Cytarabine Group Research Articles

Experimental study on aging effect of Angelica sinensis polysaccharides combined with cytarabine on human leukemia KG1α cell lines

The latest findings of our laboratory showed that Angelica sinensis polysaccharide( ASP) showed a definite effect in regulating the aging of hematopoietic stem cells. Leukemia is a type of malignant hematopoietic tumor in hematopoietic stem cells. There have been no relevant reports about ASP's effect in regulating the aging of leukemia cells. In this study,human acute myeloid leukemia( AML) KG1α cell lines in logarithmic growth phase were taken as the study object,and were divided into the ASP group, the cytarabine( Ara-C) group,the ASP + Ara-C group and the control group. The groups were respectively treated with different concentration of ASP,Ara-C and ASP + Ara-C for different periods,with the aim to study the effect of ASP combined with Ara-C in regulating the aging of human acute myeloid leukemia KG1α cell lines and its relevant mechanism. The results showed that ASP,Ara-C and ASP + Ara-C could obviously inhibit KG1α cell proliferation in vitro,block the cells in G0/ G1phase. The cells showed the aging morphological feature. The percentage of positive stained aging cells was dramatically increased,and could significantly up-regulate the expression of aging-related proteins P16 and RB,which were more obvious in the ASP + Ara-C group. In conclusion,the aging mechanism of KG1α cell induced by ASP and Ara-C may be related to the regulation of the expression of aging-related proteins,suggesting that the combined administration of ASP and anticancer drugs plays a better role in the treatment of leukemia.

Impact Of Cytarabine Dose In The Induction Regimen On The Outcome Of Patients With Newly Diagnosed Acute Myeloid Leukemia With Or Without NPM1 and/Or FLT3 Mutations: A SWOG and MD Anderson Cancer Center Report

BackgroundThe value of “high dose” cytarabine (HDAC) during initial induction therapy for patients with newly diagnosed AML remains controversial with some prior reports suggesting improved relapse-free survival (RFS) but not complete remission (CR) or overall survival (OS) (Kern and Estey, Cancer 2006; 107: 116-24), and others finding no benefit (Lowenberg, Blood 2013; 121:26-28). The benefit of HDAC in the management of more favorable subsets of AML (such as core binding factor AML) is well-established, demonstrating higher sensitivity of this group to cytarabine. It is commonly acknowledged that AML is several diseases that may respond differently to a given therapy. With the increasing use of NPM1 and FLT3-ITD to stratify patients, it seemed plausible that the value of HDAC during induction might vary according to patient's genotype as defined by NPM1 and FLT3-ITD mutation status. In particular, patients with normal cytogenetics/ NPM1 mutated/FLT3-ITD negative AML clearly have more favorable outcomes and, hence, are potentially a group that might benefit from HDAC therapy. Herein we examine this possibility. MethodsWe analyzed 1080 patients (median age 53, range 17-88) with newly diagnosed AML. The standard dose cytarabine (SDAC) group comprised 531 patients who received 7 days of cytarabine at 100 mg/m2 daily + 3 days of daunorubicin (3+7) on SWOG protocols (S0106 N=368, S9031 N=73, S9333 N=46, S9500 N=44). The HDAC group consisted of 549 patents treated on various MD Anderson (MDA) induction protocols, each of which administered cytarabine at either 1.5g/m2 daily X 4 days by continuous infusion or at 1-2 g/m2 daily X 5 days, most commonly combined with idarubicin, fludarabine, or clofarabine +/- other agents. Once in CR, both the SDAC and HDAC groups received HDAC consolidation. Only 16% of patients at MDA received allogeneic transplant in first CR (off-protocol transplant data not available for SWOG). We used log-rank tests to compare RFS and OS in the SDAC and HDAC groups and multivariate Cox regression to adjust for other potential prognostic covariates: numerical age, sex, performance status (0-1 vs. >2-4), numerical WBC count, platelets, % marrow blasts, and cytogenetics (SWOG criteria). Results15% of the 1080 patients were positive for NPM1 mutation (N+)/negative for FLT3-ITD (F-) (13% MDA, 17% SWOG), 10% N-/F+ (9% MDA, 11% SWOG), 10% were N+/F+ (9% MDA, 11% SWOG), and 65% were N-/F-(69% MDA, 61% SWOG). CR rates were similar in each of the 4 groups regardless of the cytarabine dose (interaction p=0.42). On multivariate analysis, among N+/F- patients, OS was superior in the SDAC group (HR=0.50, p=0.02)). Multivariate analysis indicated that OS was similar between SDAC and HDAC in each of the other cohorts and that RFS was similar in all four cohorts. , When we restricted the analysis to the 545 patients age 60 with de novo AML treated since 2000 (N+/F- 15%, N-/F+ 9%, N+/F+ 10%, N-/F- 65%) there was no evidence that SDAC or HDAC was associated with CR, RFS or OS. When we restricted the analysis to the 418 patients with normal cytogenetics (N+/F- 27%, N-/F+ 13%, N+/F+ 20%, N-/F- 40%), on multivariate analysis, among N-/F- patients, OS and RFS were superior in the SDAC group (OS: HR=0.4, p=0.001; RFS: HR=0.48, p=0.02). SDAC and HDAC were similar with respect to OS and RFS in the other three cohorts and had similar CR rates in all four cohorts. ConclusionOur data do not suggest that higher doses of cytarabine during induction improve response, RFS or OS in any of the 4 subsets defined by NPM1 and FLT3 mutations in newly diagnosed AML, overall. This may be at least partly due to the use of HDAC in consolidation in both groups. Disclosures:Faderl:Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kantarjian:Sanofi-Aventis: Research Funding.

