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GALLIUM is a global phase III study that demonstrated significant improvements in progression-free survival (PFS) for obinutuzumab plus chemotherapy (G-chemo) vs. rituximab plus chemotherapy (R-chemo) in previously untreated patients with follicular lymphoma (FL). This study aimed to report the results of a subgroup of patients in China.Patients were randomized to G-chemo or R-chemo. Responders received maintenance therapy for 2 years or until disease progression. The primary endpoint was investigator (INV)-assessed PFS. Secondary endpoints included the overall response rate (ORR) and complete response rate (CRR) at the end of induction chemotherapy, overall survival (OS), and safety.Overall, 58 patients with FL were randomized to the G-chemo (n = 25) and R-chemo arms (n = 33). The INV-assessed PFS rate at 3 years was 81.8% in the G-chemo arm, vs. 70.2% in the R-chemo arm (hazard ratio 0.35; 95% confidence interval: 0.09-1.34; P = 0.1120). The INV-assessed CRRs (without positron emission tomography [PET]) in these arms were 24.0% and 21.2%, respectively, whereas the ORRs were 80.0% and 90.9%, respectively. INV-assessed CRR-PET was 52.6% in the G-chemo, vs. 60.9% in the R-chemo. Median OS was not reached in either arm. Grade 3 to 5 adverse events were more frequent in the R-chemo arm (97.0% vs. 88.0%).The results of this subgroup analysis were consistent with those of the global population, and they suggest that G-chemo has a positive benefit-risk profile in patients from China with FL.ClinicalTrials.gov, No. NCT01332968.

