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Cerebellar aspergillosis: case report and literature review.

OBJECTIVE AND IMPORTANCE: An unusual, but not unique, case of cerebellar aspergillosis associated with autologous peripheral blood stem cell transplantation for breast cancer is presented. CLINICAL PRESENTATION: A 45-year-old woman with breast cancer underwent chemotherapy and radiotherapy as well as autologous peripheral blood stem cell transplantation. She developed a cerebellar aspergillosis abscess that was treated successfully with two surgical resections. INTERVENTION: After removal of pus and the abscess wall, the patient received local application of amphotericin B (AmB). She received AmB 1 mg/kg/d for 3 months and itraconazole 100 mg/kg/d for 1 year. After 3 months of AmB treatment, magnetic resonance imaging revealed that disease had not recurred. CONCLUSION: In cases of central nervous system aspergillosis, to increase the therapeutic efficiency, AmB can also be applied to the abscess cavity. Computed tomographic and contrast-enhanced magnetic resonance imaging scans play an important role in establishing early diagnosis in high-risk, immunocompromised patients.

Amphotericin B↗

Women and cancer.

Current concepts in the care of women with cancer are discussed. New diagnostic and treatment strategies for the four major cancers affecting women are discussed, including high-dose therapy with stem cell support for breast cancer. Genetic influences and their attendant ethical considerations are discussed. Finally, the psychosocial considerations specific to women with cancer are addressed.

Adult↗

Expression of the c-kit protein in human solid tumors and in corresponding fetal and adult normal tissues.

The proto-oncogene c-kit encodes a transmembrane tyrosine kinase receptor that is thought to play an important role in hematopoiesis, spermatogenesis, and melanogenesis. We previously showed that the c-kit messenger RNA is preferentially expressed in small cell lung cancer and that its ligand, stem cell factor, is expressed in a broad spectrum of human cancers. Using anti-c-kit antisera raised against synthetic peptides, in situ localization of the c-kit protein in various human solid tumors as well as in corresponding fetal and adult normal tissues was studied by the ABC method. The results suggest that the c-kit gene products may be involved in the pathogenesis of a very restricted subset of human solid tumors such as small cell lung cancer. Interestingly, nuclear protein immunologically related to c-kit was found in both normal and neoplastic medullary cells of the adrenal gland.

Adrenal Gland Neoplasms↗

High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group.

PURPOSE: Medulloblastoma is a highly lethal disease when it recurs. Very few patients survive with conventional treatment. This study evaluated the use of high-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue (ASCR) in patients with recurrent medulloblastoma. METHODS: Chemotherapy consisted of carboplatin 500 mg/m2 (or area under the curve = 7 mg/mL x min via Calvert formula) on days -8, -7, and -6; and thiotepa 300 mg/m2 and etoposide 250 mg/m2 on days -5, -4, and -3; followed by ASCR on day 0. In addition to the study-prescribed therapy, 21 patients received other treatment: neurosurgical resection in seven, conventional chemotherapy in 17, and external-beam irradiation in 11 cases. RESULTS: Twenty-three patients with recurrent medulloblastoma, aged two to 44 years (median, 13 years) at ASCR, were treated. Three patients died of treatment-related toxicities within 21 days of ASCR; multiorgan system failure in two, and Aspergillus infection with venoocclusive disease in one. Seven of 23 patients (30%) are event-free survivors at a median of 54 months post-ASCR (range, 24 to 78 months). Kaplan-Meier estimates of event-free (EFS) and overall survival are 34% +/- 10% and 46% +/- 11%, respectively, at 36 months post-ASCR. CONCLUSION: This strategy may provide long-term survival for some patients with recurrent medulloblastoma.

Adolescent↗

Vincristine-laden platelet transfusion for patients with refractory thrombocytopenia.

