Pretreatment prognostic factors and treatment outcome in elderly patients with de novo acute myeloid leukemia.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) generally have an unfavorable clinical course and are under-represented in clinical trials. The aim of this study was to analyze the prognosis and treatment outcome of elderly AML patients. PATIENTS AND METHODS: We studied 205 AML patients aged 65 years or older at our hospital. Prior to study initiation, we designated 13 variables to be analyzed for their impact on complete remission (CR) rate and overall survival (OS). RESULTS: Induction regimen (standard chemotherapy) and good performance status (PS) (Eastern Cooperative Oncology Group PS 0-1) independently influenced the achievement of CR. Multivariate analysis also determined five poor prognostic factors for OS: poor PS (score 2-4), presence of comorbidities, elevated serum lactate dehydrogenase level (> or =2x upper normal limit), extreme leukocytosis (> or =100 x 10(9)/l) and marked thrombocytopenia (< or =20 x 10(9)/l). Age was not an independent contributing factor in terms of either CR attainment or OS duration. Low-risk patients, who possessed one or less non-leukocytosis poor prognostic factor, had significantly longer disease-free survival and OS than their high-risk counterparts. CONCLUSIONS: Elderly AML patients should be risk-stratified at diagnosis. Anthracycline-based induction chemotherapy would be the best therapeutic option for such patients.     

老年正常核型急性髓系白血病患者临床特征及预后分析

目的 探讨老年正常核型急性髓系白血病(CN-AML)患者的临床特征及其预后相关因素.方法 回顾性分析104例初治老年CN-AML(M3除外)患者的临床资料.用χ2检验分析完全缓解(CR)的影响因素.用Kaplan-Meier法进行生存分析,并采用Log-rank检验对预后相关影响因素进行单因素分析,采用Cox回归模型进行多因素分析.结果 104例患者中首次化疗后可评价疗效者72例,CR率为38.9%(28/72),总有效率为55.6%(40/72).白细胞计数(WBC)<100×109/L、NPM1突变阳性患者的CR率较高[59.4%(38/64)比12.5%(1/8),83.3%(10/12)比36.4%(8/22),均P<0.05].104例患者中位总生存(OS)时间为6.9个月.单因素分析显示年龄≥70岁、继发AML、高WBC(≥100×109/L)、FLT3-内部串联重复(ITD)突变阳性、CD7阳性、达CR诱导疗程数>2个以及Charlson合并疾病指数(CCI)评分≥2分的患者OS时间较短(均P<0.05).多因素分析显示FLT3-ITD突变阳性(HR=7.61,95%CI 1.80~32.11,P=0.006)及达CR诱导疗程数>2个(HR=10.11,95%CI 2.38~43.03,P=0.002)是患者OS的独立不良影响因素.结论 老年CN-AML患者的预后是多种因素综合作用的结果,FLT3-ITD突变阳性、 达CR诱导疗程数>2个是老年CN-AML患者不良OS的独立影响因素.     

Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome

BACKGROUND: Elderly patients (age > or = 65 years) with acute myeloid leukemia (AML) generally have a poor prognosis. AML-type therapy results are often derived from studies in younger patients and may not apply to elderly AML. Many investigators and oncologists advocate, at times, only supportive care or frontline single agents, Phase I-II studies, low-intensity regimens, or 'targeted' therapies. However, baseline expectations for outcomes of elderly AML with 'standard' AML-type therapy are not well defined. The aim was to develop prognostic models for complete response (CR), induction (8-week) mortality, and survival rates in elderly AML, which would be used to advise oncologists and patients of expectations with standard AML type therapy, and to establish baseline therapy results against which novel strategies would be evaluated. METHODS: A total of 998 patients age > or = 65 years with AML or high-risk myelodysplastic syndrome (> 10% blasts) treated with intensive chemotherapy between 1980 and 2004 were analyzed. Univariate and multivariate analyses of prognostic factors associated with CR, induction (8-week) mortality, and survival used standard methods. RESULTS: The overall CR rate was 45% and induction mortality 29%. Multivariate analysis of prognostic factors identified consistent independent poor prognostic factors for CR, 8-week mortality, and survival. These included age > or = 75 years, unfavorable karyotypes (often complex), poor performance (3-4 ECOG [Eastern Cooperative Oncology Group]), longer duration of antecedent hematologic disorder, treatment outside the laminar airflow room, and abnormal organ functions. Patients could be divided into: 1) a favorable group (about 20% of patients) with expected CR rates above 60%, induction mortality rates of 10%, and 1-year survival rates above 50%; 2) an intermediate group (about 50-55% of patients) with expected CR rates of 50%, induction mortality rates of 30%, and 1-year survival rates of 30%; and 3) an unfavorable risk group (about 25-30% of patients) with expected CR rates of less than 20%, induction mortality rates above 50%, and 1-year survival rates of less than 10%. CONCLUSIONS: Prognostic models, based on standard readily available baseline characteristics, were developed for elderly patients with AML, which may assist in therapeutic and investigational decisions. These predictive models, based on a retrospective analysis, will require validation in independent study groups.     

