Search

Purpose We previously reported the prevalence of monoclonal gammopathy of undetermined significance (MGUS) to be 3.3% among an elderly Korean urban cohort recruited during 2005-2006. Here, we report a 5-year follow-up study of the previously identified MGUS cohort. Materials and Methods The 680 participants from the initial cohort were followed-up for a median of 5 years. Sera were collected between 2010 and 2011. Two-step screening was performed with standard serum electrophoresis followed by immunofixation and determination of the serum concentration of monoclonal-protein (M-protein). Results Of the 680 participants (21 with MGUS), 348 (51%) agreed to participate in the follow-up study and 10 were found to have MGUS. Among the 21 MGUS patients initially identified, nine were followed-up, six had persistent M-protein, and one patient had progressed to multiple myeloma (progression rate, 1.0%/yr). The M-protein disappeared in the remaining two individuals. Among the 339 participants without MGUS who were followed-up, four developed an M-protein. There was no significant difference in survival with respect to the presence of MGUS (p=0.66). Conclusion The 5-year follow-up data show that the natural clinical course of MGUS in Korea is similar to that in Western countries. MGUS was not associated with an increased risk of death over the 5-year study period. [ABSTRACT FROM AUTHOR]

AL Amyloidosis is a condition whereby misfolded proteins generated by plasma cells deposit in tissues causing organ dysfunction. Chemotherapy and autologous stem cell transplant when eligible are standard treatment options. Several studies report long term outcomes of patients post-transplant. However, there is a paucity of literature describing outcomes of relapsed patients post-transplant. We performed a retrospective study to assess outcomes and therapies employed upon relapse after transplant. Between 1996 and 2009, 410 patients received transplant at the Mayo Clinic as first-line therapy. Of those patients, 42 (10%) died within 3 months of transplant, 64 (16%) died without documented relapse, 158 (38%) were alive without documented progression, and 146 (36%) had documented progression. Those 146 patients are the subject of our study, and their median time to hematologic relapse/progression was 23.6 months (95%CI 18.3, 26.3 months). Their median overall survival and five year overall survival from post-transplant relapse/progression was 51.7 months (95%CI 34.1-62.3) and 39% respectively. The most common first regimen for treatment after relapse was lenalidomide or thalidomide. In conclusion our study indicates that patients with AL amyloidosis fare well post-transplant relapse/progression. Additionally, it provides a yardstick to design clinical trials to determine best treatment options. [ABSTRACT FROM AUTHOR]

The frequency of thromboembolic events (TE) in Caucasian patients with multiple myeloma (MM) receiving thalidomide as the initial treatment has been reported to be 10~58% without prophylactic anticoagulation. Korean MM patients treated with thalidomide were studied to determine the frequency of TE and associated risk factors. A retrospective medical record review of the Korean MM registry from 25 centers in Korea between 2003 and 2007 was performed. We assessed the incidence of arterial and venous TE and the associated clinical parameters. Three hundred and sixty MM patients (median age 61 years, range 32–88 years) received thalidomide treatment. Fourteen patients (3.9%) developed TE: 12 had venous and two had arterial locations. The sites for the venous TE included lungs (seven), lower extremities (four), upper extremities (one), and neck (one). Arterial TE developed in cerebral and peripheral arteries each. No single clinical parameter such as prerequisite for the metabolic syndrome, disease status, and treatment regimen were predictive for the development of TE. The frequency of TE in patients who received thalidomide as initial therapy (7/155) was not different from those who received thalidomide for progressive or relapsed disease (7/205, p = 0.592). The frequency of TE during thalidomide treatment in Korean patients with MM was low. No significant clinical factor was found to be a risk factor. The subgroup requiring thromboprophylaxis among the Korean patients with MM, receiving thalidomide, needs to be clarified. [ABSTRACT FROM AUTHOR]

