低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤35例

目的 观察低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤(MM)患者的疗效及安全性.方法 35例初治及难治复发MM患者,硼替佐米1.1 mg/m2,第0、3、7、10天,静脉注射;沙利度胺从50 mg/d开始逐渐加量至150 mg/d或患者能够耐受的最大剂量;化疗方案根据每疗程患者情况选择MP、VAD或AD方案.28 d为1个疗程,每例患者至少接受2个疗程以上治疗.达到部分缓解(PR)及以上疗效的患者应用沙利度胺150 mg/d或患者能够耐受的最大剂量维持治疗.采用2006年MM国际统一疗效标准观察疗效,根据国际癌症研究中心不良事件通用命名标准评估不良反应.结果 中位随访20个月,35例患者治疗总有效率82.8%,其中完全缓解(CR)率48.6%,良好的部分缓解(VGPR)率17.1%,PR率17.1%.3年预计无进展生存(PFS)和总生存(OS)率分别为60.92%和72.41%.达PR以上疗效患者的OS率高于未达PR患者,差异有统计学意义(P=0.004).初治及难治复发患者客观缓解率(ORR)及OS率差异无统计学意义.Ⅲ～Ⅳ度非血液学毒性主要包括乏力(3/35)、恶心、呕吐(8/35)、便秘(4/35)和周围神经病变(3/35).Ⅲ～Ⅳ度血液学毒性为粒细胞缺乏(10/35)和血小板减少(8/35).结论 低剂量硼替佐米联合沙利度胺及化疗治疗MM具有较好的疗效及安全性,沙利度胺维持治疗可延长患者PFS时间.     

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.     

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.     

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.     

Hyper CVAD B方案治疗难治性和复发性急性淋巴细胞白血病12例

目的 观察Hyper CVAD B方案治疗难治性和复发性急性淋巴细胞白血病(ALL)的疗效及患者不良反应.方法 选择12例难治性复发性ALL患者,应用Hyper CVAD B方案,具体根据患者年龄、体表面积、合并症进行调整用药剂量和用药间期,若1个疗程未达到完全缓解(CR)或部分缓解(PR),则进行第2个疗程,方案同前,2个疗程未达CR则换用其他方案.结果 12例患者中获得CR8例,PR 2例,NR 2例,总有效率83.3%.主要的不良反应是骨髓抑制、胃肠道反应、口腔溃疡,无严重的心肝肾功能改变和神经系统并发症.结论 Hyper CVAD B方案可作为难治性和复发性ALL的挽救治疗方案,患者不良反应可耐受.     

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.     

HAG预激化疗作为诱导缓解方案治疗老年人急性髓系白血病和骨髓增生异常综合征的临床观察

目的 观察HAG预激化疗作为诱导缓解方案在治疗老年急性髓系白血病(AML)和骨髓增生异常综合征-难治性贫血伴原始细胞增多型(MDS-RAEB)患者中的疗效.方法 对应用HAG预激方案治疗的21例AML和9例MDS-RAEB患者(≥60岁)的临床资料进行回顾性总结,包括疾病完全缓解(CR)率、有效率以及不良反应.结果 21例老年AML患者中,HAG诱导缓解的有效率为66.7%(14/21),其中CR率为47.6%(10/21);9例老年MDS-RAEB患者中,CR率为55.6%(5/9):HAG预激化疗的主要不良反应为因骨髓抑制继发的感染,调整化疗方案后所有患者均能耐受.结论 HAG预激化疗作为诱导缓解方案适用于老年AML和MDS-RAEB患者.     

改良VDLP方案治疗难治复发NK/T细胞淋巴瘤13例

目的 观察以左旋门冬酰胺酶为主的改良VDLP方案治疗难治复发NK/T细胞淋巴瘤的疗效及不良反应.方法 13例难治复发NK/T细胞淋巴瘤患者,治疗方案均选用改良VDLP方案:长春新碱1.4 mg·m-2·d-1,第1天;左旋门冬酰胺酶6000 U·m-2·d-1,第1天至第7天;多柔比星或表柔比星30 mg·m-2·d-1,第1天至第3天,泼尼松40mg·m-2·d-1,第1天至第7天.21 d为1个周期,所有患者均接受2～6个周期,中位3.5个周期,病灶局限的患者,化疗后加用侵犯野放疗.结果 13例患者中,总有效率61.5%(8例),完全缓解46.1%(6例),部分缓解7.6%(1例),病情稳定7.6%(1例),进展38.5%(5例).中位随访27(13～51)个月,全组预期3年生存率为63.4%;主要不良反应为骨髓抑制,Ⅲ～Ⅳ度粒细胞减少占30.4%,无治疗相关死亡.结论 以左旋门冬酰胺酶为主的VDLP方案治疗复发难治的NK/T细胞淋巴瘤患者疗效好,不良反应小且耐受性好,值得临床推荐使用.     

