羟基脲加用干扰素与羟基脲单用治疗慢性粒细胞性白血病的比较

目的探讨干扰素（α-INF）联合羟基脲（HU）治疗慢性粒细胞性白血病的效果。方法采用交叉对比的方法，对单用羟基脲与羟基脲联合α-INF治疗慢性粒细胞性白血病（CML）患者进行治疗并定期观察缓解时间、血象、骨髓象变化。结果联合治疗组血液学稳定，持续缓解时间明显大于单用羟基脲组。结论α-INF联合HU是治疗CML的有效方法，是达到CML长期彻底缓解的重要因素。     

JAK2、MPL和CALR基因突变在中国原发性骨髓纤维化患者中的预后意义北大核心CSCD

目的评价JAK2、MPL和CALR基因突变在中国原发性骨髓纤维化（PMF）患者中的预后意义。方法回顾性分析402例PMF患者的临床资料及JAK2、MPL和CALR基因突变,应用Kaplan—Meier、Log．rank和Cox回归模型进行相关预后因素分析。结果402例PMF患者中男209例,女193例,中位年龄55（15～89）岁。JAKV617F基因突变189例（47．0％）,MPLW515基因突变13例（3．2％）,CALR基因突变81例（20．1％）[1型突变30例（37．0％）,2型突变48例（59．3％）,少见型突变3例（3．7％）],119例（29．6％）未检测到JAK2、MPL和CALR基因突变。单因素分析显示,2型CALR突变或未检测到JAK2、MPL和CALR基因突变的患者中位生存期（74个月）短于检测到JAK2、MPL或1型及少见型CALR基因突变的患者（168个月）[HR=2．990（95％C11．935-4．619）,P〈0．001]。因此,将基因突变类型分为预后不良组（2型CALR突变和未检测到JAK2、MPL和CALR基因突变）和预后良好组（JAKV617F、MPLW515、1型及少见型CALR基因突变）。经多因素分析提出了中国PMF患者的动态国际预后积分系统（DIPSS—Chinese）分子预后积分系统,各参数赋值如下：DIPSS．Chinese低危组0分,中危组1分,高危组2分,2型CALR突变或未检测到JAK2、MPL和CALR基因突变积1分。402例患者中,低危组（0分）132例（32．8％）,中危-1组（1分）143例（35．6％）,中危．2组（2分）106例（26．4％）,高危组（3分）21例（5．2％）。低危组中位生存时间未达到,中危-1组为156（95％C1117～194）个月,中危．2组为60（95％CI28～91）个月,高危组为22（95％CI10～33）个月,总生存差异具有统计学意义（P〈0．001）。DIPSS．Chinese分子预后积分系统较DIPSS—Chinese有更准确的预测能力（-2log似然比分别为855．6和869．7,P=0．005）。结论在中国PMF患者中,2型CALR突变和未检测到JAK2、MPL和CALR突变是独立的不良预后因素,DIPSS—Chinese分子预后积分系统有更好的预测价值。     

Ph染色体阳性慢性粒细胞白血病患者多因素预后分析

目的 探讨影响Ph阳性慢性粒细胞白血病（CGL）患者生存期的因素。方法 对209例CGL患者的临床体征、血常规和骨髓象进行单因素预后分析,然后对有意义的单因素用COX回归模型进行多因素综合分析。结果 209例患者中位生存时间57个月（3－179个月）,5年生存率48％。经COX回归多因素综合分析,外周血原始粒细胞、早幼粒细胞、出现有核红细胞、骨髓原始粒细胞（≥0．04）为影响生存期的4个主要因素。依评分指数公式分为低危、中危和高危组,中位生存时间分别为76．0,56．0和31．5个月（P＜0．01）,5年生存率分别为70．42％、46．30％和18．18％（P＜0．01）。结论 提出适合我国CGL患者的预后评分指数公式。     

