Sokal和Hasford积分系统在慢性粒细胞白血病研究中的临床意义比较

 目的 比较Sokal和Hasford积分系统在研究慢性粒细胞白血病（CML）中的临床意义。方法 204例患者按治疗方案与两种积分系统分别进行分组,比较干扰素两种积分系统对慢性期CML患者生存期的影响,并在不同危险度组内观察干扰素对患者生存期的影响。结果 干扰素、Sokal和Hasford积分系统对CML患者的预后均有显著影响（P均<0.001）,但多变量分析发现仅有Hasford积分是影响预后的独立因素。在Hasford中高危组与Sokal高危组内,干扰素并不能明显延长患者的生存时间。结论 Sokal和Hasford积分系统能较好地预测CML 患者的预后,对确定高危组患者后者更为准确。按预后评分系统将患者分组,有利于治疗方案的合理选择。     

干扰素联合化疗与伊马替尼治疗慢性粒细胞白血病的疗效比较分析

目的比较分析干扰素联合化疗与伊马替尼治疗慢性粒细胞白血病(CML)的临床疗效。方法 72例新诊断的Ph染色体阳性CML慢性期患者根据治疗方案的不同随机分为干扰素联合化疗组和伊马替尼组,并比较2组临床疗效。结果 2组总有效率比较差异无统计学意义(P>0.05);伊马替尼组完全血液学缓解率、完全细胞遗传学缓解率、完全分子学效应率、5 a总生存率均明显高于干扰素联合化疗组(P<0.05)。结论干扰素联合化疗和伊马替尼均可作为CML慢性期的有效治疗方法。     

伊马替尼对慢性粒细胞白血病患者生育及生殖的影响

伊马替尼对慢性粒细胞白血病的分子靶向性治疗获得了极大的成功,病人的生存时间延长,生活质量接近正常人。由于伊马替尼可能导致畸形,通常建议患者服药治疗期间避免妊娠。近年来,伊马替尼治疗的患者中选择妊娠及合并妊娠、成功分娩的个案多有报告,但尚无流行病学的大样本研究结果支持伊马替尼治疗的患者可以选择生育,对伊马替尼治疗影响生育和生殖的研究也仅停留于动物实验。本文就伊马替尼对慢性粒细胞白血病患者生育和生殖的影响作一综述。     

伊马替尼治疗慢性粒细胞白血病患者在生育时中断药物治疗对胎儿和患者自身的影响

目的:分析伊马替尼治疗慢性粒细胞白血病（chronic myeloid leukemia,CML）患者在生育时中断药物治疗对胎儿和患者自身的影响。方法:回顾性分析本科室21例CML合并妊娠患者在接受伊马替尼治疗后的影响。结果:21名接受伊马替尼治疗的CML患者中有6名为意外怀孕,15名为计划怀孕。有生育意愿的女性患者需达到血液学或细胞学缓解至少两年,在受孕前1个月和孕期前3个月停服伊马替尼,男性患者则在生育前一个月停止接受伊马替尼的治疗。所有意外受孕的患者在孕期均未停止服用伊马替尼。21名患者共生产9名男婴和7名女婴（其中1名尿道下裂,1名轻度脑水肿）,其余有2名自然流产,3名选择性流产。结论:鼓励接受伊马替尼治疗的CML患者有计划的生育,对于治疗期间意外怀孕的患者,伊马替尼则会导致自然流产或先天性异常。     

三氧化二砷联合伊马替尼治疗慢性粒细胞白血病急变期五例

 目的 探讨三氧化二砷（As2O3）联合伊马替尼（STI571）治疗慢性粒细胞白血病（CML）急变期的临床疗效。方法 回顾性分析2003年12月至2006年2月采用As2O3联合STI571治疗5例CML急变期疗效及毒副反应。结果 5例患者治疗后4例获完全血液学反应（CHR）,其中1例获主要细胞遗传学反应（MCR）,1例未缓解（NR）。结论 As2O3联合STI571治疗CML急变期疗效较为显著。     

