低剂量地西他滨治疗骨髓增生异常综合征的疗效分析

目的:观察低剂量地西他滨治疗骨髓增生异常综合征(MDS)的疗效及安全性。方法:9例骨髓增生异常综合征患者应用地西他滨20mg/m2.d,静脉滴注,持续时间大于1小时,连续5天,至少连续2疗程,观察MDS患者病程的改变、生存质量和血液学指标等。依据NCICTCAE标准判断药物不良反应。结果:1例CR、1例PR、2例获得血液学改善,输血频次减少;上述4例治疗有反应的MDS患者均在随访中,目前尚未转为急性白血病;5例患者疾病进展,2周期治疗后,输血频次无明显减少,复查骨髓细胞学呈低增生性,且原始细胞比例较治疗前无明显下降,其中有2例MDS-RAEB 2 IPSS评分为高危患者原始细胞比例明显升高,短期内转化为急性髓性白血病。结论:低剂量地西他滨与其他强烈化疗方案相比,安全性强,化疗相关死亡率低,不良反应易于处理。     

小剂量地西他滨联合阿糖胞苷治疗骨髓增生异常综合征临床观察

目的：探讨小剂量地西他滨联合阿糖胞苷治疗骨髓增生异常综合征（MDS）的临床疗效和安全性。方法收集2012年1月至2015年1月接受小剂量地西他滨联合阿糖胞苷方案治疗的15例MDS 患者临床资料,评价其疗效和不良反应。结果15例患者中完全缓解4例,部分缓解5例,稳定、进展和无效6例,总有效率为60.0%（9／15）。总感染率为40.0%（6／15）,其中肺部感染率为26.7%（4／15）,Ⅲ～Ⅳ度骨髓抑制率为73.3%（11／15）。患者经积极抗感染、刺激造血及输血等支持治疗后感染得到控制。15例患者均无严重肝损害,未出现化疗相关死亡。结论小剂量地西他滨单药联合阿糖胞苷方案治疗 MDS 有一定疗效,可延缓疾病进展,患者能耐受化疗不良反应,无化疗相关死亡。     

小剂量地西他滨治疗老年低增生性高危骨髓增生异常综合征1 例

患者,女,72岁,因"全血细胞减少2年"于2009年10月29日入院.查体:贫血,余无异常.肝肾功能正常;血常规示:WBC:1.8×109/L,NEU 0.933×109/L,Hb:40g/d,PLT:39×109/L,外周血可见2%幼稚细胞.     

地西他滨为主化疗方案联合微移植巩固治疗伴TP53突变骨髓增生异常综合征老年患者一例并文献复习

目的:探讨地西他滨为主的化疗方案联合微移植巩固治疗伴TP53突变骨髓增生异常综合征（MDS）老年患者的疗效及安全性。方法:回顾性分析南京医科大学附属淮安第一医院收治的1例接受地西他滨、中剂量阿糖胞苷联合微移植治疗的伴TP53突变老年MDS患者的临床资料,并进行文献复习。结果:患者3次巩固治疗期间耐受性良好,3次移植后中性粒细胞恢复时间分别为15、16、14 d,血小板恢复时间均为16 d,均未发生急、慢性移植物抗宿主病（GVHD）;粒细胞缺乏期合并感染,积极抗感染治疗后好转,无严重脏器损伤相关并发症发生。结论:地西他滨为主的化疗方案联合微移植治疗伴TP53突变的老年MDS患者安全、有效,值得进一步研究探讨。     

