CAG方案在难治复发性急性髓系白血病中的应用

目的：寻找难治性复发性急性髓系白血病(AML)患者有效治疗途径。方法：应用阿克拉霉素(ACR)、阿糖胞苷(Ara-C)、粒系集落刺激因子(rhG-CSF)组成CAG方案,治疗难治性AML4例、复发性AML5例。1个疗程未取得完全缓解者,可接受第2疗程的治疗。同时患者接受一般对症支持治疗。结果：9例中,CR3例,PR3例,MR3例,总有效率66．7％。主要毒副反应是骨髓抑制,其他非血液学毒性表现较轻。治疗期间无治疗相关性死亡病例。结论：CAG方案对难治性复发性AML患者有积极的治疗作用,治疗过程中感染、出血等并发症少,特别是对老年患者有明显的优点。     

AML／TMDS与MDS—AML的对比研究

目的：分析三系病态造血的急性髓系白血病(AML／TMDS)与骨髓增生异常综合征演变为急性髓系白血病(MDS—AML)的差异。方法：采用常规形态学和细胞化学染色方法观察患者外周血和骨髓细胞。结果：AML/TMDS患者血小板计数和外周原始细胞百分率高于MDS—AML(P＜0．05，P＜0．01)；小巨核细胞和Pseudo-pelger异常明显低于MDS-AML(P＜0．05，P＜0．01)，2组病例MPO染色阳性率基本一致，但AML/TMDS患者MPO积分显著高于MDS—AML(P＜0．01)。AML/TMDS患者多核原始红细胞明显低于MDS—AML(P＜0．05)；AML／TMDS与MDS—AML患者巨大血小板分别为23．1％和86．7％。结论：AML/TMDS与MDS—AML白血病克隆不同，正确诊断对确定方案、判断疗效及预后有重要意义。     

地西他滨四天方案治疗骨髓增生异常综合征及老年人急性髓系白血病

 【摘要】　目的　探讨地西他滨4 d方案治疗骨髓增生异常综合征（MDS）及老年人急性髓系白血病（AML）的疗效及安全性。方法　应用地西他滨每天30 mg／m2,4 d方案治疗5例MDS及5例老年AML患者,观察其疗效及毒副作用。结果　3例患者获得了完全缓解,2例患者获得了部分缓解。不良反应主要为骨髓抑制和感染,较3 d及5 d方案毒副作用未增加。结论　地西他滨对于MDS及老年白血病患者有效,其不良反应可以耐受,4 d方案经济、方便,适合在临床上使用。     

预激方案治疗老年和难治性急性髓系白血病疗效观察

 目的 探讨预激方案治疗老年和难治性急性髓系白血病（AML）的疗效和毒副反应。方法 16 例AML,其中M1 2例,M2 6例,M4 1例,M5 3例,骨髓增生异常综合征伴原始细胞增多（MDS-RAEBT）4例,给予包括阿柔比星和阿糖胞苷联合粒细胞集落刺激因子（CAG）的预激方案治疗。结果 有效率81.3 ％。AML达完全缓解（CR）56.3 ％,其中继发MDS和难治性的AML,CR 4例,PR3例。化疗的毒副反应轻、中度。结论 预激方案对AML的治疗效果明显。且对老年性、难治性AML效果肯定。     

格列卫治疗20例慢性粒细胞白血病临床观察

目的：评价格列卫治疗慢性粒细胞白血病(CML)的效果和不良副作用。方法：CML慢性期(CP)患者口服格列卫400mg/d。CML加速期、急变期(BC)患者口服格列卫400mg-600mg/d。结果：11例CML-CP患者均取得血液学完全缓解(HCR)。9例CML-AP和CML-BC患者4例取得HCR(37％)。7例CML-CP患者在3个月～6个月内4例取得遗传学完全缓解(56％)。CML—CP患者Ⅲ级白细胞(WBC)减少1例,血小板(BPC)减少2例。CML-AP和CML-BC患者,4例发生Ⅲ级-Ⅳ级WBC减少和BPC减少。而非血液学不良副作用,无Ⅲ级或Ⅳ级以上的毒副作用。结论：格列卫治疗CML-CP具有较高的HCR和细胞遗传学反应,CML-BC患者亦可取得较好的血液学反应。格列卫不良副作用发生率低．尤其CML-CP患者为安全。而CML-AP和CML-BC患者治疗期间,需加强支持治疗。     