Background: Published data suggests that docetaxel combined with 5-fluorouracil (5-FU) may have synergistic activity in treating advanced gastric cancer. We performed a phase I study of docetaxel and 5-FU to determine the maximum tolerated dose (MTD), the recommended dose for phase II studies, and the safety of this combination. Methods: Eligible patients had recurrent and/or metastatic advanced gastric cancer with normal cardiac, renal and hepatic function. Traditional phase I methodology was employed in assessing dose-limiting toxicity (DLT) and MTD. On day 1 every 3 weeks, docetaxel 75 mg/m² (fixed dose) was infused over 1-h, followed immediately by 5-FU as a 5-day continuous infusion. Results: Dose escalation schema was as follows: dose level (DL) 1 (5-FU 250 mg/m²/day), 2 (500), 3 (750), and 4 (1000). Three patients were enrolled on DL1, without DLT. On DL2, 1 DLT (grade 3 stomatitis) was developed in first 3 patients, and this cohort was expanded to 6 patients. Three patients had been enrolled on DL3. Because two out of 3 patients had DLTs, the MTD was reached at DL3. Conclusion: The recommended phase II dose of this combination is 75 mg/m² docetaxel on day 1 immediately followed by a 5-day continuous infusion of 5-FU 500 mg/m²/day. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate efficacy and safety of the combination chemotherapy with irinotecan plus capecitabine in patients with advanced colorectal adenocarcinoma. Methods: Patients with histologically proven advanced colorectal adenocarcinoma received a first-line chemotherapy with irinotecan 240 mg/m2 on day 1 and capecitabine 2,000 mg/m2/day as an intermittent regimen of 2 weeks of treatment followed by a 1-week rest. Treatment was repeated every 3 weeks. Results: Thirty-nine patients were registered, and 36 were assessable for responses. Sixteen objective responses (44%) were observed with a median response duration of 6.9 months. Stable disease was documented in 14 cases (39%). The median time to progression was 6.7 months. The median overall survival was not reached at the time of analysis, and the 1-year survival rate was 67%. Two patients died: 1 due to sepsis not complicating myelosuppression, and 1 patient, known as a hepatitis B virus carrier prior to chemotherapy, died of hepatic failure, the cause of which was not clinically verified. Frequently encountered therapy-related events were leukopenia and gastrointestinal side effects including diarrhea. Severe hand-and-foot syndrome was observed in only 1 patient. Conclusions: The combination chemotherapy of irinotecan and capecitabine is an active and tolerable regimen for advanced colorectal adenocarcinoma, but the observed deaths suggest a future randomized trial that requires a cautious patient selection. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: The role of allogeneic stem cell transplantation (alloSCT) in multiple myeloma (MM) treatment remains controversial. We conducted a retrospective, multicenter, nationwide study in Korea to evaluate the outcomes of alloSCT in Asian patients with MM. Materials and Methods: Overall, 109 patients with MM who underwent alloSCT between 2003 and 2020 were included in this study. Data were collected from the Korean Multiple Myeloma Working Party Registry. Results: The overall response rate and stringent complete response plus complete response (CR) rates were 67.0 and 46.8%, respectively, after alloSCT. At a median follow-up of 32.5 months, the 3-year probability of progression-free survival (PFS) and overall survival (OS) rates were 69.3% and 71.8%, respectively. The 3-year probabilities of OS rates in the upfront alloSCT, tandem auto-alloSCT, and later alloSCT groups were 75.0%, 88.9%, and 61.1%, respectively. Patients who achieved CR before or after alloSCT had significantly longer OS (89.8 vs. 18 months and 89.8 vs. 15.2 months, respectively). Even though patients who did not achieve CR prior to alloSCT, those who achieve CR after alloSCT had improved PFS and OS compared to those who had no achievement of CR both prior and after alloSCT. Patients who underwent alloSCT with 1-2 prior treatment lines had improved PFS (22.4 vs. 4.5 months) and OS (45.6 vs. 15.3 months) compared to those with three or more prior treatment lines. Conclusion AlloSCT may be a promising therapeutic option especially for younger, chemosensitive patients with earlier implementation from relapse. [ABSTRACT FROM AUTHOR]

Purpose A three-drug combination of cyclophosphamide, bortezomib, and dexamethasone (CVD) shows significant efficacy and manageable toxicity as induction therapy in patients with multiple myeloma. Materials and Methods In this phase II study, we enrolled 45 patients who achieved a very good partial response (VGPR) or partial response (PR) after autologous stem cell transplantation (ASCT) and evaluated the efficacy and toxicity of CVD consolidation. CVD consolidation comprised three cycles of cyclophosphamide 300 mg/m2 orally on days 1, 8, and 15, and bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, and 22, along with dexamethasone 20 mg orally or intravenously on days 1 and 2, 8 and 9, 15 and 16, and 22 and 23. Results At enrollment, 39 patients (86.7%) showed VGPR, and nine (13.3%) presented with PR. Nineteen patients (45.2%) achieved a complete response or better as their best response after the end of consolidation. Overall, 22 of 42 patients (52.4%) experienced an improved response status with CVD consolidation. Three-year overall survival and progression-free survival rates were 89.0% and 42.7%, respectively. The most common non-hematologic toxicities were peripheral neuropathy and infection (20.5%), with no grade = 3 neuropathy observed. Conclusion These results showed that CVD consolidation therapy improved the response with reasonable toxicity in patients with residual disease after ASCT. This trial was registered with the Clinical Research Information Service, Republic of Korea (KCT0001327). [ABSTRACT FROM AUTHOR]

