老年急性髓系白血病的治疗

老年急性髓系白血病(AML)对化疗耐受性差, 早期病死率高, 化疗缓解率低。近几年, 随着AML分子机制逐渐被阐明, 一系列靶向和免疫治疗药物获批上市, 老年AML治疗模式发生了重大变化。在新药时代下, 老年AML的诊疗已经转变为分子检测指导的精准治疗。异基因造血干细胞移植(allo-HSCT)仍然是高危或中危老年AML最有潜力治愈的方法, 随着移植技术的发展和进步, allo-HSCT对老年AML患者是一种可行性选择。     

老年急性髓系白血病56例临床分析

目的探讨老年急性髓系白血病（AML）的FAB亚型分布情况、临床特点及个体化治疗的临床疗效。方法对56例初治老年AML患者的临床特点、诱导缓解及化疗进行回顾性分析;同时随机抽取非老年AML患者45例作为对照,观察二者临床特点及疗效的差异。结果老年AML组与非老年AML组FAB亚型分布均以AML-M2a为主。诱导缓解化疗1～2个疗程,老年AML组、非老年AML组完全缓解率分别为57.1%（32/56）、71.1%（32/45）,两组完全缓解率比较差异无统计学意义（P〉0.05）。老年AML组、非老年AML组诱导期病死率分别为10.7%（6/56）、6.67%（3/45）,两组病死率差异无统计学意义（P〉0.05）;死亡原因主要为颅内出血和感染性休克。结论老年AML患者FAB亚型分布以AML-M2a为主,采取个体化治疗可显著提高缓解率。     

HAG方案治疗低增生性老年急性髓细胞白血病临床研究

老年急性髓细胞白血病（AML）由于多数患者对传统的化疗方案反应不良,完全缓解率低,长期无病生存率低,用药剂量受限,治疗相关死亡率高等原因,其治疗一直是个棘手的问题。我们针对这个特殊人群的病理生理特点,尝试应用HAG方案化疗,治疗低增生性老年AML,取得了满意疗效,现报告如下。     

CHG预激方案治疗老年AML疗效观察

应用CHG方案治疗25例老年急性髓系白血病(AML)患者,并对其疗效和副作用进行观察.结果23例患者完成了2个疗程的化疗,总有效率78%,化疗副作用相对较轻.提示CHG方案是治疗老年AML的有效方法.     

个体化小剂量HAG方案治疗老年急性髓细胞白血病的疗效观察

老年急性髓细胞白血病（AML）因对化疗的耐受性差,完全缓解（CR）率低,生存期明显低于非老年急性白血病患者,经强烈化疗后的的中位生存期不超过12个月。我们从2000年1月-2005年12月应用个体化的小剂量HAG方案治疗老年性AML（AML—M3除外）23例,现报告如下。     

MA方案和粒细胞集落刺激因子联合应用治疗老年急性髓细胞白血病的临床观察

目的　评价MA方案治疗老年急性髓细胞白血病 (AML)及观察老年AML治疗中应用G CSF的临床效果。方法　MA方案治疗老年AML36例 ,2 1例化疗中联合应用G CSF ,其余 1 5例未用G CSF作为对照。结果　①MA方案治疗 36例老年AMLCR率 41 7% ,总有效率 75 0 %。②化疗中联合应用G CSF可缩短外周血白细胞减少和粒细胞缺乏的天数 ,化疗后白细胞恢复及应用抗生素的天数 ,其诱导相关死亡率明显低于未应用G CSF组。结论　MA方案可作为老年AML的一种较好的治疗方案。老年AML治疗联合应用G CSF可降低化疗药物骨髓抑制的毒副作用     

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急性髓性白血病(AML)是最常见的血液系统恶性肿瘤.由于人口老龄化,AML发生率呈上升趋势,同时淋巴瘤、肉瘤、乳腺和睾丸肿瘤等经治疗存活的患者增多,其治疗相关骨髓增生异常综合征(MDS)、AML发生率亦逐渐上升.近年来,AML的诊断、分类标准以及治疗模式有了较多变化,并在某些领域取得了较大进展,通过联合化疗,5年无病存活率已达到30%,急性早幼粒细胞白血病的治疗更取得了可喜的突破,但老年白血病、继发性白血病的治疗仍不尽如人意.     