干扰素与羟基脲联合治疗慢性粒细胞白血病的疗效观察

我科1997-02～2003—07采用干扰素α-2b（IFNα-2b）与羟基脲（Hu）联合治疗慢性粒细胞白血病（CML）慢性期患者30例，总结如下。     

α_1b-干扰素联合羟基脲治疗13例慢性粒细胞白血病疗效观察

目的 :观察干扰素联合羟基尿治疗慢性粒细胞白血病 (CML)的临床疗效。方法 :CML患者分为治疗组与对照组两组 ,两组再分慢性期、加速期两亚组 ,治疗组用干扰素 3 0× 10 6IU/d ,隔日一次皮下注射及羟基脲1～ 3g/d,口服 ;对照组单用羟基脲。结果 :治疗组慢性期亚组获血液学完全缓解 6 /8(与对照组比较有显著性差异 ) ,部分缓解 2 /8,总有效率 10 0 % (与对照组比较无显著性差异 ) ,与相应对照组比较 3年生存率无显著性差异、 5年生存率有显著性差异 ;治疗组加速期亚组总有效率与对照组比较无显著性差异 ,3年生存率与对照组比较有显著性差异。结论 :α1b -干扰素联合羟基脲治疗慢性粒细胞白血病有较好疗效。     

α1b—干扰素联合羟基脲治疗13例慢性粒细胞白血病疗效观察

目的观察干扰素联合羟基尿治疗慢性粒细胞白血病(CML)的临床疗效.方法CML患者分为治疗组与对照组两组,两组再分慢性期、加速期两亚组,治疗组用干扰素3.0×106IU/d,隔日一次皮下注射及羟基脲1～3g/d,口服;对照组单用羟基脲.结果治疗组慢性期亚组获血液学完全缓解6/8(与对照组比较有显著性差异),部分缓解2/8,总有效率100%(与对照组比较无显著性差异),与相应对照组比较3年生存率无显著性差异、5年生存率有显著性差异;治疗组加速期亚组总有效率与对照组比较无显著性差异,3年生存率与对照组比较有显著性差异.结论α1b-干扰素联合羟基脲治疗慢性粒细胞白血病有较好疗效.     

多指标危险积分在异基因造血干细胞移植预后预测中的意义简

本研究旨在探讨多指标危险积分在异基因造血干细胞移植（allo-HSCT）预后预测中的意义.回顾性分析122例接受allo-HSCT治疗的恶性血液病患者移植前、移植时和移植后因素对总体生存（Overall survival,OS）、无病生存（Disease-free survival,DFS）、复发及移植相关死亡（Transplant-related mortality,TRM）的影响,筛选独立危险因素,并联合各项独立危险因素建立多指标预后危险积分系统,分析该系统对预后的预测意义.结果表明,移植后30 d单核细胞绝对值（AMC-30）（≥536 cells/μl）（HR=0.313,95％ CI=0.156-0.63）、Wilm肿瘤相关基因1（WT1）（≥1.0％） （HR =3.268,95％CI=1.644-6.499）、移植前危险分组（HR=1.999,95％ CI =0.993-4.023）是影响OS和DFS的独立危险因素.联合三项指标建立危险积分系统,根据患者危险因素的个数进行积分,分为A组（无危险因素;0分）、B组（有1个危险因素;1分）、C组（有2-3个危险因素;2-3分）,各组5年OS分别是95.1％±3.4％、62.9％±6.6％、36.1％±9.6％ （P ＜0.0001）,5年DFS分别是92.6％±4.9％、60.4％±6.8％、15.4％±7.1％ （P＜0.0001）,累积复发率分别是4.9％、20.0％、65.4％ （P ＜0.0001）.新积分系统预测OS赤池信息量准则值（akaike information criterion,AIC）为331,小于AMC-30、WT1、危险分组预测OS的AIC（346、343、346）,预测DFS的AIC为378,小于AMC-30、WT1、危险分组预测DFS的AIC（417、397、411）,预测复发的AIC为231,小于AMC-30、WT1、危险分组（268、238、257）.结论：联合AMC-30、WT1、移植前危险分组三项指标所建立的危险积分系统能够很好的预测移植患者OS、DFS和复发,并优于任何一项单指标.     

