Double high-dose chemotherapy with adriamycin,paclitaxel, cyclophosphamide,and thiotepa followed by autologous peripheral blood stem cell transplantation in women with metastatic breast cancer

To determine the feasibility, time to progression, and event-free survival, twenty-two women with metastatic breast cancer received two cycles of high-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) early after first-line induction chemotherapy. The median age of the ten (45.5%) pre- and 12 (54.5%) postmenopausal women was 48 (range: 33-60) years. Sixteen patients (72.7%) had at least two or more metastatic sites involved. Protocol induction and mobilization chemotherapy including granulocyte-colony stimulating-factor (G-CSF) consisted of two cycles with adriamycin (60 mg/m(2)) i.v. and paclitaxel (200 mg/m(2)) i.v. After collection of at least 4 x 10(6)/kg bodyweight peripheral blood stem cells, the first HDCT-course of adriamycin (60 mg/m(2)), paclitaxel (200 mg/m(2)) cyclophosphamide (4 g/m(2)), and thiotepa (800 mg/m(2)) (ATCT) was given to at least stable disease (SD) patients. Six to eight weeks later, the second HDCT-ATCT was administered. Each HDCT-cycle was followed by PBSCT with a median of 3.81 x 10(6)/kg bodyweight CD-34 positive cells (range: 1.85-10.38). All women showed median leukocyte engraftment (>1,000 x 10(9)/l) on day +9.4 (range: 7-13) and median platelet engraftment (>20,000 x 10(9)/l) on day +12.3 (range: 8-15). There were no apparent differences in the clinical course and non-hematologic toxicity between the two HDCT-cycles. Of the 21 patients evaluable for response, eight (38.1%) patients achieved complete remission (CR), ten (47.6%) patients showed a partial remission (PR), two patients (9.5%) no change, and one patient (4.8%) progressive disease. After a median observation time of 36 (range 28-55) months, six (28.6%) women are alive, four (19.0%) of them in continuous CR, including two women with stable bone lesions, respectively, and 15 (71.4%) died due to progressive disease. Median time to progression (TTP) was 8 (range 4-19) months. A high initial response rate of early HDCT, including the most active drugs adriamycin and paclitaxel, can be achieved with tolerable toxicity in metastatic breast cancer. New approaches for maintaining primary tumor response achieved with efficacious high-dose chemotherapy are warranted.     

Hematopoietic stem cell transplantation for childhood myeloid malignancies after high-dose thiotepa, busulfan and cyclophosphamide

Seventeen children with advanced myeloid malignancies (induction failure, relapse, myelodysplasia, secondary AML, or CR >1) received thiotepa 750 mg/m2 i.v., busulfan 12 mg/kg or 640 mg/m2 p.o., and cyclophosphamide 120 mg/kg i.v. as a preparative regimen for allogeneic or autologous hematopoietic stem cell (HSC) transplantation. Of the 15 allogeneic transplants, eight were from matched siblings, one was from a mismatched sibling, and six were from unrelated donors. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine or tacrolimus and methotrexate. Regimen-related toxicity was common but tolerable, affecting mainly the skin and gastrointestinal tract. Three patients died early and were not evaluable for engraftment; engraftment occurred in the remaining patients. Nine patients with active disease at the time of transplant were evaluable for response; all achieved remission. With a median follow-up of 40 months (range, 10-71 months), nine patients are alive and disease-free. The 3-year actuarial event-free survival was 51% (95% confidence interval (CI) 27-76%). Seven patients died of transplant-related complications: infection (n = 4), chronic GVHD (n = 1), veno-occlusive disease, VOD, (n= 1) and pulmonary alveolar hemorrhage (n = 1). Only one patient had leukemia relapse and died. We conclude that the use of high-dose thiotepa, busulfan and cyclophosphamide is an effective conditioning regimen for childhood myeloid malignancies and may be tested in patients with less advanced disease (eg CR1).     

