伊立替康联合米托恩醌治疗难治／复发性非霍奇金淋巴瘤的疗效观察

目的：在国内首次报道伊立替康（开普拓）联合米托恩醌治疗难治和复发非霍奇金淋巴瘤（NHL）的疗效;为难治性NHL的治疗寻找新的方法。方法：采用开普拓联合米托恩醌为主的化疗方案治疗21例难治和复发NHL,评价其疗效及不良反应。结果：7例（33．3％）难治和复发NHL达完全缓解（CR）;8例（38．1％）达部分缓解（PR）;总有效率为71．4％。不良反应主要为骨髓抑制、迟发性腹泻以及胃肠道反应,患者均能耐受。结论：开普拓联合米蒽醌对NHL特别是部分难治和复发NHL仍有效,不良反应可以耐受。可用于治疗对其他化疗方案无效的难治和复发NHL。     

CAG方案治疗初治急性髓系白血病的疗效观察

近来，多数学者主张对急性髓性白血病(AML)进行强力联合化疗，以提高缓解率。但部分AML患者年龄偏大，或由骨髓增生异常综合征进展而来，或AML亚型不同，或染色体异常改变，往往对标准HA、DA方案化疗不但缓解率不理想而且化疗毒副反应较重。鉴于华东地区CAG临床治疗协作组制定的CAG方案在难治、复发AML治疗中的应用经验，近两年来，我们采用相同的CAG预激方案，作为部分初发AML患者的诱导缓解方案，取得较好疗效，现报告如下。     

CHG方案治疗急性髓性白血病及高危骨髓增生异常综合征患者的疗效分析

目的:评价CHG方案治疗低增生、难治、复发急性髓性白血病(AML)及高危骨髓增生异常综合征(MDS)患者的疗效及不良反应.方法:对25例次AML和高危MDS患者实施CHG方案化疗.治疗前、治疗中及治疗后进行心电图、肝肾功能、外周血常规及骨髓细胞学检查,评估近期疗效及不良反应.结果:完全缓解率68%,部分缓解率8%;主要...     

CAG方案治疗中高危骨髓增生异常综合征和急性髓系白血病的疗效观察

目的:观察阿糖胞苷、阿克拉霉素和粒细胞集落刺激因子联合方案(CAG方案)治疗中、高危骨髓增生异常综合征(MDS)和老年初治、难治、复发和继发于MDS的急性髓系白血病(AML)的临床疗效及不良反应。方法:应用CAG方案治疗MDS9例和AML23例,完成1个疗程后评估疗效,治疗失败患者则退出观察,有效者继续接受1个疗程治疗。结果:9例MDS临床均有效,其中完全缓解4例(44.4%)。部分缓解3例(33.3%),血液学进步伴骨髓缓解1例(11.1%),骨髓缓解1例(11.1%)。AML临床总有效13例(56.5%),其中完全缓解9例(39.1%),部分缓解4例(17.4%)。大部分患者出现了可以耐受的轻微不良反应,主要表现为骨髓抑制。结论:CAG治疗中、高危MDS和预后差的AML安全有效,长期疗效需进一步观察。     

拓扑替康加阿糖胞苷方案治疗急性髓系白血病16例临床观察

我们对16例急性髓系白血病（AML）应用拓扑替康（TPT）加阿糖胞苷（Ara-C）联合诱导化疗，取得了较好疗效。 一、资料与方法 1．对象：16例AML均系住院患者，男9例，女7例，中位年龄42（16-68）岁。诊断及疗效判定均按文献。     

CLAG方案治疗复发、难治急性髓系白血病疗效、安全性分析及随访

目的:观察CLAG方案(克拉屈滨+阿糖胞苷+粒细胞集落刺激因子)治疗难治、复发急性髓系白血病(acute myeloid leukemia,AML)的疗效、安全性和不良反应。方法 :回顾性分析2015年7月至2018年1月我院收治的使用CLAG方案±地西他滨治疗的7例难治、复发AML患者,观察其疗效和不良反应,并进行随访。收集国内关于CLAG方案治疗复发、难治AML的相关文献,进行综合分析。结果:7例患者经CLAG方案±地西他滨化学治疗(化疗)1个疗程后, 4例完全缓解(complete remission,CR),3例未缓解(non-remission,NR)。主要不良反应为骨髓抑制(7例),血流感染、肠道感染和消化道出血各1例,无化疗相关死亡。4例CR与2例NR患者行异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation,allo-HSCT)。最终选入5篇文献进行分析,CR率在34.6%～78.8%之间,加上本研究7例患者共104例, CR患者为61例。结论:CLAG方案对难治、复发AML有效,化疗所致骨髓抑制较重,但安全性良好,患者可耐受。一旦获得CR,尽快行allo-HSCT以延长生存期。     