Background: Patients with acute myeloid leukemia (AML) who are older or ineligible for intensive induction chemotherapy have limited treatment options and poor survival. In the VIALE-A study, venetoclax (Ven) + azacitidine (Aza) improved overall survival and response rates compared with placebo (Pbo) + Aza in older or unfit patients with newly diagnosed AML (DiNardo et al. N Engl J Med. 2020). Although cytopenia is common in AML, Ven+Aza was associated with hematologic adverse events in 83% of patients in the VIALE-A study (vs 69% in the Pbo+Aza arm). Here, the frequency and management of cytopenia are analyzed in patients achieving a best response of complete remission (CR) or CR with partial hematologic recovery (CRh) in the VIALE-A study. Methods: This double-blind, Pbo-controlled, multicenter Phase 3 study (NCT02993523) enrolled patients with newly diagnosed AML who were ineligible for intensive chemotherapy due to age ≥75 years or comorbidities. Patients were randomized 2:1 to receive 75 mg/m2 Aza (Days 1-7 of each 28-day cycle) plus either daily 400 mg Ven (Ven+Aza) or Pbo (Pbo+Aza). Disease response was assessed via bone marrow aspirate and biopsy at the end of Cycle 1 and at least every 3 cycles thereafter. After patients achieved blast clearance (bone marrow blasts Results: In total, 186 of 283 (66%) Ven+Aza-treated patients and 33 of 144 (23%) Pbo+Aza-treated patients achieved a best response of CR or CRh (CR/CRh). Of patients with a best response of CR/CRh in the Ven+Aza arm, 77% achieved blast clearance by the end of Cycle 1, 88% by the end of Cycle 2, 92% by the end of Cycle 3, and 98% by the end of Cycle 4. Of patients with a best response of CR/CRh in the Pbo+Aza arm, 33% achieved blast clearance by the end of Cycle 1, 55% by the end of Cycle 2, 76% by the end of Cycle 3, and 91% by the end of Cycle 4. After achieving blast clearance, 75% and 67% of patients in the Ven+Aza and Pbo+Aza arms, respectively, had a delay of the next cycle, with a median duration per cycle delay post-blast clearance (range) of 9.0 (1-39) and 5.5 (1-21) days. Among CR/CRh patients, more patients receiving Ven+Aza versus Pbo+Aza had post-remission cytopenia (87% vs 45%; Table 2). A similar percentage of CR/CRh patients in both arms (Ven+Aza, 26%; Pbo+Aza, 24%) had in-cycle dose interruptions (ie, days without Ven/Pbo exposure between a cycle's first and last Ven/Pbo dose), with a median duration (range) of 2.0 days (1-20) for Ven+Aza and 1.0 (1-13) for Pbo+Aza. A greater proportion of CR/CRh patients experienced post-remission cycle delays due to cytopenia in the Ven+Aza arm (77%) than in the Pbo+Aza arm (30%). Furthermore, a higher percentage of CR/CRh patients had post-remission cycles with a reduction in Ven/Pbo dosing days and/or cycle delays totaling ≥7 days due to cytopenia in the Ven+Aza arm (75%) than in the Pbo+Aza arm (27%). Among these patients, the median percentage of days without Ven/Pbo administration while in remission (out of the total number of days in remission) was 18% (range, 1-69) in the Ven+Aza arm and 13% (3-44) in the Pbo+Aza arm. Ultimately, 129 CR/CRh patients (69%) in the Ven+Aza arm and 10 (30%) in the Pbo+Aza arm received ≤21-day Ven/Pbo dosing post-remission, with a median time from remission to first ≤21-day cycle (range) of 92.0 days (1-480) for Ven+Aza and 74.0 days (6-405) for Pbo+Aza. Conclusion: In the VIALE-A study of older or unfit patients with newly diagnosed AML, the majority of responding patients in the Ven+Aza arm required dosing modifications to manage cytopenia, of which delays between cycles or within-cycle reductions of Ven dosing days were most common. Post-remission cytopenia and dosing modifications were more frequent with Ven+Aza versus Pbo+Aza treatment. The impact of cytopenia and dosing modifications on patient outcomes with Ven+Aza is currently being analyzed and will be reported at a future date. Disclosures Pratz: AbbVie: Other: Scientific Advisory Board, Research Funding; Boston BioMedical: Consultancy; Astellas: Other: Scientific Advisory Board, Research Funding; Jazz Pharmaceutical: Consultancy; Millennium: Research Funding; Daiichi Sankyo: Research Funding; Agios: Other: Scientific Advisory Board, Research Funding; Celgene: Other: Scientific Advisory Board. DiNardo:MedImmune: Honoraria; Agios: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Jazz: Honoraria; Takeda: Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Syros: Honoraria; Notable Labs: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; ImmuneOnc: Honoraria; Novartis: Consultancy; Calithera: Research Funding. Selleslag:Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Astellas: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen Cilag: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; Belgian College: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Teva: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Speakers Bureau. Yamamoto:AbbVie: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Consultancy, Research Funding; Zenyaku: Research Funding; Sumitomo Dainippon: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria; Otsuka: Consultancy, Honoraria, Research Funding; Ono: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria, Research Funding; Mochida: Honoraria; Meiji Seika Pharma: Consultancy, Honoraria; Kyowa Kirin: Honoraria; Janssen: Honoraria; Gilead Sciences: Research Funding; IQIVA/Incyte: Research Funding; HUYA: Consultancy; IQIVA/HUYA: Honoraria; Daiichi Sankyo: Consultancy; Eisai: Consultancy, Honoraria, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Yakult: Research Funding; Stemline Therapeutics: Consultancy; Solasia Pharma: Research Funding; SymBio: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Bayer: Research Funding; Aichi Cancer Center: Current Employment. Konopleva:AbbVie: Consultancy, Research Funding; Cellectis: Research Funding; Agios: Research Funding; Sanofi: Research Funding; Amgen: Consultancy; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; Ascentage: Research Funding; Eli Lilly: Research Funding; Stemline Therapeutics: Consultancy, Research Funding; Calithera: Research Funding; Forty-Seven: Consultancy, Research Funding; Ablynx: Research Funding; Rafael Pharmaceutical: Research Funding; F. Hoffmann La-Roche: Consultancy, Research Funding; Kisoji: Consultancy; AstraZeneca: Research Funding; Genentech: Consultancy, Research Funding. McDonald:venetoclax advisory board in South Africa (in CLL context): Consultancy; Alberts Cellular Therapy: Current Employment. Babu:Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; Novartis: Research Funding; Janssen Oncology: Research Funding; Syndax: Research Funding; Nektar: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Alexion Pharmaceuticals: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Lilly: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Bayer: Honoraria; AstraZeneca: Consultancy, Honoraria; AstraZeneca/MedImmune: Research Funding; Argenx: Consultancy, Research Funding; Boehringer Ingelheim: Consultancy; Merck: Research Funding; AbbVie: Research Funding; TG Therapeutics: Research Funding; Amgen: Research Funding; Lutheran Hospital: Other; Fort Wayne Medical Oncology & Hematology: Current Employment, Current equity holder in publicly-traded company; Sanofi: Research Funding. Stevens:Amgen, MorphoSys: Consultancy. Kantarjian:BioAscend: Honoraria; Delta Fly: Honoraria; Abbvie: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Ascentage: Research Funding; Janssen: Honoraria; Adaptive biotechnologies: Honoraria; Aptitute Health: Honoraria; Oxford Biomedical: Honoraria; Daiichi-Sankyo: Honoraria, Research Funding; BMS: Research Funding; Jazz: Research Funding; Immunogen: Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Sanofi: Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Traina:University of São Paulo at Ribeirão Preto Medical School: Current Employment; AbbVie: Other: Principal Investigator for Protocol Number M15-656 . Venditti:Jazz: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company); Amgen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Pfizer: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; Novartis: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Mayer:AbbVie: Research Funding; Principia Biopharma: Research Funding. Montez:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Ramsingh:Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Genentech: Current Employment, Current equity holder in publicly-traded company. Jin:Genentech: Current Employment. Ainsworth:AbbVie: Current Employment, Current equity holder in publicly-traded company. Duan:AbbVie: Current Employment, Other: may hold stock or options. Svensson:AbbVie: Current Employment, Current equity holder in publicly-traded company. Werner:AbbVie: Current Employment, Current equity holder in publicly-traded company. Potluri:AbbVie: Current Employment, Other: may hold stock or stock options. Jonas:AbbVie: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Amgen: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; GlycoMimetics: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene: Consultancy, Research Funding; Jazz: Consultancy, Research Funding; Takeda: Consultancy; Tolero: Consultancy; Treadwell: Consultancy; Forty Seven: Research Funding; Accelerated Medical Diagnostics: Research Funding; AROG: Research Funding; Daiichi Sankyo: Research Funding; F. Hoffmann-La Roche: Research Funding; Forma: Research Funding; Genentech/Roche: Research Funding; Hanmi: Research Funding; Incyte: Research Funding; LP Therapeutics: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding; Sigma Tau: Research Funding.

