初次骨髓完全缓解时血象恢复不良急性髓系白血病患者临床特征及预后分析

目的 探讨初次骨髓完全缓解(CR)时血象恢复不良[血小板计数(Plt)<100×109/L或中性粒细胞绝对值(ANC)<1.0×109/L]急性髓系白血病(AML)患者的临床特征和预后因素.方法 回顾性分析2010年1月至2015年9月郑州大学第一附属医院血液科收治的302例初次骨髓CR的AML患者(M3除外)病例资料,根据初次获骨髓CR时血象恢复情况分为血象CR组(Plt≥100×109/L且ANC≥1.0×109/L)和血象未达CR组(Plt<100×109/L或ANC<1.0×109/L),比较两组患者临床特征和预后差异,并通过单因素和多因素分析对血象未达CR的AML患者复发和生存情况进行分析.结果血象CR组216例(71.5%),血象未达CR组86例(28.5%),两组年龄、就诊时高白细胞患者比例、外周血原始细胞比例、法美英协作组(FAB)分型、细胞遗传学危险度分层和FLT3-ITD/NPM1基因突变比较差异均无统计学意义(均P>0.05).血象CR组就诊时骨髓原始细胞数和首疗程化疗获骨髓CR比例高于血象未达CR组(均P<0.05),初次骨髓CR时微小残留病(MRD)阳性比例低于血象未达CR组(P=0.004),且初次骨髓CR时血象CR组骨髓增生程度更活跃(P=0.001).血象CR组3年复发率低于血象未达CR组(P=0.003),总生存(OS)率和无病生存(DFS)率高于血象未达CR组(P=0.002,P=0.040).多因素分析显示,对于血象未达CR的AML患者,高危染色体核型、诱导疗程数≥2个、初次骨髓CR时外周血中性粒细胞未恢复是复发率、OS率和DFS率的共同独立危险因素(均P<0.05).FLT3-ITD基因突变阳性是OS率的独立危险因素(P<0.001),就诊时外周血原始细胞比例≥0.60是DFS率的独立危险因素(P=0.047).结论 初次骨髓CR时血象未达CR的AML患者预后较差,且高危染色体核型、诱导疗程数≥2个、中性粒细胞恢复不良者可能预后更差,应视为高危人群,考虑更积极的治疗.     

老年正常核型急性髓系白血病患者临床特征及预后分析

目的 探讨老年正常核型急性髓系白血病(CN-AML)患者的临床特征及其预后相关因素.方法 回顾性分析104例初治老年CN-AML(M3除外)患者的临床资料.用χ2检验分析完全缓解(CR)的影响因素.用Kaplan-Meier法进行生存分析,并采用Log-rank检验对预后相关影响因素进行单因素分析,采用Cox回归模型进行多因素分析.结果 104例患者中首次化疗后可评价疗效者72例,CR率为38.9%(28/72),总有效率为55.6%(40/72).白细胞计数(WBC)<100×109/L、NPM1突变阳性患者的CR率较高[59.4%(38/64)比12.5%(1/8),83.3%(10/12)比36.4%(8/22),均P<0.05].104例患者中位总生存(OS)时间为6.9个月.单因素分析显示年龄≥70岁、继发AML、高WBC(≥100×109/L)、FLT3-内部串联重复(ITD)突变阳性、CD7阳性、达CR诱导疗程数>2个以及Charlson合并疾病指数(CCI)评分≥2分的患者OS时间较短(均P<0.05).多因素分析显示FLT3-ITD突变阳性(HR=7.61,95%CI 1.80~32.11,P=0.006)及达CR诱导疗程数>2个(HR=10.11,95%CI 2.38~43.03,P=0.002)是患者OS的独立不良影响因素.结论 老年CN-AML患者的预后是多种因素综合作用的结果,FLT3-ITD突变阳性、 达CR诱导疗程数>2个是老年CN-AML患者不良OS的独立影响因素.     

