大剂量阿糖胞苷巩固治疗核心结合因子相关急性髓系白血病的疗效及安全性分析

目的探讨大剂量阿糖胞苷巩固治疗核心结合因子相关急性髓系白血病的疗效、安全性。方法对76例经过诱导治疗的急性髓系白血病患者进行阿糖胞苷巩固治疗,治疗结束后进行为期6~60个月的随访,观察患者的生命状态及病情、不良反应。结果 76例患者共存活52例,死亡24例;其中,6例在骨髓抑制期出现颅内出血死亡,18例出现AML复发死亡。进行阿糖胞苷巩固治疗期间或者随访期39例患者出现复发,M4Eo型6例,M2b型33例;21例在巩固治疗2个疗程结束后复发,18例在3个疗程结束后复发。Kaplan生存法分析后发现5年总生存时间(OS)为(68.2±12.7)%,预期5年无病生存时间(DFS)为(41.8±12.3)%,预期5年复发率为(55.9±14.8)%。M4Eo型和M2b型AML复发率间的差异有统计学意义(P0.05)。患者均表现为不同程度的骨髓抑制现象,以Ⅳ度最为多见,特别是白细胞、血小板的减少最为明显。白细胞计数范围为(0.04~0.68)×109/L、中位值为0.4×109/L,血小板计数范围为(2~16)×109/L、中位值为6×109/L,血红蛋白最低值(68.2±6.8)g/L。治疗过程中,76例患者的白细胞、血小板及中性粒细胞计数的最低值均达到Ⅳ度;血红蛋白最低值Ⅱ度所占比例为9.9%、Ⅲ度所占比例为90.1%。所有患者在粒缺期间出现发热等感染迹象,肺部感染6例次,菌血症感染30例次,少数患者表现为不明原因的粒缺伴发热。经过及时的抗生素药物治疗,患者病情均缓解,未出现严重感染致死的病例。肝脏系统不良反应比较轻微,其他系统如皮肤、胃肠道等都出现不同程度的不良反应,但都在可接受的范围内,而且对应的治疗可明显缓解这些不适症状。结论阿糖胞苷巩固治疗可促进CBF-AML的缓解,提高5年无病生存率;不良反应主要是骨髓抑制等,对症治疗可明显缓解,用药较为安全。     

Ph染色体阳性白血病患者经伊马替尼治疗后行异基因造血干细胞移植的疗效观察

目的探讨Ph染色体阳性白血病患者经伊马替尼治疗后行异基因造血干细胞移植的疗效。方法回顾性分析2001年6月至2005年6月北京大学人民医院血液病研究所住院的难治性Ph染色体阳性的39例白血病患者经伊马替尼治疗后再行异基因造血干细胞移植的效果,观察伊马替尼对造血重建、移植物抗宿主病(GVHD)、总存活率(OS)、无病存活率(DFS)、复发率和移植相关并发症的影响。结果伊马替尼治疗后,18例患者血液学完全缓解,9例骨髓缓解,4例部分缓解,4例无效或疾病进展,总有效率79.49%,无重度非血液学毒性反应;移植后中性粒细胞和血小板植活中位时间分别为14d和13.5d;Ⅱ~Ⅳ度和Ⅲ~Ⅳ度急性GVHD累积发生率分别为61.53%和15.38%;根据对伊马替尼治疗的效应分为完全缓解组和未完全缓解组,其3年预期OS和DFS分别为(73.51±9.61)%对(36.36±14.50)%和(61.28±12.37)%对(31.25±13.98)%,3年累积复发率为20.41%对75.00%;4例患者死于重度移植相关并发症。结论应用伊马替尼后行异基因造血干细胞移植是一种安全、有效的治疗难治性Ph染色体阳性白血病的方法,尤其达完全缓解后行移植,可望提高此类患者的临床治愈率。     

