两种方案治疗儿童急性早幼粒细胞白血病的总体预后对比分析

Objective For further improving the prognosis of childhood acute promyelocytic leukemia (APL) in China,the treatment efficacies, outcomes and costs of protocols for childhood APL between in developed countries and in our hospital were compared. Methods 30 cases aged ＜15 years were diagnosed according to the FAB classification and detection of PML-RARα rearrangement. From December 1999 to September 2004,sixteen eligible children were treated with an intensive in-house protocol including high-dose Ara-C and anthracycline for post remission treatment. From September 2004 to January 2008,14 cases enrolled were treated with a less intensive protocol modified from the PETHEMA LPA99. Results The 3.5 years EFS was 37.5 % (s-x=0.121) for total 16 patients on in-house protocol. Six patients (37.5 %) abandoned treatment,2 died of intracranial hemorrhage at diagnosis (6.3 %) and sepsis in remission (6.3 %),respectively,and 2 relapsed (12.5 %). The 14 cases treated with modified PETHEMA had a 3.5 years EFS of 79.6 % (s-x=0.136). One died of intracranial hemorrhage at diagnosis (7.1 %) and 1 relapsed (7.1 %). Patients on modified PETHEMA had a significantly higher EFS (P=0.012),lower frequency of sepsis during treatment (7.7 % vs 77.8 %; P=0.0015) and lower hospitalization cost (median,RMB 35 200 vs 150 000; P ＜0.0001) than those on in-house protocol. Conclusion Treatment with the less intensive protocol based on the PETHEMA LPA99 study for childhood APL successively reduced complication of chemotherapy and reduced hospitalization cost without increasing relapses, which led to decreases in treatment-related toxicity and treatment abandonment rate,thus improving overall outcome.     

两种方案治疗儿童急性早幼粒细胞白血病的总体预后对比分析

Objective For further improving the prognosis of childhood acute promyelocytic leukemia (APL) in China,the treatment efficacies, outcomes and costs of protocols for childhood APL between in developed countries and in our hospital were compared. Methods 30 cases aged ＜15 years were diagnosed according to the FAB classification and detection of PML-RARα rearrangement. From December 1999 to September 2004,sixteen eligible children were treated with an intensive in-house protocol including high-dose Ara-C and anthracycline for post remission treatment. From September 2004 to January 2008,14 cases enrolled were treated with a less intensive protocol modified from the PETHEMA LPA99. Results The 3.5 years EFS was 37.5 % (s-x=0.121) for total 16 patients on in-house protocol. Six patients (37.5 %) abandoned treatment,2 died of intracranial hemorrhage at diagnosis (6.3 %) and sepsis in remission (6.3 %),respectively,and 2 relapsed (12.5 %). The 14 cases treated with modified PETHEMA had a 3.5 years EFS of 79.6 % (s-x=0.136). One died of intracranial hemorrhage at diagnosis (7.1 %) and 1 relapsed (7.1 %). Patients on modified PETHEMA had a significantly higher EFS (P=0.012),lower frequency of sepsis during treatment (7.7 % vs 77.8 %; P=0.0015) and lower hospitalization cost (median,RMB 35 200 vs 150 000; P ＜0.0001) than those on in-house protocol. Conclusion Treatment with the less intensive protocol based on the PETHEMA LPA99 study for childhood APL successively reduced complication of chemotherapy and reduced hospitalization cost without increasing relapses, which led to decreases in treatment-related toxicity and treatment abandonment rate,thus improving overall outcome.     