To evaluate if raising baseline and maintaining hemoglobin (Hb) levels with red blood cell (RBC) transfusion could improve the outcomes of chemotherapy for advanced gastric cancer (AGC). Patients were randomized to receive RBC transfusion to maintain their Hb levels ≥10 g/dl (arm 1) or ≥12 (arm 2) before the start of their 5-fluorouracil-based first-line chemotherapy. Objective response, KPS and quality of life (QOL) data were measured. For 87 patients enrolled, mean baseline Hb was 10.1 g/dl, and 54 patients received RBC prior to chemotherapy initiation. Despite transfusion, we failed to maintain the Hb level above the predefined target range. Eighteen patients experienced brief and reversible adverse events during transfusion, including two patients with acute pulmonary edema. KPS was improved from baseline to post-chemotherapy in both arms. QOL data showed improvement in some symptom scores, but there was no difference in the QOL scores between the two arms at baseline and all four cycles of treatment. Similar response rates were observed in both arms (arm 1, 30%; arm 2, 35%). Both arms showed similar chemotherapy duration (3.8 and 4.1 months, respectively), progression-free survival (4.0 and 4.1 months) and overall survival (9.9 and 9.3 months). Red blood cell transfusion achieving Hb level above 10 g/dl might contribute to the improvement of the KPS and QOL seen in patients with AGC. The observation of equivalent outcomes at the two target Hb levels supports the feasibility of anemia correction to Hb 10 g/dl, which merits further evaluation. [ABSTRACT FROM AUTHOR]

Background: Patients with metastatic breast cancer (MBC) are frequently exposed to high cumulative doses of anthracyclines and are at risk of resistance and cardiotoxicity. This phase II trial evaluated the efficacy and toxicity of docetaxel plus cisplatin, as salvage chemotherapy in patients with MBC resistant to prior anthracyclines. Methods: Patients with MBC that had progressed after at least one prior chemotherapy regimen containing anthracyclines received docetaxel 75 mg/m² followed by cisplatin 60 mg/m2 every 3 weeks for a maximum of 6 cycles or until disease progression. Results: Between Jan 2000 and May 2002, 24 patients with tumors primary resistant and 15 with secondary resistant disease were accrued. All 39 patients were evaluable for safety and 36 for efficacy. The objective response rate was 31% (95% CI, 16-45%) with 3 complete responses. The median time to disease progression was 7 months, and the median overall survival was 23 months (median follow-up of 41 months). Neutropenia was the most frequently observed severe hematologic toxicity (39% of patients), whereas asthenia and nausea were the most common nonhematologic toxicities. No treatment-related death was observed. Conclusion: In conclusion, we found docetaxel plus cisplatin to be an active and safe chemotherapy regimen for patients with MBC resistant to anthracyclines. [ABSTRACT FROM AUTHOR]

Purpose Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications. Materials and Methods We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival. Results The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1!negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival. Conclusion Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome. [ABSTRACT FROM AUTHOR]

The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension. Our findings suggest that posaconazole tablets generate an optimal PPC earlier and in more patients than the oral suspension among Korean patients. [ABSTRACT FROM AUTHOR]

Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin's lymphoma arising from a B-cell lineage characterized by the formation of malignant effusion in body cavities without evidence of a detectable tumor. The effusion contains tumor cells universally infected with human herpesvirus 8 (HHV8), which is the critical factor differentiating PEL from HHV8-unrelated PEL-like lymphoma (PEL-LL). This report describes a 77-year-old male patient with pleural effusion and ascites, containing lymphoma cells expressing a B-cell phenotype, but without markers of HHV8 in immunocytochemical analysis. The patient was diagnosed with PEL-LL and treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), which resulted in a complete remission. The patient is currently disease-free 15 months post-treatment. To the best of our knowledge, this is the first report on administration of R-CHOP in a PEL-LL patient in South Korea. [ABSTRACT FROM AUTHOR]