慢性中性粒细胞白血病（附2例报告）

慢性中粒细胞白血病（CNL）是一种少见的白血病。目前诊断标准尚未统一。有人认为CNL是与CML密切相关的骨髓增生性疾病，与CGL是两种性质，病程，预后不同的慢性髓系白血病。临床特点为中性粒细胞增高，不伴发热，炎症，癌症和其他引起白细胞增高的任何原因，脾大，Ph染色体阴性，NAP积分增高。须与类白血病反应，CGL等相鉴别。治疗可选用羟基脲，干扰素，小剂量阿糖胞苷等。预后差。     

甲异靛对慢性粒细胞白血病抗血管新生作用的体外研究

远期疗效分析结果证实 ,甲异靛与目前国际上治疗慢性粒细胞白血病 (CML)的首选化疗药物羟基脲疗效相当 ,甲异靛联合羟基脲或干扰素较单用甲异靛、羟基脲、干扰素能明显延长总生存率 ,降低 5年恶变率[1 ,2 ] 。以前我们的研究结果表明 ,其主要疗效机制是抑制白血病细胞增殖、诱导凋亡。最近研究表明 ,CML患者骨髓微血管密度 (MVD)较正常人明显增高[3] 。为探讨抗血管新生是否为甲异靛治疗CML的疗效机制之一 ,我们研究了甲异靛对K5 6 2细胞系和CML原代细胞分泌血管内皮生长因子 (VEGF)的影响及其对内皮细胞的作用。材料和方法1　主要…     

羟基脲联合α-干扰素治疗慢性粒细胞白血病132例

慢性粒细胞白血病（CML）是造血干细胞恶性克隆增殖性疾病,血液科常见。曾经应用马利兰、联合化疗等方法,疾病能够有所控制。目前羟基脲（HU）及α-干扰素（α—IFN）的联合应用,为CML患者提供了新的治疗途径,现将我院1998年10月至2008年6月应用HU＋α-IFN治疗CML132例疗效观察报告如下：     

Efficacy and safety of imatinib in treatment of 151 chronic myeloid leukemia patients]

OBJECTIVE: To evaluate the safety and efficacy of imatinib in treatment of chronic myeloid leukemia (CML) patients. METHODS: From December 2003 to March 2007, 151 patients entered Glivec International Patient Assistance Program (GIPAP) in our center and received imatinib therapy. The overall and progression free survival, hematologic, cytogenetic and molecular response, and adverse events were evaluated. The factors associated with outcome of imatinib therapy were also analysed. RESULTS: One hundred and forty-two patients were evaluable with a median follow-up duration of 21.5 (6 -78) months. (1) The rate of cumulative complete hematologic response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and complete molecular response (CMoR) in chronic phase (CP) CML patients were 96.9%, 82.6%, 76.1% and 29.4%, respectively. These rates were significantly higher in patients with CP than in those with accelerated phase (AP) and blast crisis (BC) (P < 0.0001). (2) The overall survival (OS) rates at 1, 2 and 3 year were 100%, (97.3 +/- 1.9)% and (95.8 +/- 2.4)% for CP patients, they were (84.7 +/- 8.2)%, (77.0 +/- 10.4)% and (69.3 +/- 11.9)% for AP patients, and (62.9 +/- 8.9)%, (41.9 +/- 9.2)% and (28.5 +/- 9.1)% for BC patients, respectively (P < 0.0001). The progression-free survival (PFS) rates at 1, 2 and 3 year were (98.9 +/- 1.1)%, (93.9 +/- 2.7)%, (93.9 +/- 2.7)% for CP patients, (68.9 +/- 10.6)%, (61.3 +/- 11.9)%, (61.3 +/- 11.9)% for AP patients, (36.4 +/- 8.8)%, (25.4 +/- 8.1)%, (10.1 +/- 8.2)% (P < 0.0001) for BC patients respectively. (3) Among 92 CP patients, the rates of MCyR and CCyR in newly diagnosed patients were significantly higher than those in interferon therapy failure patients (P = 0.015, P = 0.010). Patients obtained CCyR at 12 months after the initiation of imatinib treatment were associated with longer PFS (P = 0.0099). According to the Sokal scoring system, the rates of MCyR and CCyR in low-risk patients were significantly higher than those in intermediate-risk and high-risk patients (P = 0.0013, P = 0.0024). Sokal score was also significantly associated with disease progression (P = 0.0467). (4) The adverse events of imatinib were moderate and tolerable. CONCLUSIONS: Treatment of CML patients in CP with imatinib can induce high hematologic, cytogenetic and molecular response and overall survival, but can not do satisfactorily for patients in AP and BC.     