77例老年急性髓性白血病患者的预后因素分析

背景与目的:老年急性髓性白血病(acutemyelogenousleukemia,AML)有独特的生物学及临床特征,患者对治疗的反应差、生存期短。本研究旨在探讨老年AML的预后因素。方法:对上海市第一人民医院1994～2005年收治的77例老年AML患者可能影响预后的因素进行Kaplan-Meier生存分析,然后对有意义的因素进行Cox比例风险模型分析。结果:可评价患者72例。年龄60～70岁者中位生存期(350天)显著长于年龄>70岁者(60天)(P<0.001),CR率显著提高(71.4%vs.29.4%,P=0.001);生存状态(performancestatus,PS)0或1分者中位生存期(402天)显著长于2、3、4分者(31天)(P<0.001),CR率显著提高(75.0%vs.15.0%,P<0.001);原发者中位生存期(98天)显著长于继发者(32天)(P=0.007),CR率显著提高(50.0%vs.0%,P=0.023);使用亚标准剂量的蒽环类药物者中位生存期(293天)显著长于减量使用者(35天)(P=0.006),CR率显著提高(63.6%vs.33.3%,P=0.02)。骨髓原始细胞(bonemarrowblastcell,BMblast)比率≤50%者中位生存期(98天)显著长于>50%者(55天)(P=0.006);预后良好核型者中位生存期(293天)显著长于预后不良或正常核型者(31天)(P=0.005);CD34阴性者中位生存期(201天)显著长于阳性者(36天)(P<0.001)。外周血白细胞数量(peripheralbloodwhitebloodcellcount,PBWBC)大于10×109/L者CR率(50.0%)显著高于PBWBC小于10×109/L者(25.0%)(P=0.043);化疗者CR率(50.0%)显著高于支持治疗者(0%)(P=0.001)。Cox比例风险模型分析显示影响生存期的7个因素均具有独立性和统计学意义。结论:年龄>70岁、PS为2～4分、骨髓原始细胞比率>50%、继发性、不良核型、CD34 以及蒽环类药物剂量强度是影响患者生存期的主要预后因素,蒽环类药物剂量显著影响CR率。     

Relapsed Childhood Acute Myeloid Leukemia: Experience from a Single Tertiary Center in Thailand

Background: Few studies have examined survival outcomes in relapsed childhood acute myeloid leukemia (AML) in resource-limited countries. This study aimed to evaluate the prognostic factors and survival outcomes of relapsed childhood AML in Thailand. Methods: The medical records of AML patients aged 0-15 years treated in a major tertiary center in Southern Thailand between December 1979 and December 2019 were reviewed retrospectively. The overall survival (OS) was calculated using the Kaplan-Meier method. Results: A total of 316 AML patients were included and relapse occurred in 98 (31%) patients. Of these, 57 (58.2%) and 41 (41.8%) patients had early [≤1 year from first complete remission (CR1)] and late (>1 year from CR1) relapses, respectively. Only 54 (55.1%) patients received chemotherapy after relapse. The 3-year OS of all relapsed patients was 3.5%. The 3-year OS of patients with early and late relapse were 0% and 8.5%, respectively (p=0.002). The 3-year OS of patients who received chemotherapy and those who did not were 6.5% and 0%, respectively (p <0.0001). The median survival time of patients who did not receive chemotherapy was 1.7 months. The 3-year OS of patients who achieved second complete remission (CR2) and those who did not were 12.6% and 0%, respectively (p <0.001). Conclusion: The relapsed AML rate was 31% and the survival outcome was poor with a 3-year OS of 3.5%. The adverse prognostic factors were early relapse, failure to achieve CR2 and those who did not receive chemotherapy after relapse.     

