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1.
The Sokal and Hasford scores were developed in the chemotherapy and interferon era and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, a new European Treatment and Outcome Study (EUTOS) scoring system was developed. We performed a multicenter retrospective study to validate the effectiveness of each of the three scoring systems. The study cohort included 145 patients diagnosed with CML in chronic phase who were treated with imatinib. In the EUTOS low‐ and high‐risk groups, the cumulative incidence of complete cytogenetic response (CCyR) at 18 months was 86.9% and 87.5% (= 0.797) and the 5‐year overall survival rate was 92.6% and 93.3% (= 0.871), respectively. The cumulative incidence of CCyR at 12 months, 5‐year event‐free survival and 5‐year progression‐free survival were not predicted using the EUTOS scoring system. However, there were significant differences in both the Sokal score and Hasford score risk groups. In our retrospective validation study, the EUTOS score did not predict the prognosis of patients with CML in chronic phase treated with imatinib.  相似文献   

2.
Aim: To report our experience of the use of dasatinib in various phases of chronic myeloid leukemia (CML). Methods: Ten patients in various phases of CML, not responding to imatinib and started on dasatinib, were included and analyzed. The baseline characteristics of the patients and their salient features including the duration and response to initial therapy as well as to dasatinib, were noted. Results: Before starting dasatinib three patients were in chronic phase of CML while seven others were in the progressive phase (accelerated and blast phase) of CML. Half the patients developed transient grade 3 and 4 toxicities to dasatinib. Overall, the tolerability of the drug in all 10 patients was acceptable and none discontinued treatment. Three patients died due to progressive disease while the remaining seven are continuing the drug with the disease still under cytogenetic or hematological remission. Of the 10 patients, seven achieved complete hematological response and two of the accelerated phase/blast crisis patients achieved complete cytogenetic response. Overall, dasatinib was able to control disease for a median of 20.6 months. Conclusion: Despite small sample size and insufficient information on mutational analysis, dasatinib is effective in CML in INdia. Cost limits the use of second‐generation tyrosine kinase inhibitors in India. Our observation is not suitable for survival analysis but the difference made by dasatinib in progressive disease and its tolerability needs to be acknowledged.  相似文献   

3.
目的:评估CD33抗体为主方案治疗难治性白血病的疗效和不良反应。方法:采用CD33抗体为主方案对11例难治性白血病进行治疗。结果:CD33抗体为主方案治疗总有效率54%,其中完全缓解(CR)为36%,除血小板未完全缓解外均达到完全缓解标准(CRP)为18%,治疗后中位生存时间4.8月,缓解后中位生存时间8.2月。2例慢性粒细胞白血病急粒变均完全缓解,且BCR/ABL(-)。1例难治性急性淋巴白血病在缓解后即行异基因干细胞移植,至今无病生存已9月。不良反应有骨髓抑制(100%)、输注相关寒战发热(90%),肝静脉闭塞综合症(VOD)发生率55%,发生在干细胞移植后的患者和年龄大于60岁的患者。结论:本组资料显示CD33抗体为主方案对表达CD33的急慢性白血病有一定疗效。对于移植后复发和年龄大于60岁的患者,在使用CD33抗体时需注意患者肝脏情况,一旦出现VOD,及时处理。对于用药后缓解的患者,应尽早行异基因干细胞移植。  相似文献   

