成人急性早幼粒细胞白血病治疗方案与疗效分析

目的:研究难治或复发性急性早幼粒细胞白血病(APL)不同诱导缓解方案的疗效,诱导缓解后不同巩固维持治疗方案对预后和生存率的影响。方法:APL57例(包括初次诱导未缓解与第1次复发的APL),按照不同的诱导缓解治疗方案分组(含砷剂组:单用亚砷酸组及亚砷酸加全反式维甲酸(ATRA)联合治疗组;不含砷剂组:单用化疗组)比较各组的完全缓解率(CR)和达到CR的时间;按照不同的缓解后治疗方案分组(亚砷酸/全反式维甲酸/化疗序贯治疗组;化疗组)比较各组复发率、总生存率(OS)、无病生存率(DFS)。采用SPSS10.0软件进行统计学分析(χ2检验、t检验、MannWhitney检验、Kaplan-Meier生存曲线、Log-Rank检验)。结果:含砷剂(亚砷酸)组诱导CR率可达80,明显高于不含亚砷酸组CR率(61.4±9.04)(P<0.05);含砷剂组达到CR时间(36.36±9.56)d,较不含亚砷酸组(47.26±22.21)d显著缩短(P<0.01)。诱导缓解后的治疗对生存影响显著,全反式维甲酸、亚砷酸、蒽环类化疗序贯治疗组复发率9.0,低于化疗组38.9(P<0.05)。序贯治疗组1年、3年生存率是(74.56±4.57)、(60.09±4.64),而化疗组1年、3年生存率仅为(57.84±8.01)、(49.13±13.14)(P<0.05)。序贯治疗组的3年DFS(71.48±1.94),显著高于化疗组的DFS(51.32±13.72)(P<0.05)。结论:含有亚砷酸诱导缓解方案诱导缓解率高,达CR时间短。全反式维甲酸、亚砷酸、蒽环类化疗序贯治疗复发率低,长期生存率高。监测PML/RARa融合基因对提示复发和调整治疗有重要意义。     

急性早幼粒细胞白血病治疗的研究

急性早幼粒细胞白血病(APL)的治疗经历了蒽环类药物为主的联合化疗,全反式维甲酸(AT-RA)和亚砷酸(As2O3)治疗3个阶段,由于早幼粒细胞白血病细胞上存在PML/RARα融合基因,ATRA和As2O3作用于PML/RARα融合基因诱导分化及凋亡,使APL在治疗上有很大的突破,甚至可以治愈。尽管如此,仍有约12%～30%的患者在早期诱导缓解失败、复发或死于相关并发     

序贯诱导治疗急性早幼粒细胞白血病长期生存分析

近年来急性早幼粒细胞白血病(APL)的分子学发病机制逐渐被阐明,其治疗经历了蒽环类药物为主的联合化疗、全反式维甲酸(ATRA)和亚砷酸(ATO)治疗3个阶段。ATRA的应用使得诱导完全缓解(CR)率从单纯蒽环类为主化疗的50%〔1〕提     

原发高白细胞型急性早幼粒细胞白血病66例临床特征及治疗研究

目的探讨原发高白细胞型急性早幼粒细胞白血病(APL)的临床特点及有效的治疗方法。方法回顾性分析1993年10月至2006年8月苏州大学附属第一医院收治的66例原发高白细胞型APL患者和152例非高白细胞型APL患者的临床资料,并对高白细胞型患者按治疗方案的不同进行了分组比较。结果高白细胞组APL患者早期病死率、弥散性血管内凝血(DIC)和维甲酸综合征(RAS)发生率分别为30.3%,57.6%和31.8%,均高于非高白细胞组(7.2%,38.1%和21.1%)(P<0.05),而完全缓解(CR)率较低(63.6%对88.2%)(P<0.05)。高白细胞组患者中61例接受了诱导治疗,其中31例单用维甲酸治疗,21例维甲酸联合亚砷酸治疗,9例单用亚砷酸治疗,各组早期病死率分别为27.3%,14.3%和55.6%,CR率分别为67.7%,81.0%和44.4%。61例患者中41例在接受诱导分化治疗的同时加用化疗,其CR率为80.5%,总病死率为19.5%;而未加用化疗的20例患者其CR率为45.0%,总病死率为55.0%,两组比较差异有显著性意义(P<0.05)。结论原发高白细胞型APL较非高白细胞型APLCR率低,早期病死率高,DIC、RAS发生率高。维甲酸加亚砷酸双诱导并联合小剂量化疗是治疗高白细胞型APL的最有效的方案,可明显减少早期病死率,提高CR率。     