以吡喃阿霉素为基础的联合化疗方案治疗急性髓系白血病的疗效及其预后因素分析

目的:分析采用以吡喃阿霉素(pirarubicin, THP)为基础的联合方案治疗急性髓系白血病(acute myeloid leukemia, AML)患者的完全缓解(complete remission, CR)率、无病生存(disease free survival, DFS)以及总生存(overall survival, OS)情况,探讨不同预后因素对于缓解率及其预后的影响.方法:采用以THP为基础的联合方案诱导治疗初治的原发AML患者29例,计算CR率、DFS期、OS期以及1、2年的DFS率和OS率.根据患者年龄、白细胞计数、FAB分型、染色体核型以及免疫表型进行分组,比较各组之间的CR率、总体有效率[部分缓解(partial remission, PR)+CR]和OS期(率).结果:经1个疗程的TA(THP+阿糖胞苷)方案诱导治疗后,19例(65.5%)患者达到CR,6例(20.7%)患者达到PR,4例(13.8%)患者未缓解(no response, NR),总体有效率(PR+CR)为86.2%.19例CR患者的中位DFS期为22.9(4.0～27.0)个月,1、2年的DFS率均为77.1%.患者的中位OS期为18.6(2.0～28.1)个月,1、2年的OS率分别为58.6%和52.8%.年龄<45岁、白细胞计数<20×109/L、FAB分型为M2、染色体核型为良好和中等组、CD9和CD56阴性者的总体有效率(PR+CR)较高.log-rank单因素分析结果显示,年龄<45岁和FAB分型为M2者的OS期较长.结论:采用TA方案诱导治疗AML具有较好的疗效,不良反应较少.患者年龄、白细胞计数、FAB分型、染色体核型以及CD9、CD56的表达是影响治疗有效率的预后相关因素.     

含高三尖杉酯碱方案治疗初治急性髓系白血病46例效果和生存分析

目的探讨以高三尖杉酯碱（HHT）为主的化疗方案治疗急性髓系白血病（AML）的缓解率,评价AML不同染色体核型、基因突变对总生存（OS）率、无事件生存（EFS）率的影响。方法将80例初治AML患者用随机信封法分为HAA、HDA、DA、IA方案治疗组,比较各组诱导完全缓解（CR）率,并将AML患者分为染色体核型“好、中、差”三组,分别比较OS、EFS。结合患者是否表达预后较差的基因突变,利用染色体与基因型两者总体评价OS、EFS。结果用含有HHT方案治疗初治AML46例,总CR率78．3％（36／46）,高于DA方案组总CR率66．7％（10／15）及IA方案组的63．2％（12／19）,三种方案组CR率差异无统计学意义（P〉0．05）。不同染色体核型对于生存具有较大影响,染色体核型“差”者OS、EFS较染色体核型“好”或“中”者下降程度显著。结合染色体和基因型分组对于显示预后总体OS、EFS的下降趋势更明显。结论含HHT的治疗方案CR率与传统DA、IA方案相似,提示高三尖杉酯碱治疗的有效性。不同染色体及基因突变对于AML预后具有较大影响。     