4.
BACKGROUND: The effect on prognosis of adding imatinib mesylate to the treatment of patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) has not been explored fully. The objective of the current study was to evaluate the benefit of adding imatinib to the treatment sequence of patients with early chronic phase Ph-positive CML who received interferon alpha (IFN)-based regimens as frontline therapy. METHODS: A total of 201 patients with early chronic phase Ph-positive CML who were treated on our 3 recent frontline IFN-based programs and were impacted early by the availability of sequential therapy with imatinib were analyzed. Their outcome was compared with that of a historical control group of 293 patients treated from 1982 until 1990 who were treated with IFN programs for early chronic phase CML and who did not have the opportunity of early access to imatinib (because it was not available during that period). Multivariate analysis was used to evaluate the independent effect of imatinib therapy on survival. RESULTS: Of 201 patients who were treated, 159 patients (79%) had their regimen changed sequentially to imatinib after a median duration of 14 months of IFN therapy. Of 139 patients who continued evaluation at our institution, 101 patients (73%; 64% of the total group) achieved a complete cytogenetic response, and 20 of 80 patients analyzed (25%; 10% of the total group) had no disease according to molecular studies (quantitative polymerase chain reaction studies). The estimated 5-year survival rate for the total study group of 201 patients was 86%. Survival of this group was significantly superior to the historic control group of IFN-treated patients who did not have the benefit of imatinib (P = 0.03). The trend also was observed within defined CML risk groups. Imatinib therapy was confirmed as an independent, significant, favorable prognostic factor for survival by multivariate analysis, after accounting for the independent prognostic effect of pretreatment prognostic factors (P = 0.005). CONCLUSIONS: The current analysis is the first to indicate the independent, favorable effect of imatinib on the survival of patients with Ph-positive CML.  相似文献   

5.
OBJECTIVE To evaluate the effects of autologous and allogeneic hematopoietic stem cell transplantation (HSCT) for patients with chronic myeloid leukemia(CML).METHODS Fifty-seven patients with CML were treated by HSCT, including 8 cases treated with autologous transplantation purged in vivo and in vitro of minimal residual disease (MRD), 39 cases with related donor allogeneic HSCT (allo-HSCT) and 10 cases with unrelated donor alIo-HSCT. The conditioning regimen was a TBI (total-body irradiation) CY (cyclophosphamide, CTX) protocol in 32 patients, a modified BuCY (hydroxyurea, busulfan, Ara-C, CTX) protocal in 24 patients, and a MACC ( Melphalan, Ara-C, CTX and chlorethyl cyclohexyl nitrosourea ) protocol in one patient. Cyclosporine (CsA) and methotrexate (MTX) were used in patients with related-donor allo-HSCT, and CsA and MTX were added to mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) in unrelated donor allo-HSCT for graft versus host disease (GVHD) prophylaxis. Otherwise, CsA was only used for GVHD prophylaxis in patients with accelerated phase (AP) and blast crisis (BC). The Kaplan-Meier survival analysis model was used to estimate the overall survival (OS) and the disease-free survival (DSF) at 5 years after transplantation.RESULTS Eight patients with autologous transplantation, except for 1 case who died of transplantation-related complications, obtained cytogenetic part or complete remission (CR) within 3 months after transplantation. One patient, who was in BC and obtained CR in hematology before transplantation, had been in molecular CR for 92 months after autologous transplantation. Among the 49 patients treated with alIo-HSCT, all obtained CR, except for one patient who died of hepatic veno-occlusive disease (VOD) and one who had not obtained CR. The incidence of infection and VOD was 33.3% and 7.0%, respectively, during transplantation. After transplantation the incidence of hemorrhagic cystitis (HC) and cytomegalovirus (CMV) interstitial pneumonia (IP) was 22.8% and 8.8%, respectively. VOD, HC and CMV IP did not occur in patients with autologous transplantation. The incidence of acute GVHD and the frequency of chronic GVHD was 41.0% and 48.6%, respectively, in patients with related and unrelated transplantation. The rate of relapse in patients with autologous and allogeneic transplantation was 57.1% and 12.8%, respectively. The DFS at 5 years after transplantation was 25.0% and 61.7%, respectively, in patients with autologous and related donor transplantation. The DFS at 5 years was 70.7% and 34.1%, respectively, in patients with CP (chronic phase) or AP and BC before transplantation.CONCLUSION AIIo-HSCT may have a higher clinical cure rate for CML patients with CP. The CsA MTX MMF ATG protocol is more effective for acute GVHD prophylaxis and can decrease the incidence and degree of GVHD in patients with unrelated donor transplantation, Autologous transplantation with purged bone marrow can prolong the survival time of CML patients and some may be cured with transplants of this type.  相似文献   

