A Rare Case of Essential Thrombocythemia with Coexisting JAK2 and MPL Driver Mutations.

Philadelphia-negative (Ph-) classical myeloproliferative neoplasms (MPNs) include polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis. Somatic driver mutations in the JAK2, CALR, and MPL genes serve as major diagnostic criteria of the Ph- MPNs and these mutations occur in a mutually exclusive manner. In this report, we describe the first case of ET harboring double mutations in JAK2 V617F and MPL. For MPL, the patient had multiple clones of MPL mutations: c.1543_1546delinsAGGG (p.Trp515_Gln516delinsArgGlu) and c.1546C>G (p.Gln516Glu). The JAK2 V617F allele burden in our patient is very low (4%) compared to the relatively high (17%-78%) allele frequency of MPL mutations. The low JAK2 mutant burden might be explained by preexisting clonal hematopoiesis before overt signs of MPNs, followed by the acquisition of a second oncogenic mutation of CALR or MPL leading to the MPN phenotype. This highlights that screening for a second driver mutation should be considered in patients with a low JAK2 mutant burden by reporting a 57-year-old Korean man with ET.

Different prognostic effects of core-binding factor positive AML with Korean AML registry data.

Core-binding factor acute myeloid leukemia (CBF-AML) data in Asian countries has been rarely reported. We analyzed 392 patients with CBF-AML [281 with t(8;21), 111 with inv.(16)/t(16;16)] among data from 3041 patients with AML from the Korean AML Registry. Interestingly, del(9q) was less frequently detected in Korean than in German patients with t(8;21) (7.5% vs. 17%), and del(7q) was more frequently detected in Korean patients with inv(16). Overall survival (OS) was similar between patients in the first complete remission (CR) who received allogeneic (alloSCT) and autologous stem cell transplantation (ASCT) for CBF-AML. OS of t(8;21) patients was poor when undergoing alloSCT in second/third CR, while OS of inv(16) patients in second/third CR was similar to that in first CR. Patients with > 3-log reduction of RUNX1/RUNX1T1 qPCR had improved 3-year event-free survival (EFS) than those without (73.2% vs. 50.3%). Patients with t(8;21) AML with D816 mutation of the c-Kit gene showed inferior EFS and OS. These poor outcomes might be overcome by alloSCT. Multivariate analysis for OS in patients with t(8;21) revealed older age, > 1 course of induction chemotherapy to achieve CR, loss of sex chromosome, del(7q), and second/third CR or not in CR before SCT as independent prognostic variables. Especially, del(7q) is the most powerful prediction factor of poor outcomes, especially in patients with t(8;21) (hazard ratio, 27.23; P < 0.001). Further study is needed to clarify the clinical effect of cytogenetics and gene mutation in patients with CBF-AML, between Asian and Western countries.

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.

Multicenter, cross-sectional observational study of the impact of neuropathic pain on quality of life in cancer patients.

PURPOSE: Neuropathic cancer pain (NCP) is a common and potentially debilitating symptom in cancer patients. We investigated the prevalence of NCP, as well as its management and association with QOL. METHODS: Cancer patients with pain ≥1 on the visual analogue scale (VAS) were surveyed with the Douleur Neuropathique (DN4) questionnaire, the Brief Pain Inventory-Short Form (BPI-SF), and the EuroQOL five dimensions (EQ-5D) questionnaire. The associations between NCP and pain severity or NCP and QOL, while controlling for variables relevant to QOL, were then analyzed. RESULTS: A total of 2003 patients were enrolled in this survey; the prevalence of NCP was 36.0% (n = 722, 95% CI, 32.5-39.5). We found that NCP in cancer patients was closely correlated to a higher pain severity (BPI-SF; 4.96 ± 1.94 versus 4.24 ± 2.02, p < 0.001), and in patients with NCP, pain more severely interfered with daily living, as compared to those without NCP (BPI-SF; 4.86 ± 2.71 versus 4.41 ± 2.87, p < 0.001). Patients with NCP also had worse QOL than those without NCP, as measured by EQ-5D index score (0.47 ± 0.30 vs. 0.51 ± 0.30, p = 0.005), and this was confirmed using multivariate analysis (p < 0.001), even after controlling for other variables such as age, sex, disease stage, cancer duration, radiotherapy, chemotherapy, and comorbidities. Importantly, adjuvant analgesics were used in less than half of patients with NCP (n = 358, 46.4%). CONCLUSIONS: We found that NCP in cancer patients was significantly associated with a worsened QOL, and current management is inadequate. Therefore, future research aimed at developing improved strategies for management of NCP is required.