急性髓系白血病细胞遗传学特征及不同剂量柔红霉素DA方案化疗效果分析

目的 分析急性髓系白血病(AML)(非M3型)染色体及相关融合基因的遗传学特征,评估其采用不同剂量柔红霉素及标准剂量阿糖胞苷组成的DA方案化疗的预后.方法 收集2013年1月至2015年1月确诊的56例初治AML(非M3型)患者,采用短期培养法处理骨髓样本,用R显带核型分析进行细胞遗传学检测,并应用反转录聚合酶链反应(RT-PCR)和10%聚丙烯酰胺凝胶电泳对标本进行31种融合基因分型检测.接受DA方案诱导治疗时按照不同柔红霉素剂量将患者分为3组(减低剂量组、标准剂量组、大剂量组),观察3组患者治疗后完全缓解(CR)率及生存期,并采用χ2检验分析细胞遗传学和分子生物学异常对3组患者化疗效果及总生存(OS)率的影响.结果 56例患者中染色体核型异常18例(32.1%),其中染色体数目异常6例(10.7%),结构异常16例(28.6%),同时有数目和结构异常4例(7.1%).最常见的结构异常为t(8;21),数目异常为+8、-Y.融合基因检出率为48.2%(27/56),其中AML1-ETO 13例,CBFβ-MYH114例,AML1-MDS13例.融合基因和染色体核型分析使AML患者的遗传学异常检出率提升至62.0%.采用DA方案诱导化疗的总CR率为73.2%,2年OS率为42.9%.标准剂量组中中危患者的化疗缓解率低于低危患者(χ2=8.976,P=0.002);低危患者中减低剂量组与标准剂量组的化疗缓解率差异无统计学意义(P>0.05),但标准剂量组2年OS率有优势(χ2=8.045,P=0.005).结论 成年人AML具有独特的细胞遗传学特征,可辅助指导临床诊断、分型及预后判断.中危患者的预后差于低危患者,低危患者采取减低剂量DA方案也可获得较好的化疗缓解率,但标准剂量DA方案在长期生存方面优势显著.     

标准剂量IA方案治疗≥55岁初诊急性髓系白血病患者效果观察

目的 探讨标准剂量IA方案治疗≥55岁初诊急性髓系白血病(AML)患者的疗效及不良反应.方法 回顾性分析江苏省人民医院血液科收治的32例≥55岁初诊AML患者应用标准剂量IA方案诱导治疗后的缓解情况、生存情况和治疗相关不良反应.结果 32例患者经IA方案诱导治疗后完全缓解(CR)率为71.9%(23/32),部分缓解(PR)率为9.4%(3/32),总有效(OR)率为81.3%(26/32).按细胞遗传学或分子生物学指标分组:预后良好组7例,CR 6例,PR 1例,OR率100.0%(7/7);预后中等组19例,CR 14例,PR 2例,OR率84.2%(16/19);预后不良组6例,CR 3例,PR 0例,OR率50.0%(3/6);三组CR率和OR率比较差异均无统计学意义(χ2=5.571,P=0.067;χ2=2.114,P=0.359).预后良好、中等和不良组的中位总生存(OS)时间分别为28.07个月(6.57~46.33个月)、16.93个月(0.40~87.57个月)和3.03个月(2.00~6.00个月),差异有统计学意义(Z=9.630,P=0.008);2年OS率分别为83.33%、46.80%和0,差异亦有统计学意义(χ2=12.206,P<0.001).化疗后主要不良反应为骨髓抑制及感染,未发生严重非血液系统不良反应.结论 ≥55岁初诊AML患者可选择标准剂量IA方案作为诱导方案.预后良好组和预后中等组患者诱导治疗后OR率、CR率高,OS时间长,而预后不良组患者未能从治疗中获益.     

急性髓系白血病（非M3）化疗后骨髓油滴和巨核细胞数变化规律及其预后意义

 目的　探讨急性髓系白血病（AML）（非M3）患者化疗后骨髓油滴和巨核细胞数变化规律及其预后意义。方法　对99例初诊AML（非M3）患者资料进行回顾性分析,评价规范治疗各阶段骨髓油滴及巨核细胞数变化及其对总体生存（OS）率、无病生存（DFS）率的影响。结果　99例患者中位DFS为 21（2～88）个月,3年DFS率为47.3 %,中位OS 70（4～89）个月,3年OS率55.8 %。诱导化疗达完全缓解（CR）后骨髓油滴随着诱导缓解后化疗次数增加呈增加趋势,而巨核细胞数呈减少趋势。将单因素分析提示有意义的诱导缓解后第2次化疗后巨核细胞数变化率、诱导缓解后第1～3次化疗后骨髓油滴变化、骨髓纤维化分级、初诊乳酸脱氢酶值、白血病细胞免疫分型、起病时骨髓白血病细胞比例及诱导化疗结束后第7～10天残留白血病细胞比例等观察指标纳入多因素分析,结果提示起病时骨髓白血病细胞比例小于50 %、诱导缓解后第3次化疗后骨髓油滴较诱导化疗CR期增多对于延长患者DFS时间有独立预后意义（P＝0.010、0.018）;而诱导化疗结束后第7～10天残留白血病细胞比例≥10 %及诱导缓解后第2次化疗后骨髓巨核细胞数变化率≤-50 %为OS的独立不良预后因素（P＝0.009、0.038）。结论　AML（非M3）患者达CR后,随着诱导缓解后化疗次数增加骨髓油滴呈增加趋势,而巨核细胞数呈减少趋势。动态观察骨髓油滴及巨核细胞计数有助于患者预后判断。     