BACKGROUND: The aim of the present study was to assess the efficacy of vincristine-laden platelet transfusion for patients with refractory thrombocytopenia. PATIENTS AND METHODS: Twenty evaluable patients who received vincristine-laden platelets for refractory thrombocytopenia were included in this retrospective study. Vincristine (1 mg) was added to the platelets and incubated for one hour prior to transfusion. Serial platelet counts following vincristine-laden platelet transfusion and units of platelets transfused in the week prior to and the week after transfusion of vincristine-laden platelets were evaluated. RESULTS: The underlying diseases of the patients were lung cancer (n =4), breast cancer following autologous hematopoietic stem cell transplantation and acute myeloid leukemia (n=3 each), myelodysplastic syndrome (n=2), acute lymphoid leukemia, chronic lymphoid leukemia, chronic myeloid leukemia, multiple myeloma, ovarian cancer, aspergillosis, cytomegalovirus infection and systemic lupus erythematosus (n = 1 each). The median rate of change of platelet count after transfusion of vincristine-laden platelets was 550/microL/day (range, -1,000 to 12,8001/microL/day; p=0.003). The median change in the number of units of platelets transfused in the week following vincristine-laden platelet transfusion was -1.5 as compared to the week prior to the transfusion (p=0.031). Patients with a primary marrow disorder exhibited no difference in either the rate of change in platelet count or in the difference in the units of platelets transfused compared to those without a primary bone marrow disorder. CONCLUSION: Vincristine-laden platelet transfusion was associated with significantly increased platelet counts and a subsequent decrease in platelet transfusion.

Adult↗

Coamplification of prostate stem cell antigen (PSCA) and MYC in locally advanced prostate cancer.

Gain of sequences on chromosome arm 8q is a common feature of prostate cancer that may correlate with metastatic and androgen-independent progression. The target gene(s) for this gain is not known, although MYC is amplified in a subset of advanced tumors and is one potential candidate. Prostate stem cell antigen (PSCA) is a prostate-specific cell surface protein that maps to chromosome region 8q24.2 and is overexpressed in prostate cancer. Our aim in this study was to test the hypothesis that PSCA overexpression may result from overrepresentation of chromosome arm 8q. Twenty locally advanced prostate cancers were analyzed by dual-probe fluorescence in situ hybridization (FISH) for alterations of MYC and PSCA. Extra copies of MYC were found in 12/20 (60%) tumors, including 5 (25%) with simple gain (no increase in MYC copy number relative to the chromosome 8 centromere) and 7 (35%) with an additional increase (AI or overrepresentation) in MYC copy number relative to the centromere. In the five cases with simple gain of MYC, there was a concomitant gain of PSCA. PSCA was overrepresented in 5/7 (71%) cases with AI of MYC. Immunohistochemical staining of the 20 tumors with monoclonal antibodies specific for PSCA showed a high degree of correlation between PSCA gene overrepresentation and protein overexpression. Four of 5 tumors with AI of PSCA overexpressed PSCA protein, compared with only 2/15 tumors with a normal PSCA copy number or simple gain of PSCA (P = 0.014). These results demonstrate that PSCA is co-overrepresented with MYC in a majority of cases, but may not be a necessary part of the 8q amplicon. PSCA protein overexpression can result from AI of PSCA and might be useful as a cell surface marker on prostate cancer cells with 8q overrepresentation. Genes Chromosomes Cancer 27:95-103, 2000.

Antigens, Neoplasm↗

Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer.

The feasibility and toxicity of allogeneic stem cell transplantation after nonmyeloablative conditioning including thiotepa, fludarabine, and cyclophosphamide have been investigated in 6 patients with breast cancer and 7 patients with renal cell cancer. The program included the use of escalating doses of donor lymphocyte infusions (DLI) and/or interferon alpha (IFNalpha) for patients showing no tumor response and no graft-versus-host disease (GVHD). Patients were at high risk of transplant-related mortality (TRM) because of age, advanced stage, and previous treatments. We observed a partial remission in 4 renal cancer and in 2 breast cancer patients (one at the molecular level in the bone marrow), occurring after cyclosporine withdrawal or after DLI and/or IFNalpha. All the responses were accompanied by the occurrence of acute GVHD. We conclude that reduced-intensity allogeneic stem cell transplantation is a feasible procedure in renal and breast cancer, and that the exploitation of graft-versus-tumor effect after DLI is a promising finding.