丙戊酸钠联合地西他滨治疗骨髓增生异常综合征疗效分析

目的 探讨丙戊酸钠联合地西他滨治疗骨髓增生异常综合征(MDS)的有效性和安全性.方法 选择2012年2月至2017年2月山西大医院血液科收治的42例MDS患者为研究对象.将患者按照随机数字表法分为对照组(21例)和试验组(21例),对照组接受地西他滨治疗,剂量20 mg·m-2·d-1,2 h完成静脉滴注,连续治疗5 d,4周为1个疗程;试验组在使用地西他滨治疗的基础上,口服丙戊酸钠0.2 g/次,3次/d,1周后加量至0.4 g/次,3次/d.两组均至少进行4个疗程的治疗.出现严重的不良反应或疾病明显进展时停用,治疗后每4周复查一次骨髓涂片,评价疗效.并分别于治疗前后用荧光定量聚合酶链反应检测患者骨髓细胞中ASXL1、DNMT3A、TET2的表达情况.结果 试验组与对照组的总体治疗反应率分别为76.2%(16/21)和57.1%(12/21),差异有统计学意义(P<0.05);两组的总缓解率分别为47.6%(10/21)和38.1%(8/21),差异无统计学意义(P>0.05);两组患者均有轻微的药物不良反应,不良反应发生率分别为42.9%(9/21)和38.1%(8/21),差异无统计学意义(P>0.05);治疗后两组TET2 mRNA、DNMT3A mRNA含量较治疗前下降,差异均具有统计学意义(P<0.05),但两组间治疗后比较差异无统计学意义(P>0.05);对照组ASXL1 mRNA含量较治疗前无显著变化,试验组患者的ASXL1 mRNA含量较治疗前下降,差异有统计学意义(P<0.05).结论 丙戊酸钠联合地西他滨治疗MDS效果良好,不良反应轻微,且对MDS相关基因TET2、DNMT3A以及ASXL1的表达均有影响.     

地西他滨序贯半量CAG方案治疗中高危骨髓增生异常综合征4例

 目的 观察地西他滨（decitabine,达珂）序贯半量CAG方案治疗4例骨髓增生异常综合征患者的临床疗效及不良反应。方法 应用地西他滨序贯半量CAG方案治疗4例MDS患者,评估其疗效。结果 2例患者治疗1疗程后达临床缓解,2例未缓解,4例患者均有不同程度的骨髓抑制,其余不良反应较轻。结论 地西他滨序贯半量CAG方案治疗MDS安全有效,疗效较理想。     

小剂量地西他滨治疗中高危骨髓增生异常综合征的Meta分析

目的 系统评价小剂量地西他滨治疗中高危骨髓增生异常综合征（MDS）疗效和安全性。方法 计算机检索PubMed、Cochrane Library、Embase、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）1995-2012年间发表的关于小剂量地西他滨治疗MDS的文献资料。并纳入随机对照试验（RCT）,采用Review manager5.0软件进行Meta分析。结果 共纳入3篇随机对照试验（RCT）,共894例患者。Meta分析结果显示,地西他滨与支持治疗相比,总生存率（OR）[OR=22.9,95%CI(7.51,69.85),P＜0.00001]、部分缓解率(PR) [OR=17.23,95%CI(2.27,130.76),P=0.006]、血液学改善（HI）[OR=3.21,95%CI(1.53,6.75),P=0.002]、中位生存期（MST）[13.5月 vs. 7.3月,P＜0.05]、Ⅲ/Ⅳ级发热伴中性粒细胞减少[OR=4.85,95%CI(2.55,9.21),P＜0.00001] 差异有统计学意义。完全缓解率（CR）[OR=6.39,95%CI(0.25,166.49),P=0.26] 、Ⅲ/Ⅳ级血小板减少症[OR=2.35,95%CI(0.63,8.69),P=0.20]差异无统计学意义。结论 小剂量地西他滨可提高骨髓增生异常综合征患者总体生存率和部分缓解率,有助于血液学改善。但是增加Ⅲ/Ⅳ级中性粒细胞减少症的发生,部分患者也会出现血小板减少症、恶心呕吐、腹泻等不良反应。     

超低剂量地西他滨单药治疗骨髓增生异常综合征临床效果

目的 探讨超低剂量地西他滨单药治疗骨髓增生异常综合征(MDS)的效果.方法 以2013年7月至2017年10月山西省汾阳医院收治的13例MDS患者为研究对象,采用地西他滨每天10 mg/m2静脉滴注,每10 d为1个疗程,每疗程间隔6周,回顾性分析其治疗效果和不良反应.结果治疗2个疗程后,13例患者中完全缓解2例,部分缓解2例,血液学改善3例,疾病稳定3例,疾病进展2例,因用药后严重肺部感染死亡1例.结论 采用超低剂量地西他滨单药治疗MDS临床效果显著,感染及血液学不良反应发生率低.     

