18例多发性骨髓瘤临床分析

目的：探讨多发性骨髓瘤(MM)的临床特征。方法：回顾性分析18例MM患者临床资料。结果：①MM起病隐匿，临床表现多样化．易误诊；②大部分患者表现骨痛和贫血．免疫分型以IgG和IgA最常见；③COP／CTHPOP化疗方案治疗5例初治患者有效率达80％；①三氧化二砷治疗1例难治复发进展期的MM患者在2个疗程后取得完全缓解。结论：①中年以上不明原因的骨痛、贫血、反复感染、白蛋白正常而白球蛋白比例降低、蛋白尿、血沉快等应考虑MM可能，应作进一步检查；②COP／CTHPOP化疗方案对初治MM有较好疗效；③三氧化二砷可用于治疗难治复发的MM患者。     

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。     

榄香烯乳加联合化疗治疗难治性急性非淋巴细胞白血病疗效观察

目的：评价榄香烯乳联合化疗治疗难治性急性非淋巴细胞白血病（ANLL）的疗效。方法：将28例ANLL患者随机分为治疗组和对照组,治疗组使用榄香烯乳300mg加入5％GS500ml中静脉滴注,持续用药14d,同时加联合化疗：高三尖杉酯碱4－6mg静脉滴注,持续7d,阿糖胞苷100－200mg/m^2,第1－7天;对照组单用化疗,方案用量用法同治疗组。结果：治疗组总有效率为75．0％,对照组总有效率为41．7％,两组差异有显著性意义（P＜0．05）。结论：榄香烯乳对难治性ANLL有肯定疗效,比单用联合化疗效果好,且不良反应少,无血常规和骨髓抑制。     

硼替佐米联合地塞米松治疗多发性骨髓瘤临床研究

目的观察硼替佐米联合地塞米松(PD)在多发性骨髓瘤(MM)中的应用。方法 2008年2月至2010年4月北京积水潭医院36例MM患者接受PD治疗。以同期46例VADT化疗的MM患者做为对照。分析病情转归及不良反应。结果 (1)PD用于初治和复发和(或)难治MM患者疗效均显著。初治组治疗有效率85.7%(18/21);复发和(或)难治组的有效率为80.0%(12/15);总有效率为83.3%(30/36)。PD与VADT治疗初治MM的有效率差异无统计学意义(85.7%对78.1%,P=0.740),PD治疗复发和(或)难治MM的有效率明显高于VADT组(80.0%对42.9%,P=0.039)。PD起效快,治疗有效的患者均在1个疗程后达PR;63.9%患者在3个疗程内达到VGPR以上缓解,优于VADT组的30.4%。(2)PD不良反应主要有乏力、周围神经病变及血小板减少等。PD治疗初治MM较复发和(或)难治MM不良反应小,耐受性好,更能坚持长期化疗以获得最大缓解。(3)PD治疗的MM患者骨痛缓解快,全身骨密度增高较VADT组更显著[(1.138±0.102)g/cm2对(1.053±0.137)g/cm2,P=0.039)]。结论硼替佐米联合地塞米松治疗MM缓解率高,可首选用于治疗初治及复发和(或)难治MM。     

以拓扑替康为基础的联合诱导方案治疗难治及复发急性粒细胞白血病16例报告

目的：评价以拓扑替康为基础的联合诱导方案治疗难治及复发急性粒细胞白血病(AML)的疗效及不良反应。方法：采用以拓扑替康为基础的联合诱导方案治疗难治及复发AML患者16例。所有患者接受1个疗程拓扑替康组成的联合化疗方案(拓扑替康、环磷酰胺、阿糖胞苷)后，定期检查血细胞计数、骨髓中白血病细胞比例，定期复查肝、肾功能等。结果：7例患者在接受1个疗程诱导缓解化疗后达到完全缓解，2例达部分缓解，总缓解率为56．3％；7例患者无反应。主要不良反应为骨髓抑制。结论：以拓扑替康为基础的诱导缓解方案对部分难治及复发AML患者具有确切疗效。     

三氧化二砷联合维生素C治疗难治或复发性多发性骨髓瘤临床研究

目的：探讨三氧化二砷（As2O3）联合维生素C（VitC）治疗难治或复发性多发性骨髓瘤（MM）的疗效及不良反应.方法：对31例难治或复发性MM患者，采用As2O310 mg加5%葡萄糖溶液500 ml，静脉滴注，每日1次;VitC 1000 mg加5%葡萄糖溶液100 ml，静脉滴注，每日1次;1疗程为28 d.根据血清M蛋白及骨髓瘤细胞减少情况判断疗效，分为部分缓解、进步、无效.同时观察MM患者贫血程度、骨髓瘤细胞百分率、肾功能及血电解质等指标的变化.结果：部分缓解5例，进步11例，无效15例，总有效率为51.6%.主要不良反应为疲劳、恶心、呕吐.结论：As2O3联合VitC治疗难治或复发性MM疗效显著，不良反应轻，患者易耐受。     