伊马替尼联合造血干细胞移植治疗慢性粒细胞白血病

 目的 研究伊马替尼（商品名：格列卫）对异基因造血干细胞移植（allo-HSCT）和自体外周血造血干细胞移植（APBSCT）的影响。方法 18例慢性粒细胞白血病（CML）分为2组：①al-lo-HSCT组14例,其中10例为CML加速期（AP）和急变期（BP）,4例为CML慢性期（CP）,移植之前格列卫疗程中位数为25（7～60）d,供受者HLA完全相合,亲缘相关供者9例、非亲缘供者5例,预处理方案为TBI+Cy+VP16或Bu／Cy±ATG,GVHD预防按常规方案进行;②APBSC动员4例,均为CML-CP患者,格列卫治疗的中位数疗程5.5（4～26）个月,动员前反复IFISH-bcr／abl阳性率0～2%,动员方案CAE+G-CSF,其中3例经TBI+Cy+VP16预处理后进行了APBSCT。结果 4例患者经G-CSF动员第5天分离自体外周血干细胞（APBSC）1次,得CD+34细胞的中位数6.8（3.9～9.6）×106／kg,动员产品中IFISH-bcr／abl阳性细胞比例高于动员前骨髓细胞（2.8 %∶0.8 %）,4例动员PBSC的患者中3例进行了APBSCT,移植后随访中位时间24（18～28）个月,2例复发,1例持续IFISH-bcr／abl阴性。14例allo-HSCT患者中位随访8（4～20）个月,造血重建需要8～21 d,发生GVHD 8例,白血病复发2例,移植相关并发症死亡2例,复发死亡1例,无病生存9例。结论 格列卫治疗后对CML患者造血干细胞的动员、移植结果无明显影响。     

伊马替尼致慢性粒细胞白血病患者玻璃体及眼底出血1例分析

0? 引言 慢性粒细胞白血病(chronic myelogenous leu-kemia, CML)为造血干细胞恶性克隆性疾病,其发病及进展缓慢,据病程分为三期:慢性期、加速期和急变期.CML的特征改变是染色体形成9, 22号染色体易位,形成BCR-ABL融合基因,其蛋白产物具有酪氨酸激酶活性,从而导致CML的发生[1...     

伊马替尼一线治疗慢性粒细胞白血病慢性期患者- 单中心十年回顾性分析*

目的：总结以伊马替尼为一线治疗的慢性粒细胞白血病（chroni cmyeloid leukemia,CML ）初治患者的疗效和生存。方法：回顾性分析南昌大学第一附属医院2003年1 月至2013年12月间收治的295 例CML 初治患者的临床资料,其中185 例为入组格列卫全球患者援助项目（GIPAP）行伊马替尼治疗、30例为干扰素（IFN-α）治疗、50例为羟基脲单药治疗和30例为异基因外周血造血干细胞移植（allogeneic hematopoietic stem cell transplantation ,Allo-HSCT）治疗的患者,分析各组患者的治疗疗效和生存情况。结果：伊马替尼治疗组和Allo-HSCT 治疗组患者完全血液学缓解率（complete hematologic remission ,CHR ）均为96.7% ,完全细胞遗传学缓解率（complete cytogenetic remission,CCyR）为89.7% 和93.3% ,完全分子学缓解率（complete molecular remission ,CMoR）为49.7% 和83.3%（P = 0.001）;而干扰素和羟基脲治疗组CHR 、CCyR和CMoR 均明显低于伊马替尼治疗组和Allo-HSCT 治疗组。伊马替尼组患者的总生存时间（overall survival,OS）明显优于其他组（P < 0.001）,甚至优于Allo-HSCT 治疗组（10年OS为89.0% vs .67.0% ,P < 0.001）。 Cox 多因素分析显示接受伊马替尼治疗（HR= 5.267,95%CI 为1.054～1.940,P = 0.022）和获得CCyR（HR= 9.541,95%CI 为1.692～10.513,P = 0.002）是影响本组患者预后良好的独立因素。结论：CML 初治患者接受伊马替尼治疗可以获得更高的CHR 和CCyR,且OS更优,伊马替尼适合作为中国初治CML 患者的一线治疗。     

慢性粒细胞白血病的治疗：停用酪氨酸激酶抑制剂能否带来治愈

 【摘要】 慢性粒细胞白血病患者应用伊马替尼（IM）等酪氨酸激酶抑制剂（TKI）治疗后可达到完全分子生物学缓解（CMR）,此时是否还要继续治疗,成为临床医生和患者都关注的问题。长期服用TKI伴随着沉重的经济负担与发生慢性不良反应的风险。约40 %的CML患者达CMR至少2年后可以停用IM,并且其CMR能维持至少2年。因而,CML患者达到稳定CMR后能否停用TKI以及停药后的复发风险,成为研究CML是否能被治愈的新焦点。就2011年第53届美国血液学会（ASH）年会在这方面的研究进展作一报道。     