6.
7.
8.
Until now, kinetic perturbations induced by cytotoxic drugs during the therapy of leukemia have mainly been investigated by measuring changes in the proportion of cells in mitosis (mitotic INDEX=IM) and/or in DNA-synthesis phase (tritiated thymidine labeling INDEX=IL). This study was designed to determine simultaneously the effect of arabinosyl cytosine (ARA-C) on the IM, the IL, and also the flux of the cells through mitosis. For that purpose, the rate of accumulation of the cells in mitosis following vincristine was measured in vivo before and after a 3-day course of ARA-C in 2 patients with Ph1 positive chronic myeloid leukemia. It was found that ARA-C increased the IL, as expected, but also the IM of granulocytic precursors, which could not have been predicted. The increased IM was due to prolonged mitosis, whereas the cell flux through mitosis (=cell birth rate) was actually reduced. The data show that cell flux studies are needed for appropriate estimation of cell kinetic effects of cytotoxic drugs and that reliance on cell cycle ‘indices’ alone in some instances may be misleading.  相似文献   

9.
Background: Some reports have suggested that chronic myeloid leukemia (CML) patients have a higherprevalence of M-bcr than acute lymphoblastic leukemia (ALL) patients, which show a higher prevalence ofm-bcr. However, the relationship between BCR-ABL subtypes and progression of CML and ALL remains unclear.Materials and Methods: 354 CML chronic phase (CML-CP) patients, 26 CML blastic phase (CML-BP) patientsand 72 ALL patients before treatment with BCR-ABL positive were recruited for blood routine examinationand bone marrow smear cytology. Some 80 CML-CP and 32 ALL patients after imatinib (IM) treatment werefollowed-up for BCR-ABL relative concentrations detected after treatment for 3, 6 and 9 months and 1 year.Results: Before treatment, CML-CP patients showed lower BCR-ABL relative concentrations with a higherproportion of M-bcr (42.7%) compared to CML-BP and ALL patients while ALL patients had a higher BCR-ABLrelative concentration with high expression of m-bcr (51.4%). Patients with M-bcr demonstrated higher WBCcounts than those with m-bcr and the mixed group and higher PLT counts were noted in the CML-CP and ALLgroups. After imatinib (IM) treatment, patients with m-bcr showed higher BCR-ABL relative concentrations inboth CML-CP and ALL groups. Conclusions: This study identified the BCR-ABL gene as an important factor inCML and ALL cases. The M-bcr subtype was associated more with CML while the m-bcr subtype was associatedmore with ALL. Patients with m-bcr seem to have a poorer response to IM in either CML or ALL patientscompared to M-bcr patients.  相似文献   

10.
目的 :研究慢性粒细胞性白血病患者的预后因素。方法 :采用 Hasford等提出的慢性粒细胞白血病(CML)患者预后公式 ,对 5 7例 CML患者的预后进行回顾性分析。结果 :高、中、低危组比例分别占 12 .3%、40 .3%和47.4%。低危组的 5 a生存率 (4 8.5± 9.4) % ,中危组为 (93.1± 1.1) % ,而高危组患者 5 a内全部死亡 ,其 3a生存率仅 (19.3± 6 .90 ) % ,三组之间差异有显著性 (P<0 .0 1)。三组的生存曲线在 2 a后明显分开。结论 :Hasford预后评分系统能较好预测 CML 患者的预后。在影响预后的因素中 ,脾脏肿大和外周血原始细胞对于预后判断的意义较大。  相似文献   

11.
A Ferrant  J L Michaux  G Sokal 《Cancer》1986,58(9):2130-2135
Forty chronic lymphocytic leukemia patients with splenomegaly were evaluated for splenectomy. Twenty were splenectomized. All but two normalized their hematocrit and all but one their platelet count. Satisfactory residual erythropoiesis as evaluated using ferrokinetics enabled prediction of a good response to splenectomy in 18 of 20 patients. The two patients who did not respond despite satisfactory residual erythropoiesis had a deteriorating blood count after splenectomy with progressive disease. The measurement of the splenic red cell volume predicted the minimal increase in hematocrit that could be expected after splenectomy. The transfusion need was abolished in 13 of 14 patients who needed red cell transfusions before splenectomy. Despite clinical improvement after the operation in all but two patients, splenectomized patients did not survive longer than nonsplenectomized patients, whether survival probability was calculated from the time of diagnosis or from the time of evaluation.  相似文献   

12.

