沙利度胺联合MP方案治疗多发性骨髓瘤的疗效评价

目的 比较沙利度胺联合美法仑+泼尼松方案(MPT)与美法仑+泼尼松方案(MP)治疗多发性骨髓瘤(MM)的疗效与患者不良反应.方法 采用回顾性分析,MPT组26例,美法仑每天9 mg/m2口服,第1天至第4天,泼尼松60 mg/m2,第1天至第4天,或者美法仑每天4 mg/m2口服,第1天至第7天;泼尼松每天40 mg/m2口服,第1天至第7天,28 d为1个疗程,沙利度胺白化疗开始持续给药,100～200 mg/d,每4周为1个疗程,MP组21例,美法仑及泼尼松用法用量同MPT组,6个疗程后评价总疗效结果 MPT组的总有效率(ORR)为65.4%,明显高于MP组的42.9%(P＞0.05);MPT组中位反应时间为2个月,MP组为3个月;MPT组患者治疗后血红蛋白及清货白升高明显高于MP组(P＜0.05);MPT组不良反应的发生率高于MP组(P＜0.05),但两组3度以上的不良反应差异无统计学意义;MPT组中位无进展生存时间(PFS)为11个月,2年PFS为66.18%.结论 与MP方案相比,MPT方案可以提高MM患者的有效率,改善生活质量,延长生存时间,耐受性良好.     

硼替佐米联合异环磷酰胺、甲泼尼龙、沙利度胺方案治疗多发性骨髓瘤

目的 观察硼替佐米联合异环磷酰胺、甲泼尼龙、沙利度胺(V-CMPT方案)治疗多发性骨髓瘤(MM)的临床疗效和患者不良反应.方法 回顾性分析应用V-CMPT方案进行治疗的24例初治和复发难治MM患者资料,3周为1个周期,治疗2个周期.应用骨髓细胞学检查、M蛋白鉴定以及其他血液学指标评价病情及疗效.结果 初治的9例患者中,完全缓解(CR)3例、部分缓解(PR)5例、轻微缓解(MR)1例;复发难治的15例患者中,CR2例、接近完全缓解(nCR)2例、PR 3例、MR 6例、无变化(NC)2例;两组间总缓解率(ORR)(P=0.511)及CR/nCR率(P=1.000)差异无统计学意义.总的CR/nCR率29.2%(7/24),ORR达到91.7%(22/24).2个周期V-CMPT化疗后,患者的血红蛋白、血清清蛋白及血清β2微球蛋白得到明显改善.不良反应包括胃肠道反应、血小板减少、周围神经病变等,经对症处理或间歇期停药多好转,不影响化疗的继续进行.结论 V-CMPT方案对初治和复发难治性MM临床疗效明显,能够明显改善血液学指标,药物耐受性良好.     

BTD、MPT方案序贯治疗新诊断的非移植多发性骨髓瘤患者的疗效分析

目的 回顾性总结BTD与MPT方案序贯治疗新诊断的非移植多发性骨髓瘤(MM)患者的临床疗效及不良反应.方法 选取2006年1月至2010年5月应用BTD、MPT方案序贯治疗的新诊断非移植MM患者36例为研究对象,其中BTD方案诱导治疗至少2个疗程.达到部分缓解(PR)及其以上疗效后,改用MPT方案巩固治疗至少2个疗程,再应用小剂量沙利度胺维持治疗,直至疾病复发、进展.观察患者疗效及不良反应.结果 应用BTD方案诱导治疗的36例MM患者中,7例(19.4%)获得完全缓解(CR),8例(22.2%)获得非常好的部分缓解(VGPR),14例(38.9%)获得PR,总缓解(OR)率为80.6%.29例有效(CR+VGPR+PR)患者应用MPT方案维持治疗,1例VGPR患者获得CR,3例PR患者获得VGPR,4例(1例既往CR,1例VGPR,2例PR)出现复发进展,其余患者病情平稳.在应用小剂量沙利度胺维持治疗的25例患者中,3例出现进展,其中2例死亡,其余患者病情稳定.中位随访16.5(2～46)个月,中位无进展生存期(PFS)尚未获得,预期1年生存率为86.0%,3年生存率为77.0%.不良反应主要包括血小板减少、周围神经病变、带状疱疹、胃肠道反应、贫血、感染、便秘、疲乏、皮疹等.3～4度不良反应发生率较低.结论 BTD、MPT方案序贯治疗可以用于新诊断的非移植MM患者的-线治疗.     

