Use of capecitabine as first-line therapy in patients with metastatic breast cancer relapsing after high-dose chemotherapy and autologous stem cell support

High-dose chemotherapy with autologous stem cell support (HDC-ASCS) can produce high complete remission rates in patients with metastatic breast cancer (MBC). However, the majority of those so treated will relapse within 3 years. The ability of such patients to tolerate further myelosuppressive chemotherapy may be limited and the best therapy is undefined. In this retrospective study we assessed the role of capecitabine as initial therapy after relapse.Ten patients (median AGE = 47 years; oestrogen receptor-positive, n = 4; visceral disease, n = 6; prior anthracycline, n = 8, prior taxanes, n = 10), whose disease progressed at a median of 246 days (range 69–480) after HDC-ASCS and who were treated with capecitabine (2500 mg/m² per day for 2 weeks of a 3–week cycle) as initial therapy for relapse, were assessed retrospectively for response and toxicity. They received a median of eight cycles (range 4–24) of capecitabine. The toxicities encountered while receiving capecitabine were: hand–foot syndrome (grade 1, n = 3; grade 2, n = 4; grade 3, n = 1); diarrhoea (grade 1, n = 1; grade 2, n = 3); nausea (n = 2) and fatigue (n = 5). Haematological toxicity was seen in only one patient. No patient required hospitalization for toxicity. Three achieved a complete remission, four a partial remission and three disease stabilization. After a median follow-up of 183 days from commencing capecitabine (range 97–540), all patients were alive and five were in remission. Five progressed after remissions that lasted between 63 and 252 days.Oral capecitabine is an active and well-tolerated agent when used alone as first-line therapy in patients who have relapsed after HDC-ASCS for MBC.     

外周造血干细胞支持下大剂量化疗治疗年轻转移性乳腺癌疗效观察

背景与目的:年轻乳腺癌的发病率成逐渐升高的趋势,预后较差,尤其对于复发转移性年轻乳腺癌的治疗更是很难达到理想的疗效,缺乏针对性的治疗措施.干细胞支持下大剂量化疗(high dose chemotherapy,HDC)在乳腺癌中的应用目前仍存在争议,有可能一些亚组人群在其中获益.本研究旨在探讨外周造血干细胞支持下大剂量化疗对于年轻复发转移性乳腺癌的治疗效果.方法:30例年龄≤40岁的转移性乳腺癌患者,其中16例接受外周造血干细胞支持下的HPC,14例接受常规剂量化疗(standard dose chemotherapy,SDC).HDC组:首先应用化疗多西他赛120mg/m2和G-CSF 5 μg/kg动员.采集外周血CD34+干细胞,然后行2个周期大剂量化疗,方案为15例接受了3药联合化疗:多西他赛120 mg/m2+塞替派175 mg/m2+卡铂AUC=6,1例接受两药联合化疗:多西他赛120 mg/m2+塞替派175 mg/m2.SDC组:多西他赛75 mg/m2+塞替派50～60 mg/m2,每21 d为1个周期,应用4～6个周期或至疾病进展.比较两组患者的无进展生存期时间(progression free survival,PFS)和总生存期(overall survival,OS).结果:HDC组部分缓解5例,有效率为31.3%;SDC组部分缓解1例,有效率为7.1%.HDC组PFS为9个月(2.3～15.7个月);SDC组PFS为3.8个月(2.7～4.9个月),两组间差异有统计学意义(P=0.044);HDC组OS为11.8～21.2个月(中位生存期18个月),SDC组OS为6.8～16.0个月(中位生存期是11.4个月),差异接近有统计学意义(P=0.058).大剂量化疗安全性良好.结论:干细胞支持下大剂量化疗对年轻转移性乳腺癌是一个有效的治疗手段,值得今后进一步推广研究.     