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Background Tubular biomarkers have been regarded as emerging and promising markers for early diagnosis of diabetic kidney disease (DKD). The study was to determine the diagnostic capabilities of tubular biomarkers (urinary neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and cystatin C) for DKD and diabetic microalbuminuria, and whether or not the tubular biomarkers appear earlier than microalbuminuria. Methods In this consecutive cohort study, 146 type 2 diabetes mellitus (T2DM) patients with a disease duration of ≥6 years were enrolled. Thirty age- and gender-matched subjects without any systemic diseases were recruited as the control group. Urinary samples collected before treatment were tested for NGAL, clusterin, and cystatin C. Results The levels of biomarkers were higher in patients with DKD (p

In recent years, 66kV vertical TCR-type SVC was put into operation in several transformer substations at home. Compared to the compensation mode of the conventional 35kV SVC which is connected to 66kV busbar through by way of step-down transformer, the vertical compensation mode has the advantages of low loss and small maintenance amount. However, it is found that damage of phase controlled reactor in TCR happens in several scenes, and the technicians and research institutions studied this problem from such aspects as phase controlled reactor manufacturing process, SVC control strategy and natural environment of the transformer substations and obtained their own conclusions. This paper uses PSCAD software to conduct a simulation research on the 66kV vertical SVC system installed on a 220kV transformer substation at home and concluded that the SVC switching overvoltage might be the direct cause leading to damage of phase controlled reactor.

Little is known on racial differences in patients with diffuse large B-cell lymphoma (DLBCL). The aim of this retrospective study is to compare characteristics, prognostic factors and outcomes of Asian and Western patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP).Patient-level data was collected from 8 centers. All patients were diagnosed with DLBCL and treated with R-CHOP. Patients were divided into Asian and Western, according to the country of report. Comparisons and univariate/multivariate survival analyses were performed.712 patients, 455 Asian and 257 Western patients were included. Westerners were more likely to present with elevated LDH (64% vs. 48%, p0.01) and advanced stage (58% vs. 49%, p0.01). After a median follow-up of 36 months, there was no difference in progression-free (PFS; p=0.33) or overall survival (OS; p=0.69). There were no PFS or OS differences between races when evaluating separately each age-adjusted International Prognostic Index category. In the multivariate analyses, performance status and stage were associated with PFS and OS in both races.There are no differences in prognostic factors, PFS and OS between Asian and Western patients with DLBCL treated with R-CHOP.

According to a series of hill area issues, such as big steep gradients, small and disperse plots, agricultural machinery climbing restriction and so on, a new 2-DOF bionic power-assisted legs mechanism driven by hydraulic is proposed. This paper states the design principle of the bionic legs mechanism and its application in agricultural machinery. A dynamic model is used to show how the hind leg assisted agricultural machinery is established, and then deduce the dynamics equation, and solve the inverse dynamics problems. The result shows that agricultural machinery movement along slope is steady with the help of the hind leg, and driving force of hydraulic cylinder changes is slightly without any distinct impact to other devices, the actuated project is feasible and the structure design is reasonable, and it can be used to research on intelligent control of bionic legs and hill area agricultural machinery.

Our objective was to evaluate the non-germinal center (GC) profile as a marker for response and survival in DLBCL and to compare the characteristics of patients with GC and non-GC DLBCL treated with rituximab-containing regimens. In this patient-level meta-analysis, retrospective data from 712 newly diagnosed DLBCL patients treated with chemoimmunotherapy from 7 centers were analyzed. GC and non-GC profiles were defined according to the Hans algorithm. Although the non-GC profile showed a trend towards worse overall survival (HR 1.24, 95% CI 0.92-1.66; p=0.15) and progression-free survival (HR 1.29, 95% CI 0.96-1.73; p=0.09), it did not retain its value in the multivariate survival analysis. Additionally, the non-GC profile was independently associated with worse complete response rates (OR 0.55, 95% CI 0.37-0.83; p

Background: Reactivation of hepatitis B virus (HBV) is less common in lymphoma patients with prior resolved HBV infection [characterized by hepatitis B surface antigen (HBsAg)-negative/hepatitis B core antibody (HBcAb)-positive status] compared with chronic HBV infection (HBsAg positive) when receiving chemotherapy alone. The use of rituximab in chemotherapy regimen might increase the risk of HBV reactivation in patients with prior resolved HBV infection. However, the incidence of HBV reactivation is uncertain, and prophylactic antiviral treatment for this group of patients during rituximab-containing chemotherapy is controversial. The objective of this study was to determine the incidence of HBV reactivation in HBsAg-negative/HBcAb-positive patients diagnosed of diffuse large B-cell lymphoma (DLBCL) and treated with CHOP-like or RCHOP-like regimen. In addition, this study also aims to explore the relationship of HBV reactivation and HBV serology. Methods: Patients were identified using data from six university hospitals collected between January 1998 and November 2008. Four hundred and thirty-seven patients with complete data were selected based on the diagnosis of CD20+ DLBCL, availability of HBV serum markers prior to initiation of chemotherapy and during the development of hepatitis, completion of at least four cycles of chemotherapy using CHOP-like or RCHOP-like regimen, and follow-up for at least 6 months after completion of treatment. The characteristics of the HBsAg-negative/HBcAb-positive patients treated with CHOP-like regimen were compared to those treated with RCHOP-like regimen. Results: Eighty-eight patients of the total 437 patients had pretreatment serology of prior resolved hepatitis B, with a prevalence of 20.1%. Among them, 45 patients received CHOP-like regimen while 43 patients received RCHOP-like regimen. Five patients developed hepatitis during treatment, two from CHOP group and three from RCHOP group. Only one patient treated with RCHOP had hepatitis associated with HBV reactivation, while the other four patients did not have evidence of HBV reactivation. Those four patients also demonstrated positive HBsAb at baseline, while the only patient who suffered from HBV reactivation had negative HBsAb status. This patient was successfully treated with antiviral medications. There were no statistically significant risk factors predictive of HBV reactivation. Conclusions: The present study revealed a low HBV reactivation rate of 2.3% in prior resolved hepatitis B among DLBCL patients undergoing RCHOP-like therapy.

