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The present study is to investigate whether extranodal (EN) metabolic tumor volume (MTV) would have a specific clinical meaning for survival in EN diffuse large B cell lymphoma (DLBCL) patients. Two hundred forty DLBCL patients with EN involvement received 18F-fluorodeoxygenase (FDG) positron emission tomography/computed tomography (PET/CT) were enrolled. Survival analysis revealed that low EN MTV (PFS [progression-free survival], HR = 0.278, 95% CI = 0.127-0.807, p = 0.001; OS [overall survival], HR = 0.320, 95% CI = 0.145-0.703, p = 0.003), low total MTV (PFS, HR = 0.194, 95% CI = 0.085-0.445, p < 0.001; OS, HR = 0.213, 95% CI = 0.092-0.491, p < 0.007), and high National Cancer Center Network-International Prognostic Index score (PFS, HR = 3.152, 95% CI = 1.732-5.734, p < 0.001; OS, HR = 2.457, 95% CI = 1.363-4.430, p = 0.003) were independently associated with survivals in the patients. Our data showed that EN MTV is a useful and novel prognostic parameter for predicting survival in DLBCL patients with EN involvement.

Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70.9%). The overall response rates were 32 and 19.7%, respectively. Median overall survival (OS) (8 vs. 8 months) and progression-free survival (PFS) (6 vs. 7 months) durations were similar in the two groups. Patients in the HMA group with less than 10% peripheral blood (PB) blasts achieved significantly better OS duration than patients in the IC group (P = 0.043). Patients in the IC group with PB blasts and bone marrow blast of ≥ 10 and ≥ 50%, respectively, achieved better PFS durations than the corresponding patients in the HMA group (P = 0.038). Multivariate analysis identified the hematologic improvement-platelet (HI-P) as an independent prognostic factor for survival in the HMA group (P = 0.005). Our results showed that HMA therapy and IC were associated with similar survival duration in elderly AML patients. This study was noteworthy because it assessed prognostic factors that would help to select elderly patients who could expect actual benefits from undergoing the different therapeutic options available, especially HMA therapy.

Autologous stem cell transplant (ASCT) is an effective treatment for non-Hodgkin lymphoma (NHL). However, recent supply issues and toxicity of carmustine have necessitated a new conditioning regimen. We conducted a multicenter, phase II study of BEB (busulfan, etoposide, and bendamustine) conditioning regimen for ASCT in patients with NHL. Thirty-one patients were enrolled and underwent ASCT with the BEB conditioning regimen. The most common subtype was diffuse large B-cell lymphoma (n = 23, 74.2%). Nine patients (29.0%) had a history of relapse, and 18 patients (58.1%) received more than 2 lines of chemotherapy before ASCT. A median number of 6.05 × 106/kg CD34 cells were infused, and all patients engrafted after a median period of 11 days. Thirteen patients (41.9%) experienced neutropenic fever, and 16 patients (51.6%) had grade 3 or 4 toxicities during ASCT. No one had a documented infection, veno-occlusive disease, or treatment-related death. Three-month complete remission rate was 81.8%. Median follow-up period of 15 months showed 6 patients (19.4%) relapsed or progressed and 3 patients died. The estimated 2-year progression-free survival and overall survival rate were 73.0% and 89.8%, respectively. Our results show that BEB conditioning regimens for ASCT are feasible with tolerable toxicity in patients with NHL.

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p = 0.005), elevated lactate dehydrogenase ratio >1 (p

We retrospectively assessed the clinical characteristics of patients with paroxysmal nocturnal hemoglobinuria (PNH) according to severity of cytopenia. A total of 282 patients with hematological parameters assessed at the time of diagnosis of PNH were included. There were 24 patients with PNH/severe aplastic anemia (SAA) (at least two of the three criteria; hemoglobin ≤8 g/dL; absolute neutrophil count (ANC)0.5 × 10(9)/L; platelet count20 × 10(9)/L), 96 patients with PNH/aplastic anemia (AA) (at least two of the three criteria; hemoglobin ≤10 g/dL; ANC 0.5-1.5 × 10(9)/L; platelet count 20-100 × 10(9)/L), and 162 classic PNH patients. Compared with the classic PNH subgroup, the PNH/SAA subgroup had a significantly lower median granulocyte PNH clone size (26.7 vs. 51.0 %, P = 0.021) and lower incidence of lactate dehydrogenase ≥1.5 times the upper limit of normal (52.9 vs. 80.0 %, P = 0.049). The incidence of thromboembolism was similar in both subgroups. Overall survival was significantly lower in the PNH/SAA subgroup than in the classic PNH subgroup (P = 0.033). Our findings suggest that identification of patients with PNH/SAA at the time of diagnosis is important because of different clinical manifestations and poorer outcome compared with patients with classic PNH (clinicaltrials.gov identifier: #NCT01224483).