米托蒽醌治疗急性白血病疗效观察

应用含米托蒽醌的联合化疗方案治疗难治性及复发性急性白血病１８例。急淋７例（Ｌ１１例，Ｌ２６例），急非淋１１例（Ｍ２３例，Ｍ４３例；Ｍ５４例，Ｍ６１例）。完全缓解率５５．６％，部分缓解率１１．１％，总有效率６６．７％。含米托蒽醌的联合化疗方案对难治、复发性急性白血病具有疗效高、副反应小的优点，是较理想的化疗方案。     

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。     

化学药物联合免疫调节剂治疗复治肺结核的疗效观察

目的：观察化学药物联合免疫调节剂治疗难治、复治肺结核的临床效果。方法：226例涂阳病人随机分为治疗组及对照组，两组化疗方案相同，治疗组加用卡介菌多糖核酸，观察疗效。结果：复治涂阳治疗组痰菌阴转率80．0％，对照组65．2％；其中耐多药结核病治疗组痰阴转率61．5％，对照组16．7％。经统计学处理皆有显著性差异（P＜0．05）。结论：治疗组疗效明显优于对照组，化学药物联合免疫调节剂是治疗耐多药结核病及其他难治、复治病例的有效措施。     

阿糖胞苷联合米托蒽醌治疗难治性白血病

目的：寻找复发性及难治性白血病有效治疗方案。方法：选用中剂量阿糖胞苷联合米托蒽醌治疗复发及难治性白血病16例。结果：显示完全缓解率83．3％，部分缓解率5.6％，总有效率为88.9％，主要毒副反应为骨髓抑制，全血象减少导致发生感染及出血。结论：本方案是治疗复发及难治性白血病的有效方案，加强支持治疗是保证疗效的关键。     

硼替佐米和沙利度胺为主的化疗方案对伴有肾功能不全的多发性骨髓瘤患者的疗效比较

目的:观察以硼替佐米为主和沙利度胺为主的化疗方案治疗伴有肾功能不全的多发性骨髓瘤(MM)患者的疗效,探讨对伴有肾功能不全的MM治疗的最佳方案.方法:40例伴有肾功能不全的MM患者,其中初治20例,复发(难治)20例.选择20例使用以硼替佐米为主的化疗方案作为试验组,以同期20例接受沙利度胺为基础的联合化疗方案治疗的MM...     

Combination chemotherapy MOCCA in resistant and relapsing multiple myeloma

Abstract: 80 patients with resistant or relapsing multiple myeloma received a combination of vincristine, cyclophosphamide, lomustine, melphalan and methylprednisolone (MOCCA) as a second-line chemotherapy. 27 of them were resistant to primary chemotherapy with alkylating agents, and 53 had relapsed after initially responding to these drugs. An objective response was achieved in 39 patients (49%): in 14 patients who were primarily resistant (52%) and in 25 patients who had a relapse (47%). Of 41 patients relapsing during maintenance chemotherapy 14 (34%) responded, while 11 of 12 patients (92%) treated for a relapse off-therapy responded. The median duration of response was 22 months. Severe complications, in most cases infections, occurred in 30% of patients, and were fatal in 9% of the cases. According to our experience the five-drug combination MOCCA is an effective second-line chemotherapy for myeloma patients primarily resistant to or relapsing after therapy with single alkylating agents.     

M-2 protocol for melphalan-resistant and relapsing multiple myeloma

33 patients with advanced refractory multiple myeloma received a combination of vincristine, cyclophosphamide, carmustine, melphalan and steroids (M-2 protocol). 20 of them had failed prior chemotherapy with alkylating agents and the remaining 13 patients had relapsed after a response to these drugs. An objective tumour cell mass reduction (greater than or equal to 50%) was achieved in 17% of the patients (6% of previously nonresponders and 33% of previously relapsing), while 9 additional patients improved (30-50% tumour reduction), for an overall response rate of 47% (39% for previously nonresponders and 58% for previously relapsing). The median duration of response was 7 months. Thrombocytopenia was the most common toxicity encountered in the study (39% of cases). Our findings indicate that M-2 protocol is an effective salvage treatment for patients who relapse from previous chemotherapy with alkylating agents. In contrast, results in patients who are primarily resistant to these drugs justify the search for different treatment programmes which can produce greater degrees of tumour reduction.     

Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single-arm study

We assessed the safety and efficacy of melphalan, arsenic trioxide (ATO) and ascorbic acid (AA) (MAC) combination therapy for patients with multiple myeloma (MM) who failed more than two different prior regimens. Patients received melphalan (0.1 mg/kg p.o.), ATO (0.25 mg/kg i.v.) and AA (1 g i.v) on days 1-4 of week 1, ATO and AA twice weekly during weeks 2-5 and no treatment during week 6 of cycle 1; during cycles 2-6, the schedule remained the same except ATO and AA were given twice weekly in week 1. Objective responses occurred in 31 of 65 (48%) patients, including two complete, 15 partial and 14 minor responses. Median progression-free survival and overall survival were 7 and 19 months respectively. Twenty-two patients had elevated serum creatinine levels (SCr) at baseline, and 18 of 22 (82%) showed decreased SCr levels during treatment. Specific grade 3/4 haematological (3%) or cardiac adverse events occurred infrequently. Frequent grade 3/4 non-haematological adverse events included fever/chills (15%), pain (8%) and fatigue (6%). This steroid-free regimen was effective and well tolerated in this heavily pretreated group. These results indicate that the MAC regimen is a new therapeutic option for patients with relapsed or refractory MM.     

沙立度胺治疗急性白血病近期临床疗效观察

目的 探讨沙立度胺(反应停)在治疗急性白血病(AL)中的作用。方法 38例AL中,初治27例,随机分为常规化疗加反应停治疗(A)组和常规化疗(B)组。复治11例,列为C组,全部应用化疗加反应停。用Ⅷ因子相关抗原和CD34单抗免疫组化染色的方法,观察患者治疗前后骨髓微血管密度(MVD)。用ELISA的方法测定患者治疗前后血清血管内皮细胞生长因子(VEGF)的浓度。反应停起始剂量200mg/d,每1周增加50mg/d,直到400-500mg／d,应用4-6个月。结果 两组初治病例的完全缓解(CR)率和有效率：CR 部分缓解(PR)及达CR所需疗程数用或不用反应停均无差异,其CR率和有效率分别为57．1％和53．8％及78．6％和76．9％。复治组CR率27．3％,有效率54．5％。A、B两组CR患者随访6个月,A组复发率较低。患者MVD、VEGF治疗前与正常对照组相比差异非常显著(P＜0．001)。治疗前VEGF水平与疗效呈负相关。用反应停组无特殊的不良反应。结论 反应停治疗可维持AL患者的持续缓解状态,减少复发。在AL的治疗中加用反应停是合理的新的治疗策略。     

Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: a bridge to transplantation

BACKGROUND AND OBJECTIVES: Arsenic trioxide (ATO) has been reported to be a safe and effective treatment for relapsed acute promyelocytic leukemia (APL). The aim of this study was to evaluate the efficacy and toxicity as well as the eligibility to stem cell transplantation (SCT) in a series of 7 patients with relapsing APL, managed with ATO. DESIGN AND METHODS: Seven patients with relapsing APL while on maintenance treatment with all-trans-retinoic acid (ATRA) or who were ATRA refractory-received ATO at a dose of 10 mg daily by 2-hour intravenous infusion until complete remission (CR). After consolidation chemotherapy, patients were programmed to receive autologous or allogeneic stem cell transplantation (SCT) according to donor availability. The median age of the patients was 55 (21-71) years: 2 patients presented with concomitant extramedullary relapse. RESULTS: Six patients (86%) achieved CR after a median of 35 ATO doses (20-49) with negligible toxicity; one patient died from pneumonia. After consolidation with a four-day course of cytarabine at 1 g/m2 and mitoxantrone 6 mg/m2, two patients underwent allogeneic SCT, two received PML/RARa negative autologous peripheral blood stem cells collected after consolidation plus granulocyte colony-stimulating factor, one failed mobilization and received a second consolidation course. One elderly patient refused further treatment and relapsed 6 months later. After a median follow-up of 15 months from CR2 achievement, 5 patients are alive in continuous CR. INTERPRETATION AND CONCLUSIONS: The high CR rate and the mild toxicity confirm that ATO represents a valid alternative to salvage chemotherapy for patients relapsing while on ATRA treatment or who are ATRA-refractory. Allogeneic or autologous SCT after ATO-induced CR is feasible in the majority of patients.     

High-dose glucocorticoid treatment of resistant myeloma

Intermittent, high-dose dexamethasone treatment was given to 49 consecutive patients with refractory multiple myeloma. In patients who were unresponsive to previous treatment, the response rate of 27% was similar to that achieved with the VAD regimen, which combines the same schedule of dexamethasone with vincristine and doxorubicin given by continuous infusion. Among patients with relapses, VAD chemotherapy induced remissions in 11 of 17 patients (65%), whereas dexamethasone alone induced remissions in 4 of 19 (21%). The median survival of all patients responding to either treatment, 22 months, was longer than that from any previous program for treatment of resistant myeloma. These findings indicate the value of frequent dexamethasone administration in patients unresponsive to standard therapy and show the major role of vincristine and doxorubicin given by continuous infusion in patients with relapses. They also suggest different mechanisms for primary and secondary resistance to chemotherapy.     