Purpose: Pharmacologic thromboprophylaxis is routinely recommended for Western cancer patients undergoing major surgery for prevention of venous thromboembolism (VTE). However, it is uncertain whether routine administration of pharmacologic thromboprophylaxis is necessary in all Asian surgical cancer patients. This prospective study was conducted to examine the incidence of and risk factors for postoperative VTE in Korean colorectal cancer (CRC) patients undergoing major abdominal surgery. Materials and Methods: This study comprised two cohorts, and none of patients received perioperative pharmacologic thromboprophylaxis. In cohort A (n=400), patients were routinely screened for VTE using lower-extremity Doppler ultrasonography (DUS) on postoperative days 5-14. In cohort B (n=148), routine DUS was not performed, and imaging was only performed when there were symptoms or signs that were suspicious for VTE. The primary endpoint was the VTE incidence at 4 weeks postoperatively in cohort A. Results: The postoperative incidence of VTE was 3.0% (n=12) in cohort A. Among the 12 patients, eight had distal calf vein thromboses and one had symptomatic thrombosis. Age > 70 years (odds ratio [OR], 5.61), ≥ 2 comorbidities (OR, 13.42), and white blood cell counts of > 10,000/౭L (OR, 17.43) were independent risk factors for postoperative VTE (p < 0.05). In cohort B, there was one case of VTE (0.7%). Conclusion: The postoperative incidence of VTE, which included asymptomatic cases, was 3.0% in Korean CRC patients who did not receive pharmacologic thromboprophylaxis. Perioperative pharmacologic thromboprophylaxis should be administered to Asian CRC patients on a riskstratified basis. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to compare the clinical and microbiological characteristics of first and breakthrough neutropenic fever in hematologic malignancy patients after chemotherapy. Methods: Breakthrough neutropenic fever was any episode of fever, not present initially, that developed either during antibiotic therapy or within 1 week of discontinuation of therapy. A total of 687 neutropenic fever episodes in 241 patients were observed from April 2003 to March 2014. Results: Blood cultures revealed 210 causative microorganisms: 199 (94.8%) were bacteria and 11 (5.2%) were fungi. Gram-negative bacteria predominated in both types of neutropenic episode (first 75% (120/160) vs. breakthrough 56% (18/32)) and the most common pathogen was Escherichia coli. Antibiotic resistance rates were higher in breakthrough episodes than first episodes (piperacillin/tazobactam 6% vs. 31%, p = 0.006; ceftazidime 9% vs. 31%, p = 0.025). Inappropriate empirical antibiotic treatment was also more frequent (0% vs. 19%, p = 0.001), as was the 30-day mortality rate (4.3% (19/442) vs. 7.9% (19/245), p = 0.058), although the latter effect was not statistically significant. Conclusion: It is concluded that the epidemiological profile of breakthrough neutropenic fever is different from that of first episode fever. These data reinforce the view that pooled reporting of neutropenic fever may be misleading, and that clinicians should approach breakthrough fever as a distinct entity. [ABSTRACT FROM AUTHOR]

Purpose: p21-activated kinases (PAKs) are involved in cytoskeletal reorganization, gene transcription, cell proliferation and survival, and oncogenic transformation. Therefore, we hypothesized that PAK expression levels could predict the sensitivity of pancreatic cancer cells to gemcitabine treatment, and PAKs could be therapeutic targets. Materials and Methods: Cell viability inhibition by gemcitabine was evaluated in human pancreatic cancer cell lines (Capan-1, Capan-2, MIA PaCa-2, PANC-1, Aspc-1, SNU-213, and SNU-410). Protein expression and mRNA of molecules was detected by immunoblot analysis and reverse transcription polymerase chain reaction. To define the function of PAK4, PAK4 was controlled using PAK4 siRNA. Results: Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment. Immunoblot analysis of signaling molecules reported to indicate gemcitabine sensitivity showed higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1), a well-known predictive marker for gemcitabine activity, in the resistant cell lines. Knockdown of PAK4 using siRNA induced the upregulation of hENT1. In resistant cell lines (Capan-2, PANC-1, and SNU-410), knockdown of PAK4 by siRNA resulted in restoration of sensitivity to gemcitabine. Conclusion: PAK4 could be a predictive marker of gemcitabine sensitivity and a potential therapeutic target to increase gemcitabine sensitivity in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background Evidences suggest an association between leukocytosis and thrombotic or hemorrhagic complication in polycythemia vera (PV) and essential thrombocythemia (ET), but clinical implication is not well known. Objective To evaluate whether leukocyte burden during follow-up is related to thrombotic or hemorrhagic events in PV and ET. Patients/Methods We retrospectively analyzed patients with PV or ET treated at Seoul National University Bundang Hospital, Korea. Time-weighted averages of leukocytes during the follow-up period were defined as leukocyte burden and were calculated for each patient and compared between patient subgroups. In each patient with events, leukocyte burden for the 3-month period before the event was compared with that for the entire follow-up period. Results In 102 patients with PV or ET, 35 events (16 thrombotic, 19 hemorrhagic) occurred in 29 patients (median follow-up, 54 months). Leukocyte burden were significantly higher in patients with events than in event-free patients (12,015 × 103/μL vs. 9,567 × 103/μL, P = 0.003). The difference was more prominent in ET patients than in PV patients, and in patients with hemorrhagic events than in those with thrombotic events. In patients with events, the leukocyte burden in the pre-event period was higher than in the entire follow-up period (16,767 × 103/μL vs. 12,015 × 103/μL, P = 0.002). In all patients, leukocyte burden during entire follow-up period of 11,000 × 103/μL or higher was an independent risk factor for vascular events. Conclusion In PV or ET patients, leukocyte burden during disease course is related to increased incidence of thrombotic or hemorrhagic events. [ABSTRACT FROM AUTHOR]