短程MEA方案为主治疗急性难治性白血病的疗效观察

目的：观察应用疗程为5d的MEA方案治疗急性难治性白血病的疗效。方法：以该方案治疗16例急性难治性白血病患者。结果：16例RAML经1个～2个疗程MEA方案治疗后CR率为56％,总有效率为75％。CR中位时间在4个月(3个月～21个月)。结论：采用疗程为5d的MEA方案为主治疗难治性白血病有较高的缓解率,所有患者均达到了骨髓抑制,住院医疗费用相对低廉,比较适合于贫困地区及基层医院应用。     

地西他滨联合CAG方案治疗骨髓增生异常综合征与急性髓系白血病临床观察

目的 观察地西他滨联合CAG方案治疗骨髓增生异常综合征（MDS）与急性髓系白血病（AML）的临床疗效与安全性.方法 2010年1月11日至2013年8月2日诊治并应用地西他滨治疗的MDS与AML共13例,观察疗效与不良反应.结果 13例患者中,完全缓解（CR）5例,其中2例治疗1个疗程即获得CR,另外3例治疗2个疗程获得CR.部分缓解（PR）2例,血液学改善（HI）3例.结论 地西他滨联合半量CAG方案可有效治疗MDS和AML,且患者如果第1个疗程血小板反应良好,则容易获得CR,但对于经过多种化疗的MDS和AML均疗效不佳.     

吡喃阿霉素为主联合化疗治疗老年急性白血病23例

目的：观察吡喃阿霉素(THP)联合化疗治疗老年急性白血病的疗效及其毒副作用。方法：对23例老年急性白血病患者进行THP为主联合化疗，年龄为l60岁-81岁(平均67岁)，ALL用VTP方案，AML用TA方案。ALL5例，AML17例。CML急淋变1例。结果：CR9例，PR5例，有效率60．9％。主要毒副作用为骨髓抑制及消化道反应。2倒脱发，1例EKG有一过性ST改变。未发现肝肾毒性。结论：THP为主的化疗方案应用于老年急性白血病，有效率高。毒副作用小，是安全、有效的诱导方案。     

小剂量地西他滨联合CAG方案治疗老年人急性髓系白血病及中高危骨髓增生异常综合征临床分析

目的 探讨小剂量地西他滨(DAC)治疗老年人急性髓系白血病(AML)和中高危骨髓增生异常综合征(MDS)的临床价值.方法 对19例老年AML和中高危MDS患者使用小剂量DAC(10 mg/d,连用7 d)联合CAG方案[重组粒细胞集落刺激因子(G-CSF)+阿糖胞苷(Ara-C)+阿柔比星]进行治疗;1个疗程后对疗效及不良反应进行综合评估;对患者进行生存期跟踪随访.结果 1个疗程治疗后,完全缓解8例,部分缓解7例;4个疗程治疗后,完全缓解13例(68.4%),总体反应率达到78.9%(15/19),化疗相关不良反应少.随访42个月,生存12例,中位生存时间为13.5个月(3~42个月).结论 对于中高危MDS和老年AML患者,小剂量DAC联合CAG方案有较好的疗效、较高的安全性、较低的经济负担,有利于改善患者的治疗依从性.     

家族聚集性骨髓增生异常综合征/急性髓系白血病家系报道一例并文献复习

目的 探讨家族聚集性骨髓增生异常综合征/急性髓系白血病(MDS/AML)的诊断、临床特点、基因突变及治疗转归.方法 分析1例家族聚集性MDS/AML家系中兄弟患者的骨髓细胞形态学、免疫分型、细胞遗传学、基因突变,对其疗效和转归进行观察,并复习相关文献.结果 先证者在确诊MDS-原始细胞过多难治性贫血Ⅰ型(RAEBⅠ)4个月后进展为AML,其兄在确诊MDS-难治性血细胞减少伴多系病态造血3个月后进展为MDS-RAEBⅡ,生存期分别为5个月和8个月.结论 家族聚集性MDS/AML临床罕见,其诊断需要结合家族史、细胞遗传学、分子生物学等进行综合判断,预后差.     

