Favorable outcome of a histiocytic sarcoma patient treated with immune checkpoint inhibitor: a case report.

Introduction and Importance: Histiocytic sarcoma (HS) is an extremely rare malignancy in which there has been no standard treatment approach. Some preclinical studies have provided rationales for the application of immunotherapy in advanced HS. Case Presentation: The authors reported a case of a 61-year-old patient with metastatic HS who had a rapid progression on ifosfamide, carboplatin, and etoposide chemotherapy. The authors performed PD-L1 testing, which showed a strong positivity in 90% of tumor cells. The patient was then treated with pembrolizumab 200 mg every 3 weeks. He refused palliative radiotherapy. A dramatic response in all sites was recorded on the PET-CT scan after three cycles. He was maintained on pembrolizumab, reaching over 30 months without disease progression. Clinical Discussion: Recent molecular data suggests there could be a role of immunotherapy in HS. In our patient, the disease was refractory to chemotherapy and pembrolizumab has been given based on the strong PD-L1 expression. Response to immunotherapy has also been recorded in several cases with malignant histiocytic neoplasm. Conclusion: Immunotherapy might bring sustained disease remission in PD-L1 high expression HS and further studies evaluating the role of immune checkpoint inhibitor in this disease are warranted.

Clinical Outcomes of Decitabine Treatment for Patients With Lower-Risk Myelodysplastic Syndrome on the Basis of the International Prognostic Scoring System.

INTRODUCTION: Decitabine has shown clinical benefits in patients with intermediate (INT)-2 or high-risk myelodysplastic syndrome (MDS), determined according to the International Prognostic Scoring System (IPSS), but the benefits have not been well demonstrated in patients with lower-risk (IPSS low or INT-1) disease. Recently, it was proposed that the prognosis for patients with IPSS lower-risk disease is heterogeneous, with a substantial proportion of these patients having poor survival. PATIENTS AND METHODS: This study included patients with IPSS lower-risk MDS from the DRAMA (An Observational Study for Dacogen Long-Term Treatment in Patients With Myelodysplastic Syndrome; NCT01400633) and DIVA (A Study for Dacogen Treatment in Patients With Myelodysplastic Syndrome; NCT01041846) studies, which were prospective observational studies on the efficacy and safety of decitabine treatment in patients with MDS. Using the Lower-Risk Prognostic Scoring System [LR-PSS], we classified IPSS lower-risk MDS. Patients in each LR-PSS category were divided according to overall response (OR) to decitabine treatment, and survival outcomes were compared. RESULTS: One hundred sixteen patients were enrolled: LR-PSS category 1 (n = 12; 10.3%), category 2 (n = 56; 48.3%), and category 3 (n = 48; 41.4%). Survival outcomes differed among the 3 categories (P = .046). The overall survival according to OR showed a significant difference in total patients (P = .008) and category 3 patients (P = .003). We analyzed predictive factors for OR, but no variable was found to significantly affect OR. CONCLUSION: Decitabine treatment showed a survival benefit in the higher-risk group of IPSS lower-risk MDS patients who responded to treatment, and classification using the LR-PSS category was helpful for this subgroup, indicating that decitabine treatment might alter the natural course of disease in these patients.

The Derived Neutrophil-to-Lymphocyte Ratio Is an Independent Prognostic Factor in Transplantation Ineligible Patients with Multiple Myeloma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is an independent prognostic marker in solid and hematological cancers. While the derived NLR (dNLR) was shown to be non-inferior to the NLR in large cohorts of patients with different cancer types, it has not been validated as a prognostic marker for multiple myeloma (MM) to date. METHODS: Between May 22, 2011 and May 29, 2014, 176 patients with MM from 38 centers who were ineligible for autologous stem cell transplantation were analyzed. The dNLR was calculated using complete blood count differential data. The optimal dNLR cut-off value according to receiver operating characteristic analysis of overall survival (OS) was 1.51. All patients were treated with melphalan and prednisone combined with bortezomib. RESULTS: The complete response rate was lower in the high dNLR group compared to the low dNLR group (7 vs. 26.1%, respectively; p = 0.0148); the corresponding 2-year OS rates were 72.2 and 84.7%, respectively (p = 0.0354). A high dNLR was an independent poor prognostic factor for OS (hazard ratio 2.217, 95% CI 1.015-4.842; p = 0.0458). CONCLUSION: The dNLR is a readily available and cheaply obtained parameter in clinical studies, and shows considerable potential as a new prognostic marker for transplantation-ineligible patients with MM.