伊马替尼联合化疗治疗成人Ph阳性急性淋巴细胞白血病的疗效评估

目的:评估伊马替尼联合化疗方案治疗成人Ph染色体阳性急性淋巴细胞白血病(Ph+ALL)的疗效。方法:回顾性分析76例初治成人Ph+ALL的病例资料,通过比较应用伊马替尼联合化疗方案的联合组(56例)及单纯化疗组(20例)的完全缓解率、复发率、总生存(OS)时间、无病生存(DFS)时间等指标,评估伊马替尼联合化疗治疗成人Ph+ALL的疗效。结果:联合组和单纯化疗组的诱导完全缓解率分别为85.7%(48/56)和45.0%(9/20),2组差异有统计学意义(P0.05)。联合组和单纯化疗组的血液学缓解持续时间分别为(6.8±5.6)个月和(5.7±4.5)个月,复发率分别为60.7%(34/56)和85.0%(17/20),2组差异无统计学意义。联合组和单纯化疗组的中位OS分别为12(2~39)个月和4.5(0~17)个月,1年、2年OS率分别为50.0%、18.0%和10.0%、0,2组差异有统计学意义(P0.05)。联合组和单纯化疗组的中位DFS分别为7(0~35)个月和3(1~13)个月,1年、2年DFS率分别为31.6%、17.4%和11.6%、0,2组差异无统计学意义。联合组和单纯化疗组的常见不良反应为骨髓抑制、感染、出血、胃肠道反应、肝功能损害、乏力,2组不良反应差异无统计学意义。结论:在成人Ph+ALL患者治疗中,采用伊马替尼联合化疗方案,可以提高完全缓解率及改善预后,并且不增加治疗相关毒副反应。     

难治性急性髓系白血病异基因造血干细胞移植治疗疗效分析

目的 :评价异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)治疗复发难治性急性髓系白血病(refractory acute myeloid leukemia,r AML)的疗效。方法:收集2000年1月至2015年6月在上海交通大学医学院附属瑞金医院和海军医科大学附属长海医院接受allo-HSCT治疗的r AML患者73例,按移植前疾病状态分为完全缓解(complete remission,CR)组(44例)和未缓解(non-remission,NR)组(29例),随访截止时间2015年12月31日,分析allo-HSCT后非复发死亡率(non-relapsing mortality,NRM)、粒细胞及血小板植入时间、移植物抗宿主病(graft versus host disease,GVHD)发生率、2年总生存(overall survival,OS)率、2年无病生存(disease-free survival,DFS)率等数据。结果 :所有患者移植后获得造血功能重建,中位随访时间470(230.5,1 011.5)d。所有患者2年OS率为56.5%,2年DFS率为41.8%。移植前CR组和NR组2年OS率分别为64.0%和45.6%(P=0.345),2年DFS率分别为45.6%和35.6%(P=0.393);移植前CR组和NR组NRM、粒细胞及血小板植入时间、GVHD发生率差异均无统计学意义。结论:allo-HSCT是治疗r AML的有效治疗手段,长期DFS为41.8%,移植前疾病状态是否达到CR对移植后的预后无显著影响。     

高龄子宫内膜癌患者的综合治疗

目的分析综合治疗对于高龄子宫内膜癌患者的疗效及生存情况影响。方法回顾性分析2004年3月至2009年5月在该院住院的96例高龄子宫内膜癌患者的临床资料,根据病理特点、临床分期及治疗方法将患者分为单纯手术治疗(36例)、手术加放疗组(22例)、综合治疗组(38例);观察对比患者治疗后的疗效、复发情况。结果 96例患者随访至2014年5月,随访率为89.6%,16例(16.7%)患者死亡失访。按寿命表法计算三组患者的3年、5年生存率(OS)及无瘤生存率(DFS),结果发现3年OS为93.8%,3年DFS为93.8%;5年OS为88.5%,5年DFS为73.6%。21例(21.9%)出现癌症复发,手术加放疗组和综合治疗组的复发率均高于单纯手术组(χ2=5.047,P0.05)。手术加放疗组和综合治疗组患者的5年OS及DFS均高于单纯手术组(P0.05),但手术加放疗组与综合治疗组两组间的5年OS及DFS比较无显著差异(P0.05)。结论与单纯手术治疗相比,手术加放疗或综合疗法可显著高龄子宫内膜癌可显著提高患者的5年OS及5年DFS,明显改善患者预后。     