Cytogenetic profiles of 2806 patients with acute myeloid leukemia-a retrospective multicenter nationwide study.

The cytogenetic and molecular data is recognized as the most valuable prognostic factor in acute myeloid leukemia (AML). Our aim was to systemically analyze the cytogenetics of Korean AML patients and to compare the cytogenetic profiles of various races to identify possible geographic heterogeneity. We retrospectively reviewed medical records of 2806 AML patients diagnosed at 11 tertiary teaching hospitals in Korea between January 2007 and December 2011. The most common recurrent chromosomal abnormality was t(8;21) (8.8 %, 238/2717), but t(15;17) showed an almost same number (8.6 %,235/2717). Among de novo AML, the most frequent aberrations were t(15;17), observed in 229 (10.7 %). The most common French-American-British (FAB) classification type was M2 (32.2 %), and recurrent cytogenetic abnormalities correlated with the FAB subtypes. Among 283 secondary AML cases, myelodysplastic syndrome was the most common predisposing factor. About 67.1 % of the secondary AML cases were associated with chromosomal aberrations, and chromosome 7 abnormalities (n = 45, 15.9 %) were most common. The incidence of FLT3 internal tandem duplication mutation was relatively low at 15 %. Our study reports certain similarities and differences in comparison to previous reports. Such discrepancies call for extensive epidemiological studies to clarify the role of genetic as well as geographic heterogeneity in the pathogenesis of AML.

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.

Concurrent chemoradiotherapy followed by L-asparaginase-containing chemotherapy, VIDL, for localized nasal extranodal NK/T cell lymphoma: CISL08-01 phase II study.

We conducted a phase II trial of concurrent chemoradiotherapy (CCRT) followed by 2 cycles of L-asparaginase-containing chemotherapy for patients who were newly diagnosed with stages IE and IIE nasal extranodal NK/T cell lymphoma (ENKTL). CCRT consisted of 40-44 Gy of radiotherapy with weekly administration of 30 mg/m(2) of cisplatin for 4 weeks. Two cycles of VIDL (etoposide (100 mg/m(2)), ifosfamide (1,200 mg/m(2)), and dexamethasone (40 mg) from days 1 to 3, and L-asparaginase (4,000 IU/m(2)) every other day from days 8 to 20) were administered sequentially. CCRT yielded a 90 % overall response rate without significant side effects in 30 patients, including 20 patients with complete response (CR); however, two patients showed distant disease progression. After CCRT, VIDL chemotherapy showed an 87 % final CR rate (26/30). Although grade III or IV hematologic toxicity was frequent during VIDL chemotherapy, no treatment-related mortality was observed, and L-asparaginase-associated toxicity was manageable. With a median follow-up of 44 months, 11 patients showed local (n = 4) and distant (n = 7) relapse or progression. The estimated 5-year progression-free and overall survival rates were 73 and 60 %, respectively. In conclusion, CCRT followed by L-asparaginase-containing chemotherapy is a feasible treatment for newly diagnosed stages IE/IIE nasal ENKTL.

Fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) combination therapy for elderly acute myeloid leukemia patients.