Relationship between physicians' perceived stigma toward depression and physician referral to psycho-oncology services on an oncology/hematology ward.

OBJECTIVE: This study was performed to identify relationships between physicians' perceived stigma toward depression and psycho-oncology service utilization on an oncology/hematology ward. METHODS: The study participants were 235 patients in an oncology/hematology ward and 14 physicians undergoing an internal medicine residency training program in Inha University Hospital (Incheon, South Korea). Patients completed the Patient Health Questionnaire-9 (PHQ-9), and residents completed the Perceived Devaluation-Discrimination scale that evaluates perceived stigma toward depression. A total PHQ-9 score of ≥5 was defined as clinically significant depression. Physicians decided on referral on the basis of their opinions and those of their patients. The correlates of physicians' recommendation for referral to psycho-oncology services and real referrals psycho-oncology services were examined. RESULTS: Of the 235 patients, 143 had PHQ-9 determined depression, and of these 143 patients, 61 received psycho-oncology services. Physicians recommended that 87 patients consult psycho-oncology services. Multivariate analyses showed that lower physicians' perceived stigma regarding depression was significantly associated with physicians' recommendation for referral, and that real referral to psycho-oncology services was significantly associated with presence of a hematologic malignancy and lower physicians' perceived stigma toward depression. CONCLUSION: Physicians' perceived stigma toward depression was found to be associated with real referral to psycho-oncology services and with physician recommendation for referral to psycho-oncology services. Further investigations will be needed to examine how to reduce physicians' perceived stigma toward depression.

A prospective, open-label, multicenter, observational study to evaluate the efficacy and safety of bortezomib-melphalan-prednisone as initial treatment for autologous stem cell transplantation-ineligible patients with multiple myeloma.

Bortezomib-melphalan-prednisone (VMP) showed superior efficacy versus MP as first-line treatment for transplantation-ineligible multiple myeloma (MM). This study investigated the efficacy of VMP for Korean patients with MM.Overall, 177 MM patients received 9 cycles of VMP in this prospective, multicenter, observational study. The primary endpoint was 2-year progression-free survival (PFS).Thirty-nine (22%) patients were aged ≥ 75 years and 83 (47.4%) patients had International Staging System stage III. A median of 5 cycles were delivered. Overall response rate (ORR) was 72.9%, and complete response (CR) rate was 20.3%. With a median follow-up of 11.9 months, median PFS was 17 months. The 2-year PFS and overall survival (OS) rates were 29.2% and 80.0%, respectively. Median OS was not reached. PFS was significantly different depending on performance status (Eastern Cooperative Oncology Group < 2 vs. ≥ 2; p = 0.0002), ß2-microglobulin level (< 5.5 vs. ≥ 5.5 mg/L; p = 0.0481), and cumulative dose of bortezomib (< 35.1 vs. ≥ 35.1 mg/m2; p < 0001). The common adverse events (AEs) were in line with the well-known toxicity profiles associated with VMP.In conclusion, VMP is a feasible and effective front-line treatment for transplant-ineligible older patients with MM in Korea. Continuing therapy with prompt adjustment of treatment according to AEs may be important to improve outcomes of elderly patients.

Prognostic Value of the Pretreatment Advanced Lung Cancer Inflammation Index (ALI) in Diffuse Large B Cell Lymphoma Patients Treated with R-CHOP Chemotherapy.