A phase I-II study of high-dose cyclophosphamide, thiotepa and escalating doses of mitoxantrone with autologous stem cell rescue in patients with refractory malignancies

Twenty-five patients with refractory solid tumors were treated with high-dose cyclophosphamide, thiotepa and mitoxantrone followed by autologous stem cell rescue in a phase I dose escalation study. The dose-limiting toxic effect was mucositis at 60 mg/m2 of mitoxantrone in combination with cyclophosphamide and thiotepa. The early death rate due to toxic effects was 24%; all deaths were attributed to infections. Hematopoietic recovery was quite prolonged with median times to granulocyte (greater than 500 x 10(6)/l) and platelet (greater than 50 x 10(9)/l) recovery at 58 and 148 days, respectively. The overall response rate was 56%. The median time to progression was 14 weeks. Thus, this regimen has activity against refractory malignancies although early and prohibitive toxicity occurs when mitoxantrone is escalated in this setting.     

Tandem and triple high-dose chemotherapy with autologous stem cell rescue in metastatic breast cancer

The purpose of this phase II study was to evaluate the therapeutic efficacy and toxicity of a tandem or triple high-dose chemotherapy (HDC) with autologous peripheral blood stem cell transplantation (PBSCT) in patients with metastatic breast cancer (MBC) as first line chemotherapy. Conventional chemotherapy consisted of two cycles of epirubicin 120 mg/m² and ifosfamide 7500 mg/m² in the case of tandem HDC and one cycle of paclitaxel 135 mg/m², epirubicin 90 mg/m² and ifosfamide 6000 mg/m² in the case of triple HDC. Tandem HDC was composed of two cycles of epirubicin 180 mg/m², ifosfamide 12000 mg/m² and carboplatin 900 mg/m². In the case of triple HDC, paclitaxel 180 mg/m², etoposide 1500 mg/m² and thiotepa 600 mg/m² was added as the third cycle. Patients with tandem HDC (n = 20) were evaluable for both survival and toxicity, and patients with triple HDC (n = 21) only for toxicity because of short-term follow-up. Both tandem and triple HDC were well tolerated and could be safely administered. Non-hematological WHO grade 3 or 4 toxicities were mucositis (8), temporary renal insufficiency (1), myocardial infarction (1), and neuropathy (1). No toxic death occurred. The Kaplan-Meier estimates for 44-months without progression and the overall survival were 12% and 38% respectively. The median survival was 22 months (95% CI: 7.4–51.7 months) and the median progression-free interval 14 months (95% CI: 5.1–43.7 months). In a population with an unfavorable prognosis, tandem HDC showed similar efficacy as to that described in other phase II studies. Triple HDC seems not to improve patient outcome compared to tandem HDC, but a long-term follow up is required. Received: 20 April 1998 / Accepted: 6 August 1998     

Longitudinal effects of high-dose chemotherapy and autologous stem cell transplantation on quality of life in the treatment of metastatic breast cancer.

This study determined the effects of high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation (ASCT) on quality of life (QL) in women with metastatic breast cancer prior to, and during treatment, and up to 1-year post-ASCT. Thirty-three women diagnosed with metastatic breast cancer participated in a phase 1 clinical trial of a new combination of cyclophosphamide (CTX) and mitoxantrone (MXT), with dose escalation of paclitaxel. Longitudinal QL data were collected using the functional living index-cancer (FLIC) and symptom scales at seven time periods: pre-induction chemotherapy (CT), post-induction CT, post-high dose CT (HDCT), and at 3, 6, 9 and 12 months post-ASCT. FLIC scores indicated that the worst problems for patients were feelings of hardship on themselves and their families, followed by psychological functioning and physical functioning problems. The time around diagnosis of the metastatic disease and following HDCT were the worst times for all levels of quality of life, but anxiety and depression symptoms continued to increase in severity across the entire follow-up period. The symptoms that were most problematic were worry about the future, loss of sexual interest, anxiety about the treatment, general worrying, and joint pain. These data highlight the problems that women with metastatic breast cancer encounter at different stages of the disease and treatment process, and can be used to tailor psychosocial interventions appropriate for treating the relevant issues at different points in time.     