Outcome of patients with acute myelogenous leukemia after second salvage therapy

BACKGROUND: Although the prognosis is poor for patients with acute myelogenous leukemia (AML) who have disease recurrence after frontline therapy, this is a general reflection of first salvage therapies. The outcome of patients undergoing second salvage therapy in relation to complete response (CR) rates and survival has not been documented. The authors analyzed the outcome of patients with AML undergoing second salvage therapy, and identified prognostic factors associated with response and survival. METHODS: The records of 594 patients with AML undergoing second salvage therapy from 1980 until 2004 were reviewed. The patient median age was 50 years. Salvage therapy included allogeneic stem cell transplantation (SCT) in 74 patients, standard-dose cytosine arabinoside (ara-C) combinations in 30 patients, high-dose ara-C combinations in 171 patients, non-ara-C combinations in 73 patients, and Phase I-II single agents in 246 patients. RESULTS: Overall, 76 patients (13%) achieved CR. The median CR duration was 7 months. The median survival was 1.5 months, and the 1-year survival rate was 8%. A multivariate analysis of prognostic factors for CR identified the following 6 independent adverse factors: first CR duration < 6 months; second CR duration < 6 months; salvage therapy not including allogeneic SCT; non-inversion 16 AML; platelet counts < 50 x 10(9)/L, and leukocytosis > 50 x 10(9)/L. Patients were divided into low-risk (1-2 adverse factors; 8%), intermediate 1 (3 factors; 20%), intermediate 2 (4 factors; 38%), and high-risk groups (5-6 factors; 33%) with respective CR rates of 54%, 26%, 8%, and 0%. The respective 1-year survival rates were 36%, 21%, 6%, and 1%. A multivariate analysis for survival identified the following 7 independent adverse factors: first CR duration < 12 months; second CR duration < 6 months; bilirubin level > or = 1 mg/dL; albumin level < 3 g/dL; age > 60 years; bone marrow blasts > or = 50%; and year of therapy before 1991. Patients were divided into low-risk (0-2 adverse factors; 39%), intermediate (3 factors; 27%), and high-risk groups (> or = 4 factors; 34%) with estimated 1-year survival rates of 22%, 6%, and 0%, respectively. The respective CR rates were 26%, 8%, and 2%. CONCLUSIONS: The current analysis established the outcome and prognostic factors associated with second salvage therapy in AML. It also proposed risk models and groups that could be used for comparison of results of present and future investigational strategies.     

Clinical outcome of older adults with acute myeloid Leukemia: An analysis of a large tertiary referral Center over two decades

ObjectiveIn older adults with acute myeloid leukemia (AML), the overall outcome is still dismal and long-term data on survival are scarce, particularly outside of clinical trials. Here, we assess characteristics, prognostic factors and long-term survival in patients ≥60 years who were treated for AML at our center over the past 17 years.Methods590 older adults with newly diagnosed AML were characterized according to Eastern Cooperative Oncology Group (ECOG) score, Charlson comorbidity index (CCI), European LeukemiaNet (ELN) risk, type of therapy, serum ferritin (SF) and further baseline characteristics. Survival analysis was performed accordingly.ResultsMedian age was 68 years and most patients were in good general condition. Median follow-up was 55.8 months. Of all patients, 66% received intensive chemotherapy (IC) +/? allogeneic hematopoietic stem cell transplantation (allo-HSCT). The remaining cohort received palliative chemotherapy (PC, 26%) or best supportive care only (BSC, 8%). Enrollment rate for interventional clinical trials was 26%. 5-year overall survival (OS) and relapse-free survival (RFS) were 18% (median 12.5 months) and 11,5% (median 10.0 months). Long-term survival was independently influenced by ECOG score, ELN risk group, baseline SF, previous myocardial infarction, and choice of therapy, but not consistently by age or CCI. Considering therapeutic subgroups, the contribution of particular parameters in predicting OS was most compelling in IC patients, but less consistent with PC or BSC.ConclusionOur results provide thorough insights into prognostication within therapeutic subgroups and emphasize the need for more detailed prognostic algorithms and routine geriatric assessment in the treatment of older adults with AML.     