Herein, we report a rare case of concurrent gastric and pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas. A 65-year-old man who had been diagnosed with Helicobacter pylori-positive gastric MALT lymphoma received eradication therapy and achieved complete remission. During follow-up, he developed de novo pulmonary MALT lymphoma as a sequela of pulmonary tuberculosis, accompanied by recurrent gastric MALT lymphoma. Polymerase chain reaction (PCR) products of the CDR3 region of the immunoglobulin heavy chain gene showed an overall polyclonal pattern with bands at 400 base pairs (bp) and 200 bp predominant in the pulmonary tissue, as well as two distinctive bands in the gastric tissue at 400 bp and 200 bp. This case suggests that multiorgan lymphomas are more likely to be independent from each other when they are far apart, involve different organ systems, and have independent precipitating factors. [ABSTRACT FROM AUTHOR]

Treatment of splanchnic vein thrombosis (SVT) is a clinical challenge due to heterogeneity of clinical presentations, increased bleeding risk, and lack of evidences from clinical trials. We performedan international registry to describe current treatment strategies and factors associated with therapeutic decisions in a large prospective cohort of unselected SVT patients. A total of 613 patients were enrolled (mean age 53.1 years, standard deviation ± 14.8); 62.6% males; the majority (468 patients) had portal vein thrombosis. Most common risk factors included cirrhosis (27.8%), solid cancer (22.3%), and intra-abdominal inflammation/infection (11.7%); in 27.4% of patients, SVT was idiopathic. During the acute phase, 470 (76.7%) patients received anticoagulant drugs, 136 patients (22.2%) remained untreated. Incidental diagnosis, single vein thrombosis, gastrointestinal bleeding, thrombocytopenia, cancer, and cirrhosis were significantly associated with no anticoagulant treatment. Decision to start patients on vitamin K antagonists after an initial course of parenteral anticoagulation was significantly associated with younger age, symptomatic onset, multiple veins involvement, and unprovoked thrombosis. Although a nonnegligible proportion of SVT patients did not receive anticoagulant treatment, the majority received the same therapies recommended for patients with usual sites thrombosis, with some differences driven by the site of thrombosis and the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Waldenström's macroglobulinemia (WM) is a B-cell proliferative malignancy characterized by immunoglobulin M monoclonal gammopathy and bonemarrow infiltration by lymphoplasmacytic cells. Clinical features and cytogenetics ofWMin Asia including Republic of Korea remain unclear. Moreover, no study has reported treatment outcomes in patients with WM treated with novel agent combined with conventional chemotherapy. This study investigated clinical features and assessed treatment outcomes with novel agent and conventional chemotherapy in Republic of Korea. Data from all (n = 71) patients with newly diagnosed WM at 17 hospitals who received chemotherapy between January 2005 and December 2012 were collected retrospectively. The median age of patients was 66 years (range: 37-92 years) and male to female ratio was 5 : 1. Patients treated with novel agent combined chemotherapy displayed higher overall response rate (ORR) compared to conventional chemotherapy alone (92.9% versus 52.6%, ρ = 0.006). The 5-year overall survival rate was 62.6% (95% confidence interval: 34.73-111.07). Use of novel agents produced higher ORR but survival benefit was not apparent due to the small number of patients and short follow-up duration. Further studies are needed to confirm the efficacy of novel agents in patients withWM. [ABSTRACT FROM AUTHOR]