BACKGROUND:

Anemia is a frequent side effect of imatinib in patients with chronic myeloid leukemia (CML). Erythropoietic‐stimulating agents have been used for treatment of imatinib‐induced anemia. There are no data on long‐term safety of erythropoietic‐stimulating agents in CML patients.

METHODS:

The records of chronic phase CML patients who received treatment with imatinib were reviewed for use of erythropoietic‐stimulating agents and occurrence of thrombotic events. Data on cytogenetic response and survival were analyzed by use of erythropoietic‐stimulating agent.

RESULTS:

A total of 608 patients were included, and 217 patients received erythropoietic‐stimulating agents. There were 30 thrombotic episodes. Patients who received erythropoietic‐stimulating agents had a higher rate of thrombosis (8.5% vs 2.6%, P = .0025). There was no difference in cytogenetic response rate and survival by use of erythropoietic‐stimulating agent. Development of grade 3‐4 anemia occurred in 62 (10%) patients and was associated with significantly worse response and survival in patients in late chronic phase. By multivariate analysis, use of erythropoietic‐stimulating agents was not a risk factor for event‐free survival.

CONCLUSIONS:

In our cohort of chronic phase CML patients, use of erythropoietic‐stimulating agents did not impact survival or cytogenetic response rate, but was associated with a higher thrombosis rate. Severe anemia is associated with worse survival and response. Cancer 2011. © 2010 American Cancer Society.  相似文献   

13.
Patients with acute myeloid leukemia (AML) secondary to myelodysplastic phase respond poorly to standard chemotherapy designed for AML. As arabinosyl cytosine (Ara-C) at low-dose has been reported to achieve promising results in certain forms of AML, we have applied the low-dose (10 mg m-2/12 h subcutaneously for 14-24 days) regimen in 11 patients with AML secondary to myelodysplastic syndromes. Though a complete remission could be achieved in 2 patients and a short partial remission in 2 further patients, complications are severe and often life threatening. The amount of hematological supportive care required often exceeded that needed for patients treated by conventional TAD regimen. Moreover, survival of the responders did not seem to be longer than that of non-responders. A review of the literature showed that the results of this low-dose Ara-C regimen might be more promising in patients in the myelodysplastic phase and in those with de novo acute leukemia.  相似文献   

14.
Patients with chronic lymphocytic leukemia (CLL) who fail fludarabine (Fluda) therapy have a poor response to subsequent salvage regimens and a poor prognosis. This study was undertaken to determine the efficacy and toxicity of a cis-platinum, (cis-p)fluda and arabinosyl cytosine (ara-C) combination in patients who were refractory to fluda or had relapsed following prior fluda therapy for CLL. Forty-one patients who had progressive CLL were treated on study. Eleven patients (27%) were sensitive to fluda and thirty (73%) refractory prior to study entry. Therapy consisted of cis-p 100mg/m2 continuous intravenous (IV) infusion over 4 days, fluda 30 m/m2 IV over 15 minutes on Days 3 and 4 either given alone (PF) or with ara-C 500 mg/m IV over 1 hour on Day 4 (PFA). The median number of PF or PFA courses received was two. No patient achieved a complete response. Eight patients (19%) achieved a partial response (PR), 28 were taken off study with progressive or refractory disease and 5 had induction deaths. The overall median survival was 6 months, 15 months in responding patients, and 4 months in non-responding patients. Rai stage 1-11 patients had a median survival of 7 months and stage 111-IV patients had a median survival of 3 months. Major toxici-ties (myelosuppression, sepsis, renal failure and tumor lysis syndrome) were frequent.

In conclusion, it can be said that the PF and PFA regimens have equivalent modest activity in patients with progressive CLL following prior fluda therapy, predominantly among patients whose disease was sensitive to fluda at last prior exposure. Ara-C did not add to the activity of the cis-plfluda combination in this study group.  相似文献   

15.

BACKGROUND:

The European LeukemiaNet recommendations for chronic myeloid leukemia (CML) defined a group of patients with suboptimal response to imatinib. The significance of this response was not well defined.