BACKGROUND: The Advanced Lung Cancer Inflammation Index (ALI, body mass index × albumin/neutrophil-to-lymphocyte ratio) has been demonstrated to be a prognostic factor of survival in some solid cancers. We retrospectively investigated the usefulness of the ALI to predict chemotherapy response and survival in 212 patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. METHODS: Patients were allocated to a low ALI group (n = 82, 38.7%) or a high ALI group (n = 130, 61.3%) according to an optimal pretreatment ALI cut-off value of 15.5 as determined by receiver operating curve analysis. RESULTS: The low ALI group displayed more adverse clinical characteristics, lower rates of complete remission (54.9 vs. 75.4%, p = 0.008), and poorer 5-year progression-free (PFS, 58.1 vs. 77.3%, p = 0.006) and overall (OS, 64.2 vs. 80.2%, p = 0.008) survival. Multivariate analysis showed that low ALI was found to independently predict shorter PFS and OS. Interestingly, a low ALI reverted to a high ALI during treatment in 58 patients (27.4%), and the 5-year OS of these patients was better than that of patients whose ALI remained low (n = 24, 72.5 vs. 24%, p < 0.001). CONCLUSIONS: ALI might be an easily available marker for predicting clinical outcomes in DLBCL patients treated with R-CHOP chemotherapy.

Salvage therapy for acute chemorefractory leukemia by allogeneic stem cell transplantation: the Korean experience.

Little is known about the characteristics that make patients with acute leukemia suitable for undergoing salvage therapy by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we analyzed the clinical outcomes of 223 patients with acute leukemia who underwent allo-HSCT while not in complete remission (CR). The primary end points were overall survival (OS) and CR rate. CR was achieved in 79.8% of patients after allo-HSCT. Acute graft-versus-host disease (GVHD) was significantly associated with CR (P = 0.045). During a median follow-up of 30.1 months, the median OS was 6.1 months. OS was significantly longer in patients with good or standard risk cytogenetic characteristics than in those with poor risk cytogenetic characteristics (P = 0.029, P = 0.030, respectively). Patients who received allo-HSCT from a matched sibling donor had better survival than those with unrelated donors (P = 0.015). Primary chemorefractoriness was not associated with poor survival (P = 0.071). The number of chemotherapies before allo-HSCT was significantly correlated with outcome (P = 0.006). Chronic GVHD was a strong predictor of a longer OS (P = 0.025). In conclusion, survival of patients with primary chemorefractory acute leukemia is not lower when treated upfront with allo-HSCT. Hence, allo-HSCT should be actively considered in such patients. Acute and chronic GVHD is associated with better outcomes patients with acute leukemia who have undergone allo-HSCT and not achieved CR.

Peritoneal lymphomatosis confused with peritoneal carcinomatosis due to the previous history of gastric cancer: a case report.

Peritoneal lymphomatosis is a very rare disease of extranodal involvement of malignant lymphoma that is occasionally confounded with other peritoneal diseases. Herein, we reported the case of a 59-year-old woman who presented with massive ascites with prior history of stomach perforation during endoscopic procedure to treat early gastric cancer. Imaging studies showed massive ascites and tumor infiltration in the omentum and peritoneal wall. Initially, relapsed gastric cancer with peritoneal seeding was suspected based on the patient's history and imaging findings. However, final diagnosis was confirmed by ascites cytology as peritoneal lymphomatosis of diffuse large B-cell lymphoma unlike prior clinical information.

BK virus-hemorrhagic cystitis following allogeneic stem cell transplantation: Clinical characteristics and utility of leflunomide treatment.