老年急性非淋巴细胞白血病23例化疗疗效分析

老年急性白血病以急性非淋巴细胞白血病(AML)为主，因其有独特的生物学及临床特征，而以往采取常规剂量化疗，因其对化疗耐受性差，完全缓解率(CR)低，CR持续时间短，化疗后骨髓受抑时间长，疗效差，是目前白血病治疗的难点。为提高其缓解率，延长无病生存期(DFS)，我们对23例老年AML进行了剂量个体化的治疗。     

化疗结合中药治疗老年急性髓细胞白血病近期疗效观察

目的 观察化疗结合中药治疗老年急性髓细胞白血病（AML）的近期疗效。方法 将26例老年AML患者随机分为化疗结合中药组（治疗组）与化疗组（对照组）。每组13例。比较2组的近期疗效。结果 治疗组有效率92．3％，对照组有效率46．2％，2组有效率比较，差异有显著性（X^2=4．51，P〈0．05），2组间不良反应发生率和严重程度差异无显著性。结论 老年AML化疗疗效较差，化疗结合中药治疗有较好的疗效，值得临床进一步探讨。     

老年CD+7急性髓系白血病生物学特征及其临床意义

目的 研究老年CD7抗原阳性急性髓性白血病（CD^＋7AML）的临床生物学特征。方法 对98便初治老年AML进行细胞形态学、免疫表型、多药耐药P糖蛋白（P120）、细胞遗传学核型分析，并采用常规AML方案诱导治疗，判定疗效。结果 老年AML中CD7阳性表达率28.57%（28/98）,28例CD^＋7老年AML（M/F，20/8）的FAB分型结果为：M03例、M13例、M2a6例、M4a2例、M4b1例、M5a1例、M5b9例。CD^＋7老年AML患者外周血白细胞计数（53.80 vs 25.21 P=0.001）、原始细胞比例（69.00% vs 41.02% P=0.001）及P-糖蛋白表达显著增高（67.85 vs 28.57 P=0.001）,肝脏肿大（46.10% vs 23.50% P=0.044）和髓外白血病易发（28.57% vs 2.78% P=0.001）,且对常规化疗反应差，预后不良，完全缓解率亚型，常提示预后不良，建议监测初诊AML患者CD7表达。     

地西他滨单药或联合低剂量化疗治疗老年急性髓系白血病医院内感染的临床分析

目的分析地西他滨单药或联合低剂量化疗治疗老年急性髓系白血病医院内感染的临床特点及易感因素。方法回顾性分析2009年9月至2012年10月接受地西他滨单药或联合低剂量化疗治疗的10例老年急性髓系白血病患者医院内感染发生率、感染部位、致病菌和易感因素等。结果10例老年患者治疗后医院内感染率为70％,例次感染率为46．7％,感染部位以呼吸系统最多见（占52．4％）,致病菌以革兰阴性杆菌为主。化疗后骨髓抑制、粒细胞减少者感染率明显增高;与地西他滨联合低剂量化疗方案比较,地西他滨单药方案骨髓抑制、粒细胞减少发生率和医院内感染率降低。结论老年急性髓系白血病患者是医院内感染的易感人群,骨髓抑制、粒细胞减少是其易感因素。地西他滨单药方案治疗老年急性髓系白血病可降低医院内感染发生率。     

LD—HA诱导治疗非M3型老年急性髓系白血病疗效观察

目的观察小剂量高三尖杉酯碱＋阿糖胞苷（LD—HA）诱导治疗非M3型老年急性髓系白血病（AML）的疗效和不良反应。方法将35例初治老年AML患者随机分为A组（19例）及B组（16例）。A组采用LD—HA方案：高三尖杉酯碱（H）1～2mg／d,阿糖胞苷（Ara—C）25mg,q12h,第1—14天化疗。B组采用标准剂量HA或DA方案。结果1个疗程结束后,A组和B组的完全缓解（CR）率分别为68．4％和37．5％;病死率分别为10．5％和18．7％,差异有统计学意义。血液学毒性两组差异无统计学意义;非血液学毒性的发生率A组低于B组。结论LD—HA诱导治疗老年AML近期疗效好,不良反应较轻。     

Mitozantrone and cytosine arabinoside as first-line therapy in elderly patients with acute myeloid leukaemia

We have prospectively evaluated a regimen of mitozantrone and cytosine arabinoside (Ara-C) as first-line therapy in elderly patients with acute myeloid leukaemia (AML). One hundred and four patients with a median age of 68 (range 60-81) were studied, in whom 86 had de-novo AML, and 18 had preceding myelodysplasia or secondary AML. Complete remission was achieved in 64% of de-novo cases, in 28% of MDS/secondary cases, and in 58% overall. The incidence of early death within 28 d of chemotherapy was 11%. The median disease-free survival (DFS) was 11 months with an actuarial DFS of 15% at 43 months. The median overall survival was 9 months with an actuarial survival of 10% at 44 months. The incidence of non-haematological toxicity was acceptably low, and usually of mild to moderate severity. Quality of life was improved, or unchanged, in 90% of responders. We conclude that mitozantrone and ara-C is an effective and well-tolerated regimen which produces high remission rates in elderly patients with AML.     