Dose-intensified chemotherapy for breast cancer: Present and future prospects

With the trend to maximize chemotherapy in breast cancer, the use of peripheral blood stem cells in addition to hematopoietic growth factors to alleviate myelosuppression caused by dose-intensified chemotherapy has been shown to be beneficial. In treatment of metastatic breast cancer, response rates and complete response rates as high as 100% and nearly 80%, respectively, have been reported. Such treatments have shown even greater promise in an adjuvant setting for high-risk breast cancer. High-dose chemotherapy studies, however, involve highly-selected patient populations who are generally compared with unselected patients, and controversy still surrounds the question of whether it is substantially superior to conventional-dose chemotherapy. There are now more than sufficient data to justify ongoing randomized trials, and the most important overall recommendation is to encourage patients to participate in these clinical trials.     

ototoxicity after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin followed by stem cell transplantation in patients with breast cancer

Our purpose was to determine the risk of ototoxicity in breast cancer patients receiving a myeloablative regimen consisting of cyclophosphamide 6000 mg/m², thiotepa 500mg/m² and carboplatin 800mg/m² (CTCb) followed by stem cell transplantation. Fourteen consecutive patients with breast cancer were treated with high dose chemotherapy consisting of the CTCb regimen followed by stem cell transplantation. A pretransplant complete hearing study was obtained which consisted of hearing case history, audiometry and tympanometry. In addition, DPOAE (Distortion Product Otoaccoustic Emissions) was done to evaluate measurable changes in the cochlear (outer hair cell) functioning. Pre-transplant, all patients had no clinical evidence of hearing impairment and hearing studies were normal. Eleven patients had hearing studies and a telephone interview posttransplant. One patient was lost to follow-up and two patients died. One of the 11 patients tested had an abnormal post-transplant hearing study but none of them had clinically detectable hearing impairment. In our prospective study of breast cancer patients treated with the CTCb regimen, we did not observe clinically detectable hearing impairment in any of the patients tested.     

Minimal residual disease in autologous hematopoietic harvests from breast cancer patients

The increasing use of high-dose chemotherapy with autologous hematopoietic transplantation for the treatment of solid malignancies has raised concern about the role of tumor cells contaminating the grafts. Minimal residual disease (MRD) in autologous grafts has became a dynamic and intensively studied field in oncology. This review discusses the current status of MRD in breast cancer autografts and presents existing data on detection methodology, clinical relevance, biologic characteristics and purging techniques.     

Isolation and transplantation of highly purified autologous peripheral CD34<Superscript>+</Superscript> progenitor cells: purging efficacy,hematopoietic reconstitution following high dose chemotherapy in patients with breast cancer: results of a feasibility study in Japan

BACKGROUND: High-dose chemotherapy with autologous stem cell support may have some therapeutic impact on certain groups of the patients with advanced breast cancer(BRCA). Since stem cell contamination by tumor cells might contribute to relapse, development of a tumor cell purging technique would improve the clinical outcome. The present study was undertaken to evaluate the purging efficacy of autologous mobilized CD34+peripheral stem cells in patients with breast cancer (BRCA) in an advanced stage or relapse. METHODS: CD34+cells were selected from autologous peripheral blood stem cells (PBSC) using a clinical scale of magnetic-activated cell sorting system (CliniMACS), followed by high-dose chemotherapy with transplantation of CD34+ selected cells. Amplification of cytokeratin 19 (CK19) and 20 (CK20) gene in leukapheresis products were measured to evaluate the performance of tumor cell elimination. RESULTS: Seven patients were entered into this study. After leukopheresis, 1 patient was dropped form this study due to poor mobilization. Among 6 patient, a total of 8 CD34+ selection was performed. The median purity and recovery rate of the CD34+ cells post selection was 85.1% (range 62.5-98.1%) and 74.2% (range 50.2-90.2%), respectively. After isolation of CD34+cells, the elimination rate in the logarithmic transformation of CK19 was 2.77 log, and that of CK20 were 2.43 log and 2.53 log. In 4 patients, high-dose chemotherapy was performed, followed by the transplantation of the isolated CD34+cells. Rapid neutrophil recovery, as well as platelet recovery was seen with a median time to reach 0.5 x 109/l neutrophils of 9 days(range 8-9), and 20 x 109/l platelets of 12 days (range 10-13). There was no treatment related death and no serious adverse events directly associated with the selection procedure or infusion of selected cells. CONCLUSIONS: The present study demonstrated that the CliniMACS system is a highly effective positive selection method and that a high purging efficacy could be obtained without compromising the hematopoietic reconstitution capacity of the graft in BRCA patients undergoing high-dose chemotherapy.     