尼洛替尼和达沙替尼作为二三线药物治疗慢性髓性白血病慢性期和加速期患者的疗效及影响因素分析

目的分析二代酪氨酸激酶抑制剂(TKI)尼洛替尼和达沙替尼作为二三线药物治疗慢性髓性白血病(CML)慢性期(CP)和加速期(AP)患者的治疗反应和预后,以及相关影响因素。方法回顾性分析2008年1月至2018年11月北京大学人民医院收治的一二线TKI治疗失败并接受尼洛替尼或达沙替尼作为二三线治疗的CML-CP和AP患者资料。结果共收集183例尼洛替尼和达沙替尼作为二线治疗和43例尼洛替尼和达沙替尼作为三线治疗的CML-CP或AP患者。二线TKI治疗患者中,中位随访21(1~135)个月,完全血液学反应(CHR)率为80.4%,完全细胞遗传学反应(CCyR)率为56.3%,主要分子学反应(MMR)率为38.3%,3年疾病无进展生存(PFS)和总生存(OS)率分别为78.7%和93.1%。二线TKI治疗中,Sokal积分为高危、女性、一线TKI治疗期间获得最佳反应相似文献   

Recent advances in the chemotherapy of leukemias]

Most recent progress in the treatment of leukemia and choice of therapies for obtaining "cure" from leukemia are discussed. Chemotherapy can now provide about 40% long term survival in acute myeloblastic leukemia (AML) and about 20% disease-free survival in acute lymphoblastic leukemia (ALL) of adults. Bone marrow transplantation (BMT) should be applied for the patients at risk in those leukemias (Cytogenetic abnormalities for AML and prognostic factors in ALL). In CML patients, BMT offers the only cure. Update result of interferon (IFN) therapy for CML is still a matter of controversy. Ex vivo treatment of autologous cells with IFN or drugs may be beneficial for CML patients without HLA identical donor.     

慢性粒细胞白血病异基因造血干细胞移植后bcr-abl动态监测对低复发患者筛选的意义

目的 寻找慢性粒细胞自血病(CML)患者异基因造血干细胞移植(allo-HSCT)后早期bcr-abl的动态变化规律,以识别不需要十预的低复发患者.方法 2004年11月至2006年11月在我院接受allo-HSCT的CML患者149例.移植前后采用实时定量PCR方法定期监测骨髓bcr-abl转录本的水平,计算未干预组患者各时间点的bcr-abl中位值,并采用Mann-Whitney U比较同一时间点不同移植模式下的bcr-abl水平.采用Kaplan-Meier曲线计算复发率、生存率和移植物抗宿主病(GVHD)发生率.结果 149例患者2年总生存率为86.0%(CI:82.9%～89.1%),累积血液学复发率为3.5%(CI:1.7%～5.3%).未干预组患者102例,bcr-abl水平中位值:移植前25.800%(0.067%～96.100%),+1个月0.025%(0～3.583%),+2个月0.011%(0～0.425%),+3个月0.002%(0～0.610%),+4个月为0(0～0.056%).本组患者至随访结束无一例复发.未干预组患者HLA配型不合组、配型相合组和非血缘关系移植组分别于移植后3、4和5个月bcr-abl下降至不能检测出其水平.结论 CML患者allo-HSCT后bcr-abl的动态监测有助于筛选出无须干预的CML患者.     

EBMT积分在异基因造血干细胞移植治疗慢性粒细胞白血病中的预后价值

目的 分析慢性粒细胞白血病(CML)异基因造血干细胞移植(allo-HSCT)治疗的危险因素,以利于更好地规避移植风险.方法 回顾性研究分析121例接受allo-HSCT的CML患者.预后评估参照EBMT积分,即Gratwohl积分,危险因素包括供者来源、患者年龄、患者移植前疾病状态、供患者性别差异、疾病确诊至移植时间.将患者分为3组:低危组(0～2分)、中危组(3～4分)和高危组(5分).结果 所有患者allo-HSCT后中位随访时间为37(1～126)个月,预期5年总生存(OS)率、无复发死亡(NRM)率及复发(RR)率分别为(56.8 ±5.0)%、(35.6±4.9)%和(12.9±3.7)%.其中低危组患者分别为(66.0±6.1)%、(28.8±6.0)%和(7.8±3.3)%,明显优于中危组[(47.2±8.7)%、(43.6±8.5)%和(18.7±8.1)%]和高危组[(16.8±15.2)%、(66.7±25.5)%和(50.0±25.0)%],差异具有统计学意义(P值分别为0.0015、0.045和0.0053).结论 EBMT危险因素积分系统能全面反映预测allo-HSCT治疗CML的疗效、复发率和移植相关死亡率.