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.     

Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome

BACKGROUND:

Secondary acute myeloid leukemia (AML) from an antecedent myelodysplastic syndrome (MDS)/myeloproliferative neoplasm is associated with a poor prognosis. The authors evaluated predictive factors in patients with secondary AML treated with anthracycline‐based induction therapy.

METHODS:

This was a retrospective review of secondary AML patients treated with induction therapy. Age, International Prognostic Scoring System, Eastern Cooperative Oncology Group performance status, cytogenetics, duration of MDS/myeloproliferative neoplasm, and prior MDS/myeloproliferative neoplasm treatment were evaluated for their impact on complete response (CR), CR with low platelets, and overall survival (OS).

RESULTS:

The authors evaluated 61 secondary AML patients who received induction chemotherapy; 59% (36 patients) achieved CR/CR with low platelets (95% confidence interval [CI], 46%‐71%), and median OS was 6.5 (95% CI, 3.9‐8.1) months. Three factors were associated with lower CR/CR with low platelets and OS: poor risk cytogenetics, prior treatment with hypomethylating agents or lenalidomide, and longer time to transformation to AML. Of those treated with hypomethylating agents or lenalidomide, 32% achieved CR/CR with low platelets versus 78% in the group not treated with a hypomethylating agent or lenalidomide (odds ratio [OR], 0.13; 95% CI, 0.04‐0.42). Median OS for those treated with a hypomethylating agent or lenalidomide was 3.7 versus 10.5 months for those not treated with a hypomethylating agent or lenalidomide (P < .0001). The CR/CR with low platelets rate for those with intermediate risk cytogenetics was 70% versus 35% for those with poor risk (OR, 4.33; 95% CI, 1.38‐13.6). Those with poor risk cytogenetics had a median OS of 2.8 versus 7.5 months for those with intermediate risk (P = .01).

CONCLUSIONS:

Prior treatment with hypomethylating agents or lenalidomide, poor risk cytogenetics, and longer time to transformation to AML are independent negative predictive factors for response and OS in patients with secondary AML after induction therapy. Cancer 2011. © 2010 American Cancer Society.     

TE T2基因阳性急性髓细胞白血病38例分析

目的：分析TET2基因阳性急性髓细胞白血病（AML）患者的临床及实验室特点,探讨可能影响治疗效果的因素。方法：收集38例TET2基因突变阳性AML患者的临床及实验室资料,并回顾性分析其中可能影响治疗效果的因素,TET2基因检测采用实时定量PCR方法。结果：38例患者中21例接受化疗,获得完全缓解（CR）12例（57．14％）,未缓解（NR）5例（23．81％）,疾病进展（PD）4例（19．05％）。应用不同化疗方案治疗后缓解率不同,应用去甲基化治疗的4例第一个疗程治疗后均达到完全缓解,未应用去甲基化治疗的17例中CR 8例（47．06％）、NR 5例（29．41％）、PD 4例（23．53％）。白血病细胞免疫表型CD34阴性、CD13阴性、CD33阳性者化疗后CR率更高,差异具有统计学意义（P＜0．05）。TET2基因阳性AML患者的CR率与年龄、性别、发病时白细胞计数、血红蛋白、血小板计数、白血病细胞免疫表型（CD56、CD9、HLA－DR）、是否伴有其他预后基因及复杂染色体核型无明显相关性。结论：TET2基因阳性AML患者的CR率与化疗方案及白血病细胞免疫表型CD34、CD13及CD33相关。去甲基化治疗可提高TET2基因阳性AML患者的CR率。影响TET2基因阳性AML患者疗效及长期生存的因素尚需进一步探讨。     

Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia

BACKGROUND: Modern intensive chemotherapy regimens have improved the prognosis for patients with adult acute lymphocytic leukemia (ALL). With these regimens, the complete response rates are now reported to be > 80%, and the long-term survival rates range from 30% to 45%. The current analysis updated the long-term results with the original hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) program, with a median follow-up time of 63 months. METHODS: Between 1992 and 2000, 288 patients were treated with Hyper-CVAD. The median age of the patients was 40 years, and 59 patients (20%) were > or = age 60 years. The incidence of Philadelphia chromosome (Ph)-positive ALL was 17%, and the incidence of of T-cell ALL was 13%. RESULTS: A complete response (CR) was achieved in 92% of patients. The induction mortality rate was 5% (2% if the patient's age was < 60 years, and 15% if the patient's age was > or = 60 years). With a median follow-up time of 63 months, the 5-year survival rate was 38% and the 5-year CR duration rate was 38%. Multivariate analysis of prognostic factors for CR duration identified the following adverse factors: age > or = 45 years, leukocytosis > or = 50 x 10(9)/L, poor performance status (an Eastern Cooperative Oncology Group score of 3-4), Ph-positive disease, French-American-British L2 morphology, > 1 course to achieve CR, and Day 14 bone marrow blasts > 5%. Patients were divided into low-risk (risk score 0-1; 37%), intermediate risk (risk score 2-3; 36%), and poor-risk groups (risk score > or = 4; 27%) with 5-year CR duration rates of 52%, 37%, and 10%, respectively. CONCLUSIONS: Compared with the previous VAD regimens, Hyper-CVAD was associated with significantly better CR rates, CR duration, and survival. The long-term follow-up results of Hyper-CVAD were favorable. Comparison of Hyper-CVAD with other established adult ALL regimens is warranted.     

急性髓系白血病预后相关因素分析

目的 探讨成年急性髓系白血病(AML)患者的预后影响因素.方法 回顾性分析182例初治AML患者临床资料,探讨患者性别、年龄(以60岁为界)、初治白细胞计数(≥30× 109/L)、骨髓细胞学免疫表型、细胞遗传学、异基因造血干细胞移植(allo-HSCT)和治疗1个疗程获得完全缓解(CR)等因素与总生存(OS)及无事件生存(EFS)的关系.结果 182例AML患者的中位年龄49岁(14～ 80岁),中位随访时间9.7个月(0.5～75.5个月),首次化疗达CR 107例,总有效率为65.9％(120/182),年龄≥60岁、CD64阴性、染色体高危组及首次诱导未达CR患者的总CR率低于无上述因素者.单因素生存分析提示年龄≥60岁、细胞遗传学高危组、CD19阴性、CD11b阳性、CD64阴性、未行allo-HSCT、首次诱导未达到CR的患者OS及EFS较短(P＜0.05),多因素分析显示年龄、细胞遗传学表达、CD11b、CD64、是否行allo-HSCT、首次诱导能否达CR是患者OS的独立预后因素,细胞遗传学表达、CD64表达、是否行allo-HSCT及首次诱导能否达CR是患者EFS的独立预后因素.结论 根据AML相关因素进行预后分析判断,有利于临床医生早期制订个体化治疗方案,对于延长患者生存期有重要意义.     