HAA方案治疗难治、复发老年急性髓系白血病的临床观察

目的:探讨HAA方案治疗难治、复发老年急性髓系白血病（acute myeloid leukemia,AML）的疗效及毒副反应。方法:回顾性分析首次接受HAA方案(HHT 2.0 mg/m2 qd,d1~7;Ara-C 100~200 mg/m2 qd,d1~7;Acla 12 mg/m2 qd,d1~7;根据情况调整具体天数)挽救治疗17例难治、复发老年AML患者的疗效及毒副反应,统计长期生存情况。结果:17例难治、复发老年AML患者中,3例达完全缓解（complete remission,CR）,3例达部分缓解(partial remisson,PR),11例未缓解(none remisson,NR),临床有效率(CR+PR)35.3%。无1例患者出现早期死亡。中位生存时间为6.2个月(0.5~32.0个月)。结论:HAA方案治疗难治、复发老年AML患者疗效与地西他滨方案相近,且安全性高,但由于样本量较小,需进一步开展多中心随机对照试验证实。     

地西他滨联合半量CAG方案治疗复发难治急性髓系白血病效果观察

目的 观察地西他滨联合半量CAG方案治疗复发难治急性髓系白血病(AML)的临床效果.方法 收集2015年1月至2017年1月大同市第三人民医院8例接受地西他滨联合半量CAG方案治疗的复发难治AML患者的临床资料,分析其疗效及不良反应.结果 1个疗程地西他滨联合半量CAG方案治疗后,完全缓解3例,部分缓解2例.主要不良反应为骨髓抑制及感染,8例患者均出现Ⅲ～Ⅳ级血液学不良反应,5例出现感染,2例出现Ⅰ级药物性肝损害,无治疗相关死亡发生.结论 地西他滨联合半量CAG方案治疗复发难治AML具有良好疗效,值得进一步研究.     

Phase II study of SM-108 (4-carbamoylimidazolium-5-olate) in hematological malignancies

A total of 165 patients were entered into this study and 140 were evaluate for effects and 165 for toxicities. Of 39 patients with chronic myelogenous leukemia (CML) 21 achieved complete remission (CR), 6 achieved partial remission (PR) with a response rate of 69.2%. In MDS, of 11 patients with chronic myelomonocytic leukemia (CMMoL), one good partial response and 4 partial response were observed (CR + PR:45.5%); of 14 patients with RAEB, one complete response, 4 partial response (CR + PR: 35.7%); of 11 patients with RAEB in T, 3 partial response were observed (response rate: 27.3%). Of 13 patients with polycythemia vera, 4 excellent effect and 7 moderate effect (84.6%) were observed. Seven of 30 patients with acute myelocytic leukemia achieved partial response (23.3%). Mean dosages of SM-108 until remission were 400-500 mg/m2/day on CMMoL, RAEB in MDS, polycythemia vera and CML, and 600-800 mg/m2/day on RAEB in T and AML. In the analysis of adverse effects of SM-108, a subjective side effects including mainly gastrointestinal toxicities were observed in 38 cases (23.0%) of the patients : 26 patients (15.8%) showed objective side effects including liver dysfunction, but these symptoms were transient and not serious. Our study indicates that SM-108 is useful agent against MDS, especially CMMoL, RAEB, RAEB in T, polycythemia vera and CML.     

Carboplatin plus cytarabine in the treatment of high-risk acute myeloblastic leukemia.

Thirty-one patients (20 male and 11 female; median age 51 years (16-79)) with high-risk acute myeloblastic leukemia (AML) (20 refractory AML and 11 secondary AML (s-AML) (four to myelodysplastic syndrome, five to chemo/radiotherapy, one to aplastic anemia and one blastic chronic myelogenous leukemia (B-CML)) were treated with CBDCA (300 mg/m2/day x 5 days in continuous i.v. infusion) plus intermediate-dose Ara-C (500 mg/m2/day x 3 days in rapid i.v. infusion). Nine patients (29%) achieved CR (five s-AML (three myelodysplastic syndromes, one CML and one ALL) and four refractory AML) and 11 patients had resistant disease. There were 11 early deaths (35%). Median disease-free survival of the nine responders was 4 months. The main toxicity was hematological, febrile episodes took place in nearly all the patients (96%). The CBDCA plus Ara-C regimen showed an evident antileukemic activity in high-risk leukemia. However, the lack of long-term disease-free survivors shows the need for innovative postremission strategies. The high initial response rate seen in AML secondary to myelodysplastic syndromes (MDS) warrants further investigation of CBDCA in combination regimens for MDS patients.     