TLS-ERG融合基因阳性急性髓系白血病9例并文献复习

目的探讨TLS-ERG融合基因阳性急性髓系白血病(AML)患者的临床特点及预后。方法回顾性分析2013年6月至2020年8月在吉林大学第一医院诊治的9例TLS-ERG融合基因阳性AML患者的临床资料, 并复习相关文献。结果 9例TLS-ERG融合基因阳性AML患者中, 男性5例, 女性4例, 中位年龄16岁(6～40岁)。5例患者接受单纯化疗, 3例患者接受异基因造血干细胞移植(allo-HSCT), 1例患者未系统治疗。8例系统治疗患者中, 首次诱导化疗完全缓解1例, 诱导治疗完全缓解5例。5例单纯化疗患者中位总生存时间为1.5个月(1～11个月);其中3例首疗程未缓解, 因感染死亡, 2例复发后死亡。3例移植患者中位总生存时间为16个月(13～17个月);其中2例复发后死亡, 1例随访截止前持续分子学完全缓解。结论 TLS-ERG融合基因阳性在AML中发生率低, 诱导治疗效果差, 造血干细胞移植可能改善部分患者的预后, 但并不能克服TLS-ERG融合基因阳性对预后的不良影响。     

急性髓系白血病细胞遗传学特征与诱导治疗反应的相关性分析

  目的　探讨急性髓系白血病（AML）细胞遗传学分布特征及其与诱导治疗反应的相关性。方法　对初诊为AML的395例患者的染色体核型进行分析,按照美国国立综合癌症网络（NCCN）白血病指南分为预后良好组、预后中等组和预后不良组。分析各组核型发生比及其1个疗程诱导治疗后的完全缓解（CR）率。结果　预后良好、中等及不良核型分别占50.56 %（180／356）、39.89 %（142／356）、9.55 %（34／356）。预后良好核型t（15;17） 113例中,接受并完成1个疗程诱导治疗的101例患者均达CR。单纯t（8;21）组与合并其他染色体异常的t（8;21）组CR率比较差异有统计学意义[92.00 %（23／25）比 50.00 %（11／22）]（χ2＝10.317,P＝0.001）。正常核型及-Y异常两组核型CR率比较差异无统计学意义[61.90 %（39／63） 比 58.82 %（10／17）]（χ2＝0.054,P＝0.817）。复杂核型中以单体核型最多见,经治疗的10例单体核型患者9例未达缓解。结论　初诊AML患者细胞遗传学分布特点与国际其他中心报道略有差异。AML患者细胞遗传学特征不仅与长期生存相关,而且与诱导治疗后CR率密切相关。     

异基因造血干细胞移植治疗急性髓系白血病的临床分析

目的 探讨异基因造血干细胞移植(allo-HSCT)对急性髓系白血病(AML)的治疗效果，分析可能影响预后的相关因素。方法 回顾性分析47例AML患者的临床资料，所有患者均行allo-HSCT治疗。应用Kaplan-Meier生存曲线评定患者的总生存率(OS),采用Log-rank检验行不同组别的比较，应用Cox回归法探究影响预后的有关因素。结果47例患者中存活32例，死亡15例，7例复发；5年OS为(61.23±6.75)%,中位生存时间77.6个月，5年复发率为(15.83±4.26)%;Log-rank检验结果表明前后期各不相同的移植方案、缓解次数、移植前缓解情况、各不相同的供者来源、是否合并移植物宿主病(GVHD)与OS无关(P>0.05);多因素分析表明，合并髓系肉瘤和复发为患者预后的主要影响因素(P<0.05)。结论 allo-HSCT在AML患者治疗中效果确切，随着移植手段的转变与支持治疗的进步，患者的生存周期逐渐延长，而合并髓系肉瘤和复发是造成不良预后的有关因素，临床需予以积极的重视。     