One hundred twelve patients with geriatric acute myeloid leukemia (AML), refractory or relapsed AML, or myelodysplastic syndrome and refractory anemia with excess of blasts in transformation (MDS-RAEBt) were entered into this study to receive CAG (aclarubicin and low-dose cytosine arabinoside [Ara-C]in combination with granulocyte colony-stimulating factor [G-CSF]) with the objective of evaluating the efficacy and tolerance of this regimen. Low-dose Ara-C was given subcutaneously at a dosage of 10 mg/m2 every 12 hours on days 1 to 14. Aclarubicin was administered intravenously at a dosage of 14 mg/m2 per day on days 1 to 4 (CAG regimen A) or 7 mg/m2 on days 1 to 8 (CAG regimen B). Recombinant G-CSF was given subcutaneously at a dosage of 200 3g/m2 per day on days 1 to 14. We demonstrated comparable overall complete remission rates for the 4 groups of patients: 30.8% (8/26) in the elderly patients, 48.4% (30/62) in the refractory AML patients, 44.4% (8/18) in the relapsed AML patients, and 38.5% (5/13) in the MDS-RAEBt patients. Of the 52 patients followed up, the 12-month progression-free survival (PFS) and overall survival (OS) rates estimated by the Kaplan-Meier method were 40.73% 3 8.15% and 42.85% 3 8.23%, respectively. The median PFS and OS times were 9.0 3 2.2 months and 11.0 3 1.6 months, respectively. Toxic effects were very rare and mainly consisted of neutropenia and thrombocytopenia due to myelosuppression; approximately 70% to 80% of patients had neutropenia or thrombocytopenia that exceeded National Cancer Institute grade II. Nonhematologic toxicities were not observed in this study. The CAG regimen seems promising, with acceptable toxicity, for the treatment of various categories of poor-prognosis AML and MDS-RAEBt.

BACKGROUND Acute kidney injury (AKI) is a frequent complication of major surgery. The current study evaluated the power of two biomarkers [urinary neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid binding protein (L-FABP)] to detect the occurrence of AKI and to predict the recovery from renal dysfunction in a major surgery cohort. METHODS In this prospective study, 199 patients undergoing major surgery were enrolled. Urinary samples collected from participants before surgery, and 0, 4, and 12 h and 1, 2, 7, and 14 days after surgery were tested for NGAL and L-FABP. RESULTS Thirty-seven (18.6%) subjects developed AKI. Urinary NGAL and L-FABP were significantly increased from the time surgery was completed (p

Vague set is a generalization of the concept of fuzzy set , similarity measure is the key to research vague set theory. At present, many methods of similarity measure have been proposed, and even been used in several areas. Based on the analysis and studies the methods of similarity measure proposed by domestic and foreign scholars, a new kind of similarity measures of vague set or value is put forward in this article, as well as compares this method with other scholars’ methods, it is verified that the new measures are more rational and practical, and shown that it can be a more useful way to measure the degree of similarity between vague set or value.

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder characterized by ineffective hematopoiesis and leukemia progression. Racial differences may exist on clinical pictures and the molecular events leading to MDS, which are heterogeneous. To better define the clinical and cytogenetic features in Chinese patients, a retrospective multicentric study was performed in 508 MDS cases. Compared with Western countries, Chinese patients showed younger age (median: 49 vs 65-73 years), lower percentages of RARS (2.8 vs 6.6-15.3%), and CMML (5.2 vs 11.7-30.6%). Cytogenetically, among 367 cases with evaluable data, abnormal karyotypes were found in 136 cases, including 56 numerical and 80 structural changes. Incidences of single chromosome 5 and 7 abnormalities were lower than those in Western countries (2.2 vs 17.8-42.5%). However, complex cytogenetic aberrations and chromosome translocations were frequently observed and related to poor prognosis. Both multiple chromosome deletions and translocations were detected in advanced subtypes (RAEB and RAEB-T). Analysis of 200 cases revealed a higher incidence of hepatitis-B-virus infection than that in non-MDS population (21.00 vs 9.75%). This study further confirmed: (1) different genetic/environmental backgrounds between Asian and Western MDS populations; (2) a strong predictive value of cytogenetic abnormalities on disease outcome and involvement of genomic instability in leukemia clone development.