Adolescent↗

Sequential high-dose alkylating therapy and stem cell support for high-risk stage III breast cancer.

Patients who receive neoadjuvant chemotherapy for locally advanced breast cancer and have four or more ipsilateral axillary lymph nodes involved at surgery are at high risk for recurrence, with a median time to relapse of 18 months. We offered such patients high-dose chemotherapy with stem cell rescue. Patients received cyclophosphamide or paclitaxel and granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells. Melphalan 140 mg/m2 was then given with stem cell rescue. Twenty-four to 35 days later, thiotepa 900 mg/m2 was given with stem cell rescue. Patients with hormone receptor-positive tumors received tamoxifen. We treated 14 patients in this fashion from 1995 to 1998. The mean age was 46.7 years. The majority of cancers were stage IIIB (79%). Thirteen women underwent mastectomy after anthracycline-containing chemotherapy and 50% had more than seven positive lymph nodes. Hospitalization was principally for neutropenic fever. Other morbidities were pneumonitis, cardiomyopathy, and grade 3/4 white blood cell (WBC) toxicity. No patient died of a treatment-related complication. Seven of 14 relapsed at 10, 12, <15, 15, 17, 21, and 36 months, with median follow-up of 26.5 months. Time to relapse in this small series is only modestly improved over historical experience with standard-dose adjuvant chemotherapy. Alternative strategies for treating locally advanced breast cancer should be pursued.

Adult↗

The effect of knocking-down nucleostemin gene expression on the in vitro proliferation and in vivo tumorigenesis of HeLa cells.

Previous studies have demonstrated nucleostemin (NS) expressed in undifferentiated cells (e.g. embryonic stem cells and myeloid stem cells) and various cancer cell lines, but didn't express in differentiated adult tissues. In this study, we examined the NS expression in several cancer cell lines and some normal human tissues. Moreover, we used RNAi techniques to knock down the NS gene expression in Hela cells. As a result, we found that all these detected cancer cell lines in our program had high levels of NS expression, which indicated NS played a really important role in the self-renewal of these cancer cells. At the same time, NS expressed in human placenta tissue also at a high level, which may be due to the existence of a mass of placenta stem cells. Only a small quantity of NS expression could be found in normal human muscle tissue due to the existence of myoblasts. And for the first time our findings demonstrated that if NS expression of Hela cells was knocked down, more Hela cells couldn't complete the DNA synthesis to pass through S phase. So the percent of G0/G1 phase increased with the decrease of S phase and cell proliferation rate and in vivo tumorigenic capacity decreased obviously. Our work would help shed light on the self-renewal and malignant growth of cancer cells.

Blotting, Northern↗

The expression of c-kit and proliferating cell nuclear antigen in oval cells of rats with hepatocellular carcinoma.