Prognostic scoring model based on multi-drug resistance status and cytogenetics in adult patients with acute myeloid leukemia

Clinical heterogenicity exists within an acute myeloid leukemia (AML) patient group with the same cytogenetic risk. Multi-drug resistance (MDR) is also regarded as one of the potential prognostic factors for AML. Accordingly, the prognostic scoring model can be generated based on both consideration of cytogenetic risk and the MDR status for AML. The CR rate, event-free (EFS) and overall survival (OS) were analysed according to cytogenetic risk, MDR status and clinical factors. Prognostic score was calculated by the sum of MDR status (0 for negative, 1 for positive) and dichotomized scoring for cytogenetic risk (0 for favorable/intermediate and 1 for unfavorable cytogenetics). MDR expression was noted in 36.6% of the patients and associated with a lower CR rate (p = 0.037). MDR, cytogenetics and the use of SCT were identified as independent prognostic factors for EFS and OS. The CR rate of the group scored with 0, 1 and 2 was 81.4, 66.7, and 44.4%, respectively (p = 0.050). The prognostic scoring model depicted a discriminating role in terms of EFS (p < 0.0001) and OS (p = 0.0001). The prognostic scoring model based on cytogenetic risk and MDR provided an improved method for evaluating the prognosis in AML and helped to stratify the risk of patients with the same cytogenetic risk.     

Disease biology rather than age is the most important determinant of survival of patients > or = 60 years with acute myeloid leukemia treated with uniform intensive therapy

BACKGROUND: The objectives of the current study were to evaluate the outcome of patients > or = 60 years with acute myeloid leukemia (AML) treated uniformly with high-dose daunorubicin containing induction and modified high-dose cytosine arabinoside containing postremission therapy, and to identify factors predictive of complete disease remission (CR) and survival. METHODS: Between 1998 and 2002, the authors treated 117 newly diagnosed patients (acute promyelocytic leukemia excluded) with AML > or = 60 years (median, 67 years; range, 60-82 years). Karyotype (Medical Research Council classification) at diagnosis was categorized as good risk (n = 3), intermediate risk (n = 69), adverse risk (n = 26), and suboptimal/not done (n = 19). A normal karyotype was seen in 41 patients and 40 (34%) had secondary AML. RESULTS: The outcome of induction included the following: CR, 62 (53%); early death, 5 (4%); death during hypoplasia, 14 (12%); and resistant disease, 36 (31%). The 3-year event-free (EFS) and overall survival (OS) rates were 9% (95% confidence interval [95% CI], 3-16%) and 17% (95% CI, 9-29%), respectively. In a univariate analysis, cytogenetics, lactate dehydrogenase level, leukocyte count, and performance status were the significant factors for EFS and OS. Age was not a significant prognostic factor for either CR or survival. In a multivariate model, adverse-risk cytogenetics, previous history of myelodysplastic syndrome or antecedent hematologic disorder, and high leukocyte count (> 30 x 10(9)/L) were independent adverse prognostic factors for survival. The impact of adverse karyotype on EFS and OS was time dependent and was observed after 50 and 150 days, respectively. CONCLUSIONS: The authors concluded that candidacy for intensive therapy in older patients should be based on biologic features of disease and fitness, rather than on age.     