地西他滨联合预激方案初治高危骨髓增生异常综合征及老年急性髓系白血病的临床观察

目的:探讨地西他滨（DAC）联合预激方案初次治疗高危骨髓增生异常综合征（MDS）及老年急性髓系白血病（AML）的疗效和不良反应。方法:回顾性分析首次接受DAC联合预激方案(DAC 25 mg qd，d1~5；Ara-C 10 mg/m2 q12h，d6~12；Acla 12 mg/m2 qd，d6~9；G-CSF 200 μg/m2 qd，WBC＞20×109/L则停用)治疗26例高危MDS及老年AML患者的疗效和不良反应。结果:26例高危MDS及老年AML患者中，完全缓解率42.3%，总体反应率(完全缓解+部分缓解)65.4%，中位生存时间为16.2个月。结论:DAC联合预激方案治疗高危MDS及老年AML患者疗效确切，且安全性高，但由于本研究样本量较小，需进一步开展多中心随机对照试验证实。     

A prospective,multicenter, observational study of long-term decitabine treatment in patients with myelodysplastic syndrome

This prospective observational study evaluated the efficacy and safety of long-term decitabine treatment in patients with myelodysplastic syndrome (MDS). Decitabine 20 mg/m²/day was administered intravenously for 5 consecutive days every 4 weeks to MDS patients in intermediate-1 or higher International Prognostic Scoring System (IPSS) risk categories. Active antimicrobial prophylaxis was given to prevent infectious complications. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to response were evaluated, as were adverse events. The final analysis included 132 patients. IPSS risk was intermediate-2/high in 34.9% patients. The patients received a median of 5 cycles, with responders receiving a median of 8 cycles (range, 2-30). ORR was 62.9% (complete response [CR], 36; partial response [PR], 3; marrow complete response [mCR], 19; and hematologic improvement, 25). Among responders, 39% showed first response at cycle 3 or later. OS at 2 years was 60.9%, with 17% progressing to acute myeloid leukemia. PFS at 2 years was 51.0%. Patients achieving mCR showed comparable survival outcomes to those with CR/PR. With active antibiotic prophylaxis, febrile neutropenia events occurred in 61 of 1,033 (6%) cycles. Long-term decitabine treatment with antibiotic prophylaxis showed favorable outcomes in MDS patients, and mCR predicted favorable survival outcomes.     

Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy

BACKGROUND:

The prognosis of patients with myelodysplastic syndrome (MDS) after decitabine failure is not known.

METHODS:

Data from 87 patients with MDS (n = 67) and chronic myelomonocytic leukemia (n = .20) after failure of decitabine regimens were reviewed.

RESULTS:

After a median follow‐up of 21 months from decitabine failure, 13 (15%) patients remained alive; the median survival was 4.3 months, and the estimated 12‐month survival rate was 28%. The estimated 12‐month survival rates were 27%, 33%, and 33%, respectively, for patients with high‐risk, intermediate‐2‐risk, and intermediate‐1‐risk disease (P = .99) by the International Prognostic Scoring System. The estimated 12‐month survival rates were 100%, 54%, 41%, and 18%, respectively, for patients with low‐risk, intermediate‐1‐risk, intermediate‐2‐risk, and high‐risk disease according to The University of Texas M. D. Anderson Cancer Center risk model (P = .01).

CONCLUSIONS:

The outcome of patients after decitabine failure is poor and appears to be predictable after decitabine failure. Cancer 2010. © 2010 American Cancer Society.     