The outcomes for patients with lower-risk myelodysplastic syndromes (LR-MDS) by the International Prognostic Scoring System (IPSS) vary widely. For more precise prognostication, this study evaluates the prognostic value of revised IPSS with the response to hypomethylating therapy (HMT). Using the Korean MDS Working Party database, treatment outcomes for 236 patients with HMT were retrospectively evaluated. The patients were then reclassified into very low/low (VL/L), intermediate (INT), and high (H) risk groups according to IPSS-R. According to the HMT response, the 3-year overall survival (OS) did not differ between the response group (37.9 ± 9.1 %) and the stable group (52.9 ± 6.6 %, p = 0. 782). When reclassifying according to IPSS-R, 42 patients (20.8 %) were reclassified into the H risk group. Most of them did not have benefit from continued HMT and progressed to secondary failure. The median OS was 59.0 months (range, 40.0–77.9 months) for the VL/L risk group, 31 months (range, 22.7–439.3 months) for the INT risk group, and 20.0 months (range, 15.9–24.1 months) for the H risk group (p

We conducted a multicenter, phase II trial to investigate the efficacy and safety of rituximab plus CVP (R-CVP) combination therapy for patients with previously untreated stage III or IV marginal zone lymphoma (MZL). The treatment consisted of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2) and vincristine 1.4 mg/m(2) (maximum 2.0 mg) being given intravenously on day 1 and oral prednisolone 100 mg on days 1-5. The treatment was repeated every 3 weeks and this was continued for six or eight cycles. Forty-two patients were enrolled from 13 institutes in Korea. Among them, two patients were dropped after the first and second cycles of chemotherapy, respectively, without evaluation. The 40 patients received a total of 287 cycles of R-CVP chemotherapy. The overall response rate was 88% (95% CI, 77-98%) with 24 complete responses (60%). The median duration of response was 28.3 months. After a median follow-up of 38.2 months, the estimated 3-year progression-free survival and overall survival were 59% and 95%, respectively. There were 30/287 cycles (11%) and 5/287 cycles (2%) of grade 3 or 4 neutropenia and febrile neutropenia, respectively. The R-CVP regimen can be an effective and tolerable first-line immunochemotherapy regimen for advanced stage MZL.

Although numerous studies about primary extranodal diffuse large B cell lymphoma (DLBCL) were reported sporadically, the literature of clinical value of immunophenotype and bulky diameter in rituximab era is limited. Ninety-six patients with primary extranodal DLBCL receiving R-CHOP therapy were analyzed to evaluate whether immunophenotype and size of bulky disease are significantly important. The International Prognostic Index was still an important prognostic factor for progression-free survival (PFS) and overall survival (OS; p = 0.003, p = 0.027). Difference of survival between germinal center (GC) type and non-GC type was not different (PFS: p = 0.192; OS: p = 0.197). In two separated groups according to extranodal maximum tumor diameter (EN-MTD) 7.5 cm as cutoff value for survival, the group of EN-MTD ≥7.5 cm had lower PFS and OS than

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.

This study analyzed the outcomes of myelodysplastic syndrome patients treated with azacitidine. Between August 2006 and June 2008, a total of 126 patients were treated with azacitidine at a dose of 75 mg/m(2)/day subcutaneously for 7 days, which was repeated every 28 days. The median age of the patients was 64 (range, 20-82) years. Forty-three patients (33.4%) were classified as intermediate-2 and high risk according to International Prognostic Scoring System (IPSS), while 61 patients (47.3%) were classified as high and very high risk according to WHO Prognostic Scoring System (WPSS). Sixty patients (47.6%) exhibited a response at the median of 3 (range, 1-5) cycles. A complete response was observed in 21 patients (16.7%), a partial response in six patients (4.8%), and total hematologic improvement in 61 patients (48.4%). For the IPSS risk group, the median survival for the patients with intermediate-1 was 20.0 months, for intermediate-2 was 14.9 months, and for high risk was 6.3 months (p = 0.008). For the WPSS risk group, the median survival duration was 21.3 months for the very low and low risk patients, 16.5 months for intermediate risk patients, and 14.9 months for the high and very high risk patients (p = 0.003). The patients with higher than normal lactate dehydrogenase (LDH) levels at the time of diagnosis showed a poor survival (p = 0.003). The median survival duration for the patients with high LDH levels was 13.9 months, while that for the patients with normal LDH levels was 20.6 months. The multivariate analyses revealed that high LDH levels [hazard ratio (HR) 4.384, p < 0.001] and high and very high WPSS risk group (HR 3.855, p = 0.014) were significantly associated with a worse survival, whereas a response to azacitidine was identified as a good prognostic factor for survival (HR 0.224, p = 0.019). In conclusion, while the pretreatment risk group and initial LDH levels were both confirmed as important prognostic factors to predict the outcomes for patients treated with azacitidine, more effective therapies are still needed to prevent disease progression.

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.