High dose chemotherapy and autologous stem cell transplantation as adjuvant therapy for primary breast cancer patients with four or more lymph nodes involved: long-term results of an international randomised trial.

BACKGROUND: The purpose of this study was to assess whether a short course of anthracycline containing chemotherapy followed by high dose therapy with autologous stem-cell support improves disease-free and overall survival as compared with conventional, anthracycline containing chemotherapy, in patients with primary breast cancer and four or more histologically involved lymph nodes. PATIENTS AND METHODS: Two hundred and eighty one patients entered into a randomised clinical trial were allocated to receive standard, conventional treatment (5-fluorouracil, epirubicin and cyclophosphamide-FEC for six cycles) or FEC for three cycles followed by high dose therapy consisting of cyclophosphamide, thiotepa and carboplatin and stem cell rescue (HDT). To be eligible, patients had to be free of overt metastatic disease and be < or =60 years of age. Analyses were according to intention to treat. RESULTS: At a median follow up of 68 months, 118 patients have experienced a relapse or death from breast cancer (62 in the FEC followed by HDT arm and 56 in the conventional FEC arm) and a total of 100 patients have died (54 in the FEC followed by HDT arm and 46 in the conventional FEC arm). No significant difference was observed in relapse-free survival [hazard ratio 1.06, 95% CI 0.74-1.52, p = 0.76] or overall survival [hazard ratio 1.18, 95% CI 0.80-1.75, p = 0.40]. Five patients died from treatment related causes, three as a consequence of HDT and two in the conventional FEC arm. CONCLUSIONS: At the present time, no benefit has been observed from replacing three cycles of conventional chemotherapy with the HDT regimen described here. Patients should continue to receive conventional chemotherapy as adjuvant therapy for breast cancer.     

自体外周血干细胞移植(APBSCT)支持下大剂量化疗治疗小细胞肺癌的长期随访

目的 探讨自体外周血干细胞移植(APBSCT)支持下高剂量化疗治疗小细胞肺癌的疗效和长期生存情况。方法 全组7例病理诊断明确的小细胞肺癌患者，6例常规化疗达到CR或PR，1例为手术切除原发病灶后给予6周期常规化疗。给予APBSCT支持下高剂量化疗，环磷酰胺CTX6g／m^2，足叶乙甙1.2g／m^2，卡铂1.2g／m^2，其中6例化疗后进行局部放疗，另1例因年龄超过60岁且合并肺炎未进行局部放疗。均进行了长期随访，中位随访时间27(25-82)个月。结果 所有病例生存均超过2年，其中3例生存超过5年，1例最长已达82个月。死亡3例，分别生存26、27、27个月。结论 APBSCT支持下高剂量化疗辅以局部放疗治疗小细胞肺癌，尤其是对年龄相对较轻、一般状况良好、常规化疗达CR的患者，有助于延长患者生存，改善预后。     