伊沙佐米全口服方案治疗复发难治多发性骨髓瘤的疗效分析

观察伊沙佐米为主的全口服方案居家治疗多药耐药的复发/难治多发性骨髓瘤(MM)的疗效及安全性。回顾分析2018年8月至2020年1月于苏州大学附属第一医院就诊并接受伊沙佐米为主的全口服方案化疗的复发/难治MM患者38例, 观察治疗后的疗效及不良反应。在多药耐药的复发难治MM患者中, 伊沙佐米联合全口服方案的总体反应率(ORR)为36.8%, 其中非常好的部分缓解(VGPR)以上23.7%, 完全缓解(CR)5.3%。伊沙佐米联合来那度胺及地塞米松(IRD)方案组ORR为41.7%。所有患者的中位无进展生存(PFS)为 5个月, 中位总生存(OS)期为 7.5个月。伊沙佐米联合全口服方案二线治疗有效缓解率为50%, 三线治疗有效缓解率为40%;四线及以上有效缓解率仅为12.5%。硼替佐米耐药组的有效缓解率达29.0%, 来那度胺耐药组的有效率较高38.0%, 而双重耐药组的缓解率仍达到了21.4%。伊沙佐米治疗中发生3～4级血液学不良反应的发生率为21%(8例), 主要血液学毒性为血小板及白细胞计数降低, 非血液学不良反应主要为乏力和腹泻。在多药耐药复发/难治MM患者治疗上, 以伊沙佐米为...     

85例18岁以下急性髓细胞白血病的疗效分析

目的研究初治18岁以下急性髓细胞白血病(AML)的疗效及影响因素,以期进一步提高儿童AML无病生存(DFS)率。方法回顾性研究分析85例年龄18岁以下AML患者的疗效,采用Kaplan-Meier生存曲线评估患者的无病生存(DFS),单因素分析用Log-rank检验,多因素分析用Cox回归模型。结果85例患者中,1个疗程完全缓解(CR)者46例(54.1%),总CR率为75.3%。4年累积DFS率(25.8±9.7)%,4年累积复发率(73.9±9.9)%。单因素分析显示血红蛋白≥90g/L、>1个疗程达CR及巩固疗程<6个是影响患者DFS的危险因素。多因素分析显示初诊时骨髓白血病细胞比例>60%、>1个疗程达CR及巩固疗程<6个与患者DFS期短显著相关(P<0.05)。同时具有1个疗程达CR和巩固疗程≥6个的患者4年累积DFS率(49.5±16.3)%。结论骨髓原始细胞比例≤60%和1个疗程达CR及巩固疗程≥6个的18岁以下AML患者DFS期显著延长。     

改良短疗程方案治疗成人急性淋巴细胞白血病疗效观察

目的:比较成人急性淋巴细胞白血病(ALL)患者不同疗程诱导化疗方案治疗的疗效。方法:回顾性分析2007-01-2013-12初治的ALL患者71例,采用SPSS19.0统计学软件分析有关数据。结果:1根据诱导缓解治疗方案分为改良短疗程方案、标准疗程方案2组,2组的1个疗程完全缓解率分别为78.8%和89.5%,复发率分别为42.4%和47.4%。2改良短疗程方案组中位总生存(OS)12(1~60)个月,中位无进展生存(DFS)9(0~59)个月;标准疗程方案组中位OS 12(1~74)个月,中位DFS 7(0~73)个月。2组的3年OS分别为27.6%和18.0%,3年DFS分别为17.8%和11.5%。3改良短疗程方案组及标准疗程方案组的粒细胞缺乏发生率分别为97.0%和100%,粒细胞缺乏持续时间分别为(10.7±2.4)d和(14.8±3.2)d。2组纤维蛋白原下降发生率分别为46.7%和41.7%,肝功能损害发生率分别为6.1%和10.5%。结论:2种方案在1个疗程完全缓解率、复发率、DFS和OS方面无差异,但诱导治疗采用改良短疗程方案较标准疗程方案不良反应少。     