We performed a phase II trial to evaluate the efficacy and safety of the modified fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) regimen in elderly acute myeloid leukemia (AML) patients. Elderly (≥60 years) AML patients who had not previously received chemotherapy were enrolled in the study. Patients received two consecutive cycles of m-FLAI chemotherapy as an induction. The m-FLAI regimen comprised fludarabine (25 mg/m(2) , days 1-4), cytarabine (1,000 mg/m(2) , days 1-4), and attenuated-dose idarubicin (5 mg/m(2) , days 1-3). The primary end point was complete remission (CR) rate. Secondary end points were overall survival (OS), event-free survival (EFS), and treatment-related mortality (TRM). There were 108 patients (median age 68.4 years, M:F = 64:44) enrolled in the study. CR was achieved in 56.5% of patients, and the TRM rate was 21.3%. Median OS and median EFS were 10.2 and 6.6 months, respectively. The mortality at 30 and 60 days was 15 and 21%, respectively. Performance status and comorbidity did not have prognostic value in this patient cohort. Bone marrow expression of CD117 was associated with increased EFS and OS. m-FLAI is an effective induction regimen for previously untreated AML in elderly patients. In addition, bone-marrow CD117 expression is an independent favorable prognostic factor in elderly AML patients. (ClinicalTrials.gov number, NCT01247493).

Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. MATERIALS AND METHODS: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. RESULTS: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). CONCLUSION: In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Pathophysiological role of hormones and cytokines in cancer cachexia.

We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-α, IFN-γ, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-α, IFN-γ, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 ± 19.5 vs 80.9 ± 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.

Clinical features and outcomes of hypocellular acute myeloid leukemia in adults: A Korean AML registry data.

ABSTRACT: The hypocellular variant of acute myeloid leukemia (AML) is defined as bone marrow cellularity of <20% in a biopsy specimen at presentation. We performed a retrospective analysis of the clinical features and survival outcomes of hypocellular AML in a Korean population. We reviewed the medical records of all patients diagnosed with AML at nine hospitals participating in the Korean AML registry from 2006 to 2012. Overall survival (OS) and event-free survival (EFS) rates were calculated from the time of diagnosis until death or an event, respectively. In total, 2110 patients were enrolled and 102 (4.8%) were identified as having hypocellular AML. Patients with hypocellular AML were older than those with non-hypocellular AML (median age: 59 vs 49 years; P < .001) and presented with leukopenia more frequently (mean white blood cell count: 5810/µL vs 40549/µL; P < .001). There was no difference between patients with and without hypocellular AML in terms of the presence of antecedent hematologic disorders (5.9% vs 5.3%; P  = .809). FLT3-ITD and NPM1 mutations were less common in hypocellular than non-hypocellular AML (FLT3-ITD mutations: 1.2% vs 14.3%, P < .001; NPM1 mutations: 0% vs 9.5%, P = .019). No differences were seen between the hypocellular and non-hypocellular AML groups in the complete remission rate (53.9% vs 61.3%, P = .139) or early death rate (defined as any death before 8 weeks; 14.7% vs 13.0%, P = .629). The OS and EFS did not differ between the hypocellular and non-hypocellular AML groups (median OS: 16 vs 23 months, P = .169; median EFS: 6 vs 9 months, P = .215). Hypocellular AML is more frequently observed in older-aged patients and have fewer FLT3-ITD and NPM1 mutation, but the clinical outcomes of hypocellular AML do not differ from those of non-hypocellular AML.

Age and remission induction therapy for acute myeloid leukemia: An analysis of data from the Korean acute myeloid leukemia registry.