High-dose chemotherapy with autologous stem cell rescue in breast cancer

SummaryBackground Because metastatic breast cancer is a lethal disease despite some responsiveness to systemic chemotherapy, high-dose chemotherapy with autologous stem cell rescue is being utilized with increasing frequency. This analysis was undertaken to determine the outcome for such patients treated with intensive chemotherapy between 1989–1994, at the Hoag Cancer Center in Newport Beach, CA.Methods During 1989, only patients with metastatic disease who had failed more than two standard breast cancer chemotherapy regimens were considered eligible for such treatment. They received high-dose BCNU/ cyclophosphamide/cisplatinum chemotherapy with autologous bone marrow rescue. After January 1990, patients with metastatic disease were eligible only if they had received limited prior chemotherapy and demonstrated responsiveness to induction chemotherapy. Beginning June 1990, patients with metastatic disease were to receive mitoxantrone and thiotepa (MiTepa) followed by peripheral blood stem cell rescue, then ifosfamide, carboplatin and etoposide (ICE) chemotherapy followed by peripheral blood stem cell rescue. High-risk adjuvant patients were to receive one course of ICE followed by rescue.Results Between 1/89–12/94, 48 breast cancer patients underwent 65 intensive chemotherapy treatments followed by autologous stem cell rescue. During 1989, three of the eight patients with metastatic disease died within 60 days because of therapy-related complications. The longest failure-free survival (FFS) of these eight was 12.2 months, and the longest overall survival (OS) 20.5 months. Since 1/90, one physician has treated 24 patients with metastatic breast cancer, 17 of whom actually underwent two successive transplants with MiTepa/ICE. For the latter group, median FFS is 23.2 months; median OS is 39.7 months. There were no acute deaths, but two patients died > 60 days after initial transplant from therapy-related complications, venoocclusive disease (5.2 months) and myelodysplastic syndrome (30.5 months), while five died of progressive disease at 22.5, 32.8, 39.4, 46.3, and 51.3 months. For the 24 metastatic patients treated 1990–1994, 1-, 2-, and 3-year FFS rates are 86%, 40%, and 17%, respectively, while OS rates are 91%, 80%, and 65%. Of 11 patients treated in the adjuvant setting, only one has relapsed (9.8 months) with follow-up from 3–61 months.Conclusions Modifications made in the program, including selection of patients responsive to induction chemotherapy, transfusion of peripheral blood stem cells, implementation of hematopoietic colony stimulating factors, and use of tandem intensive treatments has been associated with a low rate of acute morbidity and encouraging survival rates.Presented in part at the 16th Annual San Antonio Breast Cancer Symposium, November 5, 1993     

Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk medulloblastoma

Background

We assessed the feasibility and effectiveness of reduced-dose craniospinal (CS) radiotherapy (RT) followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in reducing late adverse effects without jeopardizing survival among children with high-risk medulloblastoma (MB).

Methods

From October 2005 through September 2010, twenty consecutive children aged >3 years with high-risk MB (presence of metastasis and/or postoperative residual tumor >1.5 cm²) were assigned to receive 2 cycles of pre-RT chemotherapy, CSRT (23.4 or 30.6 Gy) combined with local RT to the primary site (total 54.0 Gy), and 4 cycles of post-RT chemotherapy followed by tandem HDCT/autoSCT. Carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens were used for the first and second HDCT, respectively.

Results

Of 20 patients with high-risk MB, 17 had metastatic disease and 3 had a postoperative residual tumor >1.5 cm² without metastasis. The tumor relapsed/progressed in 4 patients, and 2 patients died of toxicities during the second HDCT/autoSCT. Therefore, 14 patients remained event-free at a median follow-up of 46 months (range, 23−82) from diagnosis. The probability of 5-year event-free survival was 70.0% ± 10.3% for all patients and 70.6% ± 11.1% for patients with metastases. Late adverse effects evaluated at a median of 36 months (range, 12−68) after tandem HDCT/autoSCT were acceptable.

Conclusions

In children with high-risk MB, CSRT dose might be reduced when accompanied by tandem HDCT/autoSCT without jeopardizing survival. However, longer follow-up is needed to evaluate whether the benefits of reduced-dose CSRT outweigh the long-term risks of tandem HDCT/autoSCT.     

自体外周血干细胞支持下高剂量化疗与常规化疗治疗小细胞肺癌的比较

比较自体外周血干细胞支持下高剂量化疗（ｈｉｇｈ－ｄｏｓｅ ｃｈｅｍｏｔｈｅｒａｐｙ,ＨＤＣＴ）与常规剂量化疗（ｃｏｎｖｅｎｔｉｏｎａｌ ｄｏｓｅ ｃｈｅｍｏｔｈｅｒａｐｙ,ＣＤＣＴ）治疗小细胞肺癌（ＳＣＬＣ）的疗效,生存期,并评价与高剂量化疗相关的毒性。方法本试验观察了２７例经病理证实的ＳＣＬＣ患者,其中１３例为例自体外周血干细胞支持下高剂量化疗,１４例为常规剂量化疗。高剂量化疗组先行１－３个周期     

Multiple cycles of high-dose doxorubicin and cyclophosphamide with G-CSF mobilized peripheral blood progenitor cell support in patients with metastatic breast cancer

