维奈克拉联合阿扎胞苷治疗急性髓系白血病合并多发性骨髓瘤1例并文献复习

目的探讨维奈克拉联合阿扎胞苷治疗急性髓系白血病(AML)合并多发性骨髓瘤(MM)患者的效果。方法回顾性分析2020年10月南京中医药大学附属苏州市中医医院收治的1例AML合并MM患者的临床资料, 并复习相关文献。结果患者, 女性, 72岁, 以血细胞减少起病。综合检查确诊为AML合并MM, 行减低剂量地西他滨联合来那度胺治疗失败后采用维奈克拉联合阿扎胞苷治疗, 获得AML完全缓解, MM非常好的部分缓解, 且耐受性良好, 随访截至2022年5月患者疾病无进展。结论对于AML合并MM患者, 维奈克拉联合阿扎胞苷可能是一种安全有效的治疗选择。     

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。     

维奈克拉联合阿扎胞苷治疗老年人急性髓系白血病五例并文献复习

目的:观察维奈克拉联合阿扎胞苷治疗老年人急性髓系白血病（AML）效果及相关不良反应。方法:回顾性分析2019年4月至2020年4月华中科技大学协和深圳医院收治的5例应用维奈克拉联合阿扎胞苷治疗的老年AML患者临床资料，结合相关文献进行复习。结果:5例AML患者中有3例预后不良，通过维奈克拉联合阿扎胞苷治疗后3例达完全缓解，血液学不良反应主要为发热性中性粒细胞缺乏、血小板减少，非血液学不良反应主要为皮疹、恶心、便秘等胃肠道症状，耐受性良好。结论:维奈克拉联合阿扎胞苷治疗不适合接受常规化疗的老年AML患者缓解率高、早期死亡率低，且耐受性良好，可作为老年AML患者的一种新的治疗选择。     

维奈克拉联合吉瑞替尼和阿扎胞苷治疗急性髓系白血病2例并文献复习

目的探讨使用维奈克拉联合吉瑞替尼和阿扎胞苷方案治疗老年难治和继发性急性髓系白血病(AML)患者的效果及安全性。方法回顾性分析上海交通大学医学院附属瑞金医院2例采用维奈克拉联合吉瑞替尼和阿扎胞苷方案治疗的老年难治和继发性AML患者的临床资料, 并进行文献复习。结果 2例患者经骨髓穿刺、流式细胞术、基因检测等确诊为AML, 均有FLT3-ITD及TKD基因突变。采用维奈克拉联合吉瑞替尼和阿扎胞苷方案治疗, 1例患者初步疗效达部分血液学改善的完全缓解(CRh), 1例达部分缓解(PR)。1例发生Ⅳ级骨髓抑制、细菌感染性发热, 1例骨髓抑制期数次出现严重肺部感、肠道感染, 均经抗感染治疗后好转, 无明显出血等其他并发症。结论维奈克拉、吉瑞替尼和阿扎胞苷三药联合方案治疗FLT3阳性的AML安全有效, 值得进一步通过扩大样本的临床试验进行探索。     

维奈克拉联合阿扎胞苷治疗伴t(6；9)急性髓系白血病1例并文献复习

目的提高对维奈克拉联合阿扎胞苷治疗伴t(6;9)急性髓系白血病(AML)的认识。方法回顾性分析宁夏医科大学总医院2020年7月收治的1例接受维奈克拉联合阿扎胞苷治疗的伴t(6;9)AML患者的临床资料, 并复习相关文献。结果患者以发热、皮下结节为临床表现, 结合骨髓细胞形态学、免疫学、遗传学、分子生物学检查, 诊断为AML-M2a伴t(6;9), 基因检测提示DEK-CAN、TP53、DNMT3A、ASXL1、TET2、FLT3-ITD均阳性。患者对常规化疗无效, 因合并严重肺部感染而接受维奈克拉联合阿扎胞苷治疗获得完全缓解, 患者家属拒绝行异基因造血干胞移植, 错过最佳治疗时机, 原发病复发后最终放弃治疗。结论伴t(6;9)AML治疗难度大, 预后极差, 常规化疗无效时维奈克拉联合阿扎胞苷治疗达完全缓解后, 桥接造血干细胞移植可作为此类患者的最佳治疗选择。     