CD56 and CD11b Positivity with Low Smac/DIABLO Expression as Predictors of Chemoresistance in Acute Myeloid Leukaemia: Flow Cytometric Analysis

Background: Resistance to chemotherapy is a major obstacle to curing acute myeloid leukaemia (AML), andseveral antigens are claimed to play primary roles in this resistance. Purpose: The aim of this study was to evaluatethe roles of CD56, CD11b and Smac/DIABLO gene expression levels as prognostic markers of the clinical outcome,response to chemotherapy and survival of AML patients. Materials and Methods: A cross-sectional observationalstudy was conducted on 60 naïve-AML patients who received induction therapy with mitoxantrone and cytarabinecombined with a high dose of cytarabine. The CD56,CD11b and Smac/DIABLO expression levels were assessed usingflow cytometry at diagnosis and were analysed for correlation with the possible associated risk factors, response tochemotherapy, and median duration of disease-free survival (DFS) and overall survival (OS). Results: The overall resultsrevealed that AML patients who exhibited positive expression for CD56 and CD11b had short median durations of DFSand OS.(P = 0.019, 0.006, 0.029 and 0.024, respectively). Additionally, low Smac/DIABLO expression had a negativeimpact on treatment outcome in terms of CR rate (p=0.012) and reduced DFS (p=0.000) and OS(p=0.000) values.Conclusions: CD56 and CD11b positivity and low Smac/DIABLO expression are important predictive factors forthe occurrence of chemoresistance, in addition to other risk factors, among AML patients.     

Clinical features,survival and prognostic factors of primary testicular diffuse large B-cell lymphoma

Objective： To assess the clinical features, survival and prognostic factors of primary testicular diffuse large B-cell lymphoma （DLBCL）. Methods： A retrospective study of 37 patients with primary testicular DLBCL was carried out from November 2003 to May 2012. Their clinical features, survival and prognostic factors were analyzed. Results： During a median follow-up period of 39.8 months （5.4-93.0 months）, the median progression-free survival （PFS） was 26.2 months （95% CI：0-65 months） and the 3-year overall survival （OS） rate was 78.4%. Within the whole cohort, the factors significantly associated with a superior PFS were limited stage （stage Ⅰ/Ⅱ）, lactate dehydrogenase （LDH） ≤245 U/L, international prognostic index （IPI） ≤1, primary tumor diameter 〈7.5 cm, and patients who had complete response （CR） and received doxoruhicin-contained chemotherapy （P〈0.05）. There was a trend toward superior outcome for patients who received combined therapy （surgery/ chemotherapy/radiotherapy） （P=0.055）. Patients who had CR, primary tumor diameter 〈7.5 cm and IPI score ≤1 were significantly associated with longer PFS at multivariate analysis. Conclusions： Primary testicular DLBCL had poorer survival. CR, primary tumor diameter and IPI were independent prognostic factors. The combined therapy of orchectomy, doxorubicin-contained chemotherapy and contralateral testicular radiotherapy （RT） seemed to improve survival.     

Timed-sequential chemotherapy with concomitant granulocyte colony-stimulating factor for newly diagnosed de novo acute myelogenous leukemia.

EMA, consisting of etoposide, mitoxantrone, and cytarabine, is a timed-sequential chemotherapy (TSC) regimen and an efficacious option for induction treatment of acute myelogenous leukemia (AML). Hematopoietic growth factors (HGFs) have been shown to recruit leukemic blasts into cell cycle. We postulated the addition of granulocyte colony-stimulating factor (G-CSF) to EMA (EMA-G) might enhance treatment efficacy. EMA-G consisted of mitoxantrone on days 1-3, cytarabine on days 1-3 and 8-10, etoposide on days 8-10, and G-CSF from day 4 until absolute neutrophil count (ANC) >500/microl. In total, 28 patients were enrolled. All patients had newly diagnosed de novo AML. The median age was 42 years. Of the 27 patients with cytogenetic analysis, six had favorable karyotype, 18 intermediate karyotype, and three unfavorable karyotype. The median follow-up was 37.5 months. The median time for both ANC recovery and last platelet transfusion was 26 days. The toxicities associated with this regimen were no more than those expected with the standard chemotherapy. In all, 24 (86%) patients achieved complete remission (CR), three (11%) patients had no response, and one patient died within 24 h of induction therapy before response could be evaluated. Of the 24 patients who achieved CR, 22 received high-dose cytosine arabinoside and two received allogeneic bone marrow transplant as initial postremission therapy. For the whole cohort, the estimated 3-year survival rate was 67%. The median relapse-free survival was 30.5 months. We conclude that EMA-G regimen is a safe regimen and administration of G-CSF during and after induction treatment is not associated with prolongation of marrow aplasia or acceleration of leukemia relapse. It is efficacious for induction therapy for newly diagnosed de novo AML. A high CR rate can be achieved with only one course of this chemotherapy.     