Practical management of patients with chronic myeloid leukemia

Although imatinib has been used as frontline therapy for chronic myeloid leukemia (CML) for nearly a decade, current debate is focused on the incorporation of newer tyrosine kinase inhibitors (TKIs) at diagnosis in light of recent US Food and Drug Administration approval of nilotinib and dasatinib for initial therapy in chronic-phase CML. Articles were identified through a PubMed search and a review of abstracts from relevant hematology congresses. Additional information was provided from the authors' libraries and expertise. With several therapies now available, it is crucial to carefully define and monitor response in patients with CML to determine whether their treatment is appropriate and is providing an optimal outcome. Different patterns of response to TKI treatment have been recognized, ranging from best-case scenarios of rapid and unwavering response to difficult situations of intolerance and resistance, either primary or secondary. Patients who develop resistance to imatinib are advised to switch to second-generation TKIs. Although specific mutations in the breakpoint cluster region-v-abl Abelson murine leukemia viral oncogene (BCR-ABL) kinase domain may guide treatment selection in such scenarios, the choice is driven by other factors in the majority of patients, including the toxicity profiles of the newer TKIs as well as a patient's comorbidities.     

Evaluation of 196 patients with chronic myeloid leukemia based on a standard prognosis model]

The clinical course of 196 patients with chronic myelocytic leukemia (CML) was studied. Prognostic factors were analyzed using a standard prognostic model. From a univariate analysis of patients with nonblastic Philadelphia chromosome-positive CML, splenomegaly, bone marrow fibrosis, percentage of blasts and promyelocytes in the peripheral blood and LDH activity were shown to be factors with a significant negative influence on survival. However, age and the platelet count did not influence survival. The standard prognostic model, generated with the 4 variables (1) percentage of blasts and promyelocytes, (2) spleen size, (3) platelet count and (4) age did not provide a useful representation of risk status in this heterogenous patient population. However, the addition of further variables (LDH, additional chromosomal aberrations, percentage of basophiles/eosinophiles and percentage of bone marrow blasts) to the standard model allowed a separation into 2 patient groups: one with low and the other with intermediate to high risk. Our data support the general validity of the prognostic model; however, the applicability of the model may be compromised in hematologic centers with a heterogenous CML population due to the selection of high-risk patients. In this situation additional risk factors may have to be added to the prognostic formula.     

HLA-G expression is irrelevant to prognosis in patients with acute myeloid leukemia

Human leukocyte antigen (HLA)-G could contribute to escape of cancer cells from host anti-tumor responses, and its potential clinical relevance in various malignancies was also addressed. However, the prognostic value of HLA-G in acute myeloid leukemia (AML) remains debated. In this study, HLA-G expression in malignant blasts was analyzed from 77 de novo AML patients (AML-M2, n = 26; AML-M3, n = 24; AML-M4, n = 10; AML-M5, n = 17) with flow cytometry. The proportion of HLA-G expressing blasts varied from 0% to 93.96% (median: 0.42%; 95% CI: 0–89.0%). Blasts with 0.5% or fewer HLA-G expressing were defined as negative according to its expression in normal CD34⁺CD45⁺ cells (n = 20, range: 0–0.5%; median: 0.13%; 95% CI: 0–0.42%). HLA-G expression status on leukemic blasts was not associated with the clinical parameters such as patient age at diagnosis, sex, sub-type of AML, percentage of blasts at diagnosis. Survival analysis revealed that HLA-G expression status on leukemic blasts is unrelated to the prognosis (p = 0.884). The mean overall survival time for the HLA-G negative and positive patients was 20.7 months (95% CI: 16.1–25.3) and 20.1 months (95% CI: 14.3–25.8), respectively. Taken together, our findings indicated that HLA-G expression is of no significance for the prognosis of patients with AML.     

Novel therapies for patients with chronic myeloid leukemia

The most immediate issues that will have a major impact on the long-term survival of patients with chronic myeloid leukemia is the optimal use of imatinib mesylate (Gleevec^®, Novartis) and the development of effective therapies for those patients who are intolerant of, or become resistant to, optimal doses of this agent. Of the multiple new agents that are currently being developed for patients with chronic myeloid leukemia, most are being investigated in patients who have developed resistance to imatinib, which is a confounding factor in itself. The mechanisms of action of novel agents are diverse and they may have a variably synergistic therapeutic relationship with imatinib. The complete blockade of the intracellular pathways that are triggered by Bcr-Abl, combined with successful reversal of apoptotic and/or angiogenic abnormalities in chronic myeloid leukemia, may well lead to a cure for the majority of patients.     