宿迁地区684例65岁以上乳腺癌患者的临床病理特征

目的调查分析宿迁地区老年性乳腺癌临床病理特征。方法收集2012年1月至2017年1月宿迁地区诊治的65岁以上的乳腺癌病例,对其临床病理特征及治疗方法进行分析并总结。结果根据患者的病理分型,一组选择直接手术,另一组采用新辅助治疗,对比两组1、3、5年无病生存率(DFS)和总生存率(OS)。684例65岁以上患者中,132例(19. 30%)为Luminal A型;Luminal B型324例(47. 37%),其中Luminal BⅠ型283例,Luminal BⅡ型(所谓三阳性)41例;Her-2过表达型132例;三阴性乳腺癌(TNBC)96例。306例新辅助治疗患者的近期疗效:新辅助化疗的患者中达到病理完全缓解(p CR)24例,完全缓解(CR)33例,部分缓解(PR)110例,稳定(SD)80例,疾病稳定(PD)19例;新辅助内分泌患者中达到p CR 3例,CR 2例,PR 6例,SD 2例,PD 20例;新辅助靶向治疗患者中达到p CR 1例,CR 1例,PR 5例,SD 0例,PD 0例。新辅助治疗患者的远期疗效:1年DFS为100%,2年DFS为84. 72%,3年DFS为76. 31%,5年DFS为66. 41%;1年OS为100%,2年OS为94. 72%,3年OS为86. 31%,5年OS为76. 41%。而直接手术的378例患者1年DFS为92. 73%,2年DFS为76. 59%,3年DFS为60. 63%,5年DFS为57. 22%;1年OS为100%,2年OS为85. 65%,3年OS为74. 71%,5年OS为48. 33%。结论老年性乳腺癌患者经历新辅助后再实施手术者DFS、OS明显优于直接手术者;宿迁地区老年性乳腺癌Luminal B型患者多于Luminal A型患者。     

免疫抑制联合脐血输注治疗重型再生障碍性贫血

目的 :评价采用免疫抑制联合脐血输注治疗重型再生障碍性贫血(severe aplastic anemia,SAA)的疗效。方法:分析2010年5月至2016年5月间我院收治的19例接受氟达拉滨、兔抗胸腺细胞球蛋白(anti-thymocyte globulin,ATG)和环孢素(cyclosporin A,Cs A)免疫抑制并联合脐带血输注患者的临床资料,统计造血恢复情况、治疗反应、治疗相关死亡率、总生存(overall survival,OS)率等。结果:中性粒细胞恢复的中位时间仅为22(13,36)d,血小板恢复的中位时间为180(48,217)d。6例患者有短暂性或持续性脐带血植入,有脐带血植入患者中位血小板恢复时间显著快于无脐带血植入的患者(46 d比206 d,P=0.006)。3个月内治疗相关死亡率仅为5.3%,12个月的累积反应率为88.7%±7.5%,其中完全缓解(complete remission,CR)率达72.2%±10.6%。预期2年和5年OS率分别为94.7%±5.1%和78.9%±15.0%。结论:免疫抑制联合脐血输注治疗SAA安全有效,脐带血输注可能加速免疫抑制治疗SAA患者的造血恢复,有助于降低早期死亡率,增加CR率,保证患者较高的OS率和良好的生活质量。     