Alternating mini-BEAM/ESHAP as salvage therapy for refractory non-Hodgkin's lymphomas

 Mini-BEAM and ESHAP are two non-cross-resistant salvage regimens that have been used separately in patients with lymphoma. The aim of the present study was to investigate the efficacy of the combination of these two regimens, administered in alternating cycles, as salvage therapy for refractory non-Hodgkin's lymphoma (NHL) patients. A total of 28 patients were included in the study: 14 patients were primary refractory, seven were partial responders, and seven were in relapse. The alternating cycles of mini-BEAM and ESHAP were given until there was maximum response or progression. The overall response rate to mini-BEAM/ESHAP was 39%; 25% of patients achieved a complete response and 14% a partial response. Nevertheless, it should be noted that none of the primary refractory patients responded to this protocol. Nine of the 11 patients who responded to mini-BEAM/ESHAP were consolidated with autologous transplantation using BEAM as a conditioning regimen. The survival at 3 years in this group of 11 patients who responded to the salvage regimen is 64%, with a disease-free survival of 67% at 2 years. No major toxic effects were observed with mini-BEAM/ESHAP. Myelosuppression was the most frequent complication, especially with the mini-BEAM cycles. Other toxicities were infrequent and no treatment-related deaths were observed. These results suggest that alternating mini-BEAM/ESHAP chemotherapy is a safe regimen that is effective in partial responders or relapsing patients with NHL who have sensitive disease, but not in primary refractory patients. Moreover, although this therapy has a potential advantage, combining as it does two non-cross-resistant regimens, it does not seem superior to ESHAP alone. Received: 16 July 1996 / Accepted: 31 October 1996     

硼替佐米为主的化疗方案治疗多发性骨髓瘤50例临床分析

目的：研究硼替佐米（万珂）为主的化疗方案治疗多发性骨髓瘤（MM）的疗效和安全性。方法：收集近4年来我科住院和随访的MM患者91例的临床资料,其中50例接受万珂为主化疗方案（VDT组）;41例接受传统化疗方案（VADT）。分析并比较2组患者的年龄、性别、β2-微球蛋白值、白蛋白值和2组的缓解率及不良反应。疗效评价按照欧洲骨髓移植协作组（EBMT）标准。结果：2组患者的年龄、性别、疾病分期无明显差异。中位随访20个月,发现VDT组50例患者总体反应率为88%,平均2个疗程即起效。其中初治患者CR＋nCR率明显优于同组复发难治患者以及传统方案治疗组,且初治患者的总缓解率在VDT组与VADT组中存在显著差异。VDT组不良反应以周围神经病变和血小板减少为常见,经对症治疗均可缓解。结论：万珂为主的化疗方案治疗初治和复发难治MM患者,起效快,其中初治患者CR＋nCR率及总缓解率更高,其不良反应可耐受。对有不良核型和IgD型MM患者,如何提高疗效尚待研究。     

P38 MAPK inhibition enhancing ATO-induced cytotoxicity against multiple myeloma cells

The resistance to arsenic trioxide (ATO) treatment is relatively common (55–80%) in multiple myeloma patients. This study found that ATO at clinically achievable concentrations (2–7 μmol/l) activated p38 mitogen-activated protein kinase (MAPK) in both myeloma cell lines and primary myeloma cells, a finding not previously well-documented in myeloma cells. Inhibition of p38 MAPK activation by pharmacological inhibitors (SB203580) or downregulation of p38 MAPK by siRNA significantly increased the apoptosis and/or growth inhibition induced by ATO treatment in myeloma cells. Combination of ATO and p38 MAPK inhibition abolished the interleukin-6 enhanced protection of myeloma cells against ATO treatment. The ATO-resistant cell line developed in our laboratory showed an increase in p38 MAPK activation. The increase of apoptosis by the combination of ATO and SB203580 was accompanied by the activation of caspase-9 and caspase-8 suggesting that both extrinsic and intrinsic apoptotic pathways are involved. Additionally, the p38 MAPK activation by ATO was associated with increased phosphorylation and upregulated expression of Heat shock protein 27. These results suggest that ATO-induced p38 MAPK activation plays an important role in the resistance to ATO in myeloma cells and that p38 MAPK inhibition may overcome resistance to ATO treatment in myeloma patients.