VD方案联合自体造血干细胞移植治疗难治性不分泌型多发性骨髓瘤一例并文献复习

目的 观察硼替佐米+地塞米松(VD)方案联合自体造血干细胞移植(ASCT)治疗一例难治性不分泌型多发性骨髓瘤(MM)患者的疗效.方法 通过对1例难治性不分泌型MM患者给予VD方案化疗4个周期,在疾病得到有效控制、临床体征改善后,进行ASCT(预处理方案为美法仑200 mg/m2),并对国内外相关文献复习.结果 患者经过化疗达到接近完全缓解(nCR),之后联合ASCT后达到完全缓解(CR).结论 VD方案联合ASCT可明显改善难治性不分泌型MM患者的临床预后.     

硼替佐米治疗难治性套细胞淋巴瘤一例并文献复习

目的 探讨硼替佐米在难治性套细胞淋巴瘤(MCL)治疗中的价值.方法 分析1例应用硼替佐米治疗的MCL患者的临床资料,并复习相关文献.结果 患者应用R-CHOP方案化疗后5月余疾病进展,改用硼替佐米化疗后达完全缓解,随访14个月,疾病仍处于缓解状态.结论 硼替佐米在治疗复发/难治的MCL中有积极作用,并且患者不良反应在可控范围.     

EPOCH方案治疗老年人外周T细胞淋巴瘤的临床研究

目的 评价EPOCH方案治疗老年外周T细胞淋巴瘤( PTCL)患者的临床疗效和不良反应.方法 对经病理确诊为PTCL老年患者28例,采用EPOCH方案治疗:依托泊苷50 mg/m2、表柔比星12mg/m2、长春新碱0.4mg/m2溶解于0.9%NaCl溶液持续静脉滴注,第1天至第4天;环磷酰胺750 mg/m2静脉滴注,第5天;泼尼松60 mg/m2口服,第1天至第5天,每21 d为1个疗程.依据WHO标准进行疗效和安全性分析和评估.结果 28例患者共完成85个疗程EPOCH方案化疗,中位化疗2个疗程,完全缓解(CR)15例,部分缓解(PR)5例,总有效(OR)率71.4%(20/28),总体平均生存时间20个月.初治患者CR率64.7%(11/17),PR率23.5%(4/17),OR率88.2%(15/17),明显高于诱导化疗失败的难治性患者[分别为36.4%(4/11)、9.1%(1/11)和45.5%(5/11)].两组OR率比较差异有统计学意义(λ2=5.99,P＜0.05),且初治患者平均生存时间长于难治性患者(24个月与13个月).EPOCH方案化疗的主要毒副作用为骨髓抑制,其中Ⅲ～Ⅳ度粒细胞和血小板减少的发生率分别为53.6%(15/28)和50.0%(14/28),非血液毒性发生率较低,初治与难治性患者的不良反应发生率差异无统计学意义(P＞0.05).结论 EPOCH方案是治疗老年PTCL患者有效而且耐受性较好的化疗方案.     

硼替佐米治疗套细胞淋巴瘤的分子学机制

套细胞淋巴瘤(MCL)是生存期最短的非霍奇金淋巴瘤(NHL),目前尚不能根治.硼替佐米是第一个用于治疗血液系统恶性肿瘤的蛋白酶体抑制剂,主要用于多发性骨髓瘤(MM)及复发难治性MCL的治疗.探讨硼替佐米治疗MCL的相关机制,其中包括调节细胞周期、影响细胞凋亡、干扰MCL的微环境以及与其他抗肿瘤药物的协同作用等,有助于未来合理应用硼替佐米治疗MCL.     