BK virus-hemorrhagic cystitis (BKV-HC) is a potential cause of morbidity and mortality in patients having undergone allogeneic stem cell transplantation (Allo-SCT). We analyzed the clinical features of BKV-HC following Allo-SCT and reported the utility of leflunomide therapy for BKV-HC. MATERIALS AND METHODS: From January 2005 to June 2014, among the 69 patients underwent Allo-SCT in our institution, the patients who experienced BKV-HC were investigated retrospectively. RESULTS: Hemorrhagic cystitis (HC) was observed in 30 patients (43.5%), and among them, 18 patients (26.1%) were identified as BKV-HC. The median age of the patients (12 males and 6 females) was 45 years (range, 13-63). Patients received Allo-SCT from acute myeloid leukemia (n=11), aplastic anemia (n=4), myelodysplastic syndrome (n=2), and non-Hodgkin lymphoma (n=1).The donor types were a HLA-matched sibling donor for 6 patients, HLA-matched unrelated donor for 9, and a haploidentical familial donor for 2. The median onset and duration of BKV-HC was on day 21 (range, 7-97) after transplantation and 22 days (range, 6-107). Eleven patients (62.1%) had grade I-II HC and seven patients (38.9%) had grade III-IV (high-grade) HC. Among the seven patients who had high-grade HC, one had complete response (CR), one partial response (PR), and five no response (NR). Among the five non-responders, one died of BKV-HC associated complications. The remaining four patients were treated with leflunomide, with achieving CR (n=2) and PR (n=2). The median duration from the start of leflunomide therapy to response was 13 days (range, 8-17 days). All patients tolerated the leflunomide treatment well, with three patients having mild gastrointestinal symptoms, including anorexia and abdominal bloating. CONCLUSION: BKV-HC was commonly observed in patients with HC following Allo-SCT. In high-grade BKV-HC patients who fail supportive care, leflunomide may be a feasible option without significant toxicity.

Factor V Deficiency in Korean Patients: Clinical and Laboratory Features, Treatment, and Outcome.

Due to rarity of factor V (FV) deficiency, there have been only a few case reports in Korea. We retrospectively analysed the clinical-laboratory features of FV deficiency in 10 Korean patients. Between January 1987 and December 2013, 10 case reports published in a Korean journal or proceedings of Korea Society on Thrombosis and Hemostasis were reviewed. Severity is defined as mild (> 5% of factor activity), moderate (1%-5%), and severe (< 1%). The median age at diagnosis, six males and four females, was 26 years (range, 1 month-73 years). Six of 10 patients were classified as moderate, three as mild, and one as severe disease. Eight patients were diagnosed as inherited FV deficiency. The most frequent symptoms were mucosal tract bleedings (40%) such as epistaxis, and menorrhagia in female. Hemarthroses and postoperative bleeding occurred in one and four patients, respectively. Life-threatening bleeding episodes occurred in the peritoneal cavity (n = 2), central nerve system (n = 1), and retroperitoneal space (n = 1). No lethal haemorrhages happened to patients with mild disease. The majority of bleeding episodes were controlled with local measures and fresh-frozen plasma replacement. Two acquired FV deficient-patients showing life-threatening haemorrhages received the immunosuppressive therapy, but one of them died from postoperative bleeding complications. Despite the small sample size of this study due to rarity of the disease, we found that Korean patients with FV deficiency had similar clinical manifestations and treatment outcomes shown in previous studies.

Prevalence and Relationships of Iron Deficiency Anemia with Blood Cadmium and Vitamin D Levels in Korean Women.

Anemia, iron deficiency (ID), and iron deficiency anemia (IDA) are common disorders. This study was undertaken to determine the prevalence of anemia, ID, and IDA in Korean females. We examined the associations between IDA, heavy metals in blood, vitamin D level and nutritional intakes. The study was performed using on data collected from 10,169 women (aged ≥ 10 yr), including 1,232 with anemia, 2,030 with ID, and 690 with IDA during the fifth Korea National Health and Nutrition Examination Survey (KNHANES V; 2010-2012). Prevalence and 95% confidence intervals were calculated, and path analysis was performed to identify a multivariate regression model incorporating IDA, heavy metals in blood, vitamin D level, and nutritional intakes. The overall prevalence of anemia, ID and IDA was 12.4%, 23.11%, and 7.7%, respectively. ID and IDA were more prevalent among adolescents (aged 15-18 yr; 36.5% for ID; 10.7% for IDA) and women aged 19-49 yr (32.7% for ID; 11.3% for IDA). The proposed path model showed that IDA was associated with an elevated cadmium level after adjusting for age and body mass index (ß=0.46, P<0.001). Vitamin D levels were found to affect IDA negatively (ß=-0.002, P<0.001). This study shows that the prevalence of anemia, ID, and IDA are relatively high in late adolescents and women of reproductive age. Path analysis showed that depressed vitamin D levels increase the risk of IDA, and that IDA increases cadmium concentrations in blood. Our findings indicate that systematic health surveillance systems including educational campaigns and well-balanced nutrition are needed to control anemia, ID, and IDA.