OBJECTIVE: To study the relationship between oval cells and primary hepatocarcinoma and the expression of c-kit and proliferating cell nuclear antigen (PCNA) in oval cells of rats with hepatocellular carcinoma. METHODS: A hundred and twenty clean SD rats were divided into three groups: normal group, cancer-induction group and intervention group. The normal group was fed with standard forage while the rest two groups were fed with 3'-methyl-2-methylamino-azobenzene (DAB) to induce carcinoma for 14 weeks and then fed with standard forage and water. Uscharidin was injected abdominally to the intervention group from the first week to the 14th week. All rats were killed and biopsy specimens were taken from the left and right liver lobes for immunohistochemical staining of c-kit and PCNA on the 2nd, 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd, and 24th week. RESULTS: From the 2nd to 14th week after liver infection, c-kit positive cells, mainly oval cells were found in the portal area in the carcinoma-induction group and dotted positive pigmentations in liver lobules. In the 22nd week, a large number of cancerous nodes occurred and nuclei heteromorphism was apparent; the number of positive cell decreased but positive cells could be sparsely observed in cancerous nodes. In the 2nd week of the carcinoma-induction process, PCNA positive cells were oval cells in the portal area. In the 4th week, a lot of hepatic cells were positively stained, especially in the central vein area. In the 6th week, PCNA positive cells could be seen in the lobules of the liver. In the 8th week, the number of PCNA cells decreased comparatively. From the 10th to 14th week, oval cells in the portal area were still over-expressed. From the 16th to 24th week, a large number of cancerous nodes occurred and PCNA was over-expressed in some of them. In necrotic cancerous nodes, the para-cancerous PCNA positive cells were sparsely distributed and their number was less than that of PCNA positive cells of cancerous tissues. CONCLUSIONS: Hepatic stem cells originating from the terminal biliary plexus of the portal area are involved in the development of hepatocarcinoma because c-kit positive cells expressed in cancerous nodes, accompany the whole process of the development. In the middle inflammatory period of carcinoma-induction, the expression of PCNA in hepatic cells peaked, but the index decreased in the late inflammatory period and in the proliferated fibrosis stage. The expression of PCNA is a tortuous process, going up, down, then up again from normal tissues to cancerous tissues. Combined with pathological findings, PCNA can be considered as a warning index for carcinomatous cells.

Analysis of Variance↗

High-dose busulfan and cyclophosphamide followed by autologous transplantation in patients with advanced breast cancer.

This study was conducted to evaluate the efficacy of high-dose busulfan (BU) and cyclophosphamide (CY) in patients undergoing autologous hematopoietic stem cell transplantation for metastatic breast cancer. Twenty-two patients with stage IV breast cancer underwent autologous marrow (n = 13), peripheral blood stem cell (PBSC) (n = 6) or marrow plus PBSC (n = 3) transplantation following BU (14-16 mg/kg) and CY (120-180 mg/kg). Of 22 patients, 18 had refractory relapse, one had primary refractory disease, two had responding relapse and one had no evidence of disease (NED) at the time of transplant. Eight patients had bone only disease, six had bone plus visceral disease, and eight had loco-regional recurrent disease. The median time for diagnosis to transplant was 1124 days (range 210-2582). Staging for evaluation of response was performed 4-6 months after transplantation. Six patients were not evaluable (NE) for response because of NED at transplant (n = 1) or early death due to transplant-related complications (n = 5) (one of RSV interstitial pneumonia, two of fungal infection and two of regimen-related toxicities) occurring at a median of 17 days (range 14-59) post-transplant. The patient who was NED at time of transplant is still NED on day 336 post-transplant. Seven of the 16 evaluable patients achieved a complete response (CR) (44%), five achieved a partial response (PR) (31%) and five had no response (NR), with an overall response rate of 75%. Five of 18 (28%) patients treated in refractory relapse, and both patients treated in responding relapse achieved a CR. Of the seven patients who achieved CR, three are alive and disease-free on days 204, 276 and 752 and three relapsed on days 209, 715 and 1127 post-transplant. One patient in CR died of aspergillus pneumonia on day 306 post-transplant. The median day to progression in five patients who achieved a PR after transplantation was 335 (range 144-507). The probabilities of survival and event-free survival (EFS) at 2 years was 0.22 and 0.15, respectively for all 22 patients. The probability of EFS at 2 years for the eight patients achieving CR (including one patient who was NED at transplant) was 0.33. The probabilities of overall survival at 2 years in patients who did and did not achieve a CR after transplantation was 0.63 and 0.14, respectively (P = 0.004). These data suggest that high-dose BU-CY followed by autologous stem cell transplantation is an effective regimen in patients with advanced breast cancer demonstrating that BU is an active agent in this disease and could be incorporated into treatment regimens requiring hematopoietic stem cell support.