全反式维甲酸联合三氧化二砷治疗初发急性早幼粒细胞白血病的疗效观察

目的观察全反式维甲酸(ATRA)联合三氧化二砷(As2O3)治疗急性早幼粒细胞白血病(APL)的完全缓解(CR)率和不良反应。方法ATRA25mg.m-2.d-1,As2O3(0.1%溶液)10mL/d联合治疗初发APL直至CR。根据外周血白细胞计数、维甲酸综合征,以及肝功能变化调整ATRA和As2O3的剂量。结果29例初发APL患者,早期死亡2例,27例获得CR,CR率93.1%。获得CR的平均时间为(25.2±3.5)d。没有发现严重不良反应。结论ATRA联合As2O3治疗初发APL疗效好,不良反应患者能耐受。     

三氧化二砷联合全反式维甲酸治疗复发及难治性急性早幼粒细胞白血病14例临床分析

急性早幼粒细胞白血病(APL)是特殊类型的急性髓细胞白血病(AML),其发病占AML的10%～15%.1997～2004年,我院应用三氧化二砷(AS2O3)联合全反式维甲酸(ATRA)治疗复发和难治性APL患者14例.现报告如下.     

全反式维甲酸联合三氧化二砷治疗初发急性早幼粒细胞白血病的临床观察

目的:观察全反式维甲酸(ATRA)联合三氧化二砷(As2O3)治疗初发急性早幼粒细胞白血病(APL)的疗效和不良反应。方法:对联合应用ATRA和As2O3治疗的55例APL患者的完全缓解(CR)率、达CR所需时间、早期病死率和不良反应进行观察,并与单独应用ATRA组31例和As2O3组26例进行比较。联合用药组治疗方法为ATRA25mg·m-2.d-1,As2O30.16mg·kg-1.d-1直至CR,根据外周血白细胞计数、不良反应调整ATRA和As2O3的剂量。结果:联合用药组与单独应用ATRA、As2O3组相比,CR率无统计学意义(分别为96.3%、83.9%、84.6%,均P>0.05);联合用药组获得CR所需的时间短于单独用药组(平均时间分别为25d、47d、41d,均P<0.05),早期死亡率亦低于单独用药组(分别为3.6%、12.9%、11.5%,均P<0.05),与单独用药组相比,联合用药组的不良反应并未增加。结论:联合用药诱导初发APL缓解的疗效优于单用药组,不良反应少,是一种值得推广应用的方案。     

全反式维甲酸与三氧化二砷治疗急性早幼粒细胞白血病临床分析

目的:观察全反式维甲酸(ATRA)与三氧化二砷(As2O3 )联合治疗初发急性早幼粒细胞白血病(APL)的疗效和不良反应。方法:As2O3 联合ATRA治疗初治APL患者16 例,As2O3 0.1%注射液10 ml加入5%葡萄糖溶液500 ml静脉点滴,持续4~5 h,1 次/d;ATRA 25 mg·m-2·d-1,分3 次口服,观察CR率、获得CR所需时间、不良反应。结果:15例患者获得完全缓解(CR),CR率93.8%,获得缓解时间(27.3±3.6) d,没有发现明显的不良反应。结论:As2O3 联合ATRA治疗初发APL患者疗效好,能缩短CR的时间,长期CR时间需要进一步观察。     