A randomized phase III clinical trial of autologous blood stem cell transplantation comparing cryopreservation using dimethylsulfoxide vs dimethylsulfoxide with hydroxyethylstarch

Hematopoietic stem cells intended for autologous transplantation are usually cryopreserved in solutions containing 10% dimethylsulfoxide (DMSO, v/v) or 5% DMSO in combination with 6% hydroxyethylstarch (HES, w/v). We performed a single-blinded, randomized study comparing these cryoprotectant solutions for patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. A total of 294 patients were evaluable; 148 received cells frozen with 10% DMSO and 146 received cells frozen in 5% DMSO/6% HES. Patients who received cells frozen with the combination cryoprotectant recovered their white blood cell count >or=1.0 x 10(9)/l at a median of 10 days, one day faster than those who received PBSC frozen with DMSO alone (P=0.04). Time to achieve neutrophil counts of >or=0.5 x 10(9) and >or=1.0 x 10(9)/l were similarly faster for the recipients of the cells frozen in the combination solution. This effect was more pronounced for patients who received quantities of CD34+ cells higher than the median for the population. Median time to discontinuation of antibiotic use was also one day faster for the recipients of cells cryopreserved with DMSO/HES (P=0.04). In contrast, median times to recovery of platelet count >or=20 x 10(9)/l were equivalent for each group (10 days; P=0.99) and the median numbers of red cell and platelet transfusions did not differ.     

Complete remission of Crohn's disease after high-dose cyclophosphamide and autologous stem cell transplantation

In a 36-year-old male with ileocolic Crohn's disease (CD) no long-lasting remission was obtained by treatment with corticosteroids, mesalazine, azathioprine and antibiotics. Surgical interventions due to relapsing fistulae and abscesses resulted in the removal of >1.5 m of small bowel and left only 40 cm of large bowel. In July 2000, a new fistula and abscess developed. The combination of corticosteroids, mesalazine, ciprofloxacin, metronidazol, azathioprine, formula diet and anti-TNF-alpha antibody largely reduced clinical activity, and resection of fistula and abscess were successful. Despite clinical remission, histology showed activity in the small bowel and the colon. In March 2001, stem cell mobilization chemotherapy with cyclophosphamide was performed. It induced an endoscopic remission for 9 months, which was maintained on azathioprine and corticosteroids. After relapse, in March 2002, high-dose chemotherapy with cyclophosphamide and reinfusion of T-cell-depleted autologous peripheral CD34+ blood stem cells were performed. This led to a complete clinical, endoscopical and histological remission for 9 months without any treatment. Thereafter, endoscopy showed initial aphthous lesions with minimal histological signs of inflammation. The patient is asymptomatic, but low-dose prednisolone and methotrexate are prophylactically given. Immunoablative chemotherapy followed by autologous peripheral blood stem cell transplantation may be a beneficial therapeutic option in complicated refractory CD.     

The effect of high-dose thiotepa, alone or in combination with other chemotherapeutic agents, on a murine B-cell leukemia model simulating autologous stem cell transplantation

The use of thiotepa (TH) is increasing, especially in stem cell transplantation, mainly due to its safety and blood-brain barrier penetration. We evaluated the use of TH in a murine model simulating autologous stem cell transplantation, with or without additional agents. Between 1 and 11 days following inoculation of BALB/c mice with 10(5)-10(8) B-cell leukemia (BCL1) cells (simulating pre-transplant leukemia loads), each group received an 'induction-like' irradiation and/or cytotoxic regimen. Animals were either followed without treatment, or an adoptive transfer (AT) was performed to untreated BALB/c mice. Administered alone without AT, high-dose TH did not change the time to appearance of leukemia. Nevertheless, in the AT experiments, TH as a single agent showed better antileukemic activity than busulfan (BU). Cyclophosphamide (CY)-containing regimens were the most effective, and the TH-CY combination was as effective as the commonly used BU-CY combination, and more effective than the BU-TH combination. Moreover, a synergistic effect was seen in the TH-CY combination (none of the animals developed leukemia, whereas 4/10 animals in the CY-TBI group developed leukemia (P=0.029)). In conclusion, although TH produced only a moderate effect against BCL1 leukemia when used alone, its combination with CY is promising and should be tested further in allogeneic murine models and clinical studies.     