硼替佐米联合VAD方案治疗多发性骨髓瘤

目的：观察硼替佐米联合VAD方案治疗初治、难治复发多发性骨髓瘤（MM）患者的疗效及安全性。方法：15例初治及难治复发MM患者,硼替佐米1.3mg/m2,d1、4、8、11或d0、3、7、10静脉注射,每28d1个疗程;每个疗程联合VAD方案化疗,每位患者接受2-6个疗程治疗。采用2006年MM国际统一疗效标准观察疗效,并按NCI/PNIH标准判断不良反应。结果：中位随访14个月,治疗总有效率80%,其中8例患者达完全缓解,1例患者达良好的部分缓解,3例患者达部分缓解,2例患者疾病无进展,1例患者治疗过程中疾病进展。最常见的不良反应包括胃肠道症状,不同程度的白细胞、血小板减少,周围神经病和乏力等,经对症治疗及调整用药剂量后均能改善。结论：硼替佐米联合VAD方案可提高MM患者治疗完全缓解率,并未增加周围神经毒性。     

拓扑替康与足叶乙甙及环磷酰胺联合治疗慢性粒细胞白血病急变的临床研究

目的：探讨拓扑替康与足叶乙甙及环磷酰胺组成TEC方案治疗慢性粒细胞白血病（CML）急变期的疗效及毒副作用.方法：将34例患者确诊后即应用柔红霉素联合阿糖胞苷（DA）方案治疗，DA方案治疗两疗程后未达缓解或缓解后复发者均予TEC方案治疗两个疗程，其疗效及毒副作用均与DA方案作自身对照.所有患者定期检查血常规、骨髓及肝、肾功能等.分别观察两种方案的疗效及毒副作用.结果：34例中经TEC方案治疗有14例达完全缓解，4例达部分缓解，完全缓解率为41.17%，总有效率为52.94%;16例无反应.主要毒副作用为骨髓抑制.TEC方案疗效优于DA方案，毒副作用无明显加重.结论：TEC方案对CML急变期具有确切疗效，宜于临床推广。     

含地西他滨方案治疗老年急性髓系白血病26例疗效分析

目的:探讨地西他滨单药及联合CAG化疗方案治疗老年急性髓系白血病(AML)患者的临床疗效及不良反应等。方法:回顾性分析接受含地西他滨方案治疗的26例老年AML患者的临床特点,评估临床疗效及不良反应。结果:26例老年AML患者首程治疗后17例达完全缓解,3个疗程后18例达完全缓解,1例达部分缓解,总有效率73.1%。不良反应主要为骨髓抑制,其中17例出现肺部感染,2例出现败血症,3例出现粒细胞缺乏伴感染。结论:地西他滨单药及联合CAG方案治疗老年AML患者具有较高的缓解率和较低的不良反应,值得进一步探究及临床推广应用。     

标准剂量去甲氧柔红霉素联合阿糖胞苷治疗急性髓细胞白血病

目的:探讨标准剂量的去甲氧柔红霉素(IDA)联合阿糖胞苷(Ara-C)治疗急性髓细胞白血病(AML)的疗效和不良反应。方法:14例AML患者,年龄13～70岁(中位年龄36岁),男8例,女6例。初治AML10例,难治、复发AML4例。所有患者均在治疗前进行染色体核型分析,4例染色体异常。诱导方案为IDA 12 mg·m-2·d-1,第1～3天,Ara-C 100 mg·m-2·d-1,持续静脉点滴,第1～7天。结果:1个疗程结束后总有效率92．9％(13／14),完全缓解率85．7％(12／14),其中初治AML的CR率为90．0％(9／10),复发、难治AML的CR率为75．0％(3／4),3例染色体异常患者达细胞遗传学缓解,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:标准剂量的IDA联合Ara-C 24 h持续静脉点滴,为初治、复发难治AML的高效、安全的方案。     

High-dose cytosine arabinoside and mitoxantrone in previously-treated acute leukemia patients

35 patients with refractory or relapsed acute leukemia received salvage chemotherapy using high-dose cytosine arabinoside 2 g/m2 intravenously for 3 hours every 12 h, in 8 doses, followed by continuous infusion of mitoxantrone 12 mg/m2/day for 2 d. 9 patients had acute myeloblastic leukemia (AML), (4 relapsed, 5 refractory), 20 had acute lymphoblastic leukemia (ALL) (11 relapsed, 9 refractory) and 6 had chronic myelogenous leukemia (CML) in the blastic phase (BP). 4 out of 9 AML and 16 out of 20 ALL achieved complete remission. Median survival was 6 months for all patients and 10 months for responders. A short (1.5 months) chronic phase was achieved in 3 patients with CML. The main toxic effect was hematologic. A pharmacokinetic study was performed on mitoxantrone. No correlation was found with clinical response. The combination of mitoxantrone and ara-C is an effective antileukemic regimen, especially in ALL.     

Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia

Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen.     

Mitoxantrone and etoposide: an effective regimen for refractory or relapsed acute myelogenous leukemia

23 adult patients with refractory or relapsed acute myelogenous leukemia (AML) received salvage chemotherapy with mitoxantrone and etoposide. The regimen consisted of mitoxantrone, 10 mg/m2/d by 30-min infusion, and etoposide 100 mg/m2/d by 30-min infusion, given 12 h apart for 5 consecutive d. Of 23 patients treated, 13 met the criteria for highly refractory disease (6 primary resistant; 4 with early relapse during maintenance; 3 relapsed and refractory to reinduction). 10 patients had relapsed off-therapy more than 6 months after achieving first CR. Overall, 14 patients (61%) achieved a complete remission (CR): 6/13 (46%) with refractory AML, and 8/10 (80%) with relapsed AML. 2 patients had a partial remission, 2 died in aplasia, and 5 were nonresponders. In responding patients, the median time for recovery of granulocyte count was 27 d. The most important nonhematologic side effect was oral mucositis, which was severe in 35% of cases. No signs of cardiac toxicity were observed. The median CR duration was 5 months (range, 2 to 12+ months). The combination of mitoxantrone and etoposide appears a highly effective and relatively well tolerated salvage regimen for refractory and relapsed AML. Its incorporation into first-line induction and consolidation programs for newly diagnosed AML patients should be considered.     

Combination of liposomal daunorubicin (DaunoXome), fludarabine, and cytarabine (FLAD) in patients with poor-risk acute leukemia

Sixty-two patients with high-risk acute leukemia were treated with the FLAD regimen [3 days of treatment with fludarabine 30 mg/m², cytarabine (AraC) 2 g/m², and liposomal daunorubicin 80 mg/m²]. The acute myeloid leukemia (AML) patients were either refractory to standard induction regimens (8), were in first or second relapse (13), or received therapy as first-line treatment [21 patients, 16 were above 60 years of age and 5 had post-myelodysplastic syndrome (MDS) AML]. The acute lymphoblastic leukemia (ALL) patients were treated for relapsed (7) or refractory disease (10). Three patients had chronic myeloid leukemia (CML) in the blastic phase. FLAD was well tolerated by most patients. Ten major infectious complications were recorded while no signs of cardiac toxicity were observed. Five patients (8%) died before day 28 with hypocellular marrow, mainly of infection or hemorrhage, and response could not be evaluated. Complete response rate was 62% and 69% among AML patients treated at diagnosis or for relapsed disease, respectively, and 59% among the ALL patients. Furthermore, FLAD managed to overcome the negative impact of poor prognosis karyotype in ALL patients, since five of the seven patients with t(9;22) or complex karyotype achieved complete remission (CR). Nine patients underwent bone marrow transplantation (BMT). Among the AML patients who were treated at diagnosis or for relapse, the median duration of CR was 7 months (range: 2–18) and 8 months (range: 2–26), respectively. Median survival among these patients was 8 (range: 1–40) and 12 (range: 1–30) months, respectively. Similar values were found in ALL patients. In conclusion, FLAD may be an effective alternative treatment for patients with relapsed AML and for patients with ALL who failed first-line therapy.     

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.     

Efficacy of fractionated gemtuzumab ozogamicin combined with cytarabine in advanced childhood myeloid leukaemia

Gemtuzumab ozogamicin (GO) monotherapy is reported to yield a 20-30% response rate in advanced acute myeloid leukaemia (AML). This study examined the efficacy and tolerability of GO combined with cytarabine (GOCYT) in children with refractory/relapsed CD33(+) AML. Seventeen children received GO 3 mg/m(2) on days 1, 4 and 7 plus cytarabine 100 mg/m(2)/d for 7 d on a compassionate-use basis. Seven patients then received GO-based consolidation. At the outset of GOCYT, two patients were refractory; eight patients were in refractory first relapse; six patients had relapsed after stem cell transplantation (SCT); and one patient [del(5q) therapy-related AML (t-AML)] had not yet been treated. Mean follow-up was 17 months (8-33 months). Ten responses were obtained after GOCYT induction, including complete remission (CR) or CR without complete recovery of platelets (CRp) in six patients (35%). The responses improved in three children who received GOCYT consolidation, increasing the CR + CRp rate to 53%. SCT was subsequently performed in eight responders. Grade 3-4 adverse events consisted of haematological disorders (n = 17, 100%) and documented infections (n = 5, 29%). No cases of sinusoidal obstructive syndrome occurred. Three patients were alive at the cut-off date for this analysis, all of whom had responded to GOCYT. GOCYT combination therapy yielded a high response rate (53%) and showed acceptable toxicity in heavily pretreated children with refractory/relapsed AML. These results warrant a larger prospective study.     

