaglandins during inflammatory conditions. To investigate the effect of curcumin on COX-2 gene expression in microglial cells, we treated lipopolysaccharide (LPS)-challenged BV2 microglial cells with various concentrations of curcumin. Curcumin significantly inhibited LPS-mediated induction of COX-2 expression in both mRNA and protein levels in a concentration-dependent manner. COX-2 enzyme activity was also inhibited in accordance with mRNA and protein levels. Furthermore, curcumin markedly inhibited LPS-induced nuclear factor kappaB (NF-kappaB) and activator protein 1 (AP-1) DNA bindings. These data suggest that curcumin suppresses LPS-induced COX-2 gene expression by inhibiting NF-kappaB and AP-1 DNA bindings in BV2 microglial cells.

To compare survival rates and long-term complications after bone marrow transplantation (BMT) or treatment with immunosuppressive agents (ISA) in the management of adult aplastic anemia (AA) and to identify prognostic factors associated with improved survival, we evaluated 229 adult AA patients treated with ISA from 1990 to 2001 and compared the results with those for 64 BMT recipients. Of 156 patients with severe aplastic anemia (SAA) or very severe AA treated with ISA (antithymocyte globulin [ATG] or ATG plus cyclosporine), 46.8% showed complete or partial response and 7.1% had relapses. After long-term follow-up, 1 case each of acute leukemia, myelodysplastic syndrome, and paroxysmal nocturnal hemoglobinuria developed. The 6-year survival rate was 69%. Response to ISA, disease severity, and low absolute neutrophil count (ANC) (< or = 200/mm3) were associated with poor survival. Patient age, sex, initial platelet count, etiology, or treatment regimen did not significantly affect survival. Cox regression analysis showed low ANC to be the only pretreatment variable significantly associated with poor survival (P = .000). Of 64 BMT recipients, 82.8% had sustained engraftment, and 12.5% experienced graft failure. Twenty (31.3%) of the patients developed grade II to IV acute graft-versus-host disease (GVHD), and 12 (18.8%) of the patients developed chronic GVHD. The 6-year survival rate was 79%. Patient age and sex, disease severity, etiology, ANC, initial platelet count, and treatment regimen did not affect survival. Survival of 83 AA patients, aged 14 to 40 years, treated with ISA was not statistically significant from that of 61 adult AA patients who underwent BMT (6-year survival rate, 65% and 79%, respectively). However, BMT in adult AA achieved long-term engraftment and a lower relapse rate than ISA. These results suggest that ISA can achieve a high response rate and long-term survival among patients with adult AA, regardless of disease severity. Further studies with larger numbers of patients and long-term follow-up are needed.

Background: This prospective phase II trial was performed to determine the efficacy and toxicity of mitomycin C, vinorelbine and cisplatin combination chemotherapy for patients with previously untreated stage IIIB or IV non-small cell lung cancer (NSCLC)., Methods: Between January 1999 and April 2001, 30 patients with chemotherapy-naive stage IIIB or IV NSCLC were entered into this study. Mitomycin C at a dose of 7 mg/m2, vinorelbine at a dose of 25 mg/m2 and cisplatin at a dose of 75 mg/m2 on day 1 and vinorelbine at a dose of 25 mg/m2 on day 8 were administered. This regimen was repeated every 4 weeks., Results: 29 patients out of 30 patients were assessable. Among the assessable patients, 15 (51.7%) patients had a partial response. The median duration of response and survival was 22 weeks and 39 weeks, respectively. Grade 3 or 4 leukopenia and thrombocytopenia were observed in 28.3% and 4.7% of all the cycles, respectively. Nausea and vomiting of grade 3 occurred only in 2.4% of all the cycles., Conclusion: The regimen of mitomycin C, vinorelbine and cisplatin for non-small cell lung cancer is active against advanced NSCLC with tolerable toxicities.

Purpose: To determine the prognostic value of pre- treatment serum LDH levels and the LDH isoenzyme pattern for non-small cell lung cancer, and to determine the relationship between the response to chemotherapy and the changes in serum LDH levels following chemotherapy., Materials and Methods: Patients with pathologically confirmed non-small cell lung cancer were entered onto this study. Their serum LDH levels were assessed prior to chemotherapy, with the LDH isoenzyme being assessed in patients with high initial serum LDH levels. The serum LDH levels were re-assessed following 2 cycles of chemotherapy. The relationship between the response to chemotherapy, pre-treatment serum LDH levels and LDH isoenzyme pattern and the changes in serum LDH levels, following chemotherapy, were evaluated., Results: 49 patients were entered onto this study. The pre-treatment serum LDH levels were normal in 26 patients, and elevated in 23. The LDH isoenzyme was evaluated in 15 patients, with LDH2 being elevated the most frequently. The response rate to chemotherapy was 42.9% in all 42 patients able to be evaluated, 45.8% in patients with normal serum LDH levels and 41.2% in patients with elevated serum LDH levels. This difference was not statistically significant (p=0.767). The median survival was 37 weeks in all patients able to be evaluated, 38 weeks in those with normal serum LDH levels and 31 weeks in those with elevated serum LDH levels. These differences were not statistically significant (p=0.202). The patients with normal serum LDH levels following chemotherapy were more responsive to chemotherapy than those with elevated serum LDH levels following chemotherapy (response rate 51.4% vs. 0%, p=0.027)., Conclusion: The LDH2 are most commonly elevated in non small cell lung cancer patients. The pre-treatment serum LDH levels do not reflect the prognosis accurately. The serum LDH levels following chemotherapy are associated with the response to chemotherapy.

Background: Mad1 protein is known to repress Myc target genes and antagonize Myc function. The authors undertook this study to investigate the clinical implication of Mad1 expression in human breast carcinoma., Methods: The authors performed immunohistochemical assays for Mad1 and Myc proteins in human breast carcinoma, along with tissues from normal breast and benign diseases. The data from protein assays were analyzed in terms of the clinical and biologic characteristics of the patients., Results: Of 66 patients with invasive ductal carcinoma, Mad1 expression was detected in 22 (33. 3%). Intensity and area of Mad1 expression significantly decreased in DCIS and invasive cancers, whereas high levels of Mad1 expression were persistent in benign breast lesions. Mad1 expression was significantly reduced in poorly differentiated tumors (P < 0.001). Expression of Mad1 was not associated with tumor size, lymph node status, or stage of disease. The authors did not observe any correlation between S-phase and expression status of Myc or Mad1. Mad1 expression was closely linked to differentiation of the cancer cells and inversely correlated with Myc expression (P = 0.042). In survival analysis, Mad1 was a significant factor in predicting recurrence of the disease, but not overall survival after CMF chemotherapy., Conclusions: In human breast carcinoma cells, expression of Mad1 seems to be down-regulated, whereas expression of Myc is amplified. Altered expression of Mad1 may play a role in the malignant transformation of human mammary epithelial cells and represent an aggressive phenotype in human breast carcinoma., (Copyright 2000 American Cancer Society.)