HER-2 expression is a prognostic factor in patients with metastatic breast cancer treated with a combination of high-dose cyclophosphamide, mitoxantrone, paclitaxel and autologous blood stem cell support

The expression levels of a circulating extracellular domain of HER-2 can be detected in the plasma and serum of patients with metastatic breast cancer using an enzyme immunoassay (ELISA) method. In this study, we evaluated the clinical significance of high and low levels of HER-2 in the plasma of 46 patients with metastatic breast cancer enrolled in a clinical trial of high-dose chemotherapy (HDCT) using cyclophosphamide, mitoxantrone, and paclitaxel with autologous stem cell transplantation (ASCT). Using 2500 U/ml as the cut-point, 20 patients (46%) had elevated HER-2 levels (HER-2 positive). Our results suggest that patients with metastatic breast cancer and high soluble plasma HER-2 have a significantly poorer overall (OS) and progression-free survival (PFS) following high-dose chemotherapy with paclitaxel and ASCT. The median OS of patients with low levels of HER-2 was significantly longer (P < 0.01) than the median OS of patients with high levels of HER-2 (29.8 months vs 15.9 months). PFS was also significantly longer (P < 0.01) for patients who were HER-2-negative, than for patients who were HER-2-positive (13.0 vs 8.6 months). Univariate analysis showed that patients with liver or lung metastases had significantly reduced OS and PFS. Patients with metastases to two or more sites also had a significantly reduced time to disease progression, but not OS. In multivariable analysis, lung metastases contributed along with HER-2-positive status to determine a group of patients with significantly poorer OS. However, HER-2-positive status remained the only independent predictor of PFS.     

A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma

We conducted a phase 1/2 trial of high-dose 90Y-ibritumomab tiuxetan in combination with high-dose etoposide (VP-16) 40 to 60 mg/kg (day -4) and cyclophosphamide 100 mg/kg (day -2) followed by autologous stem cell transplantation (ASCT) in 31 patients with CD20+ non-Hodgkin lymphoma (NHL). Patients underwent dosimetry (day -21) with 5 mCi (185 MBq) 111In-ibritumomab tiuxetan following 250 mg/m2 rituximab, followed a week later by 90Y-ibritumomab tiuxetan to deliver a target dose of 1000 cGy to highest normal organ. Bone marrow biopsy was done on day -7 to estimate radiation dose and stem cells were reinfused when the radiation dose was estimated to be less than 5 cGy. The median 90Y-ibritumomab tiuxetan dose was 71.6 mCi (2649.2 MBq; range, 36.6-105 mCi; range, 1354.2-3885 MBq). Histology included follicular lymphoma (n = 12), diffuse large B-cell (n = 14), and mantle cell (n = 5). The median number of prior chemo-therapy treatments was 2. The treatment was well tolerated. The median times to reach an absolute neutrophil count greater than 500/microL and platelet count more than 20,000/microL were 10 days and 12 days, respectively. There were 2 deaths and 5 relapses. At a median follow-up of 22 months, the 2-year estimated overall survival and relapse-free survival rates are 92% and 78%, respectively. We conclude that high-dose 90Y-ibritumomab tiuxetan can be combined safely with high-dose etoposide and cyclophosphamide without an increase in transplant-related toxicity or delayed engraftment.     

A longitudinal prospective study of health-related quality of life in breast cancer patients following high-dose chemotherapy with autologous blood stem cell transplantation

This prospective longitudinal study examined both short- and long-term changes in health-related quality of life (HRQL) in 52 breast cancer patients with poor prognosis receiving high-dose chemotherapy (HDC) treatment with autologous blood stem cell transplantation (ASCT). HRQL was measured seven times from baseline to 2 years post enrollment with the Functional Living Index-Cancer (FLIC), the EuroQol (EQ-5D), and a quality of life visual analogue scale. The percentage of questionnaires returned at each assessment time ranged from 80 to 92%. All three measures showed a similar pattern of change, with HRQL decreasing following administration of HDC, and returning to baseline levels 8 weeks post HDC. A repeated-measures analysis of variance showed that the FLIC at 2 years was significantly better than baseline (P=<0.0001). Difficulty sleeping, headaches, and decreased sexual interest were the most common symptoms reported in the longer term. Our results have implications for early psychosocial intervention in the care of breast cancer patients with poor prognosis undergoing treatment with HDC and ASCT because such interventions can further improve the quality of their survival.     