异基因造血干细胞移植治疗成人费城染色体阳性急性淋巴细胞性白血病的疗效分析

目的:探讨异基因造血干细胞移植(allo-HSCT)治疗成人费城染色体阳性(Ph+)的急性淋巴细胞白血病(ALL)的疗效。方法:回顾性分析经VDP(长春新碱、蒽环类、糖皮质激素)±C(环磷酰胺或异环磷酰胺)±L(左旋门冬酰胺酶或培门冬酶)方案诱导化学治疗(化疗)的12例Ph+ALL患者。初始诱导缓解患者在等待移植期间进行巩固化疗,并加用伊马替尼(400～800 mg/d),与化疗同步或交替应用。初始诱导失败患者及巩固治疗期间复发患者应用Hyper-CVAD/LALA(大剂量环磷酰胺、长春新碱、多柔比星、地塞米松或米托蒽醌、阿糖胞苷)方案联合伊马替尼或达沙替尼进行再次诱导。所有患者缓解后经白消安联合环磷酰胺(Bu-Cy)或改良Bu-Cy方案预处理后进行allo-HSCT。部分患者干细胞回输后2～3个月始继续服用酪氨酸激酶抑制剂。结果:12例患者移植前均获得血液学缓解、7例获得分子学缓解。其中完全缓解(CR)1期9例、CR 2期2例、初发难治性1例。移植前11例患者应用伊马替尼;移植后5例患者应用酪氨酸激酶抑制剂,其中4例应用伊马替尼、1例应用达沙替尼。中位随访时间12.7(3～54)个月,7例患者生存,3例患者死于疾病复发,2例患者死于治疗相关并发症。所有患者均植入,移植后2年总生存率66.7%±13.6%;2年累计复发率40.6%±16.0%;2年累计非复发病死率16.7%±10.8%。首次缓解(CR1)后移植治疗的2年总生存率70.0%±14.5%;2年累计复发率40.0%±18.2%;2年累计非复发病死率20.0%±12.6%。结论:酪氨酸激酶抑制剂可能会使更多患者获得缓解,从而有机会进行allo-HSCT。CR1的生存获益更大。allo-HSCT联合酪氨酸激酶抑制剂为Ph+ALL患者有前景的治疗方案。     

Comparison of high-dose cytarabine and timed-sequential chemotherapy as consolidation for younger adults with AML in first remission: the ALFA-9802 study

To assess the value of administering timed-sequential chemotherapy (TSC; 2 therapeutic sequences separated by a 4-day interval-free chemotherapy) or high-dose cytarabine (HDAraC) cycles in consolidation therapy for acute myeloid leukemia (AML), 459 patients 15 to 50 years of age were enrolled in the prospective randomized Acute Leukemia French Association-9802 trial. Complete remission was achieved in 89%. A total of 237 patients were then randomized to either TSC consolidation (120 patients) or HDAraC consolidation cycles (117 patients). Overall, there was no significant difference between the 2 consolidation arms (5-year event-free survival [EFS]: 41% for HDAraC vs 35% for TSC), or cumulative incidence of relapse, or treatment-related mortality. Cytogenetically normal AML NPM1(+) or CEBPA(+) and FLT3-ITD(-) had the same outcome as those with favorable cytogenetics. When considering favorable and unfavorable risk groups, the trend was in favor of HDAraC. However, the difference became significant when considering intermediate cytogenetics (5-year EFS: 49% vs 29%; P = .02), especially cytogenetically normal AML (5-year EFS: 48% vs 31%; P = .04), which was related to lower relapse rate and less toxicity. This study demonstrates that TSC did not produce any benefit when used as consolidation therapy in younger adults compared with HDAraC. This trial was registered at www.clinicaltrials.gov as #NCT00880243.     