硼替佐米治疗复发难治性套细胞淋巴瘤的研究进展

复发难治性套细胞淋巴瘤(MCL)的治疗是临床医师面临的严峻挑战.近年来,蛋白酶体抑制剂硼替佐米的应用给复发难治性MCL患者的治疗提供了新方法.就硼替佐米治疗复发难治性MCL的机制、临床疗效以及MCL细胞对硼替佐米耐药产生的机制和应对策略进行综述.     

MT方案治疗急性单核细胞白血病的疗效及其与染色体核型的关系

目的 研究米托蒽醌联合替尼泊苷(MT)方案在急性单核细胞白血病(M5)诱导缓解中的疗效及患者不良反应,并观察疗效与白血病染色体核型的关系.方法 将33例M5患者按治疗史分两组:初治组23例(A组)、DA(柔红霉素联合阿糖胞苷)或HDA(三尖杉酯碱、柔红霉素和阿糖胞苷)1个疗程无效组10例(B组).按核型预后分两组:预后中等组29例(C组),预后不良组4例(D组),均采用MT方案2个疗程诱导缓解,分别统计4组的临床疗效及患者不良反应.结果 MT方案对A、B组的M5诱导完全缓解(CR)率分别为83%(19/23)及60%(6/10),有效率达91%(21/23)及70%(7/10).C、D组CR率分别为83%(24/29)及25%(1/4),有效率为88%(26/29)及50%(2/4),其中复杂核型CR率为0(0/3),非复杂核型的11q23染色体异常患者一次化疗达CR率100%(4/4).MT方案对M5化疗后白细胞最低点在第(7±3)天出现,为(0.4±0.2)×109/L,白细胞<1×109/L时间达(8±5)d,未见化疗相关死亡病例.结论 MT方案简单有效、较安全,是治疗M5的较佳化疗方案,对1个疗程DA、HDA方案无效者亦可试用.MT方案化疗疗效与核型预后分组有关,对11q23染色体异常的M5患者疗效较好,对复杂核型患者疗效欠佳.     

慢性粒细胞白血病患者血浆伊马替尼浓度检测与临床疗效分析

目的 探讨慢性粒细胞白血病(CML)患者服用伊马替尼治疗后,伊马替尼血浆浓度在个体间的差异以及与临床疗效的关系.方法 2005年7月至2008年2月开始服用伊马替尼治疗的CML患者共51例纳入研究,其中男34例,女17例,服用剂量300 mg/d 9例、400 mg/d 37例,600 mg/d5例;采用高效液相色谱法(HPLC)测定患者空腹伊马替尼血浆谷浓度;SPSS13.0软件进行统计分析.结果 伊马替尼血浆谷浓度与服用剂量有关,且个体之间差异较大,为(342～4688)ng/ml;300mg/d剂量组的伊马替尼血浆谷浓度为(1037±514)ng/ml,低于400mg/d剂量组的(2123±1016)ng/ml(t=2.34,P=0.032);300 mg/d剂量组的治疗有效率为66.67%(6/9),低于400 mg/d剂量组的89.19%(33/37)(χ2=7.14,P=0.008);在300、400mg/d剂量组中,39例治疗有效,伊马替尼血浆谷浓度高于治疗效果不理想患者,差异有统计学意义(t=2.25,P=0.037);受试者工作特征曲线(ROC曲线)结果提示伊马替尼血浆谷浓度低于1050 ng/ml者,其临床疗效可能较差,敏感度为84.6%,特异度为71.1%.结论 CML患者服用伊马替尼治疗后药物血浆浓度与服用剂量有关,不同个体间差异较大,血浆谷浓度低于1050 ng/ml提示其临床疗效可能较差.     