维甲酸、三氧化二砷诱导NB4细胞TRAIL基因表达的研究

目的：研究全反式维甲酸(ATRA)或三氧化二砷(As2O3)诱导急性早幼粒细胞白血病(APL)NB4细胞肿瘤坏死因子相关的凋亡诱导配体(TRAIL)基因的表达及其治疗APL的机制。方法：采用RT—PCR检测TRAIL基因表达的变化。结果：10^-6mol／L的ATRA作用6h或10^-6mol／L的As2O3作用12h，即可诱导TRAIL基因表达。结论：ATRA或As2O3能诱导NB4细胞TRAIL基因表达，TRAIL基因可能以类似“旁分泌”的作用方式杀伤NB4细胞。诱导TRAIL基因介导的细胞凋亡可能是ATRA或As2O3治疗APL的机制之一。     

ATRA、ATO联合小剂量HHT治疗急性早幼粒细胞白血病疗效观察

目的探讨急性早幼粒细胞白血病（APL）的最佳治疗方案。方法将初诊的24例APL患者随机分为观察组13例和对照组11例。观察组予全反式维甲酸（ATRA）、三氧化二砷（ATO）联合小剂量高三尖杉酯碱（HHT）诱导治疗,HA方案巩固治疗2个疗程;对照组予ATRA＋ATO＋柔红霉素（DNR）治疗,DA方案巩固治疗2个疗程。治疗结束比较两组相关指标变化。结果诱导及巩固治疗结束时两组血液学缓解率、PML/RARa融合基因转阴率均无显著差异;观察组累计血浆输注量及血小板输注量、败血症发生率及平均住院费用均明显低于对照组,P均〈0.01。结论 ATRA、ATO联合小剂量HHT治疗初诊APL效果确切;且并发症发生率低,治疗费用少。     

Combined arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia recurring from previous relapses successfully treated using arsenic trioxide

The optimal treatment of acute promyelocytic leukaemia (APL) recurring from relapses successfully treated using arsenic trioxide (As2O3) is undefined. Three APL patients relapsing from As2O3-induced remission were studied. Re-treatment with As2O3 failed in one patient in third relapse, and resulted in morphological but not molecular remission in another patient. Combination therapy with As2O3 and all-trans retinoic acid (ATRA), however, resulted in morphological and molecular remission in all three cases, with a follow-up time ranging from 6 to 16 months. Our results suggest a synergistic therapeutic effect between As2O3 and ATRA in APL in advanced relapse.     

Successful treatment of relapsed and refractory acute promyelocytic leukemia with arsenic trioxide (As2O3)

It has been shown that arsenic trioxide (As2O3) may induce hematologic remissions in patients with acute promyelocytic leukemia (APL) refractory to all-trans retinoic acid (ATRA). We reported on a patient with ATRA and drug-resistant APL that was successfully treated with As2O3. The patient had been given a diagnosis of typical APL and was treated with ATRA and chemotherapy for 12 months. He achieved complete remission (CR), but leukemia relapsed with 43% APL cells in the bone marrow in the 16th month of treatment. ATRA and cytarabine plus daunorubicin were administered; however, the APL cells in the bone marrow increased to 97.2%. As2O3 was initiated intravenously, and bone marrow showed a decrease of APL cells (6.7%) and a partial differentiation after 9 days. The patient received idarubicin (IDA) and steroid pulse because of the development of ATRA-like syndrome, and achieved CR 37 days after the initiation of As2O3. He received an additional 2 courses of As2O3 with IDA, and is in CR. These results demonstrated the therapeutic efficacy of As2O3 in treating ATRA and drug-resistant APL.     