Comparison of Autologous Hematopoietic Cell Transplantation and Chemotherapy as Postremission Treatment in Non-M3 Acute Myeloid Leukemia in First Complete Remission

IntroductionA number of randomized trials in patients with AML in CR1 have been conducted and they showed that auto-HCT improves RFS but not OS, compared with chemotherapy. However, because these trials have had compliance problems, the value of auto-HCT still has not been clearly established.Patients and MethodsUsing a database of 2518 adult patients with AML in CR1, we retrospectively analyzed the outcome of auto-HCT and compared it with intensive nonmyeloablative chemotherapy using landmark analyses.ResultsIn 103 auto-HCT recipients, OS and RFS at 3 years from treatment were 65% and 57%, respectively. Multivariate analysis showed that unfavorable risk cytogenetics and entry into CR1 after 2 courses of induction treatment predicted a poor outcome. Because the median time interval between CR1 and auto-HCT was 153 days, landmark analyses at 5 months after CR1 were performed to compare 1290 patients who received chemotherapy alone (median age, 52 years; range, 16-70) with 103 who received auto-HCT (median age, 48 years; range, 16-67). Auto-HCT improves 3-year RFS (58% vs. 37%; P < .001) but not OS compared with chemotherapy alone. Among patients with unfavorable risk cytogenetics or those who required 2 courses to reach CR1, there was no significant difference in RFS between the 2 groups.ConclusionAuto-HCT can be considered as a postremission therapy for AML patients with favorable or intermediate risk cytogenetics who achieve CR1 after a single course of induction treatment.     

Prognostic relevance of immunophenotyping in 379 patients with acute myeloid leukemia

We investigated the prognostic relevance of immunophenotype and other clinical pathological features in 379 adult patients with de novo (acute myeloid leukemia) AML diagnosed and treated at our institution during an 8-year period. Acute promyelocytic leukemia (APL) cases were excluded because they received different treatment. The overall complete remission (CR) rate post-induction therapy with Ara-C and daunorubicin (DNR) was 60% with a median disease free survival (DFS) of 72 weeks, and a median overall survival (OS) of 54 weeks. At diagnosis, CD34, deoxynucleotidyl transferase (TdT), CD7, CD56, HLADR and CD19 were expressed in 65, 19, 32, 15, 87 and 5%, respectively, of 379 evaluable cases. CD34 positive patients had a significantly lower CR rate (P=0.0003) than CD34 negative patients and there was a trend to a lower remission rate in HLADR positive patients (P=0.067). In multi-variate analysis, co-expression of CD34 and HLADR was an independent adverse factor for achieving CR (P=0.0364). CD56 expression was associated with a significantly shorter overall survival (P=0.0262), but did not affect remission rate or disease free survival. Neither TdT nor CD7 expression was associated with treatment outcome. Age (60 years or older) and cytogenetic features (classified by favorable, intermediate and unfavorable groups) were associated with a lower CR rate, shorter disease free survival and shorter OS. Patients with higher white cell counts (WBC) also had a significantly lower remission rate (P=0.0064) and OS (P=0.0127). We propose a prognostic score for achieving CR in AML patients based on age, WBC, cytogenetics and CD34/HLADR status as four independent factors. Defined by number of factors, this score system may help to stratify AML patients to alternative treatment for better outcome.     

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.     

Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents

BackgroundHigh-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is considered the standard of care for multiple myeloma (MM) patients <65 years. Safety and outcome of ASCT for patients >65 years is currently uncertain, especially since the introduction of novel agents for induction and maintenance therapy. Furthermore, there are no conclusive data available on risk assessment in elderly patients treated with HDT.Patients and methodsWe retrospectively analyzed 202 patients ≥60 years with newly diagnosed MM who underwent ASCT at our institution. Patients were stratified by age into three groups (60–64, 65–69 and 70–75 years). For safety assessment, we compared data about hospitalization, hematopoetic reconstitution and early mortality. Remission before and after ASCT was analyzed according to age and application of novel agents. Event-free (EFS) and overall survival (OS) were analyzed to identify impact of age, remission before/after ASCT and maintenance therapy as well as ISS score and cytogenetic aberrations on outcome in elderly patients.ResultsThe assessment of safety, remission before/after ASCT as well as EFS and OS showed no significant differences between the three groups (median EFS: 60–64 years: 27 months; 65–69 years: 23 months; 70–75 years: 23 months; median OS: not reached). Patients receiving novel agents as part of induction therapy achieved significantly higher nCR + CR rates than patients treated without novel agents. In Cox regression analysis, ISS and cytogenetics as well as remission after ASCT had the highest prognostic impact on EFS and OS. Maintenance therapy was associated with longer EFS in uni- and multivariate analyses.ConclusionASCT is feasible for selected patients >65 and >70 years without increased mortality. Age at transplantation has no prognostic significance on outcome after ASCT. Novel agents during induction therapy and maintenance therapy improves outcome of older patients eligible for ASCT. ISS and cytogenetic analysis should be carried out routinely for risk assessment.     