替雷利珠单抗桥接脐血移植治疗复发难治急性髓系白血病1例并文献复习

目的探讨替雷利珠单抗联合脐血移植在复发难治急性髓系白血病(AML)中的效果。方法回顾性分析2021年11月苏州大学附属第一医院收治的1例复发难治AML患者再诱导治疗失败后使用替雷利珠单抗桥接脐血移植的诊治过程。结果患者, 男性, 59岁, 诊断为复发难治AML。初始予地西他滨+维奈克拉方案诱导化疗后达完全缓解, 后予地西他滨+中剂量阿糖胞苷、中剂量阿糖胞苷+伊达比星等方案巩固治疗。16个月后疾病复发, 先后予克拉屈滨+阿扎胞苷+维奈克拉联合化疗和高三尖杉酯碱+阿糖胞苷+粒细胞集落刺激因子方案再诱导化疗均未缓解, 之后使用替雷利珠单抗治疗, 肿瘤负荷明显降低, 桥接脐血移植后获得完全缓解。移植后给予阿扎胞苷维持治疗。随访9个月, 患者持续缓解, 无严重移植相关并发症。结论替雷利珠单抗联合脐血移植挽救性治疗复发难治AML具有潜在应用价值。     

维奈克拉联合阿扎胞苷桥接异基因造血干细胞移植治疗难治急性单核细胞白血病一例并文献复习

目的:探讨bcl-2抑制剂维奈克拉联合阿扎胞苷用于难治急性单核细胞白血病患者行异基因造血干细胞移植（allo-HSCT）前桥接治疗的可行性。方法:回顾性分析湖北医药学院附属人民医院2019年11月收治的1例接受维奈克拉联合阿扎胞苷桥接allo-HSCT移植的难治急性单核细胞白血病患者资料,并复习相关文献。结果:患者为30岁女性,初诊确诊为急性单核细胞白血病,DNMT3A、IDH2、RUNX1和BCOR基因突变阳性,采用地西他滨+DA、FLAG、阿扎胞甘+HAG+依托泊苷方案联合化疗后未达到完全缓解。予维奈克拉联合阿扎胞苷后患者获得完全缓解,微小残留病转阴,接受父供女单倍体allo-HSCT巩固治疗。术后患者造血恢复,呈完全供者植入。至截稿前无复发生存1年余。结论:难治急性单核细胞白血病存在多药耐药,单纯化疗效果差。bcl-2抑制剂维奈克拉联合阿扎胞苷治疗后桥接allo-HSCT安全有效,可能延长患者无复发生存时间。     

Venetolclax联合阿扎胞苷治疗去甲基化药物单药治疗失败的老年急性白血病/高危骨髓增生异常综合征三例

老年是急性髓细胞白血病(acute myeloid leukemia,AML)的不良预后因素[1].60～69 岁患者的5 年生存率为13％,而70～79 岁患者的5 年生存率仅为3％ [2].老年AML 的治疗具有挑战性.如阿扎胞苷(azacitidine,AZA)和地西他滨等DNA去甲基化药物(hypomethyl...     

急性髓系白血病的靶向治疗:哪些药物真正改善了患者的预后?

急性髓系白血病(AML)是一种高度异质性的髓系血液肿瘤,目前主要根据重现性的遗传学和分子生物学异常进行危险度分层和治疗,这些特征是靶向治疗的天然靶点.近年来新型靶向药物不断推陈出新,然而经过多中心随机临床试验证实能改善患者总生存或无事件生存的靶向治疗药物仍然相当有限.目前证据相对充分的药物主要包括全反式维甲酸、亚砷酸、midostaurin、enasidenib、地西他滨、阿扎胞苷和人源化重组抗CD33单克隆抗体gemtuzumab.文章将就AML靶向治疗的必要性、局限性、发展以及上述能改善AML预后的药物作一介绍.     

费城染色体阳性急性髓系白血病3例并文献复习

目的分析费城染色体阳性急性髓系白血病(Ph+ AML)的临床特点。方法收集2021年9月至2022年9月盐城市第一人民医院收治的3例Ph+ AML患者资料, 分析诊疗经过, 并复习相关文献。结果 3例患者经形态学及免疫分型检查诊断为急性髓系白血病(AML), 且检测到t(9;22)。其中例2合并近四倍体染色体核型, 例3合并+8号染色体。例1及例3均检测到BCR-ABL p210;例2 BCR-ABL检测阴性, 考虑与其复杂核型相关。例1检测到IDH1突变, 例2合并WT1高表达(表达量2.28%), 且检测到RUNX1、IDH1、STAG2突变。例1采用传统"3+7"方案化疗后达完全缓解(CR), 后因经济原因于第2个周期巩固治疗后放弃, 仅口服达沙替尼, 2022年7月28日复发后死亡;例2采用伊马替尼、阿扎胞苷联合HAG(高三尖杉酯碱、阿糖胞苷、粒细胞集落刺激因子)方案化疗后达CR, 截至2022年9月仍处于缓解状态;例3采用伊马替尼、阿扎胞苷联合维奈克拉治疗未达CR, 截至2022年9月仅口服伊马替尼靶向治疗。结论 Ph+ AML发病率较低, 预后不佳, 目前尚无统一治疗方案,...     