Adult↗

Evaluation of the predictive value of Her-2/neu overexpression and p53 mutations in high-risk primary breast cancer patients treated with high-dose chemotherapy and autologous stem-cell transplantation.

PURPOSE: To ascertain the predictive value of Her-2/neu overexpression and p53 mutations, assessed by immunohistochemistry, in high-risk primary breast cancer (HRPBC) treated with high-dose chemotherapy (HDCT). PATIENTS AND METHODS: We obtained paraffin-embedded tumor blocks from 146 HRPBC patients previously enrolled at our program onto clinical trials of HDCT for four to nine involved axillary lymph nodes, > or = 10 involved axillary nodes, or inflammatory carcinoma. All patients received the same HDCT regimen, with cyclophosphamide, cisplatin, and carmustine (STAMP-I), followed by autologous stem-cell transplantation. Median follow-up was 42 months (range, 5 to 90 months). The same pathologist, blinded to clinical outcome, reviewed all immunostained slides. RESULTS: Positive results for Her-2/neu and p53 were found in 44.5% and 34% of the patients, respectively. Positivity for Her-2/neu was significantly associated with increased risk of relapse and death. No correlation was found between p53 mutations and relapse-free survival (RFS) or overall survival (OS). Multivariate analyses included Her-2/neu overexpression and the following variables previously identified as independent predictors of outcome in this population: tumor size, nodal ratio (number of involved nodes/number of dissected nodes), and hormone receptor status. All four variables had independent value. CONCLUSION: Her-2/neu overexpression is an independent negative predictor of RFS and OS in HRPBC treated with HDCT. Its inclusion in our previously described predictive model increases the predictive capacity of this model for the low-risk subgroup. In contrast, p53 mutations lack predictive value in this setting.

Adult↗

Surgical experience with 5 n3(+) early gastric carcinoma cases.

Of 370 patients who underwent a resection for early gastric carcinoma, 317 (85.6%) were N(-), 28 n1(+), 20 n2(+) and five (1.4%) n3 respectively. In this study, n3(+) early gastric cancers were clinicopathologically evaluated and sites of the metastatic nodes were also defined. In addition, a comparative study in DNA ploidy patterns between primary and metastatic node cell was performed according to Hedley's method using a FACS-IV scan of paraffin-embedded tissues. All n3(+) early gastric cancers showed an aneuploidy pattern. R2 or R3 operations are recommended for early gastric carcinomas with aneuploidy pattern and most of the metastatic nodes arise from the identical stem cell line of cancer cells.

Aged↗

Isolation and transplantation of highly purified autologous peripheral CD34+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.

Antigens, CD34↗

Intersections between neurobiology and oncology: tumor origin, treatment and repair of treatment-associated damage.

The number of potentially intimate relationships between brain tumors and the precursor cells that contribute to normal central nervous system (CNS) development and repair now appears to be somewhat larger than would have been anticipated only a few years ago. It also appears that understanding the vulnerabilities of CNS precursor cells, and of the specific cells that they generate, might help us to reveal the biological basis for the cognitive impairment that is increasingly recognized as an adverse effect of systemic cancer therapies. Using neural stem cells as therapeutic vehicles in the treatment of brain tumors could be modified to allow repair of the damage caused by brain tumors themselves and of the neurological impairment that is frequently associated with traditional cancer treatment approaches.

Animals↗

Individualized exercise program for the treatment of severe fatigue in patients after allogeneic hematopoietic stem-cell transplant: a pilot study.