Phase II trial of sequential high-dose chemotherapy with paclitaxel,melphalan and cyclophosphamide,thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer

A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m(2)), the second melphalan (180 mg/m(2)) and the third consisted of cyclophosphamide 6000 mg/m(2) (1500 mg/m(2)/day x 4), thiotepa 500 mg/m(2) (125 mg/m(2)/day x 4) and carboplatin 800 mg/m(2) (200 mg/m(2)/day x 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR*, and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1-43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease.     

骨髓间质干细胞移植治疗原发性扩张型心肌病的疗效与安全性

目的研究自身骨髓间质干细胞经冠状动脉内移植治疗原发性扩张型心肌病的临床疗效及其安全性。方法入选24例原发性扩张型心肌病患者,随机分为对照组和细胞移植组各12例,两组均予常规抗心衰药物治疗。细胞移植组接受自身骨髓间质干细胞冠状动脉内移植,对照组冠状动脉内注射等量生理盐水。两组术前、术后48H、3个月和6个月分别检测血清白介素6(IL6)、肿瘤坏死因子Α(TNFΑ)和高敏C反应蛋白(HSCRP),术前、术后3个月和6个月分别行血浆脑钠肽(BNP)、超声心动图、动态心电检测和6MIN步行试验。结果细胞移植组术后上述三时间点的血清IL6、TNFΑ和HSCRP与对照组和自身术前比较均无统计学意义(P>0.05)。细胞移植组术后3个月和6个月BNP水平,较自身术前增高[(378.10±147.47),(420.40±148.50)比(292.40±148.54)NG/L,P<0.05],但较对照组降低,差异具统计学意义[3个月:(378.10±147.47)比(473.10±106.31)NG/L;6个月:(420.40±148.50)比(544.60±93.11)NG/L,P<0.05]。术后6个月,细胞移植组6MIN步行路程增加,与对照组和自身术前比较亦具统计学意义[(519.00±43.28)比(396.33±42.19),(464.00±76.5)M,P<0.05]。术后心超示两组间左室舒张末容积和左室射血分数无统计学意义(P>0.05)。围手术期及术后6个月随访中未见任何严重致心律失常等不良反应发生。随访期间两组患者生存率无统计学意义。结论自身骨髓间质干细胞经冠状动脉内移植治疗原发性扩张型心肌病,可降低血浆BNP水平,延长6MIN步行路程,在一定程度上增加运动耐量,无明显的致心律失常、栓塞和免疫炎症反应。     

Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized,phase III,Myeloma XI trial

The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n=2,042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib, and dexamethasone (CVD) was administered before autologous stem-cell transplantation to patients with a suboptimal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation, eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The CRD regimen was associated with significantly longer PFS (median: 36 vs. 33 months; hazard ratio [HR], 0.85; 95% confidence interval [CI]: 0.75-0.96; P=0.0116) and OS (3-year OS: 82.9% vs. 77.0%; HR, 0.77; 95% CI: 0.63-0.93; P=0.0072) compared with CTD. The PFS and OS results favored CRD over CTD across all subgroups, including patients with International Staging System stage III disease (HR for PFS, 0.73; 95% CI: 0.58-0.93; HR for OS, 0.78; 95% CI: 0.56-1.09), high-risk cytogenetics (HR for PFS, 0.60; 95% CI: 0.43-0.84; HR for OS, 0.70; 95% CI: 0.42-1.15) and ultra-high-risk cytogenetics (HR for PFS, 0.67; 95% CI: 0.41-1.11; HR for OS, 0.65; 95% CI: 0.34-1.25). Among patients randomized to lenalidomide maintenance (n=451) or observation (n=377), maintenance therapy improved PFS (median: 50 vs. 28 months; HR, 0.47; 95% CI: 0.37-0.60; P<0.0001). Optimal results for PFS and OS were achieved in the patients who received CRD induction and lenalidomide maintenance. The trial was registered with the EU Clinical Trials Register (EudraCT 2009-010956-93) and ISRCTN49407852.     