老年人急性髓系白血病治疗新进展:第56届美国血液学会年会报道

急性髓系白血病(AML)是一种老年性疾病,第56届美国血液学会(ASH)年会上老年人AML治疗是一个焦点,到目前为止,是采用传统化疗方案还是采用去甲基化治疗或采用新药治疗仍然没有定论,文章就此方面进展进行总结.     

Targeted therapy in oncology: the agony and ecstasy of personalized medicine

Cloretazine is a new sulfonylhydrazine alkylating agent with antileukemic activity. Phase I studies have shown myelosuppression to be the dose limiting toxicity in both solid tumors and leukemias. A large Phase II study of single agent cloretazine (600 mg/m²) confirmed its activity in patients with relapsed acute myeloid leukemia, and in elderly patients with previously untreated acute myeloid leukemia or myelodysplastic syndrome. It also confirmed the limited nonhematological toxicity, even in elderly patients. Cloretazine can be safely combined with cytarabine, and this combination regimen is currently being tested in a large Phase III study in patients with relapsed acute myeloid leukemia. Cloretazine is a promising new antileukemic agent that may be incorporated into an intensive combination regimen.     

Cloretazine for the treatment of acute myeloid leukemia

Cloretazine is a new sulfonylhydrazine alkylating agent with antileukemic activity. Phase I studies have shown myelosuppression to be the dose limiting toxicity in both solid tumors and leukemias. A large Phase II study of single agent cloretazine (600 mg/m2) confirmed its activity in patients with relapsed acute myeloid leukemia, and in elderly patients with previously untreated acute myeloid leukemia or myelodysplastic syndrome. It also confirmed the limited nonhematological toxicity, even in elderly patients. Cloretazine can be safely combined with cytarabine, and this combination regimen is currently being tested in a large Phase III study in patients with relapsed acute myeloid leukemia. Cloretazine is a promising new antileukemic agent that may be incorporated into an intensive combination regimen.     

血管免疫母细胞性T细胞淋巴瘤继发急性髓系白血病三例并文献复习

目的 探讨血管免疫母细胞性T细胞淋巴瘤（AITL）继发急性髓系白血病（AML）的临床特征、发病机制、诊断、治疗及预后。方法 回顾性分析3例AITL继发AML患者的临床资料,包括免疫组织化学、流式细胞术结果,并进行文献复习。结果 3例均为老年男性患者,初诊为AITL,分别于治疗后的8、14及34个月继发AML。继发AML后,1例未治疗于10个月后死亡,1例积极治疗后于13个月后死亡,另1例失访。结论 AITL有继发AML的风险,其发病机制目前尚不清楚,预后较差。     

Therapy for acute myeloid leukemia and acute lymphoblastic leukemia in adults

Using intensive induction chemotherapy, primarily with combinations of an anthracycline and cytarabine, complete remission rates of greater than 70% are now achieved in patients with acute myeloid leukemia under the age of 60 years. The treatment of elderly patients with acute myeloid leukemia is difficult and remains controversial. The prognosis for both adults and children with acute lymphoblastic leukemia has improved as more extensive chemotherapy regimens have been used. Recently, a group of leukemias have been identified that have features of both acute lymphoblastic leukemia and acute myeloid leukemia, and these are referred to as biphenotypic or hybrid leukemias. These hybrid leukemias represent an important subgroup, which appears to have a worse outcome regardless of the therapy administered.     