Second induction with high-dose cytarabine and mitoxantrone: different impact on pediatric AML patients with t(8;21) and with inv(16)

Patients with core binding factor acute myeloid leukemia (CBF-AML) benefit from more intensive chemotherapy, but whether both the t(8;21) and inv(16)/t (16;16) subtypes requires intensification remained to be determined. In the 2 successive studies (AML-BFM-1998 and AML-BFM-2004), 220 CBF-AML patients were treated using the same chemotherapy backbone, whereby reinduction with high-dose cytarabine and mitoxantrone (HAM) was scheduled for these cohorts only in study AML-BFM-1998 but not in AML-BFM-2004 against the background to minimize overtreatment. Five-year overall survival (OS) and event-free survival (EFS) were significantly higher and the cumulative incidence of relapse (CIR) lower in t(8;21) patients treated with HAM (n = 78) compared with without HAM (n = 53): OS 92% ± 3% versus 80% ± 6%, p(logrank)0.047, EFS 84% ± 4% versus 59% ± 7%, p(logrank)0.001, and CIR 14% ± 4% versus 34% ± 7%, p((gray))0.006. These differences were not seen for inv(16) (n = 43 and 46, respectively): OS 93% ± 4% versus 94% ± 4%, EFS 75% ± 7% versus 71% ± 9% and CIR 15% ± 6% versus 23% ± 8% (not significant). The subtype t(8;21), but not inv(16), was an independent predictor of worse outcome without HAM reinduction. Based on our data, a 5-year OS of > 90% can be expected for CBF-AML, when stratifying t(8;21), but not inv(16), patients to high-risk chemotherapy, including HAM reinduction.     

Timed sequential chemotherapy for advanced acute myeloid leukemia

Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1–3, etoposide on days 8–10 and cytarabine on days 1–3 and 8–10, was administered to 240 patients with advanced acute myelogenous leukemia (AML). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47% (CI: 38–55%) of refractory patients and 78% (CI: 70–86%) of late first relapse patients (p < 0.0001). Thirty percent of patients did not respond to therapy and 9% died from toxicity. Median duration of neutropenia was 32 days and of thrombocytopenia 29 days. Severe non hematologic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell transplantation in 17 and allogeneic transplantation in 20. Median survival of patients who were not transplanted was 7 months with 13% (CI: 7–19%) survival at 5 years. Median disease-free survival (DFS) was 9 months with 13% (CI: 6–20%) DFS at 5 years. Previous refractoriness was the main factor associated with poor prognosis for achieving CR, DFS and survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive post-remission therapy. These results confirm initial reports on TSC and show that some patients with first relapse off therapy can enjoy prolonged DFS using chemotherapy only.     

The superiority of haploidentical related stem cell transplantation over chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia in first complete remission

We report the results of a prospective, patient self-selected study evaluating whether haploidentical related donor stem cell transplantation (HRD-HSCT) is superior to chemotherapy alone as postremission treatment for patients with intermediate- or high-risk acute myeloid leukemia (AML) in first complete remission (CR1). Among totally 419 newly diagnosed AML patients, 132 patients with intermediate- and high-risk cytogenetics achieved CR1 and received chemotherapy alone (n = 74) or HSCT (n = 58) as postremission treatment. The cumulative incidence of relapse at 4 years was 37.5% ± 4.5%. Overall survival (OS) and disease-free survival (DFS) at 4 years were 64.5% ± 5.1% and 55.6% ± 5.0%, respectively. The cumulative incident of relapse for the HRD-HSCT group was significantly lower than that for the chemotherapy-alone group (12.0% ± 4.6% vs 57.8% ± 6.2%, respectively; P < .0001). HRD-HSCT resulted in superior survival compared with chemotherapy alone (4-year DFS, 73.1% ± 7.1% vs 44.2% ± 6.2%, respectively; P < .0001; 4-year OS, 77.5% ± 7.1% vs 54.7% ± 6.3%, respectively; P = .001). Multivariate analysis revealed postremission treatment (HRD-HSCT vs chemotherapy) and high WBC counts at diagnosis as independent risk factors affecting relapse, DFS, and OS. Our results suggest that HRD-HSCT is superior to chemotherapy alone as postremission treatment for AML.     