儿童急性早幼粒细胞白血病合并分化综合征及颅内出血一例并文献复习

目的:提高对儿童急性早幼粒细胞白血病（APL）合并分化综合征（DS）及颅内出血诊治的认识。方法:总结2020年10月12日深圳市儿童医院收治的1例APL合并DS及颅内出血患儿诊治经过，并复习相关文献。结果:患儿，男性，12岁，应用维甲酸及三氧化二砷过程中出现DS并颅内出血，暂停用维甲酸，采用糖皮质激素防治DS，联合化疗及对症治疗后病情好转。结论:APL合并DS及颅内出血病情凶险，建议暂停维甲酸，应用激素并联合化疗、对症治疗可改善预后。     

儿童方案BFM90治疗费城染色体阴性成年人急性淋巴细胞白血病

 目的　分析费城染色体阴性（Ph-）成年急性淋巴细胞性白血病（ALL）患者应用儿童ALL的BFM90化疗方案治疗后的远期疗效。方法　2004年8月至2007年10月,共60例Ph-成年ALL患者[中位年龄40（18～60）岁],接受BFM90方案治疗,并进行回顾性分析,其治疗结果同35例接受Hyper-CVAD方案化疗的患者[中位年龄42（18～56）岁]进行历史对照。结果　BFM90化疗42个月的完全缓解（CR）率、总生存（OS）率、无事件生存（EFS）率分别为93 %（56例）、65 %（39例）和60 %（36例）。45岁是本组年龄因素中影响预后的主要截断值。BFM90组CR、OS和EFS优于Hyper-CVAD方案历史对照组（均为P＜0.05）。结论　与成年人Hyper-CVAD方案相比,儿童ALL的 BFM90化疗方案治疗成年人ALL有更好的疗效。     

初诊高白细胞急性早幼粒细胞白血病患者临床特征及疗效分析

目的：探讨急性早幼粒细胞白血病（APL）患者中高白细胞的发生率、临床特征及早期疗效。方法回顾性分析初诊APL患者248例,其中高白细胞患者70例,分析高白细胞的发生率、临床特征及诱导治疗的疗效。非高白细胞APL的诱导治疗以全反式维甲酸联合三氧化二砷为主,高白细胞APL的诱导治疗以全反式维甲酸+三氧化二砷+蒽环类化疗药物为主,同时给予对症支持治疗。结果248例患者中,高白细胞的发生率为28.2%（70／248）,其中WBC为10×109／L～50×109／L 46例（18.5%）, WBC＞50×109／L且≤100×109／L 14例（5.6%）,WBC＞100×109／L 10例（4.0%）。高白细胞APL患者的临床特征为PML-RARα融合基因S型（P＝0.004）及FLT3-ITD基因突变（P＜0.01）,原发性纤溶亢进更加严重;诱导治疗完全缓解率低于非高白细胞APL患者[88.9%（48／54）比98.1%（152／155）,P＝0.013],早期死亡率高于非高白细胞患者[11.1%（6／54）比1.9%（3／155）,P＝0.013]。高白细胞患者的早期死亡原因主要为脑出血。结论高白细胞是APL不良预后因素,诱导治疗应重视凝血异常的纠正、联合化疗迅速降低白细胞,以及联合地塞米松预防诱导分化综合征,以期降低早期死亡率。     

老年人初治急性早幼粒细胞白血病的临床研究

  目的　探讨老年人初治急性早幼粒细胞白血病（APL）的临床特点、治疗及预后。方法　回顾性比较分析21例老年及89例中青年（＜60岁）初治APL患者的临床资料,并按白细胞（WBC）计数的不同进行老年人APL分组比较。结果　老年APL与中青年APL患者的性别（男女性别比 11 ∶10 对 47∶42）、治疗前的WBC（高白细胞比例：23.8 %比16.9 %）、骨髓原始细胞+早幼粒细胞（0.83±0.11 对 0.83±0.12）、诱导治疗的完全缓解（CR）率（71.4 % 对84.3 %）、达CR的天数[（35.7±10.1）d对（39.1±13.5）d]、维甲酸综合征（RAS）发生率（14.3 % 对 22.5 %）、弥散性血管内凝血（DIC）发生率（52.4 % 对 34.8 %）及2年总生存率（72.7 % 对 80.0 %）差异均无统计学意义（P＞0.05）,老年APL患者诱导治疗过程中早期死亡率明显高于中青年APL患者（28.6 % 对 11.2 %）（P＜0.05）。21例接受诱导治疗的老年患者中,5例为高白细胞型,16例为非高白细胞型,高白细胞组老年APL患者的DIC和早期死亡发生率分别为80 %、60 %,高于非高白细胞组（43.8 %、18.8 %）,而CR率较低（40.0 % 对81.3 %）。结论　老年及中青年APL患者均具有较好的预后,高白细胞型诱导治疗疗效低于非高白细胞型。     