Background: In a previous study we applied doxorubicin and cyclophosphamide in a dose-intensive regimen with GM-CSF to patients with metastatic breast cancer (MBC). That treatment failed to prolong the remission duration compared to conventional-dose chemotherapy. In the present study we escalated the dosages of the same agents to: 1) determine the maximum tolerated dosages (MTD) when given for three cycles with G-CSF mobilised peripheral blood progenitor cell (PBPC) reinfusion and 2) evaluate the antitumour effect of this regimen.Patients and methods: For mobilisation of PBPC, G-CSF 15 µg/kg/day was given subcutaneously (s.c.), and in subsequent cohorts leucapheresis was started on days 3, 4 or 6. The intention was to treat MBC patients with three cycles of doxorubicin and cyclophosphamide at a starting dose of doxorubicin 90 mg/m² and cyclophosphamide 1000 mg/m². Dosages were then escalated in subsequent cohorts of at least three patients. In case of dose-limiting mucositis, only the dose of cyclophosphamide was escalated in the next cohort.Results: Twenty-one patients entered this protocol, of which 18 patients received high-dose chemotherapy. The mobilisation of PBPC using G-CSF only was sufficient for three cycles of high-dose chemotherapy in 10 of 21 (47%) patients. Mucositis precluded dose escalation of doxorubicin beyond 110 mg/m². The MTD in this combination was 110 mg/m² for doxorubicin, and 4 g/m² for cyclophosphamide, with haemorrhagic cystitis being the dose-limiting toxicity. The overall response rate was 78% (95% confidence interval (95% CI): 57%–97%), with 22% (95% CI: 3%–41%) complete responses.Conclusion: The MTD of this three cycle high-dose regimen was doxorubicin 110 mg/m² and cyclophosphamide 4 g/m² with mucositis and cystitis being dose-limiting toxicities. Although the primary aim was not the evaluation of antitumour effect, this high-dose regimen does not appear to provide an improvement of treatment results in comparison with our previous study with the same drugs at moderately high-dosages without stem cell support.     

中/大剂量阿糖胞苷方案序贯化疗后自体造血干细胞移植治疗成年人急性白血病69例分析

 目的 观察第1次完全缓解（CR1）期成年人急性白血病（AL）患者中／大剂量阿糖胞苷（I／HIDAC）序贯强烈化疗后自体造血干细胞移植（ASCT）的安全性及移植疗效。方法 回顾性分析CR1期无HLA匹配同胞供者的成年人AL患者,早期接受I／HIDAC序贯强烈化疗并ASCT治疗。观察其毒副作用、移植相关死亡率（TRM）及总生存率（OS）和无白血病生存率（LFS）等。结果 69例患者接受I／HIDAC强化治疗中位2（1 ~ 3）疗程。患者均发生WHOⅢ ~ Ⅳ级造血系统毒性,常见的非造血系统毒性为胃肠道、皮肤、黏膜毒性、发热及感染等,多为轻微到中等程度。患者均采集到足量的骨髓和／或外周血干细胞。1例预处理后早期死亡,余患者移植后均完全造血重建。中位随访80.5个月,TRM 10.14 %。预期移植后5年OS在AML和ALL分别为（55.36±3.69）%和（56.90±3.56）%,而5年LFS分别为（55.51±3.70）%和（58.09±3.14）%。结论 成年人AL在取得CR1后早期进行以I／HIDAC为基础的强化／巩固治疗后进行ASCT,患者耐受性良好,可获得较好的长期OS和LFS。     

以紫杉醇为主的联合化疗方案治疗转移性乳腺癌

目的：评价以紫杉醇为主的联合化疗方案治疗转移性乳腺癌的近期疗效和不良反应。方法：紫杉醇135mg/m^2静脉滴注第一天，根据以往化疗用药选择顺铂30mg/m^2静脉滴注第2天至第4天，同时水化，利尿（TP方案），或给予表阿霉素70mg/m^2分2天静脉注射（TE方案）。21-28天为一周期，治疗2-3周期后评价疗效。结果：全组28例CR1例，PR16例，SD5例，PD6例，总有效率60.7%，初治有效率66.7%，复治有效率57.9%。TE方案有效率60.0%，TP方案有效率61.5%。主要不良反应为骨髓抑制，其次是消化道反应。结论：以紫杉醇为的联合化疗方案和转移性乳腺癌呈现较高疗效，对阿霉素耐药及对铂类抗药的晚期乳腺癌也有很高的疗效。     