Downregulation of neuropilin-1 in patients with acute myeloid leukemia treated with thalidomide

OBJECTIVE: Neuropilin-1 (NRP-1), a non-tyrosine kinase receptor functioning as a mediator of angiogenesis and neuronal guidance, was recently found to be significantly overexpressed in newly diagnosed acute myeloid leukemia (AML) patients with significant correlation to survival. The role of NRP-1 in refractory or relapsed AML patients and its regulation during anti-angiogenic treatment remain to be elucidated. METHODS: Bone marrow biopsies of 10 patients with refractory or relapsed AML were evaluated for NRP-1 expression by immunohistochemical analysis, and NRP-1 expression level was determined before and after start of thalidomide therapy and correlated to response and growth factor expression. RESULTS: NRP-1 expression was significantly increased in AML patients [median 7 arbitrary units (AU)] when compared with controls (n = 38, median 2.75 AU). Under thalidomide treatment, a marked difference in the course of NRP-1 expression between responders and non-responders was observed, however, without a statistical significance (P = 0.071) being reached. Additionally, a significant correlation of the NRP-1 expression level to microvessel density could be detected under treatment with thalidomide (P = 0.018). CONCLUSION: Our data provide evidence of increased NRP-1 expression in relapsed or refractory AML. Additionally, our results suggest that thalidomide-induced antileukemic properties might at least in part be mediated by NRP-1 downregulation.     

Idarubicin in the treatment of acute leukemias. An overview of preclinical and clinical studies

Idarubicin is a new derivative of Daunorubicin which was found to be more potent and more active than Daunorubicin and Doxorubicin in several experimental leukemias. Its antileukemic activity in preclinical models prompted the introduction of Idarubicin into clinical studies. As a single agent, Idarubicin produced complete remission in 20% and 30% of patients with heavily pretreated pediatric and adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) respectively. Idarubicin combined with Cytarabine and/or other antileukemic agents produced complete remissions in 46% of patients with refractory or relapsed AML and in 58% of patients with refractory or relapsed ALL (adult and pediatric). Subsequently, Idarubicin has been employed in untreated AML patients in combination with Cytarabine and/or Etoposide, producing complete remissions in more than 80% of patients. In ALL patients the drug has been used in combination with Vincristine, Cytarabine and Prednisone, producing complete remissions in 82% of patients. Recently, Idarubicin has been utilized in combination with intermediate doses of Cytarabine in refractory or relapsed ALL and AML, and 70% of patients achieved complete remission. Preliminary results of ongoing prospective randomized studies in untreated adult AML seem indicate that Idarubicin is at least equivalent, if not superior to Daunorubicin. The antileukemic activity of Idarubicin given orally as single agent, or in combination with other drugs, has been shown in AML and myelodysplastic syndromes. The toxicity of Idarubicin includes mild nausea and vomiting, alopecia and liver dysfunction. Ongoing randomized trials comparing Idarubicin to Daunorubicin should provide more information about the potential cardiotoxicity of this drug.     

Safety and efficacy of gemtuzumab ozogamicin in pediatric patients with advanced CD33+ acute myeloid leukemia

This open-label, dose-escalation study evaluated the safety and efficacy of single-agent gemtuzumab ozogamicin, a humanized anti-CD33 antibody-targeted chemotherapeutic agent, for pediatric patients with multiple relapsed or primary refractory acute myeloid leukemia (AML). Twenty-nine children 1 to 16 years of age (relapsed disease, 19; refractory disease, 10) received gemtuzumab ozogamicin ranging from 6 to 9 mg/m2 per dose for 2 doses (separated by 2 weeks) infused over 2 hours. All patients had anticipated myelosuppression. Other toxicities included grade 3/4 hyperbilirubinemia (7%) and elevated hepatic transaminase levels (21%); the incidence of grade 3/4 mucositis (3%) or sepsis (24%) was relatively low. One patient treated at 9 mg/m2 developed veno-occlusive disease (VOD) of the liver and defined the dose-limiting toxicity. Thirteen patients underwent hematopoietic stem-cell transplantation less than 3.5 months after the last dose of gemtuzumab ozogamicin; 6 (40%) developed VOD. Eight of 29 (28%) patients achieved overall remission. Remissions were comparable in patients with refractory (30%) and relapsed (26%) disease. Mean multidrug resistance-protein-mediated drug efflux was significantly lower in the leukemic blasts of patients achieving remission (P < .005). Gemtuzumab ozogamicin was relatively well tolerated at 6 mg/m2 for 2 doses and was equally effective in patients with refractory and relapsed disease. Further studies in combination with standard induction therapy for childhood AML are warranted.