三氧化二砷联合全反式维甲酸治疗初发急性早幼粒细胞白血病50例疗效观察

 目的　观察三氧化二砷（ATO）联合全反式维甲酸（ATRA）治疗初发急性早幼粒细胞白血病（APL）的疗效。方法　98例初发APL患者分为对照组和治疗组,对照组48例,治疗组50例。对照组采用常规ATRA+DA双诱导方案治疗;治疗组采用ATRA每天25 mg／m2,ATO每天0.15 mg／kg（ATRA后第10天开始）联合治疗,直至完全缓解（CR）,CR后接受ATO和ATRA联合巩固治疗。比较两组CR率、PML-RARα融合基因转阴时间及5年无病生存率。结果　对照组和治疗组CR率分别为89.5 %（43／48）和90.0 %（45／50）,获得CR时间分别为（30.0±5.1）d和（28.1±4.4）d,两组CR率（χ2＝-0.068,P＝0.946）及获得CR时间（t＝1.757,P＝0.083）相比差异均无统计学意义。在所有获得CR的患者中,3例分别在CR后第276、385和394天复发。所有患者发病时PML-RARα融合基因均阳性,对照组和治疗组CR时分别有25.0 %（5／20）和29.4 %（5／17）转阴,巩固后分别有92.5 %（37／40）和97.6 %（41／42）转阴。对照组和治疗组5年无病生存率分别为（85.3±5.9）%和（87.6±5.6）%,差异无统计学意义（χ2＝0.232,P＝0.630）。结论　ATO联合ATRA能有效治疗初发APL患者,可以作为常规化疗方案外的另一选择。     

改良的德国多中心成年人急性淋巴细胞白血病研究组方案临床应用研究

 目的　分析改良的德国多中心成年人急性淋巴细胞白血病研究组（GMALL）方案治疗成年人急性淋巴细胞白血病（ALL）的疗效和安全性。方法　2005年1月至2009年12月共37例新诊断的ALL患者,接受改良的GMALL方案单纯化疗,对其进行回顾性分析,并与同期接受该院常规方案治疗的44例成年ALL患者进行对比分析。结果　改良GMALL方案的累积完全缓解（CR）率为89.2 %（33／37）,1、2、3及4年累积总生存（OS）率分别为77.5 %、48.0 %、40.0 %和40.0 %。主要不良反应为3～4级血液学毒性和感染,不良反应易于控制,治疗相关死亡率低。改良GMALL方案组的OS优于该院常规方案组。结论　改良的GMALL方案治疗成年人ALL疗效满意,不良反应可以耐受,值得临床推广。     

急性早幼粒细胞白血病两种PML-RARα融合基因亚型的临床研究

 目的　探讨急性早幼粒细胞白血病（APL）PML-RARα融合基因亚型及其临床关系。方法　采用巢式反转录聚合酶链反应（RT-PCR）检测92例初诊APL患者PML-RARα融合基因不同转录本,根据结果分为长型（L型）和短型（S型）两组,比较两组间的临床特征、治疗反应及预后。结果　92例APL患者PML- RARα融合基因均为阳性,L型52例,占56.5 %,S型40例,占43.5 %;两组相比,患者性别、年龄、治疗前的白细胞计数、骨髓原始早幼粒细胞比例及染色体无明显差异;诱导治疗的完全缓解（CR）率、达CR的时间、维甲酸综合征（RAS）、弥漫性血管内凝血（DIC）、颅内出血的发生差异无统计学意义;两组缓解后总体生存率（OS）及无复发生存率（RFS）亦差异无统计学意义。结论　APL患者PML-RARα融合基因亚型与临床疗效、预后无关。     

