中剂量阿糖胞苷早期强化治疗急性淋巴细胞性白血病64例

目的研究中剂量阿糖胞苷早期强化治疗急性淋巴细胞白血病(ALL)的诊疗,探索提高儿童ALL长期生存的方法。方法应用标准的首次诱导缓解化疗方案治疗后,采用中剂量阿糖胞苷(Arac)1 g/(m2·次),1次/12 h×6次,配合柔红霉素(DNR)或米托蒽醌(MTZ)方案早期强化治疗,2～3个疗程进入维持治疗。采用Kaplan—Meter方法评估患儿无事件生存(EFS)率结果本组ALL完全缓解率(CR)为93.8%,标危(SR)ALL为100%,高危(HR)ALL为83 3%,5年EFS率达72 3%,SR-ALL患儿5年EFS率达84.2%,6例(10%)复发,治疗相关死亡2例(3.3%)。结论采用中剂量Arac方案早期强化治疗,降低化疗相关死亡,提高ALL患儿5年EFS率。     

AML-XH-99-M3方案治疗33例儿童急性早幼粒细胞自血病临床总结

目的 评价AML-XH-99-M,方案治疗儿童急性早幼粒细胞白血病(M3)疗效.方法 33例M3患儿接受AML-XH-99-M,方案治疗,应用Kaplan-Meier方法进行生存分析,评估患儿的无事生存期(EFS)、无疾病生存期(DFS)及总生存期(OS),所有数据采用SPSS13.0软件统计.结果 33例患儿30例(90.9%)一个疗程达完全缓解(CR),余3例二个疗程CR,总CR率为100%,复发6例(18.2%),平均复发时间为29(16～38)个月,死亡2例(6.1%),7年EFS和DFS均为(73.4±9.4)%,总OS为(91.2±6.0)%,维持治疗中间歇加用全反式维甲酸(ATRA)和无ATRA两组EFS差异有统计学意义,分别为(88.9±10.5)%和(62.5±13.6)%(P<0.05).结论 AML-XH-99-M,方案治疗儿童M3获得了很好的CR率,具有较高的EFS、DFS和OS,维持治疗中加用ATRA可明显降低复发率、提高EFS.     

AML-XH-99-M3 方案治疗33例儿童急性早幼粒细胞白血病临床总结

目的：评价AML-XH-99-M3方案治疗儿童急性早幼粒细胞白血病（M3）疗效。方法：33例M3患儿接受AML-XH-99-M3方案治疗，应用Kaplan-Meier方法进行生存分析，评估患儿的无事生存期（EFS）、无疾病生存期（DFS）及总生存期（OS），所有数据采用SPSS13.0软件统计。结果：33例患儿30例（90.9%）一个疗程达完全缓解（CR），余3例二个疗程CR，总CR率为100%，复发6例（18.2%），平均复发时间为29（16~38）个月，死亡2例（6.1%），7年EFS和DFS均为（73.4±9.4）%，总OS为（91.2±6.0）%，维持治疗中间歇加用全反式维甲酸（ATRA）和无ATRA两组EFS差异有统计学意义，分别为（88.9±10.5）%和（62.5±13.6）%(P<0.05)。结论：AML-XH-99-M3方案治疗儿童M3获得了很好的CR率，具有较高的EFS、DFS和OS，维持治疗中加用ATRA可明显降低复发率、提高EFS。     

AML-XH-99方案治疗婴幼儿急性髓系白血病临床总结

目的探讨婴幼儿急性髓系白血病(AML)的临床特征及采用AML-XH-99方案的疗效。方法 1998年5月至2009年4月诊断的0～3岁AML(除外M3)26例,采用AML-XH-99方案化疗。应用SPSS13.0软件统计,采用Kaplan-Meier生存分析法进行无事件生存(EFS)分析。结果 26例患儿中M5居首(61.54%),其次为M2(26.92%)。年龄>12个月22例,<12个月4例,7例(26.92%)起病时外周血白细胞>50×109/L,5例(19.23%)染色体核型异常,5例(19.23%)在诱导治疗结束后48 h的骨髓涂片中幼稚细胞比例>15%。24例(92.31%)第1疗程获完全缓解(CR),总缓解率为96.15%。5例(19.23%)骨髓复发,中位复发时间为完全持续缓解(CCR)15.8个月。3例在强化疗后接受异体造血干细胞移植。26例中1例失访,7例死亡(5例死于疾病复发,2例死于治疗相关并发症)。中位CCR时间为4.08年,7年EFS为60.72%。结论 AML-XH-99方案治疗婴幼儿急性髓系白血病缓解率高,预后良好。     