老年急性髓细胞白血病的临床、生物学特征及治疗进展

 急性髓细胞白血病（AML）的诸多预后不良因素中,年龄≥60岁是一个重要的不良预后指标。原因除了与老年患者本身的生理特点有关,更重要的是由于其白血病细胞的生物学特征与青年患者显著不同。现就老年AML患者的临床、生物学特征及在此基础上的治疗进展进行综述。     

High-dose homoharringtonine versus standard-dose daunorubicin is effective and safe as induction and post-induction chemotherapy for elderly patients with acute myeloid leukemia: a multicenter experience from China

The purpose of the study was to compare the antitumor efficacy and safety profile of high-dose homoharringtonine as induction and post-induction therapy compared to either standard-dose homoharringtonine or daunorubicin in elderly patients with newly diagnosed acute myeloid leukemia. A total of 254 patients, age range 60–77 years received induction and post-induction therapy containing daunorubicin, standard-dose homoharringtonine, or high-dose homoharringtonine. After one course of induction therapy, the overall complete remission rate was similar between treatment arms (58.7%, P = .92). Among 161 patients with acute myeloid leukemia (non-M5 subtype), estimated median overall survival was 39, 29, and 37 months, respectively, in the daunorubicin, standard-dose homoharringtonine, and high-dose homoharringtonine treatment groups (P = .53). In the 93 patients with acute myeloid leukemia-M5 subtype, there was a significant difference in estimated median overall survival: 24, 24, and 52 months, respectively, in the daunorubicin, standard-dose homoharringtonine, and high-dose homoharringtonine treatment groups (P = .003). There was no significant difference in drug-related adverse events between treatment arms. High-dose homoharringtonine does not clearly increase the complete remission rate of elderly patients with acute myeloid leukemia. However, in the subset of elderly patients with acute monocytic leukemia, high-dose homoharringtonine as a first-line regimen prolonged overall survival with minimal toxicity.     

国产地西他滨治疗老年急性髓系白血病的疗效及安全性

目的:探讨以国产地西他滨为基础的化疗方案治疗老年急性髓系白血病（AML）的临床疗效及安全性。方法:回顾性分析2013年1月-2016年2月收治的老年急性髓系白血病患者29例,根据其是否使用国产地西他滨分组,对比评定疗效。结果:地西他滨组和传统方案组的完全缓解率分别为60.0%（6/10）和35.7%（5/14）,差异有统计学意义（P＜0.05）;同时比较两组的总生存期（OS）,差异有统计学意义（P＜0.05）。80%的老年AML患者在使用以国产地西他滨为基础的化疗方案治疗过程出现不同程度的不良反应,多为Ⅰ-Ⅱ级,少数患者发生了Ⅲ-Ⅳ级不良反应,主要为中性粒细胞减少和血小板减少。结论:以国产地西他滨为基础的化疗方案有较高的缓解率,且延长生存期。     

老年急性髓细胞白血病的临床特点

根据老年急性髓细胞白血病的临床特点,寻求治疗老年急性髓细胞性白血病的有效措施。回顾性分析25例老年急性髓细胞白血病的临床资料,治疗按个体差异分为姑息治疗组、小剂量HA化疗组及标准剂量联合化疗组,并对其治疗效果进行比较。老年急性髓细胞白血病,具有独特的生物学及临床特征;姑息治疗组3例,CR率为0;小剂量HA化疗组7例,CR率28.6%;标准剂量联合化疗组15例,CR率33.3%。标准剂量联合化疗组的CR率及平均存活期均高于小剂量HA化疗组,而诱导期死亡率则低于小剂量HA化疗组,但其差异均无统计学意义。对老年急性髓细胞性白血病的化学治疗应个体化,并辅以积极的综合治疗,才能有望提高疗效。     

Hematological malignancies

The same progress in the recent therapeutic strategy for older adults with hematological malignancies has also been seen in younger adults. The standard initial therapy for elderly acute promylocytic leukemia is the combination with all-trans retinoic acid and anthracyclines. For other acute myeloid leukemias (AML), many trials of combination chemotherapy have not improved the outcome of elderly patients. Gemtuzumab ozogamicin,which is an immunoconjugate binding to CD 33 on the surface of AML blasts, has produced good results for elderly patients in either monotherapy or in combination with conventional chemotherapeutic drugs. One of the BCR-ABL tyrosine kinase inhibitors, imatinib mesylate, is active for elderly Philadelphia-positive leukemia including acute lymphoblastic leukemia and chronic myeloid leukemia. In the treatment of elderly diffuse large B cell lymphoma, combination of rituximab and cyclophosphamide+doxorubicin+vincristine+prednisone (CHOP) has become the therapy of choice based upon a Groupe d'Etude des Lymphomes de l'Adulte (GELA) trial even though there are some other trials for elderly patients such as dose-dense CHOP therapy. For follicular lymphoma, combination therapies of rituximab and cytotoxic drugs such as R-CHOP and R-CVP are also considered as promising therapies. For the management of multiple myeloma, high-dose chemotherapy, mainly melphalan with autologous stem cell transplantation, has become the standard treatment even for elderly patients less than 65 years of age.