MicroRNA-181b-5p insufficiency predicts treatment response failure risk and unfavorable event-free survival as well as overall survival in acute myeloid leukemia patients

The present study aimed to explore the correlation of microRNA (miR)-181b-5p expression with treatment response and long-term prognosis in acute myeloid leukemia (AML) patients. miR-181b-5p was detected in the bone marrow of 84 AML patients before therapy. After induction therapy, the patients exhibiting complete remission (CR) were recorded. Next, event-free survival (EFS) and overall survival (OS) were calculated. miR-181b-5p had excellent potential to discriminate AML patients from healthy donors [area under the curve (AUC): 0.922, 95% confidence interval (CI): 0.873-0.971)]. In addition, miR-181b-5p expression was decreased in AML patients with the FLT3-ITD mutation (P=0.032) or WT1 mutation (P=0.017) when compared to AML patients without these genetic mutations. Meanwhile, miR-181b-5p expression was negatively correlated with the National Comprehensive Cancer Network (NCCN) risk classification of AML (P=0.036). Furthermore, miR-181b-5p expression was elevated in CR AML patients compared to non-CR AML patients (P=0.030). Moreover, higher miR-181b-5p expression was associated with favorable accumulating EFS (P=0.001) and OS (P=0.024). In addition, higher miR-181b-5p expression was independently associated with better EFS (hazard ratio: 0.698, P=0.012). In conclusion, miR-181b-5p insufficiency is associated with induction therapy response failure, unfavorable accumulating EFS and OS in AML patients.     

Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia.

The purpose of our study was (i) to evaluate the impact of all-trans retinoic acid (ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged >or=61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day +3 after the initiation of chemotherapy (ATRA-arm, n=122) or no ATRA (standard-arm, n=120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n=31) or 1-year oral maintenance therapy (n=30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA- and the standard-arm (52 vs 39%; P=0.05). Event-free (EFS) and overall survival (OS) were significantly better in the ATRA-compared to the standard-arm (P=0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (P<0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML.     

Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML.

The aim of this study was to compare the pattern of karyotype abnormalities of therapy-related acute myeloid leukemia (t-AML) (n=93) with de novo AML (n=1091), and to evaluate their impact on prognosis. Favorable, intermediate, and unfavorable cytogenetics were observed in 25.8, 28.0, and 46.2% of t-AML, and in 22.2, 57.3, and 20.4% of de novo AML. The median overall survival (OS) was shorter in t-AML than in de novo AML (10 vs 15 months, P=0.0007). Favorable and unfavorable cytogenetics had a prognostic impact with respect to OS in both t-AML (P=0.001 and 0.0001) and de novo AML (P<0.0001 and <0.0001). To define the overall prognostic impact of cytogenetics and t-AML, a multivariate Cox's regression analysis was performed for OS with favorable cytogenetics, unfavorable cytogenetics, t-AML, age, and white blood cell (WBC) count as covariates. All parameters proved to be independently related to OS (P=0.001 for t-AML, P<0.0001 for all other parameters). Within patients with t-AML, there were significant correlations between OS and both unfavorable (P<0.0001) and favorable cytogenetics (P=0.001), while age and WBC count had no impact on OS. In conclusion, these data indicate that cytogenetics are an important prognostic parameter in t-AML. Furthermore, t-AML is an unfavorable factor independent of cytogenetics with respect to survival.