METHODS:

The significance of having had a suboptimal response during imatinib therapy among 281 patients with CML treated with standard‐dose (n = 73) or high‐dose (n = 208) imatinib was investigated.

RESULTS:

Rates of suboptimal response at 6, 12, and 18 months were 4%, 8%, and 40%, respectively, and were not influenced by Sokal risk score. Patients with a suboptimal response at 6 months had a significantly lower probability of eventually achieving a complete cytogenetic response (CCyR) compared with those with an optimal response (30% vs 97%; P < .001), and their event‐free survival (EFS) and transformation‐free survival (TFS) were found to be similar to those with criteria for failure at this time point. Suboptimal response at 12 months defined a group with a similar TFS as those with optimal response, but with worse EFS. In contrast, patients with a suboptimal response at 18 months had outcomes that were similar to those patients with an optimal response. A multivariate analysis confirmed the significance of response category after adjusting for pretreatment characteristics and imatinib dose.

CONCLUSIONS:

The results of the current study suggested that suboptimal response was a heterogeneous category, and some patients had an outcome that mirrored that of patients with failed therapy. Interventions aimed at improving this outcome are required. Cancer 2009. © 2009 American Cancer Society.  相似文献   

16.

BACKGROUND:

In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome‐positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow‐up are reported.

METHODS:

Patients were stratified according to whether they had CML in myeloid blast phase (MBP‐CML) or in lymphoid blast phase (LBP‐CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily.

RESULTS:

In patients with MBP‐CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP‐CML, the major hematologic response rate was 42% for once‐daily dasatinib and 32% for twice‐daily dasatinib. The major cytogenetic response rates were 25% for once‐daily dasatinib and 28% for twice‐daily dasatinib in patients with MBP‐CML, and the respective rates in patients with LBP‐CML were 50% and 40%. The overall survival rate at 24 months was 24% for once‐daily dasatinib and 28% for twice‐daily dasatinib in patients with MBP‐CML, and the respective values in patients with LBP‐CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once‐daily regimen.

CONCLUSIONS:

The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70‐mg twice‐daily regimen in patients with imatinib‐resistant, blast phase CML. Cancer 2010. © 2010 American Cancer Society.  相似文献   

17.
目的:探讨慢性粒细胞白血病(CML)起病和诊断中的多种预后相关因素。方法:选择CML患者58例,其中慢性期28例、加速期18例、急变期12例。对3组患者的原始细胞数、骨髓病理中p53、063、CD34、Bcl-2、Mib和基因重排的检测进行比较。结果:3组CML患者的预后与起病时的原始细胞百分率、骨髓活检中的p53、063、CD34、Bcl-2、Mib的免疫组化表达率、骨髓纤维化程度呈正比关系;3组患者的基因重排发现率不同,预后生存曲线亦完全不同。结论:CML的预后受到诸多因素的影响,骨髓中原始细胞的比例、骨髓病理中免疫组化的表达、骨髓纤维化程度和基因重排发现率是CML的一系列预后相关性指标。  相似文献   

18.
Aziz Z  Iqbal J  Akram M  Saeed S 《Cancer》2007,109(6):1138-1145
BACKGROUND: There is paucity of data from developing countries on the efficacy and safety of imatinib mesylate in chronic myeloid leukemia (CML). The primary objective of this study was to document complete and partial cytogenetic responses to imatinib in all phases of CML. Secondary objectives included evaluations of complete hematologic response, safety, time to progression, and survival. METHODS: Two hundred seventy-five patients in all phases of CML who received treatment with imatinib from January 2001 to December 2005 were included in the study. All patients had on bone marrow or BCR-ABL positive in peripheral blood by polymerase chain reaction. RESULTS: After a median follow-up of 18 months, major cytogenetic responses (Ph <35%) in chronic phase (CP), accelerated phase (AP), and blastic phase (BP) were documented in 61%, 57%, and 28% of patients, respectively. A complete cytogenetic response was observed in 39.4%, 35.7%, and 14.3% of patients in CP, AP, and BP, respectively; and a complete hematologic response was observed in 90%, 86%, and 30%, respectively. The median time to progression at 18 months was 91% in CP and 68% in AP. The overall survivals in CP, AP, and BP at 18 months was 92%, 74%, and 38%, respectively. CONCLUSIONS: Impressive hematologic, cytogenetic, and molecular responses to imatinib were observed, similar to the responses reported in patients from Western countries. Patients had good compliance, toxicity was limited, and overall quality of life was improved markedly. The results indicated that the biology of CML is not different in patients from developing countries.  相似文献   