阿扎胞苷联合CAG方案再诱导治疗儿童复发难治急性髓系白血病临床观察

目的:探讨阿扎胞苷联合CAG（阿糖胞苷+阿柔比星+粒细胞集落刺激因子）方案再诱导儿童复发难治急性髓系白血病（AML）的疗效和安全性。方法:回顾性分析2018年11月至2019年8月福建医科大学附属协和医院收治的3例接受阿扎胞苷联合CAG方案再诱导治疗的复发难治AML患儿的临床资料,分析疗效、预后及不良反应发生情况。结果:3例患儿中,2例为复发AML（分别距开始治疗18个月和8个月后复发）,1例为难治AML（2个疗程标准化疗不能达完全缓解）。在2个疗程阿扎胞苷联合CAG方案再诱导后,2例达完全缓解,1例达部分缓解,之后均桥接造血干细胞移植（HSCT）。随访16~21个月（距首次阿扎胞苷联合CAG方案再诱导的时间）,患儿均为无白血病生存。除了血液学不良反应及感染外,阿扎胞苷未增加其他不良反应。结论:阿扎胞苷联合CAG方案诱导儿童复发难治AML有较高的再缓解率和安全性,及时桥接HSCT可取得较好的预后。     

Etoposide, 6-thioguanine and idarubicin, an oral combination regimen (ETI) for the induction treatment of acute leukemia

Twenty patients with advanced acute leukemia (16 acute myeloid leukemia (AML), three myeloid blast crisis (BC) of chronic myeloid leukemia (CML), one acute lymphatic leukemia) were treated with a peroral regimen consisting of etoposide 80 mg/m2 and 6-thioguanine 100 mg/m2 twice daily for 5 days, and idarubicin 15 mg/m2 once daily for 3 days (ETI). Two AML patients were in first relapse. All the other patients with acute leukemia had a later relapse or were refractory to primary or salvage treatment. One to six ETI cycles were given. Four AML patients achieved remission and one patient with BC of CML entered the second chronic phase. Clearing of the blood of leukemic cells was seen in seven additional patients. Infection was the most common complication, gastrointestinal toxicity was not a major problem. In conclusion, peroral ETI treatment has a marked antileukemic effect even in an advanced disease, and the toxicity is moderate and well acceptable.     

Mylotarg combined with topotecan and cytarabine in patients with refractory acute myelogenous leukemia

PURPOSE: Mylotarg, a humanized anti-CD33 antibody linked to an antitumor antibiotic, is approved for the treatment of patients with relapsed acute myeloid leukemia (AML). Topotecan and cytarabine (ara-C) is an effective anti-AML regimen. A pilot study of Mylotarg combined with topotecan and ara-C (MTA) was conducted in patients with refractory AML. METHODS: MTA consisted of Mylotarg 9 mg/m(2) intravenously (i.v.) over 2 h on day 1, ara-C 1 g/m(2) over 2 h i.v. on days 1 through 5, and topotecan 1.25 mg/m(2) by continuous infusion i.v. on days 1 through 5. RESULTS: A group of 17 patients (9 primary resistant, 8 relapsed) with AML or advanced myelodysplastic syndrome (MDS) received 20 courses of MTA. The median age of the patients was 55 years (20-70 years). Two patients (12%) achieved complete remission. The median overall survival was 8.2 weeks. Five patients (29%) developed grade 3/4 hepatic transaminitis, including one patient (6%) who died with hepatic venoocclusive disease. CONCLUSIONS: MTA was moderately effective and associated with significant toxicity in patients with refractory AML.     