Chronic cancer-related fatigue in otherwise asymptomatic post-allogeneic hematopoietic stem cell transplant (HSCT) patients is common and debilitating. This pilot study investigated whether patients with no clinical or psychological abnormalities but severe fatigue would respond to an individually adapted aerobic exercise program. Participants were 12 patients (eight male, and four female patients), median age 47 years and 41 months post-HSCT with a variety of hematopoietic cancer diagnoses. All underwent a 12-week individualized mild aerobic exercise program, preceded by a 4-week introduction and baseline testing phase. Psychological measures included fatigue, mood and depression. Exercise-related physiological outcomes included power output at ventilatory threshold 2 (VT2) and associated changes in stroke volume, heart rate, blood lactate concentration and ratings of perceived exertion. Patients were assessed for fatigue before, immediately after and at 3, 6, 9 and 12 months post-program. Significant improvements were found on both measures of fatigue (both P<0.001), with a very large effect size of 1.82 on the The Functional Assessment of Cancer Therapy - Fatigue Module, which were maintained over the follow-up period. Exercise testing revealed a mean increase (P<0.001) of 28% in power output at VT2 with an increase (P<0.001) in stroke volume and a decrease (P<0.001) in heart rate, blood lactate and perceived exertion at pre-intervention VT2 power output.

Adult↗

Nuclear-mitochondrial genomic profiling reveals a pattern of evolution in epithelial ovarian tumor stem cells.

Analyses of genome orthologs in cancer on the background of tumor heterogeneity, coupled with the recent identification that the tumor propagating capacity resides within a very small fraction of cells (the tumor stem cells-TSCs), has not been achieved. Here, we describe a strategy to explore genetic drift in the mitochondrial genome accompanying varying stem cell dynamics in epithelial ovarian cancer. A major and novel outcome is the identification of a specific mutant mitochondrial DNA profile associated with the TSC lineage that is drastically different from the germ line profile. This profile, however, is often camouflaged in the primary tumor, and sometimes may not be detected even after metastases, questioning the validity of whole tumor profiling towards determining individual prognosis. Continuing mutagenesis in subsets with a mutant mitochondrial genome could result in transformation through a cooperative effect with nuclear genes - a representative example in our study is a tumor suppressor gene viz. cAMP responsive element binding binding protein. This specific profile could be a critical predisposing step undertaken by a normal stem cell to overcome a tightly regulated mutation rate and DNA repair in its evolution towards tumorigenesis. Our findings suggest that varying stem cell dynamics and mutagenesis define TSC progression that may clinically translate into increasing tumor aggression with serious implications for prognosis.

Adenocarcinoma, Papillary↗

Mobilization of peripheral blood stem cells with docetaxel and cyclophosphamide (CY) in patients with metastatic breast cancer: a randomized trial of 3 vs 4 g/m2 of CY.

The purpose of this study was to develop a regimen of docetaxel, cyclophosphamide (CY) and filgrastim for mobilization of peripheral blood stem cells (PBSC) in patients with metastatic breast cancer (n = 66). A phase I trial of CY 2, 3 or 4 g/m2 with docetaxel 100 mg/m2, in consecutive cohorts of four patients each, did not reveal any dose-limiting toxicities and subsequent patients were randomized to receive 3 or 4 g/m2 of CY. The median yield of CD34+ cells from all patients was 11.06x10(6)/kg (range, 0.03-84.77) from a median of two aphereses (range, 1-7); 6.52x10(6) CD34+ cells/kg/apheresis (range, 0.01-52.07). Target CD34+ cell doses > or =2.5 and > or =5.0x10(6)/kg were achieved in 89% and 79%, respectively. There were no statistically significant differences in CD34+ cell yields or target CD34+ cell doses achieved following 3 or 4 g/m2 of CY. Patients with only one prior chemotherapy regimen yielded a median of 12.82x10(6) CD34+ cells/kg/apheresis compared to 5.85 for those receiving > or =2 regimens (P = 0.03). It was concluded that the combination of docetaxel, 100 mg/m2, CY 3 g/m2 without mesna could be administered with acceptable toxicity with collection of adequate quantities of PBSC from the majority of patients.

Adult↗