Therapy-induced autoimmunity may mediate the destruction of cancer cells. Previous studies have demonstrated that presence of autoimmune thyroid disorder is associated with favorable outcome in patients with solid cancer. Patients with diffuse large B cell lymphoma (DLBCL) who achieved complete response on positron emission tomography/computed tomography (PET/CT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were enrolled in this study. The patients with and without diffuse thyroid uptake (DTU) were classified by PET/CT. A total of 270 patients were enrolled in this study. DTU related to autoimmune thyroiditis was present in 61 patients. The median time to DTU detection was 5.7 months (range, 0–21.3 months). High International Prognostic Index (IPI) score (progression-free survival [PFS], p = 0.001; overall survival [OS], p = 0.008), bulky mass ≥10 cm (PFS, p = 0.001; OS, p = 0.001), bone marrow involvement (PFS, p < 0.001; OS, p = 0.001), and DTU after R-CHOP therapy (PFS, p < 0.001; OS, p = 0.001) were significantly associated with PFS and OS. High IPI score (PFS, p = 0.003; OS, p = 0.014), BM involvement (PFS, p = 0.009; OS, p = 0.039), and DTU after R-CHOP therapy (PFS, p = 0.002; OS, p = 0.002) were independently associated with PFS and OS. DTU after R-CHOP therapy independently predicted favorable outcomes in patients with DLBCL.

The aim of this study was to investigate predictive factors for rapid engraftment after allogeneic peripheral blood stem cell transplantation (alloPBSCT) in patients with acute leukemia. Two hundred sixty-two patients receiving alloPBSCT were analyzed. Subset analyses of donor stem cells were conducted using a flow cytometric method. The correlation between rapid engraftment of neutrophils, platelets, and donor stem cells doses, as well as other recipient and donor clinical factors, was analyzed. In univariate analysis, factors correlated with neutrophil engraftment (≥0.5 × 109/L) by day 12 were achievement of complete remission (CR) after induction chemotherapy (CR1) before hematopoietic cell transplantation (HCT) and high numbers of CD34+ cells, CD3+ T cells, and CD3+/CD4+ T cells. Factors correlated with platelet engraftment (≥20 × 109/L) by day 12 were achievement of CR1 before HCT, donor and recipient sex mismatch, and high numbers of mononuclear cells, CD34+ cells, CD3+ T cells, CD3+/CD4+ T cells, CD3+/CD8+ T cells, and CD56+ NK cells. In multivariate analysis, independent predictive factors for rapid neutrophil and platelet engraftment were CR1 before HCT (p < 0.001 and p = 0.002, respectively), high number of donor CD34+ cells (p = 0.005 and p < 0.001, respectively), and high number of CD3+ T cells (p = 0.005 and p = 0.001, respectively). In conclusion, achieving CR1 before HCT, as well as larger quantities of donor CD34+ and CD3+ T cells, may predict rapid neutrophil and platelet engraftment after PBSCT.

Renal impairment (RI) is a frequent complication with higher incidence of infections and an important prognostic factor for survival. Melphalan clearance is renal function dependent whereas cyclophosphamide is renal function independent. We investigated which combination regimen should be selected between melphalan-combining regimen (MPT) or cyclophosphamide-combining regimen (TCD) in elderly multiple myeloma (MM) patients with RI. Between 2005 and 2009, 157 newly diagnosed MM patients with RI were included comparing MPT with TCD therapy as initial treatment. Seventy-four patients were given MPT regimen, and 83 patients were given TCD regimen. Baseline characteristics were similar between the MPT and TCD groups. Analysis of different cutoff levels between 25% and 75% quartiles using log-rank test determined that glomerular filtration rate (GFR), 40 ml/min/1.73 m(2) as the cutoff point, yielded the highest difference in event-free survival (EFS) and overall survival (OS). The MPT subgroup with low GFR (GFR

The objective of this study was to investigate whether metabolic tumor volume (MTV) by positron emission tomography (PET) can be a potential prognostic tool when compared with Ann Arbor stage, in stages II and III nodal diffuse large B cell lymphoma (DLBCL). We evaluated 169 patients with nodal stages II and III DLBCL who underwent measurements with PET prior to rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). Cutoff point of MTV was measured using the receiver operating characteristic (ROC) curve. During a median period of 36 months, stage II was 59.2% and III was 40.8%. Using the ROC curve, the MTV of 220 cm3 was the cutoff value. The low MTV group (

Bortezomib (VELCADE®), thalidomide and dexamethasone (VTD), as well as melphalan, prednisolone, and thalidomide (MPT) therapy, are highly effective in patients with multiple myeloma. We evaluated the responses and survival times of 35 patients treated with VTD followed by MPT. All patients were newly diagnosed and non-transplantation candidates. Patients received six cycles of VTD, which were followed by eight cycles of MPT. Approximately 97% of patients exhibited early responses to therapy, as early as the second cycle of VTD. Thirty percent of the responses were high quality, which was defined as a complete response (CR), a near-CR or a very good partial response. High-risk patients were defined as patients with any of the following aberrations: del(13), t(4;14), or del(17p). The remaining patients were defined as standard risk. Eleven high-risk patients showed 100% response rates, including 91% high-quality responses. In contrast, 13 standard-risk patients exhibited 92% response rates, including 61% high-quality responses. The overall 2-year survival rates were 60% in high-risk patients and 85% in standard-risk patients, which was not significantly different. As a first-line therapy, VTD followed by MPT has the potential to provide high-quality responses with durable remission among elderly and high-risk patients (clinicaltrials.gov identifier: NCT00320476).