All-trans retinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia

All-trans retinoic acid (ATRA) can induce complete remission (CR) in most patients with acute promyelocytic leukemia (APL) through in vivo differentiation of APL-blasts. However, it cannot eliminate the leukemic clone and must be used in combination with anthracycline-based chemotherapy. Experience accumulated over the last 10 years has clearly shown that the combination of ATRA and chemotherapy gave better survival than chemotherapy alone in newly diagnosed APL because of fewer relapses and a slightly higher CR rate. It is also strongly suggested that maintenance treatment with ATRA, and possibly with low-dose chemotherapy, can further reduce the incidence of relapse. Overall, more than 90% of patients with newly diagnosed APL can achieved CR, and about 75% can be cured by the combination of ATRA and chemotherapy. ATRA syndrome remains the major side effect of ATRA treatment, which should be prevented by addition of chemotherapy and/or dexamethasone in case of increasing white blood cell (WBC) counts. Current issues in the treatment of newly diagnosed APL include the role of early addition of chemotherapy to ATRA, whether or not ara-C is useful in combination with anthracycline, and a possible interest of arsenic trioxide during consolidation in patients remaining at relatively high risk of relapse.     

Hematopoietic stem cell transplantation in the second or later complete remission in acute promyelocytic leukemia initially treated with all-trans retinoic acid

Despite the use of all-trans retinoic acid (ATRA) as the first-line treatment for acute promyelocytic leukemia (APL), relapse occurs in about 20% of cases. Most relapsing APL patients can achieve second remission (CR2) following ATRA combined with chemotherapy or arsenic trioxide. Stem cell transplantation (SCT) has been widely adopted in CR2, but optimal SCT (auto- or allo-SCT) remains controversial. We analyzed the outcomes for 8 APL patients initially treated using ATRA, who relapsed, achieved CR2 and underwent auto-SCT (n = 4) or allo-SCT (n = 4). The mean age of patients who underwent allo-SCT was 39 years. Minimal residual disease (MRD) just prior to SCT was positive in 1 patient and negative in 3. Engraftment was achieved in all patients, but 2 patients died of transplantation-related complications within 6 months. Complete molecular remission has been maintained in the remaining 2 patients. The mean age of patients who underwent auto-SCT was 48 years. MRD just prior to SCT was negative in all 4 patients. Complete molecular remission has been maintained in all 4 patients (mean follow-up, 3 years 9 months). The results for auto-SCT are favorable in patients with MRD-negative APL.     

Treatment of acute promyelocytic leukaemia

We review improvements achieved in the treatment of acute promyelocytic leukaemia (APL) over the last ten years. The combination of all- trans retinoic acid (ATRA) and conventional anthracycline-ARA-C chemotherapy (CT) has clearly demonstrated its superiority over CT alone (in terms of relapse and survival) in newly diagnosed APL. Combination treatment probably also reduces the incidence of initial failures, and complete remission (CR) rates greater than 90% are now regularly reported in large multicentre trials. Some randomized studies strongly suggest than prolonged maintenance treatment (for 1 or 2 years) with ATRA and low dose CT, and possibly very early introduction of anthracycline CT during induction treatment (i.e. not after ATRA) may reduce the incidence of relapse. With those treatments, the risk of relapse appears to be only 10-15%, although it remains greater in patients who initially have white blood cell counts (often associated with variant M(3)morphology, short bcr(3)isoform etc.) and patients with residual disease detectable by RT-PCR at the end of consolidation courses.ATRA syndrome remains the major side effect of ATRA treatment. It occurs in 10-15% of patients and is currently fatal in at least 10% of them. Rapid onset of CT and/or high dose steroids should improve its outcome.A sizeable proportion of APL patients who relapse after ATRA and CT can be durably salvaged by the same treatment followed by allogeneic or autologous stem cell transplantation, provided the transplant (in the autologous setting) is RT-PCR negative.Arsenic trioxide can induce CR in most APL patients refractory to ATRA and CT. It acts mainly by inducing apoptosis of APL cells. A place for arsenic trioxide earlier in the treatment of APL must currently be more precisely defined. Another issue in the treatment of APL is reducing the toxicity of first line treatment without increasing the relapse risk. Preliminary findings suggest that this could be achieved by consolidation CT using an anthracycline alone, without cytarabine.     