Both all-trans retinoic acid (ATRA) and arsenic trioxide (As 2 O 3 ) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but they had not been used jointly in an integrated treatment protocol for remission induction or maintenance among newly diagnosed APL patients. In this study, 61 newly diagnosed APL subjects were randomized into three treatment groups, namely by ATRA, As 2 O 3 , and the combination of the two drugs. CR was determined by hematological analysis, tumor burden was examined with real-time quantitative RT-PCR of the PML-RAR α (promyelocytic leukemia - retinoic acid receptor α) fusion transcripts, and side effects were evaluated by means of clinical examinations. Mechanisms possibly involved were also investigated with cellular and molecular biology methods. Although CR rates in three groups were all high (≥90%), the time to achieve CR differed significantly, with that of the combination group being the shortest one. Earlier recovery of platelet count was also found in this group. The disease burden as reflected by fold change of PML-RARα transcripts at CR decreased more significantly in combined therapy as compared with ATRA or As 2 O 3 mono-therapy ( P < 0.01). This difference persisted after consolidation ( P < 0.05). Importantly, all 20 cases in the combination group remained in CR whereas 7 of 37 cases treated with mono-therapy relapsed ( P < 0.05) after a follow-up of 8–30 months (median: 18 months). Synergism of ATRA and As 2 O 3 on apoptosis and degradation of PML-RARα oncoprotein might provide a plausible explanation for superior efficacy of combinative therapy in clinic. In conclusion, the ATRA/As 2 O 3 combination for remission/maintenance therapy of APL brings much better results than either of the two drugs used alone in terms of the quality of CR and the status of the disease-free survival.

Twenty cases of patients with relapsed acute promyelocytic leukemia (APL) were entered into this study for evaluating the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide (As2O3). As2O3 was given at a daily dose of 0.08 mg/kg intravenously for 28 days. Pharmacokinetic study was carried out in eight patients. 16/20 (80%) patients achieved CR. The occurrence of some toxic events including gastrointestinal disturbance, facial edema and cardiac toxicity seemed reduced in the low-dose group than those in the standard-dose group. Differentiation changes were observed in peripheral blood, as well as in bone marrow (BM). Pharmacokinetic study showed that the plasma concentration increased soon after administration of As2O3 with the peak values of 1.535-3.424 micromol/l. After infusion, the plasma concentration was around 0.1-0.5 micromol/l. The arsenic concentration of the plasma of BM aspirates 24 h after administration in five patients was close to the level needed for differentiation-inducing effect. The estimated 2-year OS and RFS were 61.55+/-15.79% and 49.11+/-15.09% respectively, with no difference as compared with those in patients treated with conventional dose (P = 0.2865 and 0.7146, respectively). In conclusion, we demonstrated that low-dose As2O3 had the same effect as the conventional dosage and the mechanism of low-dose arsenic seemed to primarily induce differentiation of APL cells.

Abstract 2649 Background: The International Prognostic Index (IPI) is a widely accepted prognostic factor system for diffuse large B cell lymphoma (DLBCL) patients treated with chemotherapy. However, the prognostic value of IPI has been a focal point of the debate in the era of immuno-chemotherapy. Recently, the study of British Columbia group suggested that a revised IPI (R-IPI) which redistributed the IPI factors into 3 distinct prognostic groups provided a more clinically useful prediction of outcome for patients with DLBCL. In order to reassess the value of IPI and R-IPI in unselected Chinese population, we conducted this study. Methods: A multicenter retrospective analysis of DLBCL patients treated with CHOP-like chemotherapy alone or plus rituximab was performed by Shanghai Lymphoma Research Group. In total, 438 patients of newly diagnosed DLBCL treated at 6 participated hospitals were included during the period of 1997–2008. The prognostic value of IPI and R-IPI at diagnosis with regards to overall survival (OS) and progression-free survival (PFS) was evaluated. Results: The median age at diagnosis was 50 years (range, 18–83 years), and the median follow-up was 34 months (range, 3–145 months). Among them, 241 patients received CHOP-like regimen, whereas 197 had rituximab (R)-CHOP-like regimen. While IPI remained predictive in CHOP-like group, it could not distinguish between each prognostic category in the R-CHOP-like group (Fig.1). Redistribution of the IPI factors into a R-IPI identified three distinct prognostic groups with significantly different outcomes both in the patients treated with and without rituximab. In R-CHOP-like arm, these three risk groups had distinctly different rates of 3-year progression-free survival rates of 96%, 84.3% and 67.5% (P Conclusions: Our study underscores the power of R-IPI as a simplified and more clinically relevant predictor of the disease outcomes than the standard IPI in Chinese DLBCL populations in the rituximab era, and it deserves a further study in larger population-based prospective study. Disclosures: No relevant conflicts of interest to declare.