19.
BackgroundAcquisition of additional cytogenetic abnormalities (ACAs) in addition to Philadelphia chromosome is frequently observed in patients with chronic myeloid leukemia (CML) in advanced phase. The presence of core binding factor (CBF) translocations determines the diagnosis of acute myeloid leukemia regardless of blast percentage, and CBF rearrangements are rarely identified as ACAs.Patients and MethodsA retrospective chart review of patients with CML who had CBF rearrangement, t(8;21) or inv(16), in Philadelphia chromosome-positive clones was conducted. Additional cases of CML with CBF rearrangements were identified through literature review.ResultsBetween August 1997 and December 2014, we identified 11 patients who had Philadelphia chromosome and CBF rearrangement in the same clones: 1 (9%) with t(8;21) and 10 (91%) with inv(16). Nine (82%) patients were in blast phase, and 2 (18%) in second chronic phase. Four (36%) patients received tyrosine kinase inhibitor monotherapy, 2 (18%) received tyrosine kinase inhibitor and chemotherapy, and 5 (45%) received chemotherapy only. Three (27%) patients achieved complete remission with incomplete count recovery, and 4 (36%) had no response after the initial therapy. Three (27%) patients underwent allogeneic stem cell transplantation. The median event-free survival and overall survival for the 11 patients were 2 months and 6 months, respectively. Literature review identified 14 patients with CML with CBF rearrangement with a median overall survival of 14 months.ConclusionAcquisition of CBF rearrangement in addition to Philadelphia chromosome is a rare phenomenon associated with poor prognosis. CBF rearrangements as ACAs in patients with CML can be considered high-risk features.  相似文献   

20.
 【摘要】 目的 建立慢性粒细胞白血病(CML)实时荧光定量聚合酶链反应(RQ-PCR)检测方法,并研究应用此方法检测CML治疗后微小残留病(MRD)对评价MRD的意义。方法 应用RQ-PCR对80例CML患者初诊时和(或)治疗后的骨髓标本进行分析,检测bcr-abl融合基因的转录水平,回顾性分析临床资料,根据治疗方案不同分为异基因造血干细胞移植组(34例)、甲磺酸伊马替尼组(33例)、羟基脲组(13例)为,监测CML患者治疗前后bcr-abl融合基因变化。结果 RQ-PCR检测初诊CML患者bcr-abl阳性平均值为6847.67拷贝/万个细胞,加速期检测平均值为306 176.08拷贝/万个细胞;异基因造血干细胞移植组移植后1个月检测平均值为944.33拷贝/万个细胞,移植后6个月复测平均值2.37拷贝/万个细胞,移植后12个月复测平均值0.29拷贝/万个细胞,移植后24个月检测不到bcr-abl融合基因;甲磺酸伊马替尼组服用3个月后检测平均值3720.23拷贝/万个细胞,服用12个月<0.10拷贝/万个细胞;羟基脲组用药0个月平均值7290.11拷贝/万个细胞,服用9个月后检测平均值3143.24拷贝/万个细胞。基因造血干细胞移植组、甲磺酸伊马替尼组相同时间bcr-abl水平差异无统计学意义(t=1.74,P=0.17),羟基脲组与前两组间比较差异有统计学意义(t=3.74.P=0.01;t=2.97,P=0.02)。疾病进展时可检测到bcr-abl转录水平的上升;加速期患者的转录本水平明显高于慢性期患者。结论 RQ-PCR作为CML治疗后MRD检测的方法,可以评价治疗效果,预测疾病复发,早期给予干预治疗,有重要临床应用价值。  相似文献   

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