CAG预激方案联合左旋门冬酰胺酶和泼尼松诱导治疗复发难治性前体淋巴细胞白血病/淋巴瘤

目的 寻找复发难治性前体淋巴细胞白血病/淋巴瘤诱导缓解的有效方法.方法 以CAG预激方案联合左旋门冬酰胺酶(L-Asp)和泼尼松(PDN)诱导治疗6例复发难治性前体淋巴细胞白血病/淋巴瘤和1例急性杂合细胞白血病.结果 6例患者完全缓解(CR),1例部分缓解(PR),总有效率100%(7/7),CR率85.7%(6/7).患者不良反应轻,均可耐受.结论 CAG联合L-Asp和PDN是复发难治性前体淋巴细胞白血病/淋巴瘤值得尝试的诱导化疗方案.     

A case of chronic B cell lymphocytic leukemia with expression of CD8 antigen on leukemic cells

PURPOSE: To determine the toxicity and prognosis of patients with relapsed and refractory diffuse aggressive non-Hodgkin's lymphoma (NHL) who underwent an autologous bone marrow transplant (ABMT) using augmented preparative regimens, treated in a major cooperative group setting, and to examine prognostic factors for outcome. PATIENTS AND METHODS: Ninety-four patients with either chemosensitive (50 patients) or chemoresistant (44 patients) relapse, including 22 who failed induction chemotherapy, were treated with high-dose cyclophosphamide and etoposide with total-body irradiation (TBI) (67 patients) or an augmented carmustine (BCNU), cyclophosphamide, and etoposide (BCV) preparative regimen (27 patients) and an ABMT at 16 Southwest Oncology Group (SWOG) transplant centers. All relapsing patients were required to undergo a minimum of two courses of salvage therapy to determine chemosensitivity before transplant. Overall (OS) and progression-free survival (PFS) were determined and a Cox regression model was used to assess potential prognostic variables. RESULTS: Of the 94 eligible patients, there were 10 (10.6%) deaths before day 50 posttransplant because of infection (six deaths), hemorrhagic alveolitis (three deaths), or bleeding (one death). The median 3-year PFS and OS for the entire group was 33% and 44%. For those with chemosensitive disease the PFS and OS were 42% and 55%, whereas for those with chemoresistant disease the PFS and OS were 22% and 29%. The PFS and OS for those failing induction chemotherapy were 27% and 32%. The relapse rates within the first 3 years for the chemosensitive relapse, chemoresistant, and induction failure groups were 61%, 40%, and 59%, respectively. For both PFS and OS, only disease status at transplant was a significant factor in the multivariate Cox model. CONCLUSION: These results single institutional pilot trials exploring augmented preparative regimens. Patients undergoing transplantation for resistant disease, particularly those failing induction chemotherapy, appear to have an improved prognosis as compared with reports using standard preparative regimens. Therapies other than manipulation of standard preparative regimens appear to be required to decrease relapses following autotransplantation.     

Paclitaxel plus high-dose cyclophosphamide with G-CSF support in patients with relapsed and refractory aggressive non-Hodgkin's lymphoma

Based on the single-agent activity of both paclitaxel and cyclophosphamide in the treatment of non-Hodgkin's lymphoma (NHL), we conducted a phase II study to evaluate the efficacy of the combination of the two drugs in patients with refractory and relapsed aggressive NHL. All patients received 900 mg/m2 bolus of cyclophosphamide intravenously daily for 3 consecutive days with a concurrent infusion of 150 mg/m2 of paclitaxel over 72 h (50 mg/m2/d). 24 h after the completion of chemotherapy, patients received subcutaneous injections of 5 microg/kg of granulocyte-colony stimulating factor (G-CSF) daily until white cell count recovery. Treatment was repeated every 3 weeks. Patients who had at least a partial response (PR) after two courses continued to receive a maximum of four courses. Patients with responding disease were allowed to undergo high-dose chemotherapy followed by stem-cell/bone marrow transplantation if they were eligible. Of the 77 patients who were eligible for the study, 74 (96%) were evaluable for toxicity and treatment response. The overall response rate was 45% (95% CI 33-57%). Patients who received treatment after their disease relapsed from a complete response (CR) had an 81% response rate (38% CRs), whereas those with primary refractory disease had a 22% response rate. Toxicities of > grade 2 included alopecia (100%) and stomatitis (25%). Neutropenic fever of grade > 2 occurred after 18% of the courses, and platelet count of < or = 20 x 10(9)/l developed after 20% of the courses. Thus, the combination of paclitaxel plus high-dose cyclophosphamide is an effective new regimen in the treatment of refractory and relapsed NHL.     