急性白血病患者乳酸脱氢酶变化的临床意义

目的 观察急性白血病(AL)患者血清乳酸脱氢酶(LDH)的变化,探讨其对AL疗效和预后判断的临床意义.方法 采用全自动生化分析仪检测156例AL患者[包括初治组63例、完全缓解(CR)组46例、复发组47例]的LDH值,常规反带方法分析AL染色体核型,并根据核型分成预后好、预后中等及预后差3组,分析LDH值与上述分组、患者白细胞数及白血病亚型的相关性.结果 初治组和复发组的AL患者血清LDH值[其中位数(P50)分别为399和265 U/L]明显高于CR组(P50 153 U/L)(P＜0.05).LDH的增高与外周血白细胞数(rs=0.604)及骨髓中白血病细胞比例(rs=0.538)密切相关(均P＜0.01).LDH与不同白血病亚型有关(L2、M4明显增高)(P＜0.01).难治复发的AL患者初治时LDH值(P50 538 U/L)高于非难治复发组(P50 294 U/L).具有不良预后染色体核型的AL患者初治时LDH(P50 778 U/L)明显高于预后良好组(P50 306 U/L)和预后中等组(P50 405 U/L)(P＜0.01).结论 LDH在AL发病时明显升高,其升高程度与病期、亚型及恶性度有相关性,AL缓解期LDH可下降,LDH可作为AL诊治过程中判断病情、评估预后的参数.     

New antitumor drugs for non-Hodgkin's lymphoma

We summarize in this article the antitumor activity of newly developed drugs against non-Hodgkin's lymphoma. The Taxans (paclitaxel and docetaxel), complex polycyclic organic chemicals isolated from the yew tree, have a broad antitumor spectrum with impressive activity in solid tumors. In the SWOG Phase II study on relapsed non-Hodgkin's lymphomas, paclitaxel (Taxol), showed 30% CR and 14% PR. In the CALGB study on docetaxel, a 14.5% response rate (12.5% for low-grade lymphoma and 16.1% for intermediate-high grade lymphoma) was found. In the Japanese phase II study of docetaxel, the response rate was 29.4% for all patients (14.3% for low-grade lymphoma and 40.0% for intermediate-high grade lymphoma). Rituximab is a chimeric monoclonal antibody directed against the B-cell specific antigen CD20. A phase II trial was conducted with four weekly infusions of 375 mg/m2 in patients with relapsed low-grade or follicular lymphoma. The response rate was 46%. A clinical trial combining Rituximab with 6 cycles of CHOP chemotherapy in newly diagnosed patients has recently been completed. Early evaluation of this experience suggests that this combination resulted in a PR or CR in all patients. New purine nucleoside analogs (fludarabine, cladribine, pentostatin) are active against common and generally incurable low-grade lymphoproliferative disorders. These new drugs combined with other chemotherapeutic reagents are expected to overcome refractory or incurable non-Hodgkin's lymphoma.     

DIZE (dexamethasone, idarubicin, and continuous infusion of ifosfamide and etoposide): an effective and well-tolerated new regimen for patients with relapsed lymphoma

We performed a phase II study of dexamethasone, ifosfamide, idarubicin and etoposide (DIZE) in patients with relapsed or refractory Hodgkin's (HL) and non-Hodgkin's lymphoma (NHL). The regimen consisted of dexamethasone (20 mg i.v. days 1-4), idarubicin (8 mg/m2 i.v. days 1+2), continuous infusion (c.i.) of ifosfamide (1,000 mg/m2 days 1-4), and c.i. etoposide (60 mg/m2 days 1-4). G-CSF (5 microg/kg) was used to support neutrophil recovery from day 5. In older patients (> 60 years) the dosage of idarubicin and ifosfamide was reduced to 75% in the initial cycle. Fourty six patients (pts) were treated with a total of 131 cycles. Sixteen pts were primary resistant and 30 were relapsed. Median age was 54.3 years (range 22-75). The median number of different prior chemotherapies was 1.7 (range 1 to 5). 31/46 (67.4%) pts had advanced disease (stage III or IV); 19/46 had B symptoms. Of 43 evaluable pts the response rate was 58.1% including 11 complete remissions (CR) and 14 partial remissions (PR). Mean duration of response was 8 months (1-30+). DIZE was more effective in relapsed than in refractory high-grade NHL (74 % vs 16.6%; p < 0.001). Of four heavily pretreated pts with HL, one obtained CR and two PR (response rate 75%). Myelosuppression was generally moderate with a mean duration of leukocytopenia < 1,000/microl of 2.5 days (range 0-18) and of thrombocytopenia < 25,000/microl 1.5 days (range 0-17). One patient died of uncontrollable infection in treatment related neutropenia. No other serious toxicities apart from alopecia were observed. We conclude that DIZE is safe and effective in heavily pretreated pts with relapsed lymphoma. The continuous infusion of cytostatic drugs such as that used in the new DIZE protocol might reduce hematotoxicity.     