Clinical Outcome and Predictive Factors in the Response to Splenectomy in Elderly Patients with Primary Immune Thrombocytopenia: A Multicenter Retrospective Study.

BACKGROUND: Because many physicians seem reluctant to recommend splenectomy for elderly patients with immune thrombocytopenia (ITP), we investigated the safety and efficacy of splenectomy and the predictive factors for response in these patients. METHODS: 184 patients with primary ITP were retrospectively analyzed based on age at splenectomy: an elderly group (≥60 years, n = 52) and a younger group (<60 years, n = 132). RESULTS: There was no difference in the response rate of elderly versus younger patients (80.7 vs. 80.3%, p = 0.466). Relapse (45.2 vs. 22.6%, p = 0.006), complications, and median postoperative stay (9.5 vs. 7 days, p = 0.019) were significantly higher in the elderly group. The 5-year relapse-free survival of responders was 51.8% in the elderly group and 76.3% in the younger group (p = 0.002). Response to any treatment before splenectomy (HR 2.9, 95% CI: 1.24-6.80, p = 0.014) and platelet count on postoperative day 14 ≥200 × 109/l (HR 31.43, 95% CI: 4.15-238.28, p = 0.001) were independent factors for a favorable response. CONCLUSIONS: Age ≥60 years did not influence the response to splenectomy but was associated with increased relapse and postoperative complications. Splenectomy could provide a durable long-term response for elderly ITP patients.

Allogeneic clonal mesenchymal stem cell therapy for refractory graft-versus-host disease to standard treatment: a phase I study.

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose (1×10(6) cells/kg), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

Clinical efficacy and tolerability of vincristine in splenectomized patients with refractory or relapsed immune thrombocytopenia: a retrospective single-center study.

Therapeutic options for immune thrombocytopenia (ITP) patients after splenectomy failure are limited. In the present study, we evaluated the role of vincristine in patients who relapsed after or were refractory to splenectomy for ITP. Sixty-two ITP patients treated with vincristine after splenectomy were retrospectively analyzed. Vincristine was administered in doses of 1.5 or 2 mg by 2-h intravenous infusion every 7 days for 4 weeks. Twenty-six (41.9 %) and 36 (58.1 %) patients were in the persistent and chronic phases of ITP, respectively. Most patients (67.7 %) received four doses of vincristine. Two months after starting vincristine, 47 (75.8 %) patients had achieved an overall response, at a median time to response of 9 days after the first dose. There was no difference in the response rate for different ITP phases, vincristine dose received, or response to splenectomy. Thirty-two (68 %) and 24 (51.1 %) of the responders maintained the response for 6 months and 1 year, respectively. Relapse occurred mostly within 6 months, with a median relapse-free survival of 12.5 months; thereafter, a durable response was observed. The administration of vincristine was well tolerated in all patients, with grade 1 peripheral neuropathy being the most common adverse event. Our study suggests that vincristine may be an effective therapeutic option, with acceptable toxicity, for salvage treatment of ITP after splenectomy.

A prospective, multicenter, observational study of long-term decitabine treatment in patients with myelodysplastic syndrome.