Background aims. This single-center 10-year retrospective study assessed clinical efficacies and adverse events and determined prognostic factors in patients with hematologic disease and febrile neutropenia treated with granulocyte transfusions (GT) from unrelated healthy donors stimulated with recombinant human granulocyte--colony-stimulating factor (rhG-CSF) and dexamethasone. Methods. Between September 1999 and June 2009, 1027 therapeutic GT were performed for the treatment of 170 episodes of febrile neutropenia in 157 patients. Efficacy analysis included 979 GT for 138 episodes in 128 patients who received at least three GT per episode. Adverse event analysis included all patients who received at least one GT. Results. The median granulocyte dose was 0.96 ×× 109/kg/transfusion (range 0.47--1.80 ×× 109/kg/transfusion). Infection was controlled in 73 episodes (52.9%). The 28-day infection-related survival rate was 64.7 ±± 4.1%. The dose of granulocytes transfused did not correlate with clinical outcome. Multivariate analysis revealed that septic shock and pneumonia/multiple primary infection sites were related to infection control failure. Furthermore, refractory underlying disease and septic shock were associated with shorter infection-related survival. Massive hemoptysis (3.5%) and respiratory failure (5.9%) occurred in a few patients. Prior pneumonic infiltration, azotemia and a larger volume of daily GT were associated with serious respiratory complications. Conclusions. GT therapy is a viable adjunctive treatment option for febrile neutropenia as a bridge to autologous hematopoietic recovery in patients with hematologic disease with tolerable toxicity. GT therapy requires close monitoring in patients with prior pneumonic infiltration and azotemia. It is recommended that transfusion with higher volumes is avoided. [ABSTRACT FROM AUTHOR]

We conducted a phase 2 study with bortezomib, doxorubicin, and dexamethasone (PAD) followed by thalidomide and dexamethasone (TD) in patients with relapsed multiple myeloma (MM). Forty patients were enrolled between November 2005 and October 2007, with follow-up continuing until January 2009. Efficacy could be assessed in 37 patients. The overall response rate to PAD followed by TD was 83.6%: complete response 51.4%, near-complete response 13.4%, very good partial remission 5.4%, and partial response 13.4%. The median follow-up was 27 months (range 13–39). The median progression-free survival (PFS) from the start of treatment was 18 months (95% CI, 9.7–26.2 months), with a 1-year PFS rate of 56.9% and 3-year PFS rate of 25.7%. Median overall survival was 35.1 months (95% CI, 18.5–51.7), with a 1-year survival rate of 75% and 3-year survival rate of 27.3%. One hundred seventy-eight PAD cycles (median 6, range 1–6) in 38 patients were assessable for safety. The most common hematologic toxicity was thrombocytopenia, with grade 3–4 in 35.8%. Sensory neuropathy occurred at grade 2 in 26.3% and grade 3 in 10.3%. Two hundred TD treatment cycles (median 4, range 0–12 cycles) were administered. Most adverse events were of mild degree and manageable. PAD followed by TD in patients with relapsed MM is very effective and tolerable. [ABSTRACT FROM AUTHOR]

This study was performed to identify whether cytogenetics, International Prognostic Scoring System (IPSS), or World Health Organization Classification-Based Prognostic Scoring System are predictive of the efficacy of azacitidine in patients with myelodysplastic syndrome (MDS). We retrospectively reviewed the clinical records of 113 patients with MDS treated with azacitidine. The “response alternating disease natural history,” “cytogenetic response,” and “hematologic improvement” were assessed by serial bone marrow biopsy, cytogenetic study, and hemogram analyses. The complete and partial remission rates were 17.6% and 3.9% in 51 evaluable patients. There were no significant differences in response rate in the different cytogenetic/IPSS/WPSS groups. The overall hematologic response (HR) rate was 49.6%, and the HR rate was significantly greater in patients classed as “very high” risk according to the WPSS compared with other patient groups. The 1-year overall survival (OS) rate was higher among patients with HR compared with those without HR (80.9% vs 63.3%, p = 0.046), and the 1-year OS rate among patients classed as being at high risk by each criteria was similar to that of patients classed as being at low risk. The hazard ratio of death among patients with HR compared with those without HR was 0.17 (95% CI 0.04–0.69) for high + very high risk group based on WPSS. Patients in the WPSS high-risk group had an increased HR rate compared with other patient groups, and the achievement of HR was associated with a significant increase in OS. Azacitidine showed similar efficacy in all patient groups, even in patients with poor cytogenetics and in high-risk groups. [ABSTRACT FROM AUTHOR]