Haemorrhagic hydrops of the gallbladder

Primary carcinoma of the fallopian tube is uncommon; optimal primary treatment is still not well defined, and little information is available about the efficacy of cisplatin-based combination chemotherapy. Thirty-eight patients with fallopian tube carcinoma were treated with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and cisplatin (50 mg/m2) (CAP). Thirty-two patients received the combination chemotherapy as first-line treatment after cytoreductive surgery, whereas six subjects were treated for recurrent disease. The patients received a median of six cycles of therapy (range, four to nine). At the initiation of chemotherapy, 24 patients had measurable lesions. In this group of patients, 15 had a clinical complete response (CR), four had a partial response (PR), three had stable disease (SD), and two had progressive disease (PD) after chemotherapy. The overall clinical response rate (CR + PR) was 80%. Ten of the 14 CR patients who were submitted to second-look operation (SLO) were found free of disease, in pathologic complete response (pCR). Three pCR patients relapsed, and two of them died despite second-line treatment. Nine patients achieving PR, SD, and PD after first-line chemotherapy were further treated (five with chemotherapy, two with radiotherapy, two with progesteron), but none responded to second-line treatment and all died (median survival, 9 months). Fourteen patients without gross residual disease after cytoreductive surgery had no measurable lesions and were not evaluable for response. Seven of them had negative SLO and remain disease free. Three patients (two stage III and one stage II) who refused SLO relapsed 14, 16, and 26 months after completion of chemotherapy. The median survival for the entire group was 38 months, and the 5-year survival rate was 35%. The toxicity of the regimen was moderate. The CAP regimen appears to be active in primary fallopian tube carcinoma and yields response rates comparable to those reported for epithelial ovarian cancer.     

Cladribine in the treatment of advanced relapsed or refractory low and intermediate grade non-Hodgkin's lymphoma

BACKGROUND: Cladribine (2-chlorodeoxyadenosine) is a purine nucleoside analog with cytotoxic activity against both resting and proliferating cells. Clinical studies with cladribine have reported antitumor activity against various hematologic malignancies. METHODS: The authors studied responses to cladribine among patients with low and intermediate grade non-Hodgkin's lymphoma that had been refractory to or relapsed after prior chemotherapy. Cladribine was given intravenously over 2 hours at a dose of 0.14 mg/kg daily for 5 consecutive days, repeated every 4 weeks. RESULTS: Twenty-eight patients (16 males, 12 females) with a median age of 58 years (range, 41-75 years) were accrued. Twenty-three patients had low grade and 5 had intermediate grade lymphoma. Stage IV disease was present in 22 (79%), and 17 (61%) had systemic B-symptoms. The majority (57%) had received 2 or more prior chemotherapy regimens (median, 2; range, 1-5); 6 had had prior fludarabine therapy. Major responses were documented in 32% (9 of 28 patients), with 4 complete remissions (CR) and 5 partial remissions (PR) after a median of 4 cycles (range, 1-9). One CR occurred in one patient with intermediate grade diffuse large cell lymphoma, and three of six patients who had had prior fludarabine therapy experienced CR or PR with cladribine. Severe hematologic toxicities included reversible neutropenia, protracted thrombocytopenia, and lymphopenia. Other reported adverse effects included mild-to-moderate fatigue, nausea, and diarrhea. CONCLUSIONS: Cladribine is an active single agent in the treatment of patients with refractory or relapsed advanced stage indolent lymphoma, with major responses in one third of patients.     