The role of maintenance chemotherapy after autotransplantation for acute lymphoblastic leukemia in first remission: single-center experience of 100 patients

A total of 100 adults with ALL in first CR received melphalan (110 mg/m(2)) with TBI followed by autologous marrow (n=35) or single-agent melphalan (200 mg/m(2)) followed by autologous blood stem cells (n=65). After adequate hematologic recovery, maintenance chemotherapy with 6-mercaptopurine, methotrexate and vincristine-prednisone was administered for 2 years. Six patients, all TBI recipients (P=0.001), died of toxicity. In total 70 patients received 6-mercaptopurine, 53 received methotrexate and 40 received vincristine-prednisone. The cumulative incidence of relapse at 7 years was 45%. The 7-year probabilities of disease-free survival (DFS) and overall survival were 45 and 48%. Age 30 years, >4 weeks to attain remission, and karyotypes t(4;11) and t(9;22) were associated with adverse outcome. Patients with 0 (standard risk), 1 (intermediate risk), and 2-3 (high risk) adverse features had 7-year cumulative incidences of relapse of 19, 53 and 82% (P<0.0001), and 7-year DFS probabilities of 73, 36 and 7% (P<0.0001). The 7-year probabilities of DFS for patients receiving 0, 1, 2 and 3 maintenance chemotherapy agents were 15, 29, 58 and 61% (P<0.0001). Maintenance chemotherapy intensity was an independent determinant of outcome in Cox analysis. Maintenance chemotherapy after autotransplantation reduces relapse and improves outcome in adult patients with ALL.     

Timed sequential chemotherapy for advanced acute myeloid leukemia

Timed sequential chemotherapy (TSC) combining mitoxantrone on days 1–3, etoposide on days 8–10 and cytarabine on days 1–3 and 8–10, was administered to 240 patients with advanced acute myelogenous leukemia (AML). Sixty one percent of patients, with a 95% confidence interval (CI) ranging from 54 to 67%, achieved complete remission (CR), including 47% (CI: 38–55%) of refractory patients and 78% (CI: 70–86%) of late first relapse patients (p < 0.0001). Thirty percent of patients did not respond to therapy and 9% died from toxicity. Median duration of neutropenia was 32 days and of thrombocytopenia 29 days. Severe non hematologic toxicity included sepsis in 45% of patients and mucositis in 27%. Post-remission therapy varied but included maintenance chemotherapy in most patients, a second course of TSC in 27, autologous stem cell transplantation in 17 and allogeneic transplantation in 20. Median survival of patients who were not transplanted was 7 months with 13% (CI: 7–19%) survival at 5 years. Median disease-free survival (DFS) was 9 months with 13% (CI: 6–20%) DFS at 5 years. Previous refractoriness was the main factor associated with poor prognosis for achieving CR, DFS and survival in a multivariate analysis. There was no difference in DFS between patients receiving the different modalities of intensive post-remission therapy. These results confirm initial reports on TSC and show that some patients with first relapse off therapy can enjoy prolonged DFS using chemotherapy only.     

Phase 1 study of quizartinib in combination with induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia

Novel therapies have potential to improve outcomes in patients with acute myeloid leukemia (AML) harboring FLT3‐ITD mutations that have high risk of relapse and poor survival following standard of care (SOC) cytarabine/anthracycline‐based induction/consolidation chemotherapy. Quizartinib is a selective and highly potent FLT3 inhibitor that has shown strong single‐agent activity in relapsed or refractory (R/R) AML. This phase 1, open‐label, sequential group dose‐escalation trial (NCT 01390337) is the first evaluating safety and tolerability of quizartinib in combination with SOC chemotherapy in newly diagnosed AML (ndAML). Nineteen patients unselected for FLT3 mutational status received one of three quizartinib dihydrochloride dose levels (DL): 60 mg/d for 7 days (DL1; n = 6), 60 mg/d for 14 days (DL2; n = 7), and 40 mg/d for 14 days (DL‐1; n = 6); administered orally starting on day 4 of chemotherapy. Median age was 43.8 years. Ten patients completed induction and consolidation. Three patients experienced dose‐limiting toxicities (DLTs): 2 at DL2 (1 pericardial effusion; 1 febrile neutropenia, decreased platelet count, and QT prolongation); 1 at DL‐1 (pericarditis). Maximum tolerated dose (MTD) was identified as DL‐1. Most common grade 3/4 adverse events were febrile neutropenia (47%), neutropenia (42%), thrombocytopenia (32%), and anemia (26%). There were no apparent additional toxicities with addition of quizartinib to chemotherapy although grade ≤1 QT prolongation was observed at MTD. Sixteen patients (84%) achieved a response; 14 (74%) composite complete response; 2 (11%) morphologic leukemia‐free state. The phase 3 QuANTUM‐First trial (NCT02668653) is further evaluating the effect of quizartinib plus SOC chemotherapy in ndAML FLT3‐ITD mutated patients.     

Impact of cytogenetics on the outcome of autotransplantation for acute myeloid leukemia in first remission: is the benefit of intensive pretransplant therapy limited to patients with good karyotypes?

A total of 81 adults with acute myeloid leukemia (AML) (47% favorable karyotypes) were autografted in first remission after melphalan-total body irradiation, having received 0 (n=7), 1 (n=19), 2 (n=51), or 3 (n=4) consolidation chemotherapy cycles before harvest. The cumulative 5-year incidences of relapse and transplant-related mortality were 37 and 17%, respectively. The actuarial 5-year probability of disease-free survival (DFS) was 46%. In Cox analysis, favorable karyotypes, increasing numbers of consolidation cycles (0 vs > or =1 or 1 vs >1), and higher nucleated cell doses were associated with lower relapse rates and higher DFS. Patients with favorable karyotypes benefited from every additional cycle of consolidation therapy (0 vs > or =1 as well as 1 vs >1). Among patients with other karyotypes, while the benefit of one cycle of consolidation was clear (0 vs > or =1), there was no obvious beneficial impact of further consolidation therapy (1 vs >1). Administration of consolidation chemotherapy prior to harvest is essential in AML. While it is possible to enhance the benefit of consolidation with favorable karyotypes by delivering two cycles, its usefulness is limited in others. In them, it may be worthwhile exploring alternatives not normally used in AML (eg high-dose cyclophosphamide) that could have antileukemic effects while permitting mobilization of stem cells.     

GIMEMA AIDA 0493 amended protocol for elderly patients with acute promyelocytic leukaemia. Long-term results and prognostic factors

To reduce toxicity in elderly patients with acute promyelocytic leukaemia, in 1997 the Gruppo Italiano Malattie Ematologiche Dell'Adulto (GIMEMA) started an amended protocol for patients aged >60years, with the same induction [all-trans retinoic acid (ATRA)+idarubicin] as in younger patients, followed by a single consolidation course (idarubicin+ cytarabine) and maintenance with intermittent ATRA. Among 60 enrolled patients, 54 (90%) achieved haematological remission and six died during induction. Four additional patients died in complete remission (CR) from haemorrhage (2) and infection (2) prior or during consolidation therapy. Eleven patients relapsed at a median time of 17·5months from CR. The 5-year overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) rates were 76·1%, 64·6% and 27·4%, respectively. Univariate analysis identified a performance score (PS)=2 as the only significant adverse prognostic factor for both OS (P=0·017) and DFS (P=0·0003). Male sex had an unfavourable impact on DFS (P=0·021) and on CIR (P=0·019), but not on OS (P=0·234). In multivariate analysis for DFS, only PS=2 retained prognostic significance (HR=4·5, P=0·0083). In conclusion, the amended GIMEMA protocol is effective, with similar relapse rate and inferior toxicity compared to the original AIDA 0493. However, considering the recent availability of effective new agents, a less aggressive approach should be tested in this setting.