改良BFM-90方案治疗儿童青少年淋巴母细胞淋巴瘤并发感染的防治

背景与目的：改良BFM-90方案明显提高儿童青少年淋巴母细胞淋巴瘤（lymphoblastic lymphoma,LBL）的疗效,但化疗强度大,主要并发症是感染,如处理不当可影响化疗及预后。本研究总结改良BFM-90方案化疗相关感染的特点,同时探讨其有效防治方法。方法：分析104例接受改良BFM-90方案化疗的儿童青少年LBL患者在各化疗阶段的感染发生率、感染部位、感染类型及化疗强度、骨髓抑制与感染的关系,评价降钙素原（procalcitonin,PCT）鉴别发热性质的价值,评价抗感染治疗效果。结果：全部患者在诱导缓解Ⅰa和Ⅰb阶段、再诱导缓解Ⅱa和Ⅱb阶段感染发生率分别为52．5％、60．7％、48．6％、28．2％：巩固化疗阶段低／中危患者感染发生率为17．2％．高危患者为100％。全组患者共发生感染302次,其中部位明确的感染为167次（553％）,以呼吸道感染最多,而仅有发热而部位不明的感染为135次（44．7％）;病原明确的感染为95次（31．5％）,以G-细菌感染最多．而病原未明的感染为207次（68．5％）;同时伴有骨髓抑制的感染为262次（86．8％）,不伴骨髓抑制的感染为40次（13．2％）。PCT诊断败血症的灵敏度和特异度分别为83．3％和70．2％,但未能鉴别感染性质。302例感染经治疗后．296例治愈,4例感染未愈但因经济困难而放弃治疗,2例因败血症死亡。结论：改良BFM-90方案治疗儿童青少年LBL并发感染的特征明显,与骨髓抑制密切相关。病原学诊断阳性率较低,感染性质不易鉴别,治疗上仍以经验性用药为主。     

全反式维甲酸联合化疗治疗小儿急性早幼粒细胞白血病

目的观察全反式维甲酸（ATRA）联合化疗治疗小儿急性早幼粒细胞白血病（APL）的疗效。方法22例初治患儿用ATRA诱导治疗;当患儿获完全缓解（CR）后,给予DA方案或IDA方案或HA方案或AA方案巩固治疗3个疗程;以后再用ATRA、化疗交替巩固治疗36个月。结果2例在诱导治疗前死于弥散性血管内凝血（DIC）、颅内出血;22例获CR,CR率100％（20／20）。1、3、5年无病生存（DFS）率分别为100％（20／20）、93．3％（14／15）、84．7％（11／13）。ATRA常见毒副作用依次为皮肤和口唇干燥、头痛、恶心、呕吐、肝功能损害及维甲酸综合征。结论ATRA联合化疗治疗小儿APLCR率高、远期疗效好;在诱导治疗前,DIC、颅内出血仍是APL患儿死亡的主要原因;ATRA毒副作用可耐受。     

Outcome of childhood acute promyelocytic leukemia with all-trans-retinoic acid and chemotherapy.

PURPOSE: To determine the results of treatment combining all-trans-retinoic acid (ATRA) and chemotherapy (CT) in childhood acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Children (< 18 years) with newly diagnosed APL were included in the APL93 trial, treated by ATRA followed or combined with daunorubicin-cytarabine, and then randomly assigned between no maintenance, intermittent ATRA, continuous CT, or both. RESULTS: Of the 576 patients included in APL93 trial, 31 (5%) were children, including 22 girls (71%) and nine boys (29%). Thirty of the children (97%) obtained complete remission (CR). ATRA syndrome occurred in four children (13%), who all achieved CR, and headaches occurred in 12 children (39%), with signs of pseudotumor cerebri in five children (16%). Seven patients (23%) relapsed. None of the eight patients who received both ATRA and CT for maintenance relapsed. All relapsing patients achieved a second CR. Twenty-two patients remained in first CR after 43+ to 96+ months, six remained in second CR after 17+ to 66+ months, and three patients had died. The 5-year event-free survival (EFS), relapse, and overall survival rates were 71%, 27%, and 90%, respectively. No difference between adults and children included in the APL93 trial was seen for CR rate, 5-year relapse rate, EFS, and overall survival, but significantly better survival was seen in children after adjustment on WBC counts (P =.02) and incidence of microgranular M3 variant (P =.04). CONCLUSION: ATRA combined with CT for induction and also probably for maintenance provides as favorable results in children with APL as in adults and currently constitutes the reference first-line treatment in both age groups.     