Epigenetic priming with decitabine followed by low dose idarubicin and cytarabine in acute myeloid leukemia evolving from myelodysplastic syndromes and higher-risk myelodysplastic syndromes: a prospective multicenter single-arm trial

Patients with acute myeloid leukemia (AML) evolving from myelodysplastic syndrome (MDS) or higher-risk MDS have limited treatment options and poor prognosis. Our previous single-center study of decitabine followed by low dose idarubicin and cytarabine (D-IA) in patients with myeloid neoplasms showed promising primary results. We therefore conducted a multicenter study of D-IA regimen in AML evolving from MDS and higher-risk MDS. Patients with AML evolving from MDS or refractory anemia with excess blasts type 2 (RAEB-2) (based on the 2008 WHO classification) were included. The D-IA regimen (decitabine, 20 mg/m² daily, days 1 to 3; idarubicin, 6 mg/m² daily, days 4 to 6; cytarabine 25 mg/m² every 12 hours, days 4 to 8; granulocyte colony stimulating factor [G-CSF], 5 μg/kg, from day 4 until neutrophil count increased to 1.0 × 10⁹/L) was administered as induction chemotherapy. Seventy-one patients were enrolled and treated, among whom 44 (62.0%) had AML evolving from MDS and 27 (38.0%) had RAEB-2. Twenty-eight (63.6%) AML patients achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi): 14 (31.8%) patients had CR and 14 (31.8%) had CRi. Six (22.2%) MDS patients had CR and 15 (55.6%) had marrow complete remission. The median overall survival (OS) was 22.4 months for the entire group, with a median OS of 24.2 months for AML and 20.0 months for MDS subgroup. No early death occurred. In conclusion, the D-IA regimen was effective and well tolerated, representing an alternative option for patients with AML evolving from MDS or MDS subtype RAEB-2.     

Troxacitabine, a novel dioxolane nucleoside analog, has activity in patients with advanced leukemia.

PURPOSE: To investigate the toxicity profile, activity, and pharmacokinetics of a novel L-nucleoside analog, troxacitabine (BCH-4556), in patients with advanced leukemia. PATIENTS AND METHODS: Patients with refractory or relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP). Troxacitabine was given as an intravenous infusion over 30 minutes daily for 5 days. The starting dose was 0.72 mg/m(2)/d (3.6 mg/m(2)/course). Courses were given every 3 to 4 weeks according to toxicity and antileukemic efficacy. The dose was escalated by 50% until grade 2 toxicity was observed, and then by 30% to 35% until the dose-limiting toxicity (DLT) was defined. RESULTS: Forty-two patients (AML: 31 patients; MDS: six patients [five MDS + one CMML]; ALL: four patients; CML-BP: one patient) were treated. Median age was 61 years (range, 23 to 79 years), and 29 patients were males. Stomatitis and hand-foot syndrome were the DLTs. The MTD was defined as 8 mg/m(2)/d. The pharmacokinetic behavior of troxacitabine is linear over the dose range of 0.72 to 10.0 m/m(2). Approximately 69% of troxacitabine was excreted as unchanged drug in the urine. Marrow hypoplasia occurred between days 14 and 28 in 73% of AML patients. Three complete remissions and one partial remission were observed in 30 assessable AML patients. One MDS patient achieved a hematologic improvement. A patient with CML-BP achieved a return to chronic phase disease. CONCLUSION: Troxacitabine has a unique metabolic and pharmacokinetic profile and significant antileukemic activity. DLTs were stomatitis and hand-foot syndrome. Troxacitabine merits further study in hematologic malignancies.     

Treatment of myelodysplastic syndrome and atypical leukemia with low-dose aclarubicin

To study the therapeutic effect of low-dose aclarubicin (ACR), we carried out comparative treatment of 15 patients with myelodysplastic syndrome (MDS) and atypical leukemia using this drug. Complete remission (CR) was achieved in three patients with RAEB-t and one patient with AML, partial remission was obtained in one patient with RAEB and hematological improvement in one patient with refractory anemia (RA). Interestingly, prolonged CR for more than 26 months with persistent chromosomal abnormalities was observed in a case of AML, which progressed from RA. Myelosuppression caused by low-dose ACR was milder than that caused by low-dose Ara-C. Furthermore, in vitro studies indicated that ACR induced differentiation of bone marrow cells from one patient with MDS. From these observations, it is suggested that low-dose ACR may be an alternative to low-dose Ara-C for treatment of MDS, and that the in vivo effect of ACR may be mediated by the differentiation of abnormal hemopoietic clones.