Comparing Induction and Consolidation with or without Cytarabine In the Treatment of Acute Promyelocytic Leukaemia In Hong Kong Chinese

AbstractAbstract 4366Previous studies suggested that cytarabine was not required in the treatment of newly diagnosed acute promyelocytic leukaemia (APL). They suggested that omitting cytarabine in the treatment of APL could reduce treatment toxicity without increasing relapses and affecting survival. No previous study assessed the effect of cytarabine in the treatment of Chinese APL patients.We compared the outcome of APL patients with or without cytarabine in induction and consolidation therapy in Hong Kong Chinese in a local hospital. MethodIt was a retrospective study of newly diagnosed APL patients from Jan 1996 to Dec 2009. They were divided into two groups. One group was given ATRA (All-trans-retinoic acid) 45mg/m2/day combined with daunorubicin 60mg/m2/day for 3 days plus cytarabine 200mg/m2/day for 7 days as induction therapy. It was followed by two courses of consolidation with daunorubicin and cytarabine and then 2-year maintenance with low dose chemotherapy and intermittent ATRA. Another group was given the same treatment without cytarabine. The remission rate, relapse rate, overall survival and event-free survival were compared in the two groups of patients. ResultsEighteen patients with median age of 41 (range 24–62) received cytarabine. 22% of them had initial WBC count >10,000/uL. Eight patients with median age of 42 (range 16–57) received no cytarabine. 25% of them had WBC count >10,000/uL. The complete remission rates were 100% in both groups. The two-year relapse rate was 5.5% (1/18) for cytarabine group and 62% (5/8) for no cytarabine group (p=0.004, Fisher's exact test).The two-year event-free survival was 82% for cytarabine group and 37% for no cytarabine group (p=0.0017). The two-year overall survival was 89% for cytarabine group and 75% for no cytarabine group (p=0.18). The adverse effects profile was similar in both groups. ConclusionThe results support a role of cytarabine in addition to ATRA and daunorubicin in the treatment of newly diagnosed APL. The relapse rate was much lower in patients receiving cytarabine. The two-year event-free survival and two-year overall survival were also significantly better in the cytarabine group. Disclosures:No relevant conflicts of interest to declare.

Re-analysis of the Outcomes of Post-Remission Therapy for Acute Myeloid Leukemia with Core Binding Factor According to Years of Patient Enrolment

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. 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. 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. 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).