Methylguazone, vindesine and cisplatin for the treatment of patients with relapsed or refractory malignant lymphoma: an Eastern Cooperative Oncology Group Study (PA482)

A new regimen not cross-resistant with standard regimens was developed for patients with relapsed or refractory Hodgkin's disease and non-Hodgkin's lymphoma. The regimen consisted of cisplatin, 70 mg/M2 given intravenously on day 1, vindesine, 3 mg/M2 given intravenously on days 1 and 8 (and also on day 15 of the first cycle only), and methylguazone, 600 mg/M2 given intravenously on days 8 and 15. Courses were repeated every 21 days. Thirty-nine patients (35 with non-Hodgkin's and 4 with Hodgkin's lymphoma) were treated and all were evaluable for response and toxicity. There were 5 complete and 14 partial responses for a total response rate of 49% (C.I. = 35%-63%). The median durations of partial and complete response were only 2.8 and 4.2 months, respectively. Only one patient remained in complete response for more than a year. There was one treatment-related death from renal failure on the study. Although this regimen was, in general. well tolerated the results are disappointing and seem no better than those obtained with many other salvage regimens for lymphoma.     

Busulfan and melphalan as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma

Twenty-four patients with multiple myeloma (MM), three (12.5%) in complete remission (CR) and 21 (87.5%) in partial remission (PR) were treated with high-dose chemotherapy (HDCT) (busulfan 12 mg/kg+melphalan 140 mg/m2) as preparative regimen for autologous peripheral blood stem cell (PBSC) transplantation. These cells were previously collected by leukapheresis after mobilization by high-dose cyclophosphamide (HD Cy)+rhGM-CSF (18 patients) or rhG-CSF alone (six patients). Considering 23 evaluable patients following HDCT, the CR rate was 58% (14 patients) and the PR rate was 38% (nine patients). One transplant-related death occurred following this regimen (4%). With a median follow-up of 20 months (range 4-34) after transplantation, 21 patients are alive (87%). Disease progression after transplantation was observed in four patients. Overall and relapse-free actuarial survival at 24 months was 91% and 74%, respectively. 12 patients (50%) remain in CR 15 months (4-34) post transplant. The major toxicity was mucositis. Busulfan+melphalan is a safe and feasible conditioning regimen for APBSCT in MM with acceptable toxicity and a high objective response rate, which may result in prolonged survival.     