Abstract：

Objective To analyze the risk factors of allogeneic stem cell transplantation (allo-SCT)for chroninc myeloid leukemia (CML) in an attempt to avoid transplant risks. Methods A total of 121 CML patients received allo-SCT were analyzed retrospectively. The risk analysis was based on the EBMT score (gratwohl score) which included donor type, age of patients, disease status before transplantation, donor/recipient sex match and time interval between diagnosis to allo-SCT. Patients were divided into 3 risk groups based on their EBMT score: low risk (score 0-2), inzermediate risk(3- 4 ) and high-risk (5). Results The median follow-up duration was 37(1-126) months. The estimated 5-year overall urvival (5 y-OS),non-relapse mortality (5 y-NRM) and relapse rate (5 y-RR) were (56.8 ±5.0)％, (35.6 ±4.9)％ and ( 12.9 ± 3.7) ％, respectively. The 5y-OS, NRM and RR were ( 66.0 ± 6.1 ) ％, ( 28.8 ± 6.0 ) ％ and ( 7.8 ± 3.3 ) ％ in the low risk group being significantly superior to both intermediate-risk [ (47.2 ± 8.7 ) ％,(43.6±8.5)％and(18.7 ±8.1)％] and high-risk group [(16.8±15.2)％, (66.7 ±25.5)％ and (50.0 ± 25.0) ％ ] (P = 0.0015, 0.045 and 0.0053 for OS, NRM and RR respectively ). Conclusion The EBMT risk score can effectively predict the overall outcome, relapse and transplant-related mortality of allo-SCT for CML patients.     

Low doses of alpha-interferon preparations in the treatment of patients with chronic myeloleukemia

AIM: To compare the effects of low-dose alpha-interferons with those of cytostatics (hydroxyurea or myelosan) on survival of patients and duration of chronic phase of chronic myeloid leukemia (CML). MATERIAL AND METHODS: 107 CML patients were divided into two groups. 28 patients (15 males and 13 females) aged 17-59 entered group treated with alpha-interferon drugs. 79 control patients (35 males and 44 females) aged 15-79 received standard chemotherapy (hydroxyurea or myelosan). RESULTS: 3-year survival in the study group and controls was 94 and 67.5%, respectively. 5-year survival--70.8 and 28.9%, respectively. The survival medians for the groups were 66 and 48 months, respectively. 36 months after CML diagnosis, chronic phase of the disease still continued in 90.2% of the study group patients and in 53.4% of patients on chemotherapy. 54 months after the diagnosis the chronic phase was registered in 56.5 and 24% of patients, respectively. The medians made up 54 and 39 months, respectively. CONCLUSION: Treatment of CML with low-dose alpha-interferons increases duration of the CML chronic phase and survival of CML patients.     

Developing a multivariable prognostic model for pancreatic endocrine tumors using the clinical data warehouse resources of a single institution

OBJECTIVE: Current staging systems are not accurate for classifying pancreatic endocrine tumors (PETs) by risk. Here, we developed a prognostic model for PETs and compared it to the WHO classification system. METHODS: We identified 98 patients diagnosed with PET at NewYork-Presbyterian Hospital/Columbia University Medical Center (1999 to 2009). Tumor and clinical characteristics were retrieved and associations with survival were assessed by univariate Cox analysis. A multivariable model was constructed and a risk score was calculated; the prognostic strength of our model was assessed with the concordance index. RESULTS: Our cohort had median age of 60 years and consisted of 61.2% women; median follow-up time was 10.4 months (range: 0.1-99.6) with a 5-year survival of 61.5%. The majority of PETs were non-functional and no difference was observed between functional and non-functional tumors with respect to WHO stage, age, pathologic characteristics or survival. Distant metastases, aspartate aminotransferase-AST and surgical resection (HR=3.39, 95% CI: 1.38-8.35, p=0.008, HR=3.73, 95% CI: 1.20-11.57, p=0.023 and HR=0.20, 95% CI: 0.08-0.51, p<0.001 respectively) were the strongest predictors in the univariate analysis. Age, perineural and/or lymphovascular invasion, distant metastases and AST were the independent prognostic factors in the final multivariable model; a risk score was calculated and classified patients into low (n=40), intermediate (n=48) and high risk (n=10) groups. The concordance index of our model was 0.93 compared to 0.72 for the WHO system. CONCLUSION: Our prognostic model was highly accurate in stratifying patients by risk; novel approaches as such could thus be incorporated into clinical decisions.     