Intensified double induction therapy with high dose mitoxantrone,etoposide, m-amsacrine and high dose ara-C for elderly acute myeloid leukemia patients aged 61-65 years

BACKGROUND AND OBJECTIVES: Treatment outcome in elderly patients with acute myeloid leukemia (AML) is still disappointing. However, some trials showed that increasing the dosage of anthracyclines within induction therapy improved treatment outcome substantially. We, therefore, tried to escalate induction therapy further in a group of young elderly AML patients. DESIGN AND METHODS: In a multicenter trial 33 patients aged 61-65 years with de novo or secondary AML were treated with double induction therapy including high dose mitoxantrone, etoposide and ara-C (MAV) in the first course and m-amsacrine together with high dose ara-C (MAMAC) in the second course. Treatment results were compared to those in 39 AML patients older than 65 years receiving conventional double induction therapy including daunorubicin and ara-C (DA I and DA II) within the same time period. RESULTS: Compared to results achieved with conventional induction therapy, intensified double induction therapy did not significantly improve CR rates, overall or disease-free survival. Hematologic toxicity was not different between the two groups, but non-hematologic toxicity was significantly higher with MAV/MAMAC. This was mainly due to gastro-intestinal or liver toxicity. The rate of early mortality (death within the first 12 weeks) was 42% in the group receiving intensified therapy and 18% in that given conventional induction therapy (p=0.04). INTERPRETATION AND CONCLUSION: Intensification of double induction therapy using high dose mitoxantrone and high dose ara-C in AML patients aged 61-65 years did not lead to improved treatment outcome and conferred an unacceptable early death rate due to high non-hematologic toxicity. Risk-adapted or alternative treatment strategies are needed to improve treatment outcome in these young elderly AML patients.     

Antibody therapy for acute myeloid leukemia

Due to the high rate of relapse in younger patients and the overall poor outcome in older patients, novel therapies are needed for the treatment of acute myeloid leukemia (AML). Monoclonal antibodies have become an important treatment modality in cancer therapy. Gemtuzumab ozogamicin (GO), an anti-CD33 immunoconjugate, was approved by the US Food and Drug Administration (FDA) for the treatment of elderly patients with relapsed AML who are not candidates for standard chemotherapy. Single-agent GO and combinations with standard chemotherapeutics have been explored extensively in this disease. Hepatotoxicity and delayed myelosuppression have been dose-limiting. Its toxicity profile is reduced with decreased doses of GO and even by administering only a single infusion. In patients with acute promyelocytic leukemia (APL), the addition of GO can produce molecular remissions and is well tolerated. Targeted immunotherapy with GO for treatment of AML has produced remissions. In order to reduce toxicity and improve efficacy, its optimal dose and schedule and pairing with other standard chemotherapeutic agents need to be defined better in large clinical trials.     

Farnesyltransferase inhibitors and their potential role in therapy for myelodysplastic syndromes and acute myeloid leukaemia

Novel strategies are required for treatment of acute myeloid leukaemia (AML) and higher risk myelodysplastic syndrome (MDS) patients who are not eligible for intensive chemotherapy and/or allogenic stem cell transplantation. As activating RAS mutations are frequent in these diseases, one novel approach, consisting of interfering with isoprenylation of RAS proteins by farnesyltransferase inhibitors (FTIs), has been proposed. Clinical phase II studies with the oral FTIs tipifarnib and lonafarnib in previously untreated AML, MDS and chronic myelomonocytic leukaemia yielded rather encouraging results while results in relapsed and/or refractory AML were disappointing. Results of a phase III trial in untreated AML in the elderly with tipifarnib were also disappointing. Clinical responses were not related to RAS mutations, suggesting additional actions of FTIs on other molecular targets. The combination of existing FTIs with other treatments, such as chemotherapy (in AML) and hypomethylating agents (in MDS and AML), is under investigation. Ongoing studies will also determine if gene profiling analysis may help to identify patients that will respond to FTIs.     