Nerve-induced histamine release is of little importance in psoriatic skin

To evaluate the efficacy of systemic ifosfamide, cisplatin (CDDP) combination as first line treatment followed by intraperitoneal (IP) chemotherapy with carboplatin (CBCDA) and etoposide as consolidation in patients with stage III and IV epithelial ovarian cancer. A total of 40 patients with stage III and IV ovarian cancer were entered into the study. Ifosfamide 1 g/m2 plus mesna 1 g/m2 was given as six hour infusion daily for six days and CDDP 75 mg/m2 was given on day seven. Patients completing six cycles of systemic therapy underwent second look laparotomy followed by four cycles of IP chemotherapy with CBCDA 300 mg/m2 and etoposide 200 mg/m2. Of the 40 patients entering the protocol 27 patients completed six cycles with a complete remission (CR) of 65% and overall response of 67.5%. Twenty-two patients underwent second look laparotomy with pathological CR in ten patients, microscopic disease in seven and macroscopic disease in five. Eleven patients completed four cycles of IP chemotherapy. At 52 months was the overall survival (OS) was 36%. The disease free survival (DFS) at 45 months was 38%. Factors affecting OS were ascites (p < 0.011), stage (p < 0.04), weight change (p < 0.017), residual disease (p < 0.001), number of chemotherapy cycles (p < 0.0001) and IP chemotherapy (p < 0.006). Presently 35% patients are alive in CR, 15% are alive with disease, one patients has been lost to follow up while 47.5% have died. Of these four patients had progressive disease, seven relapsed, four died due to treatment related complications and two died in CR due to other causes. Subset analysis of 22 patients who had second look laparotomy and completed four cycles of IP chemotherapy revealed a distinct survival advantage. IFOS + CDDP is an effective combination as first time treatment in advanced ovarian cancer. IP chemotherapy is effective as consolidation and seems to provide a significant survival advantage. Further studies with larger number of patients need to be done to confirm these results.     

Longitudinal observation and outcome of nonfamilial childhood haemophagocytic syndrome receiving etoposide-containing regimens

The long-term outcome of 22 children treated with etoposide-containing regimens for haemophagocytic syndrome (HS) were longitudinally studied; none of them had a family history of the disease. All patients received etoposide-containing (150 mg/m2/d) regimens, combined, in 16 cases, with intravenous immunoglobulin (IVIG) and prednisolone. Complete remission (CR) was achieved in 12 patients, partial remission in seven, and early mortality occurred in three. Of the 12 CR patients, only four remain alive and disease-free, with a median follow-up of 47.4 months; one CR patient died due to infection and the remaining seven had relapsed diseases. Three patients with a partial response or with relapsed disease progressed to T-cell lymphoma, characterized, in the two cases tested, by clonal chromosomal abnormalities. Epstein-Barr virus (EBV) infection was implicated in disease pathogenesis in 15/22 patients. The overall survival was 45.5%, 40.9% and 40.9% at 1, 3 and 5 years, respectively, and disease-free survival for CR patients at these same times was 45.5%, 36.4% and 36.4%. The etoposide-containing regimen would appear to be an effective initial therapeutic option for childhood HS. However, in view of the frequency of partial remissions and relapsed disease, a more intensive chemotherapy or bone marrow transplantation should be applied. The progression to EBV-containing T-cell lymphoma in three patients is consistent with the previous observation that EBV-associated HS is a potentially malignant disease.     

Cardiac sympathetic nerve stimulation enhances cardiovascular performance during hyperkalaemia in the anaesthetized pig

A total of 74 patients with poor risk AML (median age 36.7 years, range 4.5-60.6) received a single course of a regimen including mitoxantrone (6 mg/m2 intravenous bolus daily, days 1 to 6), etoposide (80 mg/m2 intravenous over 1 h, daily, days 1 to 6) and intermediate-dose Ara-C (1 g/m2 over 6 h, daily days 1 to 6). 28 patients had failed initial remission induction with daunorubicin and conventional doses of Ara-C, 16 patients had secondary AML and 30 patients had relapsed from initial remission (five within six months, 15 over six months and ten after autologous or allogeneic bone marrow transplantation). Overall 41/74 patients (55%) achieved complete remission, 26 (35%) had resistant disease and seven (10%) died of infection during marrow hypoplasia. A 4-day course of the same regimen was given as consolidation to patients in complete remission. Subsequent antileukemic therapy was individualized. Profound myelosuppression and pancytopenia were universal resulting in fever or documented infections in almost 100% of patient; major hemorrhagic complications occurred in 39% of patients. Extrahematologic toxicity was mild to moderate consisting mostly of nausea and vomiting, oral mucositis and transient liver and cardiac dysfunction. We conclude that the MEC combination chemotherapy program seems to be an effective antileukemic regimen for secondary and advanced AML, with acceptable toxicity.