The benefit of induction chemotherapy in patients age > or = 75 years

BACKGROUND: Patients age > or = 75 years with acute myeloid leukemia (AML) generally are offered palliative treatments instead of induction chemotherapy. The authors conducted a retrospective study comparing the outcomes among these elderly patients with the outcomes among younger patients to assess the impact of intensive treatment approaches in this age group. METHODS: One hundred ten consecutive patients age > or = 75 years with newly diagnosed AML (excluding patients with acute promyelocytic leukemia) were treated in the authors' center over 10 years. Initial treatment was comprised of anthracycline-based induction chemotherapy (i.e., intravenous idarubicin or daunorubicin for 3 days plus cytarabine [ARAC] for 7 days [3 + 7 regimen] or oral idarubicin) for 62 patients (56%), antimetabolite-based chemotherapy (including low-dose ARAC, oral 6-mercaptopurine plus methotrexate, or hydroxyurea) for 40 patients (36%), and supportive care only for 8 patients (7%). Results were compared with the results from 200 patients ages 65-74 years who were treated during the same period. RESULTS: A complete response (CR) to anthracycline-based induction therapy was achieved by 23 of 62 patients (37%), and the 2-year overall survival rate was 22% (which was not statistically different from the group of patients ages 65-74 years). In a multivariate analysis of the entire study group (310 patients), treatment (anthracycline-based vs. other) and age as continuous variable were found to affect survival significantly. In a Landmark analysis, the achievement of a CR translated into improved survival in patients age > or = 75 years. CONCLUSIONS: Patients age > or = 75 years should not be excluded systematically from intensive chemotherapy regimens. Decisions should be based on stratification systems that include functional status and comorbidity assessments as well as prognostic factors, such as cytogenetics.     

Disease biology rather than age is the most important determinant of survival of patients > or = 60 years with acute myeloid leukemia treated with uniform intensive therapy

BACKGROUND: The objectives of the current study were to evaluate the outcome of patients > or = 60 years with acute myeloid leukemia (AML) treated uniformly with high-dose daunorubicin containing induction and modified high-dose cytosine arabinoside containing postremission therapy, and to identify factors predictive of complete disease remission (CR) and survival. METHODS: Between 1998 and 2002, the authors treated 117 newly diagnosed patients (acute promyelocytic leukemia excluded) with AML > or = 60 years (median, 67 years; range, 60-82 years). Karyotype (Medical Research Council classification) at diagnosis was categorized as good risk (n = 3), intermediate risk (n = 69), adverse risk (n = 26), and suboptimal/not done (n = 19). A normal karyotype was seen in 41 patients and 40 (34%) had secondary AML. RESULTS: The outcome of induction included the following: CR, 62 (53%); early death, 5 (4%); death during hypoplasia, 14 (12%); and resistant disease, 36 (31%). The 3-year event-free (EFS) and overall survival (OS) rates were 9% (95% confidence interval [95% CI], 3-16%) and 17% (95% CI, 9-29%), respectively. In a univariate analysis, cytogenetics, lactate dehydrogenase level, leukocyte count, and performance status were the significant factors for EFS and OS. Age was not a significant prognostic factor for either CR or survival. In a multivariate model, adverse-risk cytogenetics, previous history of myelodysplastic syndrome or antecedent hematologic disorder, and high leukocyte count (> 30 x 10(9)/L) were independent adverse prognostic factors for survival. The impact of adverse karyotype on EFS and OS was time dependent and was observed after 50 and 150 days, respectively. CONCLUSIONS: The authors concluded that candidacy for intensive therapy in older patients should be based on biologic features of disease and fitness, rather than on age.     

Quantitation of minimal residual disease in acute myeloid leukemia by tryptase monitoring identifies a group of patients with a high risk of relapse.