High-dose multimodality therapy with autologous stem-cell support for stage IIIB breast carcinoma

PURPOSE: Women with locally unresectable and inflammatory breast carcinoma (IBC) have an approximately 30% 5-year disease-free survival (DFS) rate with conventional multimodality therapy. A short but dose-intensive multimodality phase II trial was designed in an attempt to improve outcome in stage IIIB disease. Mastectomy was performed after high-dose therapy to evaluate pathologic response to treatment. METHODS: Women with newly diagnosed disease received four 2-week cycles of doxorubicin 90 mg/m2 with granulocyte colony-stimulating factor (G-CSF), followed by cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) with marrow and peripheral-blood progenitor cell (PBPC) support. Local therapy consisted of mastectomy and radiotherapy. Tamoxifen (5 years) was begun if the patient was estrogen receptor-positive (ER+). RESULTS: Fifty women (46 stage IIIB [91% IBC], four stage IIIA) entered the study and 47 are assessable. Ten had mastectomy before any systemic therapy (seven with pathologic IBC, three with residual tumor after mastectomy). Eighty percent received full-dose doxorubicin with 60% on schedule. Clinical response rates to induction were 15% complete response (CR), 5% very good partial response (VGPR), 59% partial response (PR), and 21% minor response (MR)/stable disease (SD). Mastectomy after CTCb in 37 patients showed a 14% pathologic CR rate, 29% microscopic foci in breast and/or axilla, and 57% gross tumor. Fifteen (32%) patients have relapsed (median, 17 months post-CTCb). The 30-month DFS is estimated at 64%. For those in pathologic CR, with microscopic, or with gross disease remaining after CTCb, the 30-month DFS is estimated at 100%, 70%, and 38%, respectively. Those with zero, one to three, or > or = four positive nodes at axillary dissection had a median DFS of 31, 18, and 13 months, respectively. CONCLUSION: This short but dose-intensive multimodality approach for stage IIIB breast carcinoma is feasible with encouraging results to date.     

Early phase II study of KRN8602 (MX2), a novel anthracycline derivative for acute leukemia

We performed an early phase II study of KRN8602, a new anthracycline derivative for refractory or relapsed acute leukemias. KRN8602 was given at a dose of 15 mg/m2 for 3 to 5 consecutive days, repeating every 3-4 weeks. Among 53 patients entered in the study, 51 were evaluable for safety, and 46 were evaluable for efficacy. The response rate at schedules of 3 and 4 consecutive days was 9.1% (1 PR/11), while that at a schedule of 5 consecutive days was 22.9% (3 CR + 5 PR/35). With the 5 consecutive day schedule, the response rates were 21.4% (1 CR + 2 PR/14) for acute myelogenous leukemia and 29.4% (2 CR + 3 PR/17) for acute lymphocytic leukemia, but no response was observed in 4 patients with blastic crisis of chronic myelogenous leukemia. Major toxicities were nausea/vomiting and anorexia, however, all these toxicities were clinically manageable. From these results it is concluded that KRN8602 is effective against acute leukemias, and the optimal dose is 15 mg/m2 for 5 consecutive days.     

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.     

Ischemic stroke in the elderly. Role of the common factor V mutation causing resistance to activated protein C

Twenty-one previously untreated multiple myeloma (MM) patients and 10 previously treated patients with refractory or relapsed disease received two or three cycles of intermediate-dose melphalan (70 mg/m2) (IDM), administered intravenously every 6 weeks. Seven previously untreated patients received three and all other patients received two courses of IDM. The objective of the study was to reduce the toxicity of high-dose melphalan (140 mg/m2) (HDM) while maintaining its cytotoxic efficacy and secondly to ensure the possibility of collecting sufficient numbers of peripheral blood stem cells (PBSC) for transplantation. 18 (85%) previously untreated patients responded, of whom four achieved CR (18%). In addition five out of 10 previously treated patients with refractory or relapsed disease responded although bone marrow toxicity in this category was a major drawback. Toxicity was moderate, consisting of alopecia and moderate bone marrow suppression: the granulocyte count dropped below 0.5 x 10(9)/l and platelets below 25 x 10(9)/l for a median of 8 and 6 d, respectively. No serious infections occurred and the majority of patients attended the out-patient clinic. In 12/14 previously untreated patients sufficient peripheral blood CD34+ cells for harvest were present in the repopulation phase after the first IDM. In nine patients peripheral blood stem cells were collected and eight patients have undergone successful transplantation. Repeated IDM followed by filgrastim is highly effective in untreated MM and may be safely administered to reduce tumour load prior to PBSC collection. Autologous stem cells harvested after repeated IDM have a full long-term repopulating capacity.