Impact of FLT3 receptor tyrosine kinase activation via internal tandem duplication (ITD) of the juxtamembrane region on outcome of acute myeloid leukemia (AML) is still controversial. Recent researches reveal a role of FLT3 in monocyte differentiation in hematopoiesis. We analyzed the clinical impact of FLT3 alterations in adult AML patients excluding acute promyelocytic leukemia (APL) who received induction chemotherapy according to morphologic classification. Retrospective review of medical records from three centers in Korea between 1997 and 2007 was performed. Polymerase chain reaction was performed on genomic DNA derived from blood samples of patients before induction chemotherapy for FLT3-ITD detection. We assessed overall survival (OS), first disease-free survival (1-DFS), and response to induction chemotherapy. One hundred eighty-four patients (median age 49.1 years, range 16.0–76.5) with AML excluding APL received induction chemotherapy from three centers. FLT3-ITD was detected in 22 patients. One hundred forty-one patients were below age 60. One hundred seventy-nine patients received induction chemotherapy with cytarabine and idarubicin (AId) regimen. One hundred nineteen patients achieved complete remission (CR) after first induction chemotherapy. FLT3-ITD was not related to achievement of CR. 1-DFS was longer in patients without FLT3-ITD (median 1-DFS 16.5 vs. 8.5 months, p = 0.025). 1-DFS was not different according to FLT3-ITD status in nonmonocyte lineage leukemia ( p = 0.355), while 1-DFS was shorter in monocyte lineage leukemia for FLT3-ITD positive patients (20.9 vs. 2.4 months, p < 0.001). FLT3-ITD had no impact on OS except for monocyte lineage, where OS was significantly shorter in FLT3-ITD positive group (39.4 vs. 6.0 months, p = 0.026). Moreover FLT3-ITD was stronger prognostic factors in monocyte lineage AML than risk stratification based on cytogenetics. Status of FLT3-ITD should be analyzed differently in AML patients according to morphologic profile. FLT3-ITD is a predictive and prognostic marker only in monocyte lineage patients. This result suggests an existence of distinct subset of monocyte lineage AML with leukemogenesis involving FLT3 activating pathway. [ABSTRACT FROM AUTHOR]

Although several studies have described the prognostic implication of bone marrow (BM) involvement (BMI) in lymphoma, studies focused on BM-involved diffuse large B-cell lymphoma (DLBCL) are very rare and small-sized. This study was performed to examine the prognostic impact of morphologic findings of BMI by lymphoma and risk factors for central nervous system (CNS) relapse in BM-involved DLBCL. Between 1993 and 2005, 675 patients were diagnosed with DLBCL, and 88 patients who had BMI at initial diagnosis were eligible for this study. The median overall survival (OS) and failure-free survival (FFS) of 88 patients were 36.6 and 20.1 months, respectively. When three variables from BM morphologic findings (the pattern of BM infiltration, extent of BMI by lymphoma, and percentage of large cells in the infiltrate) were simultaneously included into multivariate model, the increased extent of BMI by lymphoma (≥10%) in BM area was the only negative prognostic factor, independent of the International Prognostic Index (IPI). Patients with both lower IPI scores and less extent of BMI showed an excellent prognosis with chemotherapy alone (5-year OS and FFS rates, 80% and 69%). However, morphologic BM features were not independent predictive factors for CNS recurrences. An increased lactate dehydrogenase (LDH) level at initial diagnosis was the only independent predictive factor for CNS relapse. Further efforts should be directed toward finding optimal treatment modalities based on the IPI and the extent of BMI by lymphoma. CNS prophylaxis may be considered only in patients with initial elevated LDH levels. [ABSTRACT FROM AUTHOR]