Treatment of elderly patients (> or =60 years) with newly diagnosed acute promyelocytic leukemia. Results of the Italian multicenter group GIMEMA with ATRA and idarubicin (AIDA) protocols.

In all, 134 elderly patients (median age 66 years, range 60-75 years) with newly diagnosed acute promyelocytic leukemia (APL) were enrolled in two successive protocols of the Italian multicenter group GIMEMA. All patients received an identical induction with all-trans retinoic acid and idarubicin; 116 (86%) entered complete remission (CR), two (2%) were resistant and 16 (12%) died during induction. After CR, 106 patients received further therapy whereas 10 did not, because of refusal (n=5) or toxicity (n=5). Consolidation consisted of three chemotherapy courses in the AIDA protocol (AIDA, 67 patients) or, since 1997, of an amended protocol including only the first cycle (amended AIDA, aAIDA, 39 patients). In the AIDA group, 43 patients (64%) completed consolidation, while seven (11%) and 17 (25%) patients were withdrawn after first and second courses, respectively; nine patients (13%) died in CR and 12 (18%) relapsed. In the aAIDA group, all patients received the assigned treatment; two patients (5%) died in CR and six (15%) relapsed. In the AIDA and aAIDA series, the 3-year overall and discase-free survival rates were 81 and 83% (P=NS), 73 and 72% (P=NS), respectively. We highlight here the frequency and severity of complications linked to intensive chemotherapy in this clinical setting and suggest that, in APL of the elderly, less intensive postremission therapy allows significant reduction of severe treatment-related toxicity and may be equally effective.     

Improved outcome in children with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol

From July 1990 to March 1996, 112 children with stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) with up to 70% FAB L3-type blasts (n = 42) in the bone marrow without central nervous system (CNS) disease were treated on the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol (identical to the French LMB 84). The median age was 8.3 years. There were 81 boys and 31 girls. According to the extent of the primary disease, patients were sub-staged into three groups: IIIA with unresectable abdominal tumour (n = 39); IIIB with abdominal multiorgan involvement (n = 57) and IIIX with extra-abdominal primary lymphoma often presenting as pleural effusion (n = 16). Univariate and multivariate analyses were carried out to evaluate the prognostic significance of lactate dehydrogenase (LDH) level at diagnosis, the sub-stage and the time to achieve complete remission (CR). With a median follow up of 48 months (range 12-92), the overall and event free survival (EFS) is 87% (95% confidence interval (CI) 79.2-92.1 %) and 83.7% (95% CI 76.3-89.2%) respectively. Six patients (5.4%) never achieved CR, of whom one is alive following high-dose therapy. Eight patients (7.1%) relapsed after achieving CR, three are alive after second-line therapy. There were three early toxic deaths (2.7%), mainly from infection, and one late death from a second cancer. There was no significant difference in EFS according to LDH level at diagnosis, the sub-stage or the time to CR. This study confirms the overall good prognosis and low rate of toxic deaths in patients with advanced B-NHL treated with this intensive regimen. No significant difference in EFS according to the sub-stage, the time to achieve CR or LDH level at diagnosis making it difficult to identify a group that should not receive intensive therapy.     

Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: A retrospective analysis of JALSG‐APL97

For patients with relapsed acute promyelocytic leukemia (APL), all‐trans retinoic acid‐based salvage regimens can achieve second complete remission (CR2), but the optimal post‐remission strategy for APL patients after CR2 remains unclear. Hematopoietic stem cell transplantation (HSCT) during CR2 might be effective, but data on the role of HSCT for APL patients after CR2 are limited in Japan. We retrospectively analyzed outcomes for 57 relapsed APL patients who achieved CR2 in the JALSG APL97 study. Of those, six received autologous (auto)‐HSCT, 21 received allogeneic (allo)‐HSCT, and 30 received various regimens other than HSCT. The 5‐year event‐free survival (EFS) rate, overall survival (OS) rate and cumulative incidence of relapse (CIR) were 50.7%, 77.4% and 51.0% in the non‐HSCT group, 41.7%, 83.3% and 58.3% in the auto‐HSCT group and 71.1%, 76.2% and 9.8% in the allo‐HSCT group, respectively. Both the EFS rate and CIR were significantly better in the allo‐HSCT group than in other groups. Allo‐HSCT appears effective in APL patients in CR2, with a low relapse rate beyond a relatively early transplantation‐related mortality (19%). Among older patients (age ≥40 years), the 5‐year OS was significantly better in the non‐HSCT group than in the HSCT group (78.0% vs 40.5%; P = 0.04). Further prospective studies with larger patient numbers are required to confirm the impact of HSCT alone and in combination with arsenic trioxide on outcomes for patients with APL in CR2.     

Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention.

To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally, age 相似文献   

HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt's lymphoma and B-cell acute lymphoblastic leukemia

We designed a protocol that included 2 months of intensive Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), high-dose methotrexate (MTX), high-dose cytarabine (ara-C), and vincristine (HiC-COM) to improve event-free survival (EFS) for patients with advanced-stage Burkitt's lymphoma and B-cell acute lymphoblastic leukemia (ALL). We also wished to test the feasibility of rapidly cycling Cytoxan and high-dose ara-C based on signs of early marrow recovery. Twenty patients including 12 with stage III Burkitt's lymphoma and eight with stage IV Burkitt's lymphoma or B-cell ALL were entered onto this pilot study. The rate of complete remission was 95%. Four patients have relapsed. The 2-year actuarial EFS was 75% (median follow-up, 37 months). Two of the initial five patients developed transverse myelitis, which we believe may have been secondary to the concomitant administration of intrathecal (IT) and high-dose systemic ara-C. We conclude that this short but intensive regimen is highly effective for patients with advanced Burkitt's lymphoma and B-cell ALL. EFS has improved over previous less intensive regimens, and is comparable to regimens of longer duration.     

Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia. European APL group.

First results of a randomized trial (APL91 trial) and other randomized or non-randomized studies have shown that ATRA followed by chemotherapy significantly increased event-free survival (EFS) and survival, and decreased the incidence of relapse by comparison to chemotherapy alone in newly diagnosed APL. We present here long-term follow-up of the APL91 trial. In this trial, 101 patients had been randomized between ATRA followed by three courses of daunorubicin-AraC chemotherapy (ATRA group) and the same chemotherapy alone (chemotherapy group). Results were reanalyzed 73 months after closing of patient entry. Updated results of APL 91 trial found a Kaplan-Meier estimate of EFS and relapse rate at 4 years of 63% and 31% in the ATRA group, as compared to 17% and 78% in the chemotherapy group (P= 10(-4) and relative risk 2.95, P= 10(-4) and relative risk 3.68, respectively). Kaplan-Meier survival at 4 years was 76% in the ATRA group and 49% in the chemotherapy group (P= 0.026, relative risk 2.7). In the chemotherapy group, seven of the 27 relapses occurred after 18 months, but no relapse was seen after 43 months. In the ATRA group, four of the 17 relapses occurred after 18 months, including two late relapses (at 58 and 74 months). In the chemotherapy group, 23 of the 25 patients who relapsed achieved a second CR with ATRA, and the Kaplan-Meier estimate of second relapse was 40% at 30 months. In the ATRA group, the 10 patients who relapsed and were retreated with ATRA achieved a second CR. In conclusion, long-term results of APL91 trial confirm the superiority of the combination of ATRA and chemotherapy over chemotherapy alone in newly diagnosed APL, and that ATRA should be incorporated in the front-line treatment of APL.