Treatment of older adults with acute promyelocytic leukaemia

Only 15 to 20% of acute promyelocytic leukaemia (APL) patients are older than 60 years, and the characteristics and outcome of APL in that age range are not well known. Published studies show that APL in elderly patients has haematological features similar to those of APL in younger patients. However, using the current combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy, the outcome for these patients, although it has much improved, remains less favourable than that for younger patients. This is due to a higher incidence of early deaths and deaths in complete remission (CR), during consolidation chemotherapy courses, whereas the relapse rate appears similar in older and younger adults.Treatment approaches with more limited myelosuppression, especially consolidation chemotherapy with an anthracycline alone (without Ara-C), low-dose maintenance treatment with 6-mercaptopurine, methotrexate and ATRA, and consolidation with arsenic trioxide, should be tested especially in elderly patients in order to replace more toxic 'classical' anthracycline-Ara-C consolidation treatment, after achieving CR with ATRA.     

Delayed recovery of normal hematopoiesis in arsenic trioxide treatment of acute promyelocytic leukemia: a comparison to all-trans retinoic acid treatment

OBJECTIVE: To examine laboratory data including total blood cell count, leukocyte morphology and coagulation parameters during treatment for acute promyelocytic leukemia (APL) at a single institute, and compare the precise differences between all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) treatment. PATIENTS AND METHODS: Sixteen patients with APL who were treated with ATRA or As2O3 alone and achieved complete remission (CR) were analyzed. ATRA 45 mg/m2/day was given orally until CR. As2O3 0.15 mg/kg/day was given intravenously until leukemic blasts and promyelocytes were eliminated from the bone marrow. RESULTS: All 7 patients in the ATRA-treated group were primary cases and all 9 patients in the As2O3-treated group were relapsed cases after the achievement of CR with the ATRA. There was no difference in the data before treatment between these two groups. The duration of leukocytopenia and neutropenia during As2O3 treatment was significantly longer than those of ATRA treatment. The nadir of leukocyte and neutrophil counts was observed later in the As2O3-treated group. Terminal neutrophil differentiation was observed more obviously in the ATRA-treated group. The red blood cell count and hemoglobin concentration decreased significantly at the end of As2O3 treatment and were lower than those of ATRA treatment. Platelets recovered earlier in the ATRA-treated group. Coagulation parameters were not significantly changed between the two groups. CONCLUSION: In comparison with ATRA treatment, the recovery of several components in the peripheral blood cells was delayed in As2O3 treatment. Therefore we should pay more and longer attention in As2O3 treatment.     

三氧化二砷联合化疗治疗急性早幼粒细胞白血病的疗效观察

目的:观察三氧化二砷(As2O3)联合化疗治疗急性早幼粒细胞白血病(APL)的疗效.方法:46例初治APL患者均采用As2O3诱导治疗,完全缓解(CR)后用DA或MA方案巩固1个疗程,以后As2O3与化疗交替治疗,每3月1次,连续治疗3年.再继以甲氧蝶呤片与巯嘌呤片维持治疗1年.结果:46例患者有38例(82.6％)达到CR,34例坚持治疗者持续缓解,缓解时间17～119个月,中位缓解时间67个月;4例CR2患者缓解时间43～ 71个月,中位缓解时间54个月.38例患者仍处于CR,生存时间131～ 18个月,中位生存时间65个月.结论:APL患者CR后,采取每年4个周期的巩固和维持方案序贯治疗,减少了化疗及As2O3的疗程,避免了长期连续用药所致的耐药,减少了药物的副作用,复发率很低.