Abstract 4718 Cytogenetic-molecular signature plays an important role in diagnosis, treatment and prognosis evaluation in acute lymphoblastic leukemia (ALL). With examination of karyotype and gene rearrangement, we investigated retrospectively the cytogenetic characteristics in 1331 adults and children with primary acute lymphoblastic leukemia (ALL) diagnosed from November 1989 to July 2007. Cytogenetic and molecular genetic analysis was carried out successfully in 1030 (77.39%) of 1331 cases, abnormal clone was detected in 629 (61.07%) cases. The abnormalities of t(9;22)/BCR-ABL and/or t(4;11)/MLL-AF4 were presented more commonly in adults than in children (25.39% Vs 10.34%,P50) was more frequently seen in children than in adults (13.18% Vs 4.30%,P Ik6, one of IKZF1 deletion isoforms, was detected in 72.29% of ALL patients with Ph chromosome using reverse transcription-PCR amplification. In T-ALL, the frequency of the expression of SIL-TAL,CALM-AF10,HOX11,HOX11L2 gene and the mutation of NOTCH1 gene was 12.38%,4.69%,25.49%,24.51% and 32.99%, respectively. The overall survival of the children was superior to that of the adults, which was the same as previous reports by many other groups. According to the prognosis of patients, these cytogenetic-molecular signatures could be further classified into three subgroups in adult and four subgroups in children. Patients with Ik6 deletion isoform of IKZF1 gene had a significantly worse prognosis than those with wild type isoform (P=0.009). In T-ALL, patients with NOTCH1 mutation were related with poor outcome (P=0.007). Disclosures: No relevant conflicts of interest to declare.

Abstract 4275 Imatinib as an oral Bcr-Abl tyrosine kinase inhibitor is approved as first-line therapy for patients with CML chronic phase (CP), accelerated phase (AP) and blast crisis (BC). As the appointed clinical center for the International Patient Assistance Programs (GIPAP) program, a total of 339 CML patients with CML-CP (n=274), AP (n=30) and BC (n=35) were registered and received imatinib treatment in our center. The starting dose of Imatinib treatment was 400mg daily and dose escalation to 600mg was allowed in patients of CML-AP or BC and in patients who failed to obtained optimal response. All patients were evaluated regularly according to the GIPAP protocol. In this study, we analysed the outcome of Imatinib treatment in these patients in terms of cytogenetic response, overall and progression-free survival and adverse events. The median age was 42 (13-81) years old. The median time from diagnosis to imatinib therapy was 4.4 (0-273) months. The median follow-up was 29 (3-103) months. The overall survival for patients received Imatinib treatment were 92.8±3.1%, 57.3+11.3% and 12.3±9.7% for CML-CP, AP and BC respectively. Among patients with CML-CP, the cumulative complete cytogenetic response (CCyR) were 71.9% at 12 months and 79.9% at the censored follow-up timepoint. In prognosis analysis, there were two major impact factors associated with progression-free survival (PFS) for the CML-CP patients: achievement of CcyR and Imatinib as initial therapy. The estimated 60 month PFS was 87.1±3.7% for patients who achieved a CCyR irrespective of time and only 46.7±1.37% for patients who failed to obtain a CCyR (P Disclosures: No relevant conflicts of interest to declare.

Abstract 1934 Poster Board I-957 A better understanding of the biology of diffuse large B cell lymphoma(DLBCL) is needed in the developement of potential therapeutic agents that target specific intracellular pathway. In this study, expression of the important members of PI3K/Akt/mTOR signaling pathway and their clinical significance were investigated in 73 cases of DLBCL. Immunohistochemical analyses showed that activation of Akt and its downstream targets such as p-p70S6K, p-4E-BP1, YB-1 and Mcl-1 were present in DLBCL cases. Activation of PI3K/Akt/mTOR pathway was related to poor disease outcome in DLBCL patients treated by CHOP but not in those treated by R-CHOP. Rituximab combined with chemotherapy could down-regulate PI3K/Akt/mTOR activation and reverse its negative effect on chemotherapy-treated patients. The effect of Rituximab alone or combined with the mTOR inhibitor Rapamycin was further evaluated in DLBCL cell line SUDHL-4. Rituximab combined with Rapamycin possessed synergic effect in down-regulating PI3K/Akt/mTOR signaling pathway, inhibited proliferation and caused G1 arrest in DLBCL cell line. The results showed that PI3K/Akt/mTOR signaling pathway activation presented in DLBCL may be considered as a prognostic biomarker and a promising target for therapeutic intervention. Disclosures: No relevant conflicts of interest to declare.

Objectives: We performed this prospective study with single arm to evaluate the long term efficacy and safety of rituximab in combination with CHOP regimen in B cell non-Hodgkin’s Lymphoma (NHL) patient. Methods: All patients received 4~8 cycles of CHOP plus rituximab. For each cycle, Rituximab (375 mg/m2 per dose) was given on day 1 and CHOP regimen on day 3. CHOP regimen consisted of cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 (maximum dose, 2.0 mg/d) given intravenously on day 3, and oral prednisone 60 mg given from day 3 to 7. Results: 102 patients were enrolled in this trial, 65 of them are males and 37 are females, with the median age of 47.5 (range 16–76). The main subtypes were diffuse large B cell lymphoma (DLBCL, 82/102), follicular lymphoma (FL, 9/102), mucosa associated lymphoma (MALT, 3/102), marginal zone lymphoma (MZL, 3/102), lymphoplasmacytic lymphoma (LPL, 2/102) and mantle cell lymphoma (MCL, 3/102). The overall response (OR) rate was 91.2% and complete response (CR) rate was 71.6%. The OR and CR of DLBCL were 90.2% and 70.7%, respectively; and the OR and CR of indolent lymphoma (MALT, FL, and LPL) were 100.0% and 82.4%, respectively. The patients with lower (0,1) and higher (≥2) IPI score achieved CR rate and OR rate of 87.88% and 59.18%, and 100.00% and 83.67%, respectively. International prognosis index (IPI) score showed significant impact on both CR and OR rate (P=0.006 and 0.019, respectively). The patients with and without bulky disease achieved CR rate and OR rate of 50.00% and 74.29%, and 83.33% and 91.43%, respectively, and there was no statistical significance (P=0.100 and 0.332, respectively). The patients were followed after achieving objective response (CR+PR) for 2–64 months (median 20 months). Estimated 5 year progress free survival (PFS) rate and estimated 5 year overall survival (OS) rate was 60.33%±6.94% and 75.88%±6.94%, respectively. In DLBCL patients, PFS and OS rate was reached at 56.45%±8.26% and 74.12%±7.48%, respectively. 4 year PFS rate and OS rate of the patients with indolent lymphoma was 86.15%±9.11% and 100%, respectively. IPI score showed significant survival impact on OS and PFS in DLBCL patients, respectively (P=0.0339 and 0.0122, respectively); however, the bulky disease showed impact on PFS but not on OS (P=0.0472 and 0.106, respectively). Conclusions: The results suggested that the rituximab in combination with chemotherapy regimen in most B cell NHL patient was effective and safe.