Idarubicin Plus Behenoyl Cytarabine and 6-thioguanine Compares Favorably with Idarubicin Plus Cytarabine-based Regimen for Children with Previously Untreated Acute Myeloid Leukemia: 10-Year Retrospective, Multicenter Study in Korea

We investigated the outcome of idarubicin plus N4-behenoyl-1-β-D-arabinofuranosyl cytosine (BHAC)-based chemotherapy (BHAC group, n=149) compared to idarubicin plus cytarabine-based chemotherapy (cytarabine group, n=191) for childhood acute myeloid leukemia (AML). Between January 1996 and December 2005, 340 children with AML from 5 university hospitals in Korea received the BHAC-based or cytarabine-based chemotherapy, with or without hematopoietic stem cell transplantation. After induction therapy, 264 (77.6%) of 340 children achieved a complete remission (CR) and 43 (12%) achieved a partial remission (PR). The CR rate in the BHAC group was higher than in the cytarabine group (85.2% vs. 71.7%, P=0.004). However, the overall response rate (CR+PR) was not different between the two groups (93.3% vs. 87.9%, P=0.139). The 5-yr estimates of overall survival (OS) of children in the two groups were similar (54.9% for the BHAC group vs. 52.4% for the cytarabine group, P=0.281). Although the results were analyzed according to the treatment type and cytogenetic risk, the OS showed no significant difference between the BHAC group and the cytarabine group. In the present study, the clinical outcomes of the BHAC-based chemotherapy, consisting of BHAC, idarubicin, and 6-TG, are comparable to that of the cytarabine-based chemotherapy for childhood AML.

High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial

Chemotherapy with high-dose methotrexate is the conventional approach to treat primary CNS lymphomas, but superiority of polychemotherapy compared with high-dose methotrexate alone is unproven. We assessed the effect of adding high-dose cytarabine to methotrexate in patients with newly diagnosed primary CNS lymphoma. This open, randomised, phase 2 trial was undertaken in 24 centres in six countries. 79 patients with non-Hodgkin lymphoma exclusively localised into the CNS, cranial nerves, or eyes, aged 18-75 years, and with Eastern Cooperative Oncology Group performance status of 3 or lower and measurable disease were centrally randomly assigned by computer to receive four courses of either methotrexate 3.5 g/m(2) on day 1 (n=40) or methotrexate 3.5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice a day on days 2-3 (n=39). Both regimens were administered every 3 weeks and were followed by whole-brain irradiation. The primary endpoint was complete remission rate after chemotherapy. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00210314. All randomly assigned participants were analysed. After chemotherapy, seven patients given methotrexate and 18 given methotrexate plus cytarabine achieved a complete remission, with a complete remission rate of 18% (95% CI 6-30) and 46% (31-61), respectively, (p=0.006). Nine patients receiving methotrexate and nine receiving methotrexate plus cytarabine achieved a partial response, with an overall response rate of 40% (25-55) and 69% (55-83), respectively, (p=0.009). Grade 3-4 haematological toxicity was more common in the methotrexate plus cytarabine group than in the methotrexate group (36 [92%] vs six [15%]). Four patients died of toxic effects (three vs one). In patients aged 75 years and younger with primary CNS lymphoma, the addition of high-dose cytarabine to high-dose methotrexate provides improved outcome with acceptable toxicity compared with high-dose methotrexate alone. Swiss Cancer League.

Randomized trials between behenoyl cytarabine and cytarabine in combination induction and consolidation therapy, and with or without ubenimex after maintenance/intensification therapy in adult acute myeloid leukemia. The Japan Leukemia Study Group.

We analyzed complete remission (CR), disease-free survival (DFS), and event-free survival (EFS) rates in two groups of patients treated with either N4-behenoyl-1-beta-D-arabinosylcytosine (BHAC) or cytarabine, and analyzed DFS with or without ubenimex, a biologic response modifier. Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either BHAC or cytarabine as remission-induction combination chemotherapy and two courses of consolidation therapy. After maintenance/intensification therapy, patients in CR were randomized to receive either ubenimex and no drug. Of 341 patients registered, 326 were assessable. The age of assessable patients ranged from 15 to 82 years (median, 48). The overall CR rate was 77%: 72% in the BHAC group and 81% in the cytarabine group, and there was a significant difference between the two groups (P = .035, chi 2 test). The predicted 55-month EFS rate of all patients was 30%: 23% in the BHAC group and 35% in the cytarabine group, with a significant difference between groups (P = .0253). The predicted 55-month DFS rate of all CR patients was 38% and that of CR patients less than 50 years of age was 47%. There was no significant difference in DFS between the ubenimex group and the group that did not receive ubenimex. Analyses of our clinical trial showed that the use of BHAC in remission-induction therapy and in consolidation therapy resulted in poorer CR and EFS rates in adult AML patients compared with the use of cytarabine at the doses and schedules tested. Immunotherapy with ubenimex after the end of all chemotherapy did not improve DFS.