OBJECTIVE: The clinical characteristics and therapeutic strategy in acute myeloid leukemia (AML) are influenced by patients' age. We evaluated the impact of age on remission induction therapy for AML. METHODS: We retrospectively analyzed 3,011 adult AML patients identified from a nationwide database between January 2007 and December 2011. RESULTS: Three hundred twenty-nine (10.9%) acute promyelocytic leukemia (APL) and 2,682 (89.1%) non-APL patients were analyzed. The median age was 51 years and 55% of patients were male. Six hundred twenty-three patients (21%) were at favorable risk, 1522 (51%) were at intermediate risk, and 743 (25%) were at poor risk. As the age increased, the proportion of those at favorable risk and who received induction chemotherapy decreased. After induction therapy, complete response (CR) was achieved in 81.5% (243/298) of APL and 62.4% (1,409/2,258) of non-APL patients; these rates decreased as the age increased, with an obvious decrement in those older than 60 years. The median overall survival of non-APL patients was 18.7 months, while that of APL patients was not reached, with a 75% five-year survival rate. CONCLUSIONS: Age impacts both the biology and clinical outcomes of AML patients. Further studies should confirm the role of induction remission chemotherapy by age group.

Re-analysis of the outcomes of post-remission therapy for acute myeloid leukemia with core binding factor according to years of patient enrollment.

OBJECTIVE: The purpose of this study was to re-evaluate post-remission therapy outcomes after first remission according to years of patient enrollment in patients with core binding factor acute myeloid leukaemia. METHODS: We conducted a retrospective study on 138 patients aged less than 60 years diagnosed with core binding factor acute myeloid leukaemia between 1994 and 2006, comparing allogeneic stem cell transplantation and high-dose cytarabine chemotherapy as post-remission treatment options after the first remission. RESULTS: The 5-year probabilities of disease-free survival and overall survival were not different between allogeneic stem cell transplantation and high-dose cytarabine groups. However, 3-year probabilities of disease-free survival (86.7% vs. 67.0%) and overall survival (90.0% vs. 67.3%) showed a trend towards improvement in the allogeneic stem cell transplantation group compared with the high-dose cytarabine group in cohort after 2003 (2003-2006), whereas outcomes were not different in cohort before 2003 (1994-2002). Especially, 3-year probabilities of disease-free survival (95.2% vs. 59.3%, P = 0.008) and overall survival (95.2% vs. 59.6%, P = 0.032) of allogeneic stem cell transplantation group were significantly better than high-dose cytarabine group in cohort after 2003 of acute myeloid leukaemia patients with t(8;21). The relative risk of overall survival with allogeneic stem cell transplantation, compared with high-dose cytarabine chemotherapy, was significantly improved in the cohort after 2003 (0.33; 95% CI, 0.07-1.48) when compared with that before 2003 (1.92; 95% CI, 0.77-4.82). In multivariate analysis in cohort after 2003, allogeneic stem cell transplantation as post-remission therapy was associated with better disease-free survival. CONCLUSIONS: Allogeneic stem cell transplantation is currently the more effective post-remission therapy than it was prior to 2003 for core binding factor acute myeloid leukaemia achieving first remission. On the contrary to previous findings, allogeneic stem cell transplantation provides significantly improved outcomes than high-dose cytarabine chemotherapy in acute myeloid leukaemia with t(8;21).

Safety and effectiveness of central venous catheterization in patients with cancer: prospective observational study.

This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catheterization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catheterization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P<0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P<0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC.

Is immunological recovery clinically relevant at 100 days after allogeneic transplantation?

BACKGROUND/AIMS: Immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT) is affected by multiple variables during the transplantation. METHODS: We assessed the clinical factors contributing to immune function reconstitution at 100 days post-allogeneic HSCT in 114 patients receiving fludarabine-based conditioning. Immunophenotypic analysis using flow cytometry was performed to evaluate the percentage and the absolute numbers of T-cell subsets, natural killer cells, and B-cells as clinical outcomes. RESULTS: Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, T-cell depletion, and acute GVHD were significantly associated with delayed immune reconstitution of T-cell subsets. The incidence of chronic GVHD was significantly increased in the normal recovery group compared to the abnormal group (p = 0.01). Epstein-Barr virus reactivation was more frequently observed in the abnormal group of T-cell subsets (p = 0.045). All viral reactivation events including cytomegalovirus reactivation appeared to be more frequent in the abnormal group of T-cell subsets. CONCLUSION: The immune recovery status post-allogeneic HSCT was affected by GVHD prophylactic regimens, especially in cases receiving tacrolimus-based GVHD prophylaxis, T-cell depletion, and possibly those manifesting acute GVHD. Delayed immune reconstitution might increase the morbidity due to viral reactivation. Treatment strategies are needed to prevent infectious complications and enhance immune reconstitution based on the immune recovery status following allogeneic HSCT with fludarabine-based conditioning.