Objective: We performed this prospective, multi-center study to evaluate the efficacy and safety of fludarabine-based regimes in the treatment of previously untreated and refractory, or relapsed, indolent non-Hodgkin’s lymphoma (NHL). Methods: Two fludarabine-based regimens were used in the clinical study. The FC regimen which consisted of fludarabine 50 mg/day, and cyclophosphamide 200 mg/day, intravenously, for 3 consecutive days, was given to the previously untreated patients. The FMD regimen which consisted of fludarabine 50 mg/day, intravenously, for 3 consecutive days, mitoxantrone 10 mg/m2, intravenously, on the first day, and dexamethasone 20 mg/m2/day, intravenously, for 5 consecutive days, was given to the relapsed and refractory patients. Results: Forty-seven indolent NHL patients (29 male and 18 female) were enrolled in this study from February 2003 to May 2005. The main disease subtypes were: chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL; n = 25), follicular lymphoma (FL; n = 18), lymphoplasmic lymphoma (LPL; n = 3), marginal zone lymphoma (MZL; n =1). Overall response (OR) rate was 93.62%, and 44 of 47 patients achieved a response. The complete response (CR) rate was 63.83%, and 30 of 47 patients achieved a response. In the 16 previously untreated patients, the CR rate was 75.0% (n =12); the OR rate was 93.8% (n = 15). In the 31 relapsed and refractory patients, the CR rate was 61.3% (n =19) and OR rate was 93.5% (n =29). Median patient follow-up was 12 months (range, 1–27 months). The 12-month progression free survival (PFS) rates of previously untreated patients and relapsed or refractory patients were 93.3±6.4% and 91.04±6.1%, respectively; and the 18-month overall survival (OS) rates were 90.9±8.67% and 90.32±6.90%, respectively. Both regimens were well tolerated and the major toxicities were bone marrow suppression and gastrointestinal response. Conclusion: The FC and FMD regimens are effective and safe for indolent NHL patients.

PURPOSE: To confirm the potential benefit of front-line use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (As2O3) in patients with newly diagnosed acute promyelocytic leukemia (APL) with prolonged follow-up to median of 3-year and compared with historical control. PATIENTS AND METHODS: Two groups of newly diagnosed patients with APL were included in the analysis. The study group received combination therapy of ATRA and As2O3 includes 56 patients since April 2001. The historical control groups included 56 patients from May 1998 to March 2001. No statistically significant differences of clinical characteristics such as sex, age and hematological data were documented between two groups. For the study group groups, all patients received 25mg/m2 ATRA orally and 0.16mg/kg As2O3 intravenously per day till CR. Once CR achieved, they were given 3 courses of consolidation chemotherapy and then 5 cycles of sequential treatment of ATRA, As2O3 and 6-MP/MTX. For the historical group, the induction therapy was ATRA given at 25mg/m2 daily till CR and chemotherapy was added in case of leukocytosis. The post-remission therapy consists of chemotherapy with ATRA. RESULT: In study group, 52 (92.9%) patients achieved CR and the time to CR was 26.4±4.5 days. At last follow-up at February 2005, only two patients underwent extramedullary relapse and one died from CNS leukemia while all other patients were alive and remained in hematological remission. With a median follow-up of 34 months (21 to 46 months), the 3-year OS and EFS were estimated as 97.4% and 93.5%. For the historical control groups, the median follow-up was 56 months (12 to 79 months). The 3-year estimated OS and EFS was 83.2% and 57.7% (P=0.069 and 0.00001 respectively). Of notice, in the last follow-up, all evaluable patients in clinical remission maintained a complete molecular response (undetectable PML-RARa via both regular and real-time RT-PCR). CONCLUSION: Our 3-year follow-up data demonstrate a solid clinical benefit of front-line combination of ATRA and As2O3 in terms of EFS. There was also a trend toward improvement in OS which might translate into better chance of curing the disease.