New strategies in marrow purging for breast cancer patients receiving high-dose chemotherapy with autologous bone marrow transplantation

Summary High-dose chemotherapy and autologous bone marrow transplantation (ABMT) are commonly used to treat selected patients with high-risk breast cancer. A limitation of ABMT is that clonogenic cancer cells could be collected with the bone marrow and produce a relapse of disease when reinfused into patients. Purging the marrowex vivo may eliminate the tumor cells, but it can also delay engraftment. We employed two different purging methods whereby breast cancer cells were depleted without delaying engraftment. The addition of WR-2721 (amifostine) to 4-hydroperoxycyclophosphamide (4-HC) reduced the time to engraftment by 10 days compared with marrow purged with 4-HC alone (26 versus 37 days, respectively). The positive selection of CD34+ hematopoietic progenitors produced engraftment within 21 days. The use of granulocyte colony-stimulating factor (G-CSF) accelerated the engraftment time of CD34+ hematopoietic progenitors to 11 days.Held in conjunction with the 15th Annual San Antonio Breast Cancer Symposium, December 1992, and supported by an educational grant from Lederle Oncology; editing by The Medicine Group USA, Inc.     

Successful treatment of disseminated extragonadal germ cell cancer with intensive conventional chemotherapy after first-line high-dose chemotherapy

High-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) support has been investigated as a first-line treatment in patients with poor risk germ cell cancer. However, effective management of patients with residual cancer after HDCT has not been well addressed, and the outcome in such patients is poor. Here, we report a case of disseminated germ cell cancer successfully treated with intensive conventional chemotherapy after HDCT. A 31-year-old man presented with a bulky mass at the retroperitoneum, which had invaded the lumbar and sacral vertebra, and multiple lung and liver metastases. The patient's serum beta subunit of human chorionic gonadotrophin (β-hCG) was elevated to 2600 IU (cut-off value <0.1 IU). At the time of diagnosis of poor risk germ cell cancer of extragonadal origin, he underwent two cycles of BEP (bleomycin, etoposide, and cisplatin) chemotherapy and PBSC harvest followed by three cycles of HDCT with PBSC transplantation. The liver metastases disappeared. The retroperitoneal bulky mass and multiple lung metastases shrank but were still present, and the serum β-hCG level was not completely normalized. An additional three courses of BEP and five courses of VIP (cisplatin, ifosfamide, etoposide) normalized the β-hCG level. Pathological evaluation of the residual masses revealed no viable cancer cells at either site. The patient is alive without disease recurrence 5 years after completion of chemotherapy.     

造血干细胞移植治疗恶性血液病的临床观察

目的:观察我院骨髓移植治疗恶性血液病的疗效、探讨移植相关并发症的预防及处理等问题。方法:4例行HLA相合的同胞间异基因外周干细胞移植(Allo-PBSCT)、2例行自体外周干细胞移植(APBSCT)和1例行自体骨髓移植(Au-to-BMT)。结果:全部病例均成功造血重建。中性粒细胞≥0·5×109/L平均时间为11天;血小板≥20×109/L平均时间为16天;发生Ⅱ~Ⅲ度aGVHD1例,cGVHD1例,溶血性贫血2例,间质性肺炎2例,中位随访时间18(6~42)月,全部病例现均存活。结论:骨髓移植治疗恶性血液病有较好疗效。     

Treatment of refractory metastatic choriocarcinoma with tandem high-dose chemotherapy supported by peripheral blood stem cell transplantation: A case report

Currently, 70% to 80% of patients with advanced germ cell tumors can be cured with cisplatin-based chemotherapy, followed by surgical resection of the residual tumor. The prognosis, however, is uniformly poor for patients who fail to respond to induction chemotherapy. In this report, we describe a patient with retroperitoneal choriocarcinoma and multiple lung metastases, who was refractory to cisplatin-based chemotherapy, but who achieved a durable marker-negative partial response after 2 cycles of high-dose chemotherapy, supported by autologous, peripheral blood stem cell transplantation. The patient is now alive and well, without recurrence, more than 24 months after this therapy.     