Repetitive high-dose therapy with cyclophosphamide, thiotepa and docetaxel with peripheral blood progenitor cell and filgrastim support for metastatic and locally advanced breast cancer: results of a phase I study

This phase I study was designed to determine the optimal dosages of a novel repetitive high-dose therapy regimen for patients with metastatic breast cancer (MBC). The planned treatment was three cycles of high-dose cyclophosphamide, thiotepa and docetaxel delivered every 35 days with progressive dose-escalation in successive cohorts. Each cycle was supported by peripheral blood progenitor cells (PBPC) and filgrastim. Eighteen patients were entered into this trial. Of the planned 54 treatment cycles, 44 were delivered and 11 patients completed all three cycles. The dose-limiting toxicities were interstitial pneumonitis and mucositis with moderately severe diarrhea (n = 3) and rash (n = 3). There were no treatment-related deaths. Of the 17 patients with evaluable disease, 16 patients responded with six patients achieving a complete remission and an additional four patients achieving no detectable disease (negative restaging including PET scan) but a persistently abnormal bone scan. At a median follow-up of 12 months, median progression-free survival was 11 months with the median overall survival not reached. The recommended doses for phase II/III studies are cyclophosphamide (4 g/m2), thiotepa (300 mg/m2) and docetaxel (100 mg/m2).     

Idiopathic pneumonia syndrome after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for high-risk breast cancer

Our aim was to describe the incidence, clinical course, and risk factors for idiopathic pneumonia syndrome (IPS) after high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa followed by autologous stem cell transplantation for high-risk breast cancer. Charts for patients who underwent high-dose chemotherapy for high-risk breast cancer at a single center from 1992 to 2000 were retrospectively reviewed, and potential risk factors for development of IPS were sought with the log-rank test. Of 164 patients reviewed, 20 developed IPS at a median onset of 87 days after the transplant (range, 2-257 days). The actuarial incidence of IPS in the first 100 days after the transplant was 8%, and 95% of patients developed symptoms within the first 6 months after transplant. Patient age, smoking status, breast cancer stage at diagnosis, and pretransplant lung function did not predict development of IPS. Three patients died of progressive pulmonary failure and the IPS resolved in the other 17. We concluded that IPS is an important cause of morbidity and mortality in patients with high-risk breast cancer undergoing high-dose chemotherapy. Given the absence of predictive factors, any pulmonary symptoms appearing in the first year after the transplant should be evaluated carefully.     

High-dose thiotepa,melphalan and carboplatin (TMCb) followed by autologous stem cell transplantation in patients with advanced breast cancer: a retrospective evaluation

This study was conducted to evaluate the efficacy of high-dose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m(2)), melphalan (100 mg/m(2)) and carboplatin (1200-1350 mg/m(2)). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n=2) or early death due to transplant-related complications (n=3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%),(10) are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n=17) and responsive (n=10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR(*) following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR(*) following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.     

Syngeneic hematopoietic stem cell transplantation for women with metastatic breast cancer

Metastatic breast cancer has been a common indication for autologous hematopoietic stem cell transplantation (HSCT). Previous reports indicate 3-year survival and progression-free survival (PFS) rates after autotransplant to be about 30 and 15%, respectively. Most deaths are from recurrent disease. One potential cause for high relapse rates is graft contamination with tumor. We describe 14 women with metastatic breast cancer transplanted between 1991 and 1998 with hematopoietic cells from identical twins. Median age was 41 y (range 34-50). Most women (12 of 14) were treated with mastectomy, and all received anthracycline-based regimens in their pretransplant course; nine women also received a taxane, seven radiotherapy and three hormonal therapy. Four women were in complete remission (one CR, three CRU) at transplant, five were in partial remission, two had stable disease and two had progressive disease. Eight women have died, one of treatment-related causes and seven of progressive breast cancer. Three-year survival was 48% (21-71%) and 3-year PFS was 21% (5-45%). Although the number of patients is small, outcomes for women transplanted with syngeneic grafts are similar to those of women receiving autologous grafts. This suggests that residual cancer in the patient is the major contributor to relapse after transplantation for breast cancer.