低剂量地西他滨联合减量IAG方案治疗老年骨髓增生异常综合征转化的急性髓系白血病疗效观察

目的:观察低剂量地西他滨联合减量IAG方案（IDA、Ara-C、G-CSF）诱导治疗老年骨髓增生异常综合征（myelodysplastic syndrome,MDS）转化的急性髓系白血病（acute myeloid leukemia,AML）的疗效及安全性。方法:回顾性分析我中心2015年7月至2017年9月收治的53例老年MDS转化的AML患者,采用低剂量地西他滨联合减量IAG方案诱导治疗,观察疗效并评价其安全性。结果:所有53例患者均完成2疗程化疗,骨髓造血恢复后复查骨髓象评估疗效。其中完全缓解（complete remission,CR）23例（43.4%）,部分缓（partial remission,PR）11例（20.8%）,总有效率（overall remission rate,ORR）64.2%（34/53）。所有患者均出现Ⅲ-Ⅳ级血液学毒性,主要合并症为粒细胞减少所致的感染及血小板减少所致的出血。恶心呕吐、肝肾功损害、心脏毒性等非血液学毒性均可耐受,无治疗相关死亡。性别、年龄、KPS评分对完全缓解率无明确影响,细胞遗传学良好者较细胞遗传学不良者缓解率高,差异有统计学意义（P＜0.05）。结论:低剂量地西他滨联合减剂量IAG方案治疗老年MDS转化的AML疗效确切,缓解率高,不良反应可耐受,临床值得推广。     

地西他滨联合减量IAG方案治疗中高危骨髓增生异常综合征及其转化急性髓系白血病的临床观察

目的:分析国产地西他滨联合减量IAG方案[粒细胞集落刺激因子(G-CSF)+伊达比星(IDA)+阿糖胞苷(Ara-C)]在治疗骨髓增生异常综合征(myelodysplastic syndrome,MDS)及其转化急性髓细胞白血病(acute myeloid leukemia,AML)患者中的临床疗效及其安全性.方法:选取2014年10月至2016年5月收治的中高危MDS以及AML(MDS转化)患者共20例,应用国产地西他滨联合减量IAG方案治疗,观察临床疗效及不良反应发生情况.结果:20例患者至少进行2疗程化疗,完全缓解者9例,部分缓解5例,总有效率为70%(14/20).所有患者均出现III-IV级血液学毒性,第1、2疗程粒细胞缺乏及III、IV级血小板减少持续时间无统计学差异(P>0.05).年龄≥60岁患者粒细胞缺乏时间更长,与年龄<60岁患者相比差异有统计学意义(P<0.05),所有患者非血液学不良反应均可耐受.染色体核型预后良好者疗效佳,预后不良者预后差,患者的年龄、性别与疗效无显著相关性.结论:地西他滨联合减量IAG方案治疗MDS和AML疗效显著,不良反应可控,耐受性较好,值得在临床上进一步推广.     

Cladribine- and decitabine-containing conditioning regimen has a low post-transplant relapse rate in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome

To reduce the risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), there have been continuing efforts to optimize the conditioning regimens. Our study aimed to analyze the risk factors associated with the relapse of relapsed/refractory (R/R), high-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) post-transplant and the efficacy of a new conditioning regimen involving decitabine and cladribine. Clinical data of 125 patients with R/R AML, high-risk AML and high-risk MDS who underwent allo-HSCT were collected. In addition, 35 patients with R/R AML, high-risk AML and high-risk MDS received treatment with a new conditioning regimen including decitabine and cladribine. Cox regression analysis was used to identify risk factors associated with OS, RFS and relapse. Among 125 patients who underwent allo-HSCT, CR before allo-HSCT and matched sibling donors were independent protective factors for OS. DNMT3A abnormality was an independent risk factor for both relapse and RFS. Among 35 patients who received a new conditioning regimen containing decitabine and cladribine, only six patients relapsed and 1-year cumulative incidence of relapse was 11.7%. Moreover, this new regimen showed efficient MRD clearance early after allo-HSCT. The combined decitabine- and cladribine-based conditioning regimen showed a low relapse rate and a high survival without an increased incidence of GVHD or adverse effects and thus has potential for use in allo-HSCT for R/R AML, high-risk AML and high-risk MDS.     

Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome

BACKGROUND:

Secondary acute myeloid leukemia (AML) from an antecedent myelodysplastic syndrome (MDS)/myeloproliferative neoplasm is associated with a poor prognosis. The authors evaluated predictive factors in patients with secondary AML treated with anthracycline‐based induction therapy.