PURPOSE: To determine the efficacy of front-line use of all-trans retinoic acid (ATRA) combined with arsenic trioxide (As2O3) in patients with newly diagnosed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Since 2001, 61 patients have received ATRA (25mg/m2) and As2O3 (0.16mg/kg) daily till CR and all patients received 3 consolidation chemotherapy and then received 5 cycles of sequential treatment of ATRA, As2O3 and 6-MP/MTX. The efficacy of treatment protocol in induction remission, molecular response and relapse-free survival were compared with our historical control. RESULT: 58 (95.1%) patients achieved CR and all remain relapse free with the current protocol. Though ATRA/As2O3 duet did not improve the hematological/molecular remission rate and reduced the early mortality after induction, it did induce an early hematological response (26.1±4.1 days). During limited follow-up (20 to 39 months), both RFS and OS are significantly increased in patients who received the ATRA/As2O3/chemotherapy triad as post-remission therapy compared to the historical control. PML-RARa mRNA was retrospectively assessed by quantitative real-time reverse transcription-polymerase chain reaction (RQ-RT-PCR) before treatment, after CR, after consolidation and during follow-up period in 36 patients with ATRA and As2O3 combination treatment. PML-RARa normalized dose was found to be more significantly decreased after remission induction (median fold reduction: 335.8), and after consolidation (median fold reduction: 358362.2), as compared with ATRA or As2O3 mono-therapy. The addition of As2O3 into post-remission therapy can further increase the post-remission molecular response through either qualitative or quantitative RT-PCR measurement. CONCLUSION: Our current follow-up data suggested a potential benefit of front-line combination of ATRA and As2O3, which might translate into better chance of curing the disease.

112 patients with senile acute myelocytic leukemia (AML), refractory or relapsed AML, and MDS-RAEBt entered this study to receive aclarubicin and low dose Arabinoside Cytosine (Ara-C) in combination with Granulocyte Colony Stimulating Factor (G-CSF) for evaluation of efficacy and tolerance of this CGA regimen. Low dose Ara-C was given at the dosage of 10mg/m2/12h, subcutaneously, D1-14 and aclarubicin 14mg/m2/d, intravenously, D1-4 (regimen A) or 7mg/m2 D1-8 (regimen B). Recombinant G-CSF was given at the dosage of 200μg/m2/d, subcutaneously, D1-14. We proved that overall response rate was 19/26 (73.1%) in senile AML, 48/62 (77.4%) in refractory AML, 12/18 (66.7%) in relapsed AML and 10/13 (76.9%) in MDS-RAEBt; and CR rate was at 8/26 (30.8%) in senile patients, 30/62 (48.4%) in refractory AML, 8/18 (44.4%) in relapsed AML and 5/13 (38.5%) in MDS-RAEBt, which were comparable in four groups of patients. 52 patients were followed up. Median progression free survival (PFS) and overall survival (OS) were 9.0±2.2 months and 11.0±1.6 months, respectively. The Kaplan-Meier estimated PFS and OS rate at 12 months were 40.73±8.15% and 42.85±8.23%, respectively. 1 year OS and PFS rate of the patients with CR were 60%±10.8% and 51.3%±13.7%, respectively, compared with the patients with PR, 17.7%±9.3% and 6.4%±6.1%, respectively. The toxic effects were very rare, mainly manifested as hematological changes, neutropenia and thrombocytopenia due to myelosuppression, which was around 70–80% exceeding NCI grade II. And non-hematological toxicities were not observed in this study. CAG regimen seems to be promising for the treatment of various categories of poor-prognosis AML or MDS-RAEBt, with acceptable toxicity.

OBJECTIVE: To evaluate the safety and efficacy of Glivec in combination with As4S4 in the treatment of advanced CML patients. PATIENTS AND METHODS: 9 Ph+ CML patients in advanced phase were entered into the study. The first 3 patients received Glivec 400mg/d plus As4S4 150mg/kg/d (day 1–14, each month). If no patient were to experience grade 3/4 CTC toxicity after one month of treatment, the dose of Glivec would be increased to 600mg. All the patients were treated and followed up for 6 months. Adverse events, hematological, cytogenetic, molecular response and real-time RT-PCR were evaluated in each regular visit. RESULTS: From Dec.2003 to June.2004, 9 patients consisting of 6 males and 3 females were enrolled in this trial, 5 in accelerated phase and 4 in blast crisis, aged 22–53 years (median 33). The first 3 patients received Glivec 400mg/d plus As4S4, and other 6 patients received increased dosage of Glivec to 600mg/d. By the time of report, 6 patients had finished the study. 7/9 patients (77.8%) achieved complete hematological response (CHR). 2 patients relapsed after 4 and 5 months of treatment, respectively, and 2 patients withdrew from the study after 1 and 2 months respectively to receive chemotherapy due to progression of the disease. Notably, 3 of these 4 patients had complex cytogenetic abnormalities. Cytogenetic response was observed in 3 patients (33.3%), including 2 major cytogenetic response (1 complete response) and 1 minor response. No molecular response was obtained so far in any patients. Bcr-Abl fusion transcript copy number was measured by real-time RT-PCR in 3 patients, 1 patient with CCR had 3140 fold reduction of BCR-ABL DoseN. Non-hematologic toxicities such as gastrointerstinal discomfort, edema, liver dysfunction and myalgia/bone pain were common and mild (grade 1/2). Grade 3/4 hematological toxicities including neutropenia, thrombocytopenia and anemia occurred in 3 patients. CONCLUSIONS: Glivec in combination with As4S4 has potential effect in advanced CML with acceptable toxicities. Further investigation will be performed to compare the efficacy of Glivec/As4S4 combinative therapy with Glivec mono-therapy in advanced CML.