短疗程化疗方案治疗儿童标危型B系急性淋巴细胞白血病65例分析

儿童B系急性淋巴细胞白血病（B-ALL）在儿童急性淋巴细胞白血病（ALL）中占80％～85％。目前,国内外治疗儿童ALL的疗程均为3年左右,且加口服化疗药物维持治疗。为了改进治疗,1992年1月至1999年12月,我科对初治的65例标危型B-ALL患儿采用CODPL（环磷酰胺、长春新碱、柔红霉素、左旋门冬酰胺酶和泼尼松）方案诱导完全缓解（CR）后加HDMTX（大剂量甲氨蝶呤）和HAD（大剂量阿糖胞苷和柔红霉素）方案巩固强化治疗,短疗程不加口服药物维持治疗和头颅放疗。现对其临床疗效进行回顾性总结。     

FLAG方案治疗儿童复发性急性淋巴细胞白血病及非霍奇金淋巴瘤短期疗效观察

目的 观察FLAG方案治疗儿童复发性急性淋巴细胞白血病(ALL)及非霍奇金淋巴瘤(NHL)短期疗效及安全性.方法 回顾性分析经FLAG方案[氟达拉滨30 mg/m2,d 1 ～ 5,阿糖胞苷2 g/m2,d 1 ～ 5,粒细胞集落刺激因子5 μg/(kg·d)]治疗的19例复发性ALL和NHL患儿临床资料,其中ALL 15例(初诊时高危8例,中危2例,低危5例),NHL 4例(临床分期为Ⅳ期);早期复发12例,晚期复发7例.观察其疗效、生存时间及不良反应.结果 经1个疗程后,11例(73.3%)ALL患儿达完全缓解(CR),其中高危5例,中危1例,低危5例;2例(50.0%)NHL患儿达CR;6例(50.0%)早期复发患儿达CR,7例(100.0%)晚期复发患儿均达CR,CR率明显高于早期复发患儿(P ＜ 0.05).13例CR患儿,中位无病生存时间5.5个月(2 ～ 12个月).血液学毒性Ⅳ级8例,Ⅲ级4例,Ⅱ级4例;合并感染13例(68.4%),均得到有效控制;肝脏毒性Ⅲ级1例,Ⅰ级2例,经治疗后均恢复.结论 FLAG方案治疗儿童复发性ALL及NHL疗效显著,尤其对于晚期复发患儿疗效较好;不良反应可以耐受.     

10例伴TLS-ERG融合基因阳性儿童急性白血病临床病例分析

目的探讨TLS-ERG融合基因对于儿童急性白血病的影响。方法回顾及总结分析2006年1月-2014年12月在北京儿童医院血液肿瘤中心诊断急性白血病且TLS-ERG融合基因阳性患儿的临床特征、治疗、危险度评估及预后。结果 1500例急性白血病患儿中检测出10例(0.6%)伴有TLS-ERG融合基因,其中男7例,女3例,中位年龄8岁,急性淋巴细胞白血病(ALL)6例,急性髓细胞白血病(AML)4例。6例ALL患儿中,免疫分型:4例为普通B淋巴细胞表型,1例为前B淋巴细胞表型,1例为带髓系标记的B淋巴细胞表型;危险度评估:2例为标危,4例为中危。4例AML患儿中,3例为AML-M2型,1例为AML-M5型。ALL患儿按照中国儿童白血病协作组(CCLG)-ALL 2008方案进行化疗,6例均在诱导缓解期达到完全缓解,按照化疗方案规律治疗,定期检测微小残留病(MRD)均小于1×10~(-4)。4例AML患儿中,2例患儿在第一疗程ADE(阿糖胞苷+柔红霉素十依托泊苷)化疗第21d复查骨穿提示未缓解,放弃治疗;1例患儿完成第一轮ADE化疗后骨髓完全缓解,按照化疗方案完成两轮ADE、MIT+ARA(米托蒽醌+阿糖胞苷)、CLASP(阿糖胞苷+左旋门冬酰胺酶)化疗后复发,后放弃治疗;1例患儿第一疗程化疗后完全缓解,后经过2疗程ADE、MIT/ARA、CLASP后骨髓细胞学完全缓解,TS-ERG融合基因仍阳性,故行父亲6/10HLA半相合造血干细胞移植,随访至今。结论 TLS-ERG融合基因在儿童急性白血病中阳性率低,但在ALL及AML患儿中均可发生。根据本中心资料,该融合基因对于ALL患儿的治疗及预后影响不大,但伴有TLS-ERG融合基因的急性髓细胞白血病患儿治疗困难,预后较差。该融合基因发生率较低,单中心资料有限,故需要多中心更大宗的资料进一步证实。     

急性粒细胞白血病患儿免疫表型及其临床意义

目的探讨儿童急性粒细胞白血病（AML）免疫分型及其临床意义。方法总结81例儿童AML的免疫表型与FAB分类、1个月骨髓缓解（CR）率及3年无病生存（EFS）率的关系。结果AML儿童1个月CR率为71.6%,3年EFS率为50.8%。HLA-DR缺失,CD34缺失主要见于急性早幼粒细胞白血病（M3）型,阴性患儿CR、EFS率明显高于阳性患儿。CD13阳性患儿的CR明显高于缺失患儿。CD33缺失在M2型中多见,特别是ETO阳性患儿。除外M3病例后分析,CD33缺失患儿的CR率明显高于阳性患者。淋系抗原表达率占34.6%,其中CD7阳性者CR率、EFS率均低于对照组,但无统计学差异。CD56与FAB分型中M2型有显著相关性,其CR率、EFS率均低于对照组。结论HLA-DR、CD34缺失主要见于M3型,是预后良好的指标。CD33缺失多见于M2型中ETO阳性患儿,预后好。淋系抗原、CD56表达多见于M2型,可能是预后差的指标。     

尼莫地平对儿童急性非淋巴细胞性白血病化疗增效的研究

急性非淋巴细胞性白血病 (ＡＮＬＬ)是一种严重危害儿童生命的疾病 ,尽管通过骨髓移植等有效的治疗可使患儿长期无病生存率达 6 0 %以上 ,但目前在国内仍然以联合化疗为主要治疗手段。采用柔红霉素 +阿糖胞苷 (ＤＡ)方案治疗2个疗程 ,其诱导缓解率为 70 %～ 80 % ,大约 2 0 %的患儿达不到完全缓解[1] 。为增强诱导期患儿的化疗效果 ,我们采用尼莫地平联合ＤＡ方案对曾单纯采用ＤＡ方案治疗 2疗程仍未达缓解的患儿进行治疗 ,取得了较满意的临床效果 ,现总结如下。对象和方法1 对象 :1995年 9月～ 2 0 0 0年 2月 ,我们采用尼莫地平联合ＤＡ方…     

儿童急性淋巴细胞白血病单中心临床研究

目的 初步评估所采用的2004全国小儿血液病学术会议关于儿童急性淋巴细胞白血病诊疗建议方案(简称04方案)的诊断、治疗效果.方法 对2004年10月-2007年6月282例急性淋巴细胞性白血病(简称急淋)患儿,参照04方案诊疗建议进行诊断、分型及治疗;按危险度分型进行统计并用SPSS统计软件对结果进行生存分析.结果 2004年10月-2007年6月88例新诊急淋患儿接受了04方案化疗,总完全缓解(CR)率为91.30%(63/69),标、中危组CR率均为100%(37/37),高危组CR率为81.25%(26/32);总4年无病生存率(EFS)为(59.73±7.22)%,标、中危患儿的EFS分别为(75.60±9.71)%和(65.50±11.69)%,高危组EFS为(44.03±12.36)%;总复发率为18.18%,骨髓复发占87.50%,单纯的中枢复发占12.50%;化疗相关死亡率为9.09%,其中诱导缓解治疗阶段因感染死亡7例(7.95%),真菌是主要病原菌.结论 应用04方案对儿童急淋进行诊治疗效满意;化疗第19天(d_(19))骨髓幼稚细胞数和临床危险度分型是独立的预后指标,大剂量甲氨蝶呤对中枢神经系统白血病的预防起到了重要作用;诱导期化疗过强,化疗相关死亡率高.     

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目的总结应用包括大剂量阿糖胞苷(Ara-C)的短疗程化疗方案治疗儿童急性淋巴细胞白血病(ALL)的临床疗效。方法总结1992-01—2001-07在北京大学人民医院儿科初治并长期随访的ALL患儿84例,其中男52例,女32例,长期无病生存(EFS)5年以上,随访时间至2006-07。结果标危型患儿EFS率79.59%,高危型患儿的EFS率为25.81%;长期存活患儿中最长EFS为14年6个月,最短EFS为5年,中位EFS为9年11个月。有6例发生中枢神经系统白血病。未出现与大剂量Ara-C化疗相关的患儿死亡。结论(1)采用包括大剂量Ara-C的短疗程化疗方案能够获得较高的完全缓解率及EFS率,且副反应小。(2)采用该短疗程方案不加用颅脑放疗,中枢神经系统白血病的发生率无提高。(3)ALL患儿对Ara-C的敏感性存在明显的个体差异。     

AML1-ETO阳性的儿童急性髓系白血病疗效分析

目的探讨儿童急性髓系白血病m2型伴AML1-ETO阳性患儿的疗效及预后相关因素。方法2003年1月至2008年12月收住AML1-ETO阳性儿童m233例,并对患儿进行总结分析、随访。了解患儿临床特征,免疫分型,染色体核型治疗及疗效,生存情况及影响治疗的因素。结果33例AML1-ETO阳性儿童第一疗程诱导缓解率为63.5%,中位随访时间32个月,目前仍处于CR状态25例占75.5%,5例患儿骨髓复发,复发率为15.1%,高白细胞数,多脏器受累,免疫表型CD5＋6以及第一疗程诱导治疗未达缓解者预后不良,并伴有较低的生存率。结论儿童急性髓系白血病M2伴有AML1-ETO阳性患儿预后是好的。强烈化疗高剂量阿糖胞苷能帮助提高疗效。提高生存率。高白细胞计数,累及多脏器以及CD56标记阳性和初次诱导治疗的缓解不佳,影响总的生存率。     

Novel multiagent chemotherapy for bone marrow relapse of pediatric acute lymphoblastic leukemia

BACKGROUND: Despite improvements in the treatment of pediatric acute lymphoblastic leukemia, approximately one in five patients will develop recurrent disease. The majority of these patients do not survive. This limited institution study sought to improve event-free survival (EFS) by intensification of chemotherapy. PROCEDURE: Twenty-one patients with either an isolated marrow (n = 16) or a combined marrow and central nervous system relapse (n = 5) received treatment according to Children's Hospital of Philadelphia protocol CHP-540. Six patients had an initial remission of <36 months, and five patients had relapsed within 1 year of completion of phase III therapy. Induction and reinduction therapy consisted of idarubicin, vincristine, dexamethasone, asparaginase, and triple intrathecal chemotherapy. Consolidation and reconsolidation therapy employed high-dose cytarabine, etoposide, and asparaginase given in a sequential manner. Maintenance therapy included courses of high- or low-dose cytarabine followed by sequential etoposide and asparaginase pulse, moderate-dose methotrexate with delayed leukovorin rescue, and vincristine/dexamethasone pulses. Therapy continued for 2 years from the start of interim maintenance in the 16 patients who did not receive a bone marrow transplant (BMT). Two patients underwent an HLA-identical sibling BMT specified by protocol. Four received a nonprotocol-prescribed alternative donor BMT. RESULTS: The complete remission induction rate was 95%. With a median follow-up from date of relapse of 49 months in survivors, the actuarial EFS based on intent to treat is 75%. There were three toxic deaths in patients in CR and two deaths from relapse. CONCLUSIONS: This regimen is toxic but effective and deserves study in a larger setting.     

Remission maintenance of adult acute lymphoblastic leukemia

This report describes the results of a study of central nervous system (CNS) prophylaxis and combination chemotherapy for the maintenance of remission in adult acute lymphoblastic leukemia. Adults with acute lymphoblastic leukemia who achieved complete remission were treated with 2,400 rads cranial irradiation and intrathecal methotrexate for CNS prophylaxis followed by continuation systemic chemotherapy with oral methotrexate, 6-mercaptopurine and cyclophosphamide. There were no CNS relapses following treatment. One-half of the patients relapsed within 11 months, with 5 patients remaining in remission for 27+ to 31+ months. The toxicity was acceptable with no treatment-related deaths. This regimen is capable of producing long remissions in a significant proportion of adults with acute lymphoblastic leukemia and appears to be effective in reducing the incidence of CNS relapse. It has the additional advantage of ease of administration and can be largely administered in the community.     

AML_1-ETO阳性的儿童急性髓系白血病疗效分析

目的探讨儿童急性髓系白血病m2型伴AML1-ETO阳性患儿的疗效及预后相关因素。方法2003年1月至2008年12月收住AML1-ETO阳性儿童m233例,并对患儿进行总结分析、随访。了解患儿临床特征,免疫分型,染色体核型治疗及疗效,生存情况及影响治疗的因素。结果33例AML1-ETO阳性儿童第一疗程诱导缓解率为63.5%,中位随访时间32个月,目前仍处于CR状态25例占75.5%,5例患儿骨髓复发,复发率为15.1%,高白细胞数,多脏器受累,免疫表型CD5+6以及第一疗程诱导治疗未达缓解者预后不良,并伴有较低的生存率。结论儿童急性髓系白血病M2伴有AML1-ETO阳性患儿预后是好的。强烈化疗高剂量阿糖胞苷能帮助提高疗效。提高生存率。高白细胞计数,累及多脏器以及CD56标记阳性和初次诱导治疗的缓解不佳,影响总的生存率。     

Low relapse rate in children with acute lymphoblastic leukemia after risk-directed therapy

PURPOSE: Even though acute lymphoblastic leukemia (ALL) responds well to chemotherapy, relapse remains the major problem. This study documents relapse and survival rates in 85 consecutive children (33 at good risk, 52 at high risk) with ALL diagnosed in 1991 to 1996. PATIENTS AND METHODS: Until 1993, the New York II protocol for the high-risk group and a combination of UKALL XI (induction) and R blocks of ALL-REZ BFM-87 (intensification) regimens for patients at good risk were used. To reduce toxicity, the protocols were subsequently modified. Consolidation treatment was the same for both groups, consisting of a lower cytarabine dose and methotrexate removal, whereas intensification was changed only for the high-risk group using the BB block of the NHL-BFM-90 protocol. The bone marrow clearance of leukemia was assessed on day 22, and minimal residual disease was detected using polymerase chain reaction analysis of Ig heavy-chain gene rearrangements. RESULTS: Seventy patients had common precursor B lineage ALL, six had pre-B-ALL, eight had T-ALL, and one had B-ALL. Two patients never achieved remission and died. Six patients died of consolidation-related complications. Four more patients died, two during induction and two during maintenance therapy. Two other children had relapse (2.3%), both of whom were treated with the earlier protocols and then underwent bone marrow transplantation. Four more children with morphologically complete remission showed minimal residual disease (which reached the levels of 1 leukemic cell among 10(2)-10(4) normal cells) with the use of clone-specific probes at several points of the study intervals, but never had relapse. The 5-year overall and event-free survival rates were 86% and 83%, respectively. The 5-year overall survival rates for good-risk and high-risk groups were 94% and 81%; the corresponding event-free rates were 91% and 78%. The 5-year event-free survival rate in the patients at high risk was significantly higher after the protocol change (90% vs. 65%, P = 0.04). CONCLUSIONS: The modification proved to be effective in diminishing the therapeutic toxicity and improving the efficacy, mainly for the high-risk group.     

A study of intermittent alternating drug program reinduction therapy on the frequency and duration of response in adult acute leukemia

Of 41 adults with a diagnosis of acute leukemia that were randomized for induction therapy in combination with methotrexate, 6-MP, vincristine and prednisone (POMP) versus a combination of cytosine arabinoside, cytoxan, vincristine and prednisone (COAP), 23 (56%) patients achieved a complete remission. During remission, patients received consolidation therapy with the three courses of remission induction regimen that they had not received initially. They then received daunomycin (three courses) and L-asparaginase and were then maintained for two years with their induction therapy. The median duration of survival for all patients was 40 weeks; the median duration of survival of those patients that responded to chemotherapy was 80 weeks. There was no significant difference between the two induction regimens with regard to complete remission more than four and one half years from diagnosis and two and one half years from discontinuation of all therapy.     

RALLE pilot: response-guided therapy for marrow relapse in acute lymphoblastic leukemia in children

Despite improved treatment results of childhood acute lymphoblastic leukemia (ALL), 20% to 30% have a relapse, and then the outcome is very poor. We studied 40 children with ALL marrow relapse piloting an ALL relapse protocol with well-known drugs and drug combinations by using a concept of response-guided design. We also measured response in logarithmic fashion. Our primary end points were achievement of M1 marrow status, minimal residual disease status below 10, and second remission. The remission induction rate was 90% with 10% induction mortality. After the A blocks (dexamethasone, vincristine, idarubicin and pegylated L-asparaginase), 85% had M1 status, 39% had minimal residual disease ≤1×10, and 66% had 2 to 3 log response. After B1 block (cyclo, VP-16) the figures were 92%, 58%, and 83%, respectively. Twenty-five of 40 patients received allogeneic stem cell transplantation. Three-year event-free survival of the whole cohort was 37%, and the relapse rate was 38%. Three-year event-free survival by risk group was 53% for late, 34% for early, and 21% for very early relapses. An ALL marrow relapse nonresponsive to steroids, vincristine, asparaginase, anthracyclines, and alkylating agents is uncommon, and these classic drugs can still be advocated for induction of ALL relapse. The problems lie in creating a consolidation capable of preventing particularly posttransplant relapses.     

儿童急性巨核细胞白血病临床特点及预后分析

目的 研究儿童急性巨核细胞白血病（acute megakaryocytic leukemia,AMKL）的临床特点及急性髓系白血病（acute myeloid leukemia,AML）03方案的疗效及预后。方法 收集2011年5月至2019年12月确诊为AMKL的47例患儿的临床资料,分析其疗效及预后因素。采用Kaplan-Meier法及log-rank检验进行生存分析。结果 47例AMKL患儿中,22例非唐氏综合征AMKL患儿使用AML03方案治疗,中位随访时间为11.4个月。非唐氏综合征AMKL患儿诱导Ⅱ后骨髓细胞学缓解率为85%,微小残留病（minimal resident disease,MRD）阴性率为79%;2年总生存（overall survival,OS）率及无事件生存（event-free survival,EFS）率分别为50%± 13%和40%±12%。单因素分析提示：免疫表型标志物CD56阳性组2年EFS率、OS率均低于CD56阴性组（P < 0.05）;诱导Ⅱ后骨髓细胞学未缓解组2年EFS率及OS率均低于缓解组（P < 0.05）;诱导Ⅱ后MRD阳性组2年EFS率低于MRD阴性组（P < 0.05）;移植与非移植患儿2年OS率与EFS率比较差异无统计学意义（P > 0.05）。结论 儿童AMKL缓解率低,预后较差。免疫表型标志物CD56阳性、早期治疗反应中的骨髓细胞学及MRD结果是影响预后的重要因素。异基因造血干细胞移植对AMKL预后无显著影响。     

儿童非核心结合因子急性髓系白血病的疗效及预后因素分析

目的 回顾性分析比较非核心结合因子（CBF）急性髓系白血病（AML）儿童采用CAMS-2005方案及CAMS-2009方案治疗的疗效及预后的影响因素。方法 选择2005年4月至2015年12月161例初诊为非CBF-AML患儿为研究对象，根据化疗方案分为CAMS-2005方案组（n=52）和CAMS-2009方案组（n=109），对两种化疗方案疗效进行回顾性分析。结果 CAMS-2009方案组第1个疗程完全缓解率高于CAMS-2005方案组（63.3% vs 46.2%，P < 0.05）。CAMS-2009方案组治疗相关病死率（11.9% vs 17.3%）、复发率（27.5% vs 28.8%）、3年总生存（OS）率（44%±5% vs 28%±6%）与CAMS-2005方案组相比差异无统计学意义（P > 0.05）。第1个疗程获得完全缓解患儿的3年OS率、3年无事件生存率高于第1个疗程未完全缓解患儿（P < 0.01）。结论 CAMS-2009方案较CAMS-2005方案可改善非CBF-AML患儿诱导治疗完全缓解率，第1个疗程是否获完全缓解可影响非CBF-AML患儿OS率。