Telomere length in breast cancer patients before and after chemotherapy with or without stem cell transplantation

High-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) may accelerate telomere length loss in haematopoietic stem cells. As data including pre-and post-treatment samples are lacking, we studied leukocyte telomere length and telomerase activity before and after treatment in breast cancer patients randomized to receive 5 adjuvant courses FEC (5-FU, epirubicin and cyclophosphamide) (n = 17), or 4 x FEC followed by high-dose cyclophosphamide, thiotepa, carboplatin and autologous PBSCT (n = 16). Haemoglobin, MCV, leukocyte-and platelet numbers were assessed prior to (t(0)), 5 months after (t(1)) and 9 months after chemotherapy (t(2)); these parameters were decreased at t(1)and t(2)compared to t(0)(high-dose: all parameters; standard-dose: leukocytes and platelets), and all parameters were lower after high-dose than standard-dose treatment at t(1). Paired individual leukocyte samples of t(0)and t(1)showed telomere length change (determined by telomere restricted fragment (TRF) assay) ranging from +0.8 to -2.2 kb, with a decreased TRF length in 9 patients of both groups. Telomerase activity (determined by TRAP assay) was below detection limit in leukocyte samples of t(0)and t(1). Thus, standard-and high-dose chemotherapy negatively affect haematological reconstitution in this setting. In individual patients, telomere length can be remarkably changed following haematological proliferative stress after treatment.     

自体外周血造血干细胞移植联合大剂量化疗的高危乳腺癌患者生活质量分析

目的分析自体外周血造血干细胞移植（ASCT）联合大剂量化疗（HDCT）的高危乳腺癌患者在移植前后生活质量的变化情况,以期为医务工作者选择有针对性和有效性的干预措施改善患者的生活质量提供参考。方法选取2000～2003年本院经手术病理确诊并接受ASCT联合HDCT的61例女性高危乳腺癌患者,中位年龄46岁,作为病例组;用随机数字表法在320个普通健康人群中选取50例35～65岁健康女性作为对照组。采用欧洲癌症研究与治疗组织生活质量问卷第三版（EORTCQLQ-C30version3．0）作为问卷调查表。病例组选取5个时间点在患者返院复查时填写调查表,对照组经得同意后填写调查表,根据各个条目得分情况进行分析。采用重复测量法和两独立样本￡检验进行统计分析。结果总体上患者在ASCT结束后3个月生活质量最差,此后逐渐恢复接近健康人水平,但很多方面仍与健康人相比存在明显差别。躯体功能在ASCT前后无显著性差别,但ASCT后5年的患者与对照组之间差异有统计学意义（P一0．000）。患者的情绪功能在ASCT后3个月时较ASCT前明显降低（P=0．000）,虽然ASCT后3年较ASCT前显著升高（P：0．000）,但ASCT后5年与健康对照组比较差异有统计学意义（P=0．011）。患者疲劳症状在ASCT后3个月比ASCT前显著增加（P=0．000）,而随着时间推移有所缓解,ASCT后5年此症状才出现明显减轻,但较健康对照组差异有统计学意义（P=0．031）。病例组患者恶心呕吐症状在ASCT后3个月最明显,此后逐渐缓解,ASCT后3年明显改观,ASCT后5年与健康对照组相比差异无统计学意义（P=0．474）。病例组患者疼痛症状在ASCT前后一直存在,ASCT后5年与健康对照组比较差异有统计学意义（P=0．014）。病例组患者经济困难在ASCT前与ASCT后3个月间差异有显著的统计学意义（P=0．000）,ASCT后5年有所缓解,但与健康对照组相比仍存在较为严重的经济问题（P=0．005）。结论ASCT后患者普遍存在躯体功能受损、记忆力减退、社会家庭功能退缩、精神紧张、易疲劳、疼痛、经济困难等生活质量下降的情况,大部分可在移植后5年恢复到健康人水平,而躯体功能、疼痛症状、经济等方面仍存在严重问题。医护人员及患者家人应当给予精心护和理解照顾,帮助患者尽快改善生活质量、恢复正常生活。