METHODS:

This was a retrospective review of secondary AML patients treated with induction therapy. Age, International Prognostic Scoring System, Eastern Cooperative Oncology Group performance status, cytogenetics, duration of MDS/myeloproliferative neoplasm, and prior MDS/myeloproliferative neoplasm treatment were evaluated for their impact on complete response (CR), CR with low platelets, and overall survival (OS).

RESULTS:

The authors evaluated 61 secondary AML patients who received induction chemotherapy; 59% (36 patients) achieved CR/CR with low platelets (95% confidence interval [CI], 46%‐71%), and median OS was 6.5 (95% CI, 3.9‐8.1) months. Three factors were associated with lower CR/CR with low platelets and OS: poor risk cytogenetics, prior treatment with hypomethylating agents or lenalidomide, and longer time to transformation to AML. Of those treated with hypomethylating agents or lenalidomide, 32% achieved CR/CR with low platelets versus 78% in the group not treated with a hypomethylating agent or lenalidomide (odds ratio [OR], 0.13; 95% CI, 0.04‐0.42). Median OS for those treated with a hypomethylating agent or lenalidomide was 3.7 versus 10.5 months for those not treated with a hypomethylating agent or lenalidomide (P < .0001). The CR/CR with low platelets rate for those with intermediate risk cytogenetics was 70% versus 35% for those with poor risk (OR, 4.33; 95% CI, 1.38‐13.6). Those with poor risk cytogenetics had a median OS of 2.8 versus 7.5 months for those with intermediate risk (P = .01).

CONCLUSIONS:

Prior treatment with hypomethylating agents or lenalidomide, poor risk cytogenetics, and longer time to transformation to AML are independent negative predictive factors for response and OS in patients with secondary AML after induction therapy. Cancer 2011. © 2010 American Cancer Society.     

Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome

BACKGROUND: Therapy for patients with myelodysplastic syndrome (MDS) with hypomethylating agents, like decitabine and 5-azacitidine, has produced favorable results. In this study, the authors update their experience with decitabine in patients with MDS and analyze the cytogenetic response patterns and prognostic factors associated with decitabine therapy. METHODS: One hundred fifteen patients with higher risk MDS who received treatment with decitabine were reviewed. Patients received decitabine 100 mg/m(2) per course every 4 weeks in 3 different schedules: 1) 20 mg/m(2) intravenously daily x 5, 2) 20 mg/m(2) subcutaneously daily x 5, and 3) 10 mg/m(2) intravenously daily x 10. Decitabine was given for a median of >or=7 courses (range, 1-23 courses). RESULTS: Overall, 80 patients (70%) achieved a response according to the modified International Working Group criteria (IWG): complete response (CR), 40 patients (35%); partial response, 2 patients (2%); bone marrow CR with or without other hematologic improvements (HI), 26 patients (23%); and other HI, 12 patients (10%). Cytopenias were improved in 50% of patients. The median remission duration was 20 months, and the median survival was 22 months. Mortality was 3% at 6 weeks and 7% at 3 months. In a multivariate analysis, poor prognostic factors for achieving IWG CR were MDS (vs chronic myelomonocytic leukemia), longer duration of MDS, and prior MDS therapy. For survival, independent adverse prognostic factors were chromosome 5 and/or 7 abnormalities, older age, and prior MDS therapy (excluding growth factors). CONCLUSIONS: The longer term experience with decitabine in MDS was favorable. Pretreatment prognostic factors may predict the outcome of patients who receive decitabine therapy for MDS.     

亚砷酸、维甲酸联合小剂量化疗治疗骨髓增生异常综合征的临床疗效

目的分析亚砷酸联合维甲酸(ATRA)及小剂量化疗治疗骨髓增生异常综合征(MDS)的临床疗效。方法收集21例MDS患者，应用亚砷酸联合ATRA及小剂量化疗，观察其有效率及副作用的发生情况。结果治疗后，总有效率达76．2％，长期随访治疗8例，均保持持续缓解状态。未发现严重毒副作用。结论亚砷酸联合ATRA及小剂量化疗治疗MDS安全、有效。