Outcomes of decitabine treatment for newly diagnosed acute myeloid leukemia in older adults​.

PURPOSE: We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors, including a baseline mini nutritional assessment short form (MNA-SF) score, of response and survival. PATIENTS AND METHODS: Between 2010 and 2018, 96 AML patients aged 65 and above who received decitabine treatment at 6 centers in Korea were retrospectively evaluated. Response rates, hematologic improvements (HI), progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The median age at diagnosis was 73.9 years, and the median number of decitabine treatments administered to the patients was 4 (range, 1-29). Of 85 patients, 15 patients (17.6%) achieved complete remission (CR) or CR with incomplete blood count recovery. Twelve patients (14.1%) showed partial remission (PR), and 18 (21.2%) demonstrated HI without an objective response. The median PFS and OS were 7.0 (95% confidence interval [CI], 4.9-9.0) and 10.6 (95% CI, 7.7-13.5%) months, respectively. In multivariate analyses, MNA-SF score ≥ 8 and the absence of peripheral blood (PB) blasts were significant predictors for improved PFS and OS. CONCLUSIONS: For older patients with newly diagnosed AML, a high MNA-SF score and the absence of PB blasts were independently associated with improved survival.

GnRH agonist therapy in a patient with recurrent ovarian granulosa cell tumors.

A 65-yr-old woman presented 17 yr status post-hysterectomy with bilateral ovarian salpingo-oophorectomy, attributable to ovarian cancer. She was admitted to our hospital, with multiple cystic liver masses and multiple large seeded masses in her abdomen and pelvic cavity. Histological examination of the pelvic masses demonstrated granulosa cell tumors. After two courses of systemic combination chemotherapy, with paclitaxel and carboplatin, the masses in the abdomen and pelvic cavity increased, and debulking surgery also failed because of peritoneal dissemination with severe adhesion. Finally, she underwent palliative radiotherapy for only the pelvic masses obstructing the urinary and GI tracts, and monthly hormonal therapy with a gonadotrophin-releasing hormone agonist; leuprorelin 3.75 mg IM. Subsequently, multiple masses beyond the range of the radiation as well as those within the radiotherapy field partially decreased. This partial response had been maintained for more than 8 months as of the last follow-up visit. Owing to its long and indolent course and the low metabolic rate of the tumors, advanced or recurrent granulosa cell tumor (GCT) requires treatment options beyond chemotherapy, surgery, and radiotherapy. Hormonal agents may provide another treatment option for advanced or recurrent GCT in those who are not candidates for surgery, chemotherapy, or radiotherapy.

Multicenter Phase 2 Study of Reduced-Dose CHOP Chemotherapy Combined With Rituximab for Elderly Patients With Diffuse Large B-Cell Lymphoma.