This prospective observational study evaluated the efficacy and safety of long-term decitabine treatment in patients with myelodysplastic syndrome (MDS). Decitabine 20 mg/m(2)/day was administered intravenously for 5 consecutive days every 4 weeks to MDS patients in intermediate-1 or higher International Prognostic Scoring System (IPSS) risk categories. Active antimicrobial prophylaxis was given to prevent infectious complications. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to response were evaluated, as were adverse events. The final analysis included 132 patients. IPSS risk was intermediate-2/high in 34.9% patients. The patients received a median of 5 cycles, with responders receiving a median of 8 cycles (range, 2-30). ORR was 62.9% (complete response [CR], 36; partial response [PR], 3; marrow complete response [mCR], 19; and hematologic improvement, 25). Among responders, 39% showed first response at cycle 3 or later. OS at 2 years was 60.9%, with 17% progressing to acute myeloid leukemia. PFS at 2 years was 51.0%. Patients achieving mCR showed comparable survival outcomes to those with CR/PR. With active antibiotic prophylaxis, febrile neutropenia events occurred in 61 of 1,033 (6%) cycles. Long-term decitabine treatment with antibiotic prophylaxis showed favorable outcomes in MDS patients, and mCR predicted favorable survival outcomes.

Cardiac involvement in CD56 negative primary pancreatic extranodal NK/T-cell lymphoma, nasal type, presenting with ventricular tachycardia during the early stages of chemotherapy.

We herein report the case of a 23-year-old man who presented with recurrent pancreatitis and was diagnosed with primary pancreatic extranodal natural killer/T-cell lymphoma, nasal type, involving the right ventricle. The cardiac involvement was screened and confirmed by transthoracic echocardiography (TTE), cardiac magnetic resonance imaging and fluorodeoxyglucose positron emission tomography. Although the patient did not have any cardiac symptoms or evidence of arrhythmia before chemotherapy, he presented with fatal newly developed ventricular tachycardia during the early stages of chemotherapy. The follow-up TTE after his chemotherapy demonstrated markedly decreased thickness of the invaded myocardium, thus suggesting that the myocardium infiltrated by lymphoma cells might become vulnerable to fatal arrhythmia with tumor regression.

Clinical characteristics and treatment outcome of acute myeloid leukemia in elderly patients in Korea: a retrospective analysis.

BACKGROUND: The clinical characteristics of elderly patients with AML differ from those of younger patients, resulting in poorer survival and treatment outcomes. We analyzed retrospectively the clinical data of AML patients 65 years old and above to describe patients' characteristics and treatment patterns, and to define meaningful prognostic factors of survival in the Korean population. METHODS: Basic patients' characteristics, clinical outcomes according to treatments, and prognostic factors associated with survival and treatment intensity were examined in a total of 168 patients diagnosed in 5 institutes between 1996 and 2012 as having AML. RESULTS: Herein, 84 patients (50.0%) received high-intensity regimens (HIR), 18 (10.7%) received low-intensity regimens (LIR), and 66 (39.3%) received supportive care (SC) only. The median survival of all patients was 4.5 months; and median survival times with HIR, LIR, and SC were 6.8 months, 10.2 months, and 1.6 months, respectively. Median survival times with HIR and LIR were significantly longer than that with SC (P<0.0001 and P=0.006, respectively). Multivariate analysis identified age, Eastern Cooperative Oncology Group-performance status (ECOG-PS), hemoglobin (Hb) level, and serum creatinine (Cr) level as statistically significant prognostic factors for survival. In the HIR group, prognostic factors for survival were ECOG-PS, Hb level, and C-reactive protein level. CONCLUSION: Even in elderly AML patients, an intensive treatment regimen could be beneficial with careful patient selection. Further prospective studies designed to identify specific prognostic factors are required to establish an optimal treatment strategy for elderly AML patients.

A Phase I Study of Oral Paclitaxel with a Novel P-Glycoprotein Inhibitor, HM30181A, in Patients with Advanced Solid Cancer.

