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PubMed2001

Infectious complications the year after autologous bone marrow transplantation or peripheral stem cell transplantation for treatment of breast cancer.

Few studies have examined the specific incidence of infections after autologous bone marrow transplantation (BMT) or peripheral stem cell transplantation (PSCT) for treatment of breast cancer. We reviewed the medical records of 127 consecutive patients who underwent autologous BMT or PSCT for breast cancer at the University of Pennsylvania Medical Center from 1 May 1991 through 31 March 1995 and through 1 year of follow-up. The mean duration of neutropenia after transplantation was 10 days. Initial infections included catheter-site cellulitis (in 20 patients [16%]), bacteremia (17 [13%]), Clostridium difficile colitis (13 [10%]), and urinary tract infection (in 10 [8%]); there was only 1 documented invasive fungal infection (1% of patients). The mortality from infection was 2%. Infections during the 1 year follow-up included upper respiratory infections (11 patients [10%]) and dermatomal zoster (9 [8%]); neither was significantly associated with death. This group of patients who underwent BMT or PSCT for breast cancer had a low rate of infectious morbidity and mortality. Viral and fungal infections were rare despite inconsistent prophylaxis.

Adult↗
PubMed1995

Ifosfamide/carboplatin/etoposide chemotherapy for metastatic breast cancer with or without autologous hematopoietic stem cell transplantation: evaluation of dose-response relationships.

We conducted a phase I/II trial to investigate the activity of ifosfamide/carboplatin/etoposide given over 2 or 3 days (mini-ICE) to patients with anthracycline-refractory or recurrent metastatic breast cancer. In a companion phase I/II dose-escalation study, those patients with responsive or stable disease following either anthracycline-based chemotherapy or mini-ICE and with adequate organ function were then considered eligible for treatment with a 6-day ICE regimen (maxi-ICE) followed by autologous hematopoietic stem cell transplantation. Our results showed that the ICE regimen has activity against anthracycline-refractory metastatic breast cancer. A dose-response relationship was not apparent with the mini-ICE regimen; however, among patients receiving maxi-ICE, a dose-response relationship was suggested in those patients responding to anthracycline-based chemotherapy.

Antibiotics, Antineoplastic↗
PubMed1997

[Hematopoietic stem cell transplantation for children with cancer].

More than 15 years passed since bone marrow transplantation (BMT) have first introduced to the field of treatment of pediatric cancer. During this period, technology and modality of BMT have been improved steadily and several kinds of hemopoietic stem cell transplantation, for instance, allogeneic BMT from related or unrelated donor, unpurged or purged autologous BMT by 4-hydroperoxycyclophosphamide (4-HC) or magnetic immuno-beads, allogeneic or autologous peripheral blood stem cell transplantation and cord blood stem cell transplantation became available. Now we can choose the most suitable transplantation method for each patient from our repertory according to the patient's condition. In this article, treatment result of allogeneic BMT and 4-HC purged autologous BMT for children with acute leukemia and several kinds of hematopoietic stem cell transplantation for children with solid tumors in my hospital were reported.

Adolescent↗
PubMed2006

Genomic models of metastatic cancer: functional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG) protein chromatin silencing pathway.

A recent discovery of death-from-cancer signature genes identifies potential markers predicting the high likelihood of treatment failure in cancer patients. This knowledge provides the opportunity to analyze in functional terms the therapy-resistant and metastasis-enabling phenotypes of cancer cells. Here we summarize the current data regarding the biological functions of genes comprising a death-from-cancer signature. This analysis predicts that cancer cells manifesting a stem cell-like expression profile of a death-from-cancer signature would exhibit the following features: a concomitantly increased expression of certain members of inhibitor of apoptosis protein (IAP) family (Survivin and XIAP); activation of mitotic spindle check point proteins (BUB1, BUB3, KNTC2, Mad2, PLK1, PLK4, STK6/Aurora A); and elevