去甲氧柔红霉素联合HA方案治疗急性髓细胞白血病初治患者的临床观察

目的:探讨去甲氧柔红霉素(IDA)联合HA方案[(高三尖杉酯碱(HH)加阿糖胞苷(Ara-C)]治疗初发急性髓细胞白血病(AML)的疗效和不良反应。方法:14例AML患者,年龄17～62岁(中位年龄40岁),男8例,女6例,均为初治AML病例。诱导方案为IDA10mg/d,第1～3天,HH3mg/d第1～7天,Ara-C100mg.m-2.d-1第1～7天,静脉滴注。结果:总有效率92.9(13/14),完全缓解率78.6(11/14),治疗过程中未发生早期死亡。化疗的不良反应主要为骨髓抑制和粒细胞缺乏所致感染,未见严重的非造血系统不良反应。结论:IDA联合HA方案为初治AML的高效、安全的方案。     

CAG方案治疗复发性急性髓细胞白血病疗效观察

目的:探讨CAG方案对复发性急性髓细胞白血病(AML)的临床疗效和不良反应.方法:选择在我院治疗的复发AML 46例,复发后20例选用CAG方案:阿克拉霉素(ACR)10～14 mg·m-2·d-1 (第1～4天,10～14天),静脉滴注;阿糖胞苷(Ara-C)10 mg·m-2·d-1 q12h(第1～14天),皮下注射;粒细胞集落刺激因子(G-CSF)200 μg·m-2·d-1(第1～14天),皮下注射.26例选用对照方案:①DAH:柔红霉素40 mg·m-2·d-1(第1～3天);Ara-c 200 mg·m-2·d-1(第1～7天),高三尖杉酯碱(HHT)3～4 mg·m-2·d-1(第1～7天);②MAE:米托蒽醌(Mito)10 mg·m-2·d-1(第1～3天),Ara-c 200 mg·m-2·d-1(第1～7天),依托泊甙(VP-16)60 mg·m-2·d-1(第1～5天).结果:强化疗组26例,经上述化疗1个疗程后6例获得完全缓解(CR),部分缓解(PR)10例,未缓解(NR)10例.PR和NR 20例患者中6例一般情况差,未能继续强化疗,换用CAG方案;14例予第2个疗强化疗,CR 4例,NR 10例;2疗程CR共10例(38.4%).26例CAG组第1个疗程CR 12例,PR 10例,NR 4例.PR和NR 14例予以CAG第2个疗程治疗,CR 8例,PR 2例,NR 4例,2疗程CR共18例(69.2%).2组CR率差异有统计学意义(P<0.05).CAG组骨髓抑制不明显,不良反应也低.结论:复发AML治疗中,CAG方案是较对照组方案更为有效的且不良应低的治疗方法.     

HA预激方案治疗老年急性髓系白血病的疗效观察

目的:探索含HA预激方案治疗老年急性髓系白血病(AML)的疗效。方法:11例老年AML患者(治疗组)予高三尖杉酯碱(HHT)1 mg·m-2·d-1,静脉滴注,第1-14天;阿糖胞苷(Ara-C)10 mg·m-2·12 h-1,皮下注射,第1-14天;粒细胞集落刺激因子(G-GSF)200μg·m-2·d-1,皮下注射,第1天注射Ara-C之前开始使用,至最后1次Ara-C之前停用。如果中性粒细胞>10×109/L,G-GSF用量减半,>20×109／L,则暂停用G-CSF,但不停化疗,待白细胞回落后再用。如果1个疗程未获完全缓解(CR),则进行第2个疗程,方案同第1疗程。如果2个疗程未获缓解,则视为治疗无效。对照组予标准DA方案治疗。结果:11例患者中第1个疗程CR 7例,第2个疗程CR 1例,1例第2疗程达部分缓解,CR率72．7％,有效率81.8％。结论:小剂量HA与G- CSF预激方案治疗老年AML有较高的疗效且不良反应少。     

CAG预激方案治疗老年人急性髓细胞白血病的临床观察

目的探讨小剂量阿糖胞苷（Ara-C，C）和阿克拉霉素（Acla，A）联合粒细胞集落刺激因子（G-CSF，G）治疗老年人急性髓细胞白血病（AML）的疗效和不良反应。方法回顾性分析60-81岁的AML患者52例，男28例，女24例。5例曾接受2个疗程正规剂量的化疗，均未缓解；40例作染色体核型分析，10例为预后不良染色体异常。52例均采用CAG预激方案治疗，即Acla 10mg／d，第1～8天，Ara-C10 mg／m^2，1次／12h，第1～14天，G-CSF200μg·m^-2·d^-1，第1～14天。结果化疗后总有效率69．2％，完全缓解（CR）率55．8％。初诊患者CR率为65．7％；复发、难治患者为35．2％；≥70岁患者为44．4％。10例预后不良染色体异常的患者完全缓解4例。全组早期病死率7．7％，总生存期中位时间14个月。化疗的不良反应主要为骨髓抑制，未见严重的非造血系统不良反应。结论CAG预激方案为治疗老年人AML的比较有效、安全的方案。     

FLAG方案治疗复发、难治急性白血病的疗效观察

目的:观察FLAG方案治疗复发、难治急性白血病的临床疗效.方法:对21例复发、难治急性白血病患者给予FLAG方案,即Flud 30 mg·m-2·d1(1～5 d),每天1次静脉滴注;Ara-C 1～2 g· m-2·d-1 (1～5d),Flud 4 h后静脉滴注,每12h1次静脉滴注;G-CSF 5μg·kg-1·...     

粒细胞集落刺激因子预激下小剂量Ara-C和ACR治疗复发难治急性髓细胞性白血病及骨髓增生异常综合征

目的:观察并评价在粒细胞集落刺激因子(GCSF)预激下小剂量阿糖胞苷(AraC)联合阿克拉霉素(ACR)方案(以下称AGA方案)治疗复发和(或)难治急性髓细胞性白血病(AML)和骨髓增生异常综合征(MDS)患者有效性和不良反应,从细胞凋亡方面探讨治疗方案的可能机制。方法:对复发难治的18例AML及4例MDS患者行AGA方案治疗。化疗方案:AraC10mg/m2,第1～14天,1次/12h,皮下注射;ACR8mg·m-2·d-1,第1～8天,静脉滴注;GCSF200μg·m-2·d-1,第1～14天,皮下注射,每次先于皮下注射AraC前1h开始。结果:9/18(50%)例AML接受1个AGA治疗即获完全缓解(CR),中位数缓解期4个月,其中6/10(60%)例M2获CR,22例治疗病例均无治疗相关死亡。20例接受传统标准剂量化疗对照组7例获得CR,4例死于化疗相关毒性。体外研究证实AGA方案明显提高新鲜白血病细胞凋亡率。结论:AGA方案对正常造血抑制较轻,非血液学不良反应小,外周血白细胞和血小板恢复较常规化疗组明显缩短。适于不能耐受常规治疗的、骨髓呈低增生的复发难治或老年AML患者,该药物协同诱导凋亡可能是该方案的治疗机制之一。     

去甲氧柔红霉素与柔红霉素方案对初治白血病疗效比较

目的:比较去甲氧柔红霉素(ID)与柔红霉素(DNR)联合阿糖胞苷2种化疗方案对初治急性髓系白血病(AML)的诱导缓解疗效及不良反应。方法:回顾性分析41例初治AML患者应用IDA方案和DA方案治疗的临床资料,比较2组病例的临床疗效、不良反应等指标上的差异。结果:IDA方案组22例中完全缓解(CR)15例,部分缓解(PR)2例,未缓解(NR)5例,有效率77.3%;DA方案组19例中CR6例,PR3例,NR10例,有效率47.4%,2组疗效差异有统计学意义(P<0.05)。IDA组22例中初次完全缓解(CR1)>1年的患者14例(63.6%),DA组19例中CR1>1年的患者7例(36.8%)。2组不良反应差异无统计学意义,主要是较强烈的骨髓抑制。结论:IDA组与DA组治疗初治AML疗效差异有统计学意义,不良反应差异无统计学意义,疗程中支持治疗非常重要。     

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。     

外周血淋巴细胞早期恢复在IA诱导治疗初治AML患者预后中的临床意义

目的:探讨外周血淋巴细胞绝对计数(ALC)与IA方案即标准剂量的去甲氧柔红霉素(IDA)联合阿糖胞苷(Ara-C)诱导治疗初治急性髓系白血病(AML)(除外急性早幼粒细胞白血病)患者预后的关系。方法:155例初治AML患者均接受IA方案诱导治疗:IDA 10~12mg/(m~2·d),第1~3天,Ara-C 100mg/(m~2·d),持续静脉滴注第1~7天。126例IA诱导治疗达完全缓解(CR)患者的后继治疗包括:70例采用以大剂量Ara-C为主的化疗;32例行自体干细胞移植(auto-HSCT);24例行异基因造血干细胞移植(allo-HSCT)。回顾性分析诱导治疗后第10天ALC(ALC-10)、第14天ALC(ALC-14)与总生存时间(OS)、无复发生存时间(RFS)的关系。结果:首次诱导治疗后,5例(3.2%)发生早期死亡,其余150例进行疗效评估,其中126例(84.0%)达到CR,9例(6.0%)获得部分缓解。ALC-10≥0.435×10~9/L者与ALC-100.435×10~9/L者中位OS分别为13.6个月、18.5个月(P=0.019),前者中位RFS优于后者(13.6个月∶10.0个月,P=0.007);ALC-14≥0.270×10~9/L者与ALC-140.270×10~9/L者中位OS分别为14.8个月、17.0个月(P=0.002),前者中位RFS优于后者(11.8个月∶10.0个月,P=0.002)。多因素分析显示,ALC-14是影响RFS的独立危险因素。在以大剂量Ara-C为主的化疗组和auto-HSCT组,ALC-14≥0.270×10~9/L者与ALC-140.270×10~9/L者相比,RFS均明显延长(P=0.025、0.028)。在allo-HSCT组,ALC-14对RFS的影响无统计学意义。结论:ALC-14可以作为判断IA方案诱导治疗初治AML患者预后的指标,尤其是CR后接受以大剂量Ara-C为主的化疗和auto-HSCT患者。     

外周血淋巴细胞早期恢复在IA诱导治疗初治AML患者预后中的临床意义

目的:探讨外周血淋巴细胞绝对计数(ALC)与IA方案即标准剂量的去甲氧柔红霉素(IDA)联合阿糖胞苷(Ara-C)诱导治疗初治急性髓系白血病(AML)(除外急性早幼粒细胞白血病)患者预后的关系。方法:155例初治AML患者均接受IA方案诱导治疗:IDA 10~12mg/(m~2·d),第1~3天,Ara-C 100mg/(m~2·d),持续静脉滴注第1~7天。126例IA诱导治疗达完全缓解(CR)患者的后继治疗包括:70例采用以大剂量Ara-C为主的化疗;32例行自体干细胞移植(auto-HSCT);24例行异基因造血干细胞移植(allo-HSCT)。回顾性分析诱导治疗后第10天ALC(ALC-10)、第14天ALC(ALC-14)与总生存时间(OS)、无复发生存时间(RFS)的关系。结果:首次诱导治疗后,5例(3.2%)发生早期死亡,其余150例进行疗效评估,其中126例(84.0%)达到CR,9例(6.0%)获得部分缓解。ALC-10≥0.435×10~9/L者与ALC-100.435×10~9/L者中位OS分别为13.6个月、18.5个月(P=0.019),前者中位RFS优于后者(13.6个月∶10.0个月,P=0.007);ALC-14≥0.270×10~9/L者与ALC-140.270×10~9/L者中位OS分别为14.8个月、17.0个月(P=0.002),前者中位RFS优于后者(11.8个月∶10.0个月,P=0.002)。多因素分析显示,ALC-14是影响RFS的独立危险因素。在以大剂量Ara-C为主的化疗组和auto-HSCT组,ALC-14≥0.270×10~9/L者与ALC-140.270×10~9/L者相比,RFS均明显延长(P=0.025、0.028)。在allo-HSCT组,ALC-14对RFS的影响无统计学意义。结论:ALC-14可以作为判断IA方案诱导治疗初治AML患者预后的指标,尤其是CR后接受以大剂量Ara-C为主的化疗和auto-HSCT患者。     

A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation

The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.     

Fludarabine, cytarabine, G-CSF and idarubicin (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute myeloid leukaemia

Nineteen patients with high-risk myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) received fludarabine, cytarabine, granulocyte-colony stimulating factor (G-CSF), and idarubicin chemotherapy ( de novo MDS/MDS-AML, nine; relapsed/refractory MDS/AML, seven; therapy-related MDS, three). Median age was 44 years and median disease duration 10 months. 16/19 (84%) patients had abnormal cytogenetics with seven (37%) harbouring abnormalities of chromosome 7. 18/19 (94.7%) patients responded to FLAG-idarubicin with 12 (63%) achieving complete remission (CR) (<5% blasts and normal cytogenetics). 7/9 (78%) patients with de novo MDS/MDS-AML achieved CR compared to 5/10 (50%) with alternative diagnoses. Response was associated with age < 50 years, disease duration < 3 months, and cytogenetics other than abnormalities of chromosome 7. Haemopoietic regeneration was rapid in most patients and there were no toxic deaths. Nine patients received a second course of chemotherapy, three have proceeded to allogeneic bone marrow transplant and three to autologous blood stem cell/bone marrow transplantation. Follow-up is short (median 10 months). 12/19 (63%) patients remain alive and 5/12 (42%) have relapsed at a median 5 months following CR achievement. FLAG-idarubicin was well tolerated. High rates of morphological and cytogenetic remission, especially in de novo MDS, offer a window of opportunity for assessment of autologous BMT in this group of diseases where no treatment except alloBMT has led to prolongation of survival.     

Idarubicin, cytarabine, and topotecan in patients with refractory or relapsed acute myelogenous leukemia and high-risk myelodysplastic syndrome.

In an effort to develop more effective therapy for patients with refractory or relapsed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of a combination chemotherapy consisting of idarubicin, cytarabine, and topotecan. Twenty-seven patients were treated: four with primary refractory AML, nine with AML in first relapse, four with AML in second relapse, and 10 with MDS-RAEB/RAEBT. Patients received as salvage therapy a single course of idarubicin 12 mg/m(2) IV bolus on days 1-3, cytarabine 1 g/m(2) over two hours q 12 hr on days 1-5, and topotecan 1.25 mg/m(2) over 24 hr on days 1-5. Median age was 42 years (range 17-65 years). All patients were evaluable for response: 14 (51.9%) achieved complete remission, 10 with AML (59%) and four with MDS (40%), respectively. Thirteen AML patients (excluding four relapsed after autologous stem cell transplantation) were grouped into four categories to stratify the probability of achieving complete remission (CR): group 1, first CR duration > or = 2 years and receiving first salvage treatment (S1); group 2, first CR duration 1-2 years and receiving S1; group 3, first CR duration 0-1 years and receiving S1; and group 4, first CR duration 0-1 years and receiving S2, S3, or S4 after failing S1. The response rate of each group was as follows: group 1, one of two (50%); group 2, one of one (100%); group 3, four of four (100%); group 4, two of six (33.3%). The median remission duration and survival of patients with AML were six and 12 months, respectively. Median duration of survival in 10 MDS patients was 15 months, and all four MDS patients achieving a CR maintained continuous CR with a median follow-up of 11 months. Severe myelosuppression was observed in all patients, resulting in fever or documented infections in 89% of patients. Median time to recovery of neutrophils > or =0.5 x 10(9)/l was 22 days (11-34) and for platelets > 20 x 10(9)/l 35 days (11-58). Reversible grade 3-4 toxicities included diarrhea (two patients) and mucositis (seven patients). We conclude that combination chemotherapy with intermediate dose cytarabine, idarubicin, and topotecan has significant antileukemic activity and acceptable toxicity in salvage AML and high-risk MDS.     

Combination chemotherapy with low-dose cytarabine, homoharringtonine, and granulocyte colony-stimulating factor priming in patients with relapsed or refractory acute myeloid leukemia

As sensitization of leukemic cells with granulocyte colony-stimulating factor (G-csf) can enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML), a pilot study was conducted in order to evaluate the effect of G-csf priming combined with low-dose chemotherapy in patients with relapsed and refractory AML. The regimen, G-HA, consisted of cytarabine 7.5 mg/m2/12 hr by subcutaneous injection, days 1-14, homoharringtonine 1.5 mg/m2/day by intravenous continuous infusion, days 1-14, and G-csf 150 microg/m2/day by subcutaneous injection, days 0-14. Thirty-six AML patients were enrolled, 23 refractory and 13 relapsed. Eighteen patients (50%, 95% confidence interval: 33-67%) achieved complete remission (CR) with a median CR duration of 7.2 months, and two elderly patients continued a regimen of maintenance therapy and remained in remission for 26.3 and 14.1 months, respectively, as of last follow-up. Eight patients (22%) experienced neutropenia (median duration: 6 days; range: 2-22 days). Thirteen of the 36 (36%) developed severe infections. Grade 1-2 nonhematologic toxicities were documented, including nausea and vomiting (20%), liver function abnormality (6%), and heart function abnormality (6%). No central nervous system and kidney toxicity was observed. The G-HA regimen is effective in remission induction for refractory and relapsed AML patients and well tolerated in maintenance therapy in some subgroups of elderly patients. Further studies are necessary to elucidate optimum dose and schedule for this regimen to enhance the treatment efficacy of relapsed or refractory AML patients.     

Idarubicin in combination with intermediate-dose cytarabine in the treatment of refractory or relapsed acute leukemias

13 patients with refractory or relapsed acute lymphoblastic leukemia (ALL) and 7 patients with acute myeloid leukemia (AML) were treated with a regimen that included idarubicin 12 mg/m2 intravenously daily for 3 d plus cytarabine 2 g/m2 by infusion over 3 hours daily for 3 d. There were 10 remissions (ALL:7; AML:3) in the 15 relapsed patients and 4 (ALL:3) in the 5 patients with primary refractory disease. Severe myelosuppression was observed in all patients. Toxicity of this regimen caused nausea and vomiting, stomatitis, infections and/or liver enzymes increase. Cardiac toxicity was not observed. 2 patients died in aplasia of Gram-negative septicemia and brain hemorrhage. In conclusion, the combination of idarubicin and intermediate-dose cytarabine (IDARA-C) seems to be highly effective and sufficiently well-tolerated for the treatment of refractory and relapsed acute leukemias.     

FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience

We evaluated the efficacy and toxicity profiles of the combination of fludarabine, high-dose cytosine arabinoside (AraC), idarubicin, and granulocyte colony-stimulating factor (G-CSF) in refractory/relapsed acute myeloblastic leukemia (AML) patients. Between October 1998 and February 2002, 46 AML patients were treated with FLAG-IDA (fludarabine 30 mg/m(2), AraC 2 g/m(2) for 5 days, idarubicin 10 mg/m(2) for 3 days, and G-CSF 5 micro g/kg from day +6 until neutrophil recovery). Thirty patients were in relapse after conventional chemotherapy including cytarabine, etoposide, and daunorubicin or mitoxantrone according to the GIMEMA protocols. Four were in relapse after autologous peripheral stem cell transplantation and two after allogeneic bone marrow transplantation. Ten patients had refractory disease (after 10 days of standard doses of cytarabine, 3 days of mitoxantrone or daunorubicin, and 5 days of etoposide). Recovery of neutrophils and platelets required a median of 19 and 22 days from the start of therapy. Complete remission (CR) was obtained in 24 of 46 patients (52.1%) and 3 of 46 (6.6%) died during reinduction therapy: 2 due to cerebral hemorrhage and 1 due to fungemia ( Candida tropicalis). Fever >38.5 degrees C was observed in 40 of 46 patients (86.9%), 27 had fever of unknown origin (FUO) and 13 documented infections; 31 of 46 (67.3%) developed mucositis and 14 of 46 (30.4%) had grade 2 WHO transient liver toxicity. After achieving CR, 11 patients received allogeneic stem cell transplantation, 4 patients received autologous stem cell transplantation, 4 were judged unable to receive any further therapy, and 5 refused other therapy. Ten patients are at present in continuous CR after a median follow-up of 13 months (range: 4-24). In our experience, FLAG-IDA is a well-tolerated and effective regimen in relapsed/refractory AML. The toxicity is acceptable, enabling most patients to receive further treatment, including transplantation procedures.     

Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: A phase-II study (no. 06901) of the EORTC Leukemia Cooperative Group

 Twenty-one patients with acute myeloid leukemia (AML) who failed to enter complete remission (CR) after first-line standard-dose remission-induction therapy with 7 days of cytarabine and 3 days of daunorubicin were treated with a salvage regimen containing intermediate-dose cytosine arabinoside (Ara-C) 2×500 mg/m²/day during 7 days in combination with continuous infusions of idarubicin 12 mg/m²/day on days 1, 3, and 5. Twenty patients were considered primary resistant, and one patient had a partial remission after two remission-induction courses. Overall, 11 patients (52%, 95% confidence interval: 30–74%) entered CR. Three patients died during hypoplasia and seven patients had resistant disease or a partial remission. The remission rate in this study compares favorably with the results obtained in similar patient categories. The toxicity of this salvage regimen was remarkably mild. No extramedullary toxicity was observed except for hepatic dysfunction in seven patients. The median duration of remission was 8.5 months, and ultimately, all complete remitters have relapsed except the patient who died from infectious complications after allogeneic bone marrow transplantation (BMT). This study shows that new intensive chemotherapy regimens may be effective after failure of primary treatment. Salvage regimens containing intermediate/high-dose Ara-C and/or alternative anthracyclines or anthracenes should be induced in the treatment of young patients with de novo AML. Received: 12 September 1995 / Accepted: 24 November 1995     

A phase I–II study of plerixafor in combination with fludarabine,idarubicin, cytarabine,and G-CSF (PLERIFLAG regimen) for the treatment of patients with the first early-relapsed or refractory acute myeloid leukemia

Clinical outcomes of patients with acute myeloid leukemia (AML) showing the first primary refractory or early-relapsed disease remain very poor. The Programa Español de Tratamientos en Hematología (PETHEMA) group designed a phase I–II trial using FLAG-Ida (fludarabine, idarubicin, cytarabine, and G-CSF) plus high-dose intravenous plerixafor, a molecule inducing mobilization of blasts through the SDF-1α-CXCR4 axis blockade and potentially leading to chemosensitization of the leukemic cells. We aimed to establish a recommended phase 2 dose (RP2D) of plerixafor plus FLAG-Ida, as well as the efficacy and safety of this combination for early-relapsed (first complete remission (CR/CRi)?<?12 months) or primary refractory AML. Between 2012 and 2015, 57 patients were enrolled, and 41 received the RP2D (median age 52 years [range, 18–64]). Among these patients, 20 (49%) achieved CR/CRi, and 3 (7%) died during induction. CR/CRi rate was 50% (13/26) among primary refractory and 47% (7/15) among early relapse. Overall, 25 patients (61%) were allografted. Median overall and disease-free survivals were 9.9 and 13 months, respectively. In summary, the combination of plerixafor plus FLAG-Ida resulted in a relatively high CR/CRi rate in adult patients with primary refractory or early relapsed AML, with an acceptable toxicity profile and induction mortality rate, bridging the majority of patients to allogeneic stem cell transplantation. ClinicalTrials.gov Identifier: NCT01435343     

Intensive induction chemotherapy with regimen containing intermediate dose cytarabine in the treatment of de novo acute myeloid leukemia

To improve long‐term outcome of de novo acute myeloid leukemia (AML) patients by intermediate dose of cytarabine integrated in induction therapy and to explore the impact of cytogenetic abnormalities on the prognosis. Eighty‐seven AML patients were treated with HAD regimen containing intermediate dose cytarabine (IDAra‐C) as induction therapy, 83 from which with karyotype results were divided into three cytogenetic groups according to SWOG criteria. Complete remission (CR) rate, disease‐free survival (DFS), and overall survival (OS) among different groups were evaluated. The CR rate of the 87 cases was 80/87 (92%). Median DFS and OS have not reached (NR). DFS rates at 1 and 3 years were 76.3% and 63.4%, respectively. OS rates at 1 and 3 years were 86.0% and 58.7%, respectively. According to SWOG criteria, CR rate, median DFS, and OS were 100%, NR and NR for the favorable group; 88.9%, NR, and 16 months for the intermediate group; 83.3%, 4.5 months, and 7.5 months for the adverse group. The differences among the three groups were statistically significant excepting for CR rate between adverse and intermediate groups. HAD regimen containing IDAra‐C as induction chemotherapy regimen is effective in de novo AML of adult patients and can achieve higher CR rate and longer survival than standard dose of cytarabine (SDAra‐C) regimen. Most of the patients were able to endure the therapy. Cytogenetics is still an important prognostic factor despite of the incorporation of IDAra‐C in induction chemotherapy. The differences among the three groups were statistically significant. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.     

Phase II evaluation of an intensified induction therapy with standard daunomycin and cytarabine followed by high dose cytarabine for adults with previously untreated acute myeloid leukemia: a Southwest Oncology Group study (SWOG-9500)

Induction therapy for acute myeloid leukemia (AML) usually consists of 7 days of cytarabine at 100-200 mg/m(2)/day and an anthracycline. Such combinations produce complete response (CR) rates of 60-80% in patients with de novo AML. On the basis of a previous report, suggesting a higher CR rate using a regimen of standard daunomycin and cytarabine followed by 3 days of high-dose cytarabine (HDAC), 101 eligible patients received this regimen in a phase II trial. Sixty patients [59%, 95% confidence interval (CI) 49-69%] achieved a CR, and 10 patients died of infection during induction. Although cytogenetic risk group affected overall survival (P = 0.0016) and relapse-free survival (P = 0.0043), it had no impact on CR rate (P = 0.63). Patients received postremission therapy with repetitive courses of alternate day high-dose cytarabine; this was associated with considerable toxicity and the majority of patients could not receive all of the scheduled postremission therapy. The estimated median survival was 23 months (95% CI 15-34 months), and the estimated probability of surviving 5 years was 34% (95% CI 24-43%). The results of this intensive induction regimen were similar to that seen in previous trials and were not as promising as reported in the previous pilot study.