PURPOSE: Recent data suggest that tryptase is produced by blast cells in a group of patients with acute myeloid leukemia (AML). In these patients, serum tryptase levels are elevated at diagnosis and decrease to normal (<15 ng/mL) or near normal values in those achieving complete hematologic remission (CR) after chemotherapy. PATIENTS: In this study, we examined the value of tryptase as a marker of minimal residual AML. In 61 patients with de novo AML exhibiting elevated serum tryptase (>15 ng/mL) at diagnosis, tryptase levels were measured serially during and after chemotherapy by a fluoroenzyme immunoassay. RESULTS: Of the 61 patients, 42 (68.9%) entered hematologic CR in response to induction chemotherapy. Twenty-nine of these 42 patients also entered biochemical remission (BR) defined by a decrease of tryptase levels to normal (<15 ng/mL). The remaining 13 patients exhibited elevated enzyme levels despite of hematologic CR. As assessed by multivariate analysis, the elevated tryptase in CR was found to be an independent prognostic variable concerning disease-free survival. Thus, AML relapses occurred in 15 of 29 patients with CR + BR (52%) and in 12 of 13 patients with CR without BR (92%), resulting in a significantly reduced probability of continuous CR for patients with CR without BR (P < 0.05). In all patients with continuous hematologic CR, tryptase levels remained constantly normal, whereas a recurrent elevation of tryptase in CR was invariably followed by a hematologic relapse. CONCLUSION: A persistently elevated tryptase level in AML in CR is indicative of minimal residual AML and associated with a high risk of relapse.     

Continuous drip infusion of low dose cytarabine and etoposide with granulocyte colony-stimulating factor for elderly patients with acute myeloid leukaemia ineligible for intensive chemotherapy

BACKGROUNDS AND OBJECTIVES: The optimal strategy for the management of elderly patients with acute myeloid leukaemia (AML) is still controversial. We previously reported the effectiveness of low dose cytarabine (Ara-C) and etoposide (VP-16) (AV therapy) for those elderly AML patients ineligible for intensive chemotherapy. We initiated the present feasibility study to improve the efficacy by using glanulocyte-colony stimulating factor (G-CSF) with AV therapy (AVG therapy). PATIENTS AND METHODS: The eligibility for enrolment was AML patients according to the World Health Organization (WHO) criteria who were over 60 years of age and who had difficulty in tolerating intensive chemotherapy due to their poor performance status (PS) or some comorbidities. They were given continuous drip infusion of Ara-C (20 mg/body) and VP-16 (50 mg/body) for 7-14 days, and were also simultaneously administered G-CSF (150 microg/m2) once daily. RESULTS: The median age of consecutively enrolled 25 patients was 73 years. Eighteen (72%) patients achieved complete remission (CR). The 1-year overall survival (OS) and the 3-year OS rates were 69% and 22%, respectively. The 1-year disease free survival (DFS) rate in CR patients was 44%. The major regimen related toxicities of grade 3 or 4 were only febrile neutropenia in 15 patients (60%). No regimen-related mortality was observed. CONCLUSION: AVG therapy was therefore found to be an effective and well-tolerated regimen for remission induction in elderly AML patients with poor PS or comorbidity.     

HA联合替尼泊苷或表柔比星治疗急性髓系白血病疗效观察

目的:探讨高三尖杉脂碱+阿糖胞苷联合替尼泊苷（HAT）或表柔比星（HAE)治疗急性髓系白血病（AML)的疗效及毒副反应。方法:回顾性分析了初治急性髓系白血病患者以HAT或HAE方案进行诱导化疗的疗效和毒性反应。统计完全缓解率（CR）及总生存（OS）率分析。结果:初治AML患者在HAT和HAE组一疗程诱导化疗CR率分别为90%和81%。两组中CR患者3年实际OS率分别为33.3%和53.8%。至随访结束HAT组无复发生存22.2%,HAE组30.7%。预期5年总生存率HAT组为20%,HAE组为44%。化疗相关的毒副反应主要为造血抑制和感染,患者可以耐受。结论:HA联合替尼泊苷或表柔比星诱导化疗疗效满意,不良反应可以耐受,可以作为一线诱导化疗方案。