Novel therapies for patients with chronic myeloid leukemia

The most immediate issues that will have a major impact on the long-term survival of patients with chronic myeloid leukemia is the optimal use of imatinib mesylate (Gleevec, Novartis) and the development of effective therapies for those patients who are intolerant of, or become resistant to, optimal doses of this agent. Of the multiple new agents that are currently being developed for patients with chronic myeloid leukemia, most are being investigated in patients who have developed resistance to imatinib, which is a confounding factor in itself. The mechanisms of action of novel agents are diverse and they may have a variably synergistic therapeutic relationship with imatinib. The complete blockade of the intracellular pathways that are triggered by Bcr-Abl, combined with successful reversal of apoptotic and/or angiogenic abnormalities in chronic myeloid leukemia, may well lead to a cure for the majority of patients.     

影响老年急性髓系白血病患者预后的危险因素分析

目的 探讨影响老年急性髓系白血病患者预后的危险因素.方法 回顾性分析121例老年急性髓系白血病患者的临床资料.对比不同临床资料患者的完全缓解率和中位生存期.通过多因素Cox模型分析统计影响老年急性髓系白血病患者预后的危险因素.结果 本研究患者的中位生存期为131 d(95%可信区间109~154 d),诱导化疗后的完全缓解率为29.75%.年龄≤70岁、PS评分﹤2分、原发急性髓系白血病、骨髓原始细胞比例≤50%、接受标准化疗以及白细胞CD34表达阴性患者的完全缓解率升高(P﹤0.05);年龄≤70岁、PS评分﹤2分、原发急性髓系白血病、初治时的白细胞计数≤50×109/L、骨髓原始细胞比例≤50%、接受标准化疗以及白细胞CD34表达阴性患者的中位生存期延长(P﹤0.05);多因素Cox模型分析结果显示,年龄、PS评分、初治时白细胞计数以及治疗方案是影响老年急性髓系白血病患者预后的危险因素(P﹤0.05).结论 年龄、PS评分、初治时白细胞计数以及治疗方案是影响老年急性髓系白血病患者预后的危险因素.临床应通过整体评估,制定个体化的化疗方案,以改善患者的预后.     

Alpha-interferons in the treatment of patients with chronic myeloid leukemia]

Chronic disease duration and survival have been investigated in three groups of patients suffering chronic myeloid leukemia (CML). The first group included 13 patients on alpha-interferons 6-9 mln MU/24 h (mean dose--48 mln MU/week). 31 patients received 2 mln MU/m2/24 h; mean weekly dose--15 x 10(6) MU. Standard chemotherapy was given to another 79 patients (group III). Actual survival and chronic disease duration were computed after Kaplan-Meyer: 4-year survival in group I--88%; group II--85.6% and group III--54%. Five-year survival in patients who had received standard or lower doses of alpha-interferon was 78.7%; chemotherapy alone--28.9%. Median survival in alpha-interferon-treated patients was 66 months; chemotherapy--48 months. After standard alpha-interferon, chronic disease three years after CML diagnosis was in 87% of those treated with standard alpha-interferon, 89% of those receiving lower doses of the drug and 53.4% of chemotherapy-treated patients. After 4 years, chronic disease was registered in 75.5% (alpha-interferon)--74.8% in group I and 72.9% in group II, and in 34.4% of patients treated with myelosan or hydroxyurea. Median chronic stage duration after interferon was 51 months and 39 months in group III, hence, both standard and lower doses of alpha-interferon prolong chronic disease and improve survival in CML patients.     

Considerations in the management of elderly patients with chronic myeloid leukemia

The introduction of tyrosine kinase inhibitor (TKI) treatment has provided a remarkable survival benefit such that it is possible that patients with chronic myeloid leukemia might live a normal life span. Coupled with a median age of onset of 65 years, many patients will be elderly at diagnosis or can expect to attain elderly status during their course of treatment. Unfortunately, few clinical studies have focused on treating elderly patients, which leads to fewer data on the efficacy and safety of TKI therapy in older patients than in younger patients. Perhaps as a consequence, there is evidence that elderly patients do not receive lifesaving TKI treatment as uniformly as do those who are younger. This review examines the available data on TKI therapy in elderly patients with chronic myeloid leukemia and addresses special considerations in treating this patient population. Overall, analysis of the data suggests that TKI therapy is equally effective regardless of patient age and that safety findings with TKI therapy in elderly patients are similar to those observed in younger individuals.