PURPOSE: The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and recommended phase II dose of an oral drug composed of paclitaxel and HM30181A, which is an inhibitor of P-glycoprotein, in patients with advanced cancers. MATERIALS AND METHODS: Patients with advanced solid tumors received standard therapy were given the study drug at escalating doses, using a 3+3 design. The study drug was orally administered on days 1, 8, and 15, with a 28-day cycle of administration. The dose of paclitaxel was escalated from 60 to 420 mg/m(2), and the dose of HM30181A was escalated from 30-210 mg/m(2). RESULTS: A total of twenty-four patients were enrolled. Only one patient experienced a doselimiting toxicity-a grade 3 neutropenia that persisted for more than 2 weeks, at 240 mg/m(2) of paclitaxel. MTD was not reached. The maximum plasma concentration was obtained at a dose level of 300 mg/m(2) and the area under the curve of plasma concentration- time from 0 to the most recent plasma concentration measurement of paclitaxel was reached at a dose level of 420 mg/m(2). The absorption of paclitaxel tends to be limited at doses that exceed 300 mg/m(2). The effective plasma concentration of paclitaxel was achieved at a dose of 120 mg/m(2). Responses of 23 patients were evaluated; 8 (34.8%) had stable disease and 15 (65.2%) had progressive disease. CONCLUSION: The study drug appears to be well tolerated, and the effective plasma concentration of paclitaxel was achieved. The recommended phase II dose for oral paclitaxel is 300 mg/m(2).

The relationship between the success rate of empirical antifungal therapy with intravenous itraconazole and clinical parameters, including plasma levels of itraconazole, in immunocompromised patients receiving itraconazole oral solution as prophylaxis: a multicenter, prospective, open-label, observational study in Korea.

To identify the role of therapeutic drug monitoring of itraconazole (ITZ) in the setting of empirical antifungal therapy with intravenous (IV) ITZ, we performed a multicenter, prospective study in patients with hematological malignancies who had received antifungal prophylaxis with ITZ oral solution (OS). We evaluated the plasma levels of ITZ and hydroxy (OH) ITZ both before initiation of IV ITZ and on days 5-7 of IV ITZ. A total of 181 patients showed an overall success rate of 68.0 %. Prolonged baseline neutropenia and accompanying cardiovascular comorbidity were significantly associated with poor outcomes of the empirical antifungal therapy (P = 0.005 and P = 0.001, respectively). A significantly higher trough plasma level of OH ITZ per body weight was found in the patients who achieved success with empirical antifungal therapy (P = 0.036). There were no significant correlations between plasma concentrations of ITZ/OH ITZ (baseline or trough levels) and toxicities. Seven patients had a discontinuation of ITZ therapy due to toxicity. This study demonstrated that IV ITZ as empirical antifungal therapy was effective and therapeutic drug monitoring was helpful to estimate the outcome of empirical antifungal therapy in patients receiving antifungal prophylaxis with ITZ OS. To predict the outcome of empirical antifungal therapy with IV ITZ, we should evaluate baseline clinical characteristics and also perform the therapeutic drug monitoring of both ITZ and OH ITZ.

Clinical features and survival outcomes of patients with diffuse large B-cell lymphoma: analysis of web-based data from the Korean Lymphoma Working Party Registry.

BACKGROUND: This study aimed to survey the clinical spectrum of diffuse large B-cell lymphoma (DLBCL) in terms of epidemiology, pathologic subtypes, stage, and prognostic index as well as treatment outcomes. METHODS: In 2007-2008, 13 university hospitals evenly distributed in the Korean peninsula contributed to the online registry of DLBCL at www.lymphoma.or.kr and filed a total of 1,665 cases of DLBCL recorded since 1990. RESULTS: Our analysis showed a higher prevalence of DLBCL in male than in female individuals (M:F=958:707), and extranodal disease was more common than primary nodular disease (53% vs. 47%). Among the 1,544 patients who had been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or rituximab-CHOP (R-CHOP) therapy with or without radiation, 993 (63.9%) were alive, with 80% free of disease, 417 were dead (26.8%), with 13% free of disease, and 144 (9.3%) were lost to follow-up, with 23% free of disease. Age below 60 years, stage at diagnosis, international prognostic index (IPI) score regardless of age, and addition of rituximab to CHOP therapy in low- and low-intermediate-risk groups according to IPI scores significantly increased survival duration. CONCLUSION: The epidemiology, clinical spectrum, and biological behavior of DLBCL in Korea are similar to those observed in Western countries, and the advent of rituximab improved survival.