Therapy of acute myeloid leukemia in the elderly patient

Incidence and mortality rates of acute myeloid leukemia (AML) increase exponentially with advancing age. AML diagnosed in elderly patients differs from that diagnosed in younger patients. But not only disease-specific differences are important. Treating elderly patients with AML age-associated differences in the patients general presentation, such as physiological changes in organ function, decreased ability to react to stress, dependence in activities of daily living, existence of other morbidities (co-morbidity), the need to take drugs for those diseases and the reduced life expectancy can force alterations in the disease management. Clinical trials for the treatment of AML have been excluding elderly patients for years. Even trials accepting elderly patients with AML did select the group of otherwise healthy elderly patients for participation in the trial. Thus the data for AML management in elderly patients do not reflect the whole group of elderly patients with AML. If the patient is treated with curative intention, therapy of choice is the so-called 3 + 7 protocol for induction of complete remission, followed by a consolidation therapy and in some cases by maintenance therapy. In some situations, especially in very old patients, a palliative intention to treatment is favored. There are no generally accepted criteria to measure treatment benefit in this setting nor established chemotherapy protocols for this situation. Further trials for elderly patients with AML have to offer treatment options for the whole group of patients and have to determine what treatment approach is the best for which individual patient.     

Therapeutic decision-making in elderly patients with acute myeloid leukemia: conventional intensive chemotherapy versus hypomethylating agent therapy

Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70.9%). The overall response rates were 32 and 19.7%, respectively. Median overall survival (OS) (8 vs. 8 months) and progression-free survival (PFS) (6 vs. 7 months) durations were similar in the two groups. Patients in the HMA group with less than 10% peripheral blood (PB) blasts achieved significantly better OS duration than patients in the IC group (P = 0.043). Patients in the IC group with PB blasts and bone marrow blast of ≥ 10 and ≥ 50%, respectively, achieved better PFS durations than the corresponding patients in the HMA group (P = 0.038). Multivariate analysis identified the hematologic improvement-platelet (HI-P) as an independent prognostic factor for survival in the HMA group (P = 0.005). Our results showed that HMA therapy and IC were associated with similar survival duration in elderly AML patients. This study was noteworthy because it assessed prognostic factors that would help to select elderly patients who could expect actual benefits from undergoing the different therapeutic options available, especially HMA therapy.     

Acute myeloid leukemia in the elderly: conventional and novel treatment approaches

Acute Myeloid Leukemia (AML) is a disorder affecting primarily elderly individuals and poses significant treatment challenges. Much has been learned about the underlying immunologic, cytogenetic and molecular features of AML in recent years, and many features have been identified that portend a poor prognosis for elderly patients with newly diagnosed AML. Despite this, treatment outcomes for elderly patients remain poor for both newly diagnosed and relapsed disease. While conventional treatment approaches may be appropriate for some elderly patients, the vast majority do not tolerate intensive chemotherapy well, thus alternative strategies have been investigated. Here we review both conventional and novel treatment approaches for elderly patients with AML, including agents in early clinical trials. Treatment options have been divided into several discussions, including conventional treatments, agents complementary to conventional treatments, alternatives to conventional induction therapies, post-induction treatment, and relapsed disease. Current and developing research focuses upon identifying subgroups of patients that benefit more from specific chemotherapeutic agents. Treating elderly patients with AML requires an organized, multidisciplinary approach, taking into account individual patient characteristics, preferences, and comorbidities when formulating treatment plans.     

Etiology of acute myeloid leukemia in the elderly

The biologic and epidemiologic study of acute myeloid leukaemia (AML) in the elderly is in its infancy. Most epidemiologic data attempting to ascertain the etiology of AML have been obtained from younger cohorts or patients with therapy-related AML. The increasing prevalence of deletional and complex karyotypes in elderly AML patients implies a cumulative genotoxicity over time for this subgroup, given the similar spectrum of abnormalities following exposure to known genotoxic agents such as alkylating chemotherapeutic drugs. Exposure to benzene, radiation, and tobacco smoke are clear but weak risk factors for AML. Polymorphic variants in several genes responsible for genomic protection and integrity are now also weak risk factors for AML. Future epidemiologic studies should correlate exposure data with well-defined biologic subtypes of AML.