Cytogenetic response as a marker of efficacy of chronic myeloid leukemia therapy with a BCR-ABL thyrosine kinase inhibitor glivek

AIM. Clinical practice with the drug glivek (imatinibe mesilate, ST1571) blocking activity of oncoprotein p210 shows that a cytogenetic response can be reached in 50-60% of patients with chronic myeloid leukemia (CML), in a late chronic phase (CP) in resistance to or intolerance of interferon alpha (IF-alpha) and in 24-43% of patients in the acceleration phase (AP). This study aimed at assessment of the rate and stability of a cytogenetic response (CR) and long-term results of survival in CML patients on glivek. MATERIAL AND METHODS. Glivek was given to 195 CML patients (median of the treatment duration was 42 months, 1-156 months, of the patients' age--46 years). 79 patients were in CP, 116--in AP. The doses were 400 mg/day and 116 mg/day, respectively. Karyotype was studied before the treatment and later after each 6 months. RESULTS: A considerable CR was achieved in 57% patients in CP and 44%--in AP. Of them complete CR was obtained in 48 and 35%, respectively. Marked CR is a favourable prognostic factor. Survival of patients with marked CR in CP (97% 0 and AP (89%) was significantly higher than without CR (58 and 47%, respectively, p < 0.05). Marked CR persisted in 95% cases in both phases of CML. In complete CR, a repeated study of karyotype revealed residual number of Ph+ cells both in CP and AP in 86% patients. This demonstrates necessity to take glivek continuously in achievement of a complete CR by karyotypic test. Glivek inhibits the disease progression, lowers annual lethality. 42-month (median of glivek treatment duration) overall survival reached 91 and 59% in CP and AP, respectively. CONCLUSION: CR is an integral index prognosticating CML course. Survival rose significantly in patients with marked CR both in CP and AP of CML. Marked CR is persistent in continuous glivek therapy. The rate of a CR depends much on the disease stage.     

A new palliative prognostic score: a first step for the staging of terminally ill cancer patients. Italian Multicenter and Study Group on Palliative Care

In recent years, extensive research has been performed to identify prognostic factors that predict survival in terminally ill cancer patients. This study describes the construction of a simple prognostic score based on factors identified in a prospective multicenter study of 519 patients with a median survival of 32 days. An exponential multiple regression model was adopted to evaluate the joint effect of some clinico-biological variables on survival. From an initial model containing 36 variables, a final parsimonious model was obtained by means of a backward selection procedure. The Palliative Prognostic Score (PaP Score) is based on the final model and includes the following variables: Clinical Prediction of Survival (CPS), Karnofsky Performance Status (KPS), anorexia, dyspnea, total white blood count (WBC) and lymphocyte percentage. A numerical score was given to each variable, based on the relative weight of the independent prognostic significance shown by each single category in the multivariate analysis. The sum of the single scores gives the overall PaP Score for each patient and was used to subdivide the study population into three groups, each with a different probability of survival at 30 days: (1) group A: probability of survival at 30 days > 70%, with patient score < or = 5.5; (2) group B: probability of survival at 30 days 30-70%, with patient score 5.6-11.0; and (3) group C: probability of survival at 30 days < 30%, with patient score > 11.0. Using this method, 178/519 (34.3%) patients were classified in risk group A, 205 (39.5%) patients were in risk group B, and 136 (26.2%) patients were in risk group C. The patients classified in the three risk groups had a very different survival experience (logrank = 294.8, P < 0.001), with a median survival of 64 days for group A, 32 days for group B, and 11 days for group C. The PaP Score based on simple clinical and biohumoral variables proved to be statistically significant in a multivariate analysis. The score is valid in this population (training set). An independent validation on another patient series (testing set) is required and is the object of a companion paper.