INTRODUCTION: Elderly patients are more prone to encounter some adverse factors when they receive chemotherapy compared to younger patients. Addition of rituximab to a reduced dose (RD) of cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy might improve patient outcomes with an improved toxicity profile when provided to elderly patients with diffuse large B-cell lymphoma. PATIENTS AND METHODS: A total of 53 patients aged ≥ 65 years with diffuse large B-cell lymphoma diagnosed between August 2012 and December 2014 were enrolled onto this study. RD-R-CHOP regimen consisted of rituximab at 375 mg/m2, cyclophosphamide at 600 mg/m2, doxorubicin at 30 mg/m2, and vincristine at 1 mg on day 1 of each cycle and 40 mg of prednisone on days 1 to 5. Patients received granulocyte colony-stimulating factor if they experienced grade 3/4 neutropenia or febrile neutropenia during any cycle. RESULTS: The median follow-up duration was 18 months (range, 1-44 months). Complete response and overall response rates were 64.1% and 81.1%, respectively. Three-year event-free and overall survival rates were 45.7% ± 8.4% and 62.7% ± 8.1%, respectively. Grade 3/4 neutropenia occurred in 20 patients (37.7%), while febrile neutropenia occurred in 7 patients (20.7%). CONCLUSION: Outcomes of RD-R-CHOP chemotherapy were comparable to those of standard-dose R-CHOP or previous dose-adjusted R-CHOP chemotherapy. In the future, strategies such as tailored therapy based on geriatric assessment results are needed to determine the chemotherapeutic dosage.

Serum biomarkers for predicting overall survival and early mortality in older patients with metastatic solid tumors.

OBJECTIVES: We aimed to explore serum biomarkers for predicting survival of older patients with metastatic solid tumors who received first line palliative chemotherapy. MATERIALS AND METHODS: Serum samples were prospectively collected before first-line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors. Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D were measured by ELISA and interleukin-6 (IL-6), myostatin, irisin, FGF-19, FGF-21, FGF-23 by Luminex multiplex assay. Overall survival (OS) was determined. RESULTS: Serum samples from 138 patients (median age: 75 years, range: 70-92 years) were collected from February 2014 to December 2016. During a median follow up time of 13.8 months, 73 (52.9%) patients died. Among 13 serum markers, CRP (log-rank, P = 0.009), activin A (P = 0.007), and myostatin (P = 0.047) were significantly correlated with OS in univariate analyses. Activin A (hazard ratio [HR] 2.22, 95% confidence interval [CI] 1.32-3.72; P = 0.003) and myostatin (HR 3.02, 95% CI 1.39-6.57; P = 0.005) were significantly associated with OS after adjustment for other clinical factors. In predicting early (6-month) mortality, two inflammatory markers, IL-6 and CRP, were included in the decision-tree model. CONCLUSION: In older patients with cancer, high serum concentrations of activin A and myostatin were predictive of poor OS. IL-6 and CRP might be useful to select older patients at risk of early mortality. These markers could be incorporated into predictive tools for clinical decision-making and warrant further investigation.

A phase II study of capecitabine plus gemcitabine in patients with locally advanced or metastatic pancreatic cancer.

PURPOSE: This open-label, multicenter phase II study was conducted to investigate the efficacy and safety of capecitabine plus gemcitabine combination chemotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: We enrolled 63 patients who received capecitabine 830 mg/m(2) orally twice daily on days 1-21 plus gemcitabine 1000 mg/m(2) as a 30-min infusion on days 1, 8 and 15 every 4 weeks for up to six cycles. RESULTS: A total of 14 patients had partial responses giving an overall response rate of 22% (95% confidence interval [CI] 13-34%) in the intent-to-treat population. The median time to progression and overall survival were 3.9 months (95% CI 3.5-5.7) and 7.5 months (95% CI 5.0-10.0), respectively, and 1-year survival rate was 27.1% in the intent-to-treat population. Capecitabine plus gemcitabine was well tolerated. Grade 3 hematological adverse events were neutropenia (21%) and thrombocytopenia (2%); the only grade 4 hematological events were anemia (2%) and neutropenia (6%). Non-hematological adverse events were mainly gastrointestinal events and hand-foot syndrome, which affected 16% of patients. Grade 3/4 non-hematological events were infrequent. CONCLUSION: The combination of capecitabine plus gemcitabine appears to be active and well tolerated as first-line treatment in patients with advanced/metastatic pancreatic cancer.