Abstract Goals of work  Fatigue is highly prevalent in cancer and greatly inferences with daily life. The goal of this study was to identify the most informative score in the Brief Fatigue Inventory and to define cut points for “mild,” “moderate,” and “severe” fatigue based on their relevance to quality of life (QOL). Patients and methods  We surveyed cancer patients at five hospitals in Korea with self-administrated questionnaires. The patients were older than 18 years, have a histological diagnosis of malignancy, gave informed consent to participate, and were able to understand the questionnaires. We analyzed 150 cancer patients who reported fatigue. Main result  “Usual fatigue” was a sensitive and reliable indicator of fatigue severity and was defined as mild (1–3), moderate (4–7), or severe (8–10) because it had the strongest correlation with the functional interference, symptoms, depression, and QOL. Conclusion  These cutpoints might be useful in clinical evaluation of fatigue in cancer. Our findings suggest a simple technique for the rapid screening of fatigue and for evaluating its impact on the symptoms and daily functioning of cancer patients. [ABSTRACT FROM AUTHOR]

Background: Although numerous chemotherapeutic agents have been tested, the role of systemic chemotherapy for hepatocellular carcinoma (HCC) has not been clarified. New therapeutic strategies are thus needed to improve outcomes, and we designed this study with new effective drug combination. Methods: Twenty-nine patients with histologically-confirmed, metastatic HCC received a combination chemotherapy with doxorubicin 60 mg/m2 and cisplatin 60 mg/m2 on day 1, plus capecitabine 2000 mg/m2/day as an intermittent regimen of 2 weeks of treatment followed by a 1-week rest. Results: The median age was 49 years (range, 32-64) and 19 patients were hepatitis B virus seropositive. Child-Pugh class was A in all patients and 4 had Zubrod performance status of 2. The objective response rate was 24% (95% CI 9-40) with 6 stable diseases. The chemotherapy was generally well tolerated despite one treatment-related death. Conclusion: Combination chemotherapy with doxorubicin, cisplatin and capecitabine produced modest antitumor activity with tolerable adverse effects in patients with metastatic HCC. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to evaluate the antitumor activity and safety of an epirubicin, cisplatin, and capecitabine (ECX) combination in patients with metastatic or advanced gastric cancer. Patients and Methods: Patients with metastatic or advanced measurable gastric adenocarcinoma received ECX combination chemotherapy. Epirubicin 50 mg/m2 and cisplatin 60 mg/m2 were administered on day 1 by intravenous injection. Capecitabine 1,000 mg/m2 twice daily was administered orally on day 1–14. The cycle was repeated every 3 weeks. Results: Fifty-four patients were enrolled in this study. Fifty patients were assessable for responses and 53 for toxicity. A total of 250 cycles were administered. The overall best response rate by intent-to-treat analysis was 59% including 52% partial responses and 7% complete responses. Median response duration and time to progression was 5.8 and 6 months, respectively. Median survival for all patients was 9.6 months (95% CI, 8.7–10.5 months). The most common grade 3/4 hematological adverse event was neutropenia in 31% (76 cycles) including febrile neutropenia in 4.8% (11 cycles). Non-hematological toxicity was generally mild and reversible. Grade 3/4 nausea, vomiting and stomatitis occurred in 8, 9, and 8% of the patients, respectively. Hand-foot skin reactions developed in 51% of patients, but most were self-limited. Grade 3 occurred in only 4%. One patient died of neutropenic sepsis. Conclusions: ECX combination regimen showed high anti-tumor activity with a tolerable toxicity pattern as a front-line chemotherapy for patients with metastatic or advanced gastric cancer. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: We conducted this study to identify factors influencing the burdens cancer brings to a patient’s family and to evaluate the association between the burdens and the caregiver’s quality of life (QOL). Methods: Participants were drawn from the primary family caregivers of cancer patients at 6 university hospitals and the National Cancer Center in Korea. Of the 738 eligible caregivers, 704 (95.4%) completed the questionnaire packets (Family Impact Questions and Caregiver’s QOL-Cancer). Results: Caregivers, who were poor (OR, 2.11; 95% CI, 1.44–3.10), whose health status was poor (OR, 1.87; 95% CI, 1.29–2.70), who were married (OR, 1.75; 95% CI, 1.12–2.72), who provided care for a long time (OR, 2.29; 95% CI, 1.59–3.28), who cared for patients with poor performance status (OR, 1.35; 95% CI, 1.00–1.82), and who paid high medical expenses (OR, 1.70; 95% CI, 1.21–2.40), were more likely to lose their family savings. In multiple regression analysis, most burden variables – including requiring caregiving assistance, major life change, inability to function normally, loss of savings, loss of income, and altered educational plans – were associated with caregiver QOL. Loss of family income, which was related to economic issues, was most strongly associated with it (16.0%). Conclusions: Our study suggests that to improve caregiver QOL, we should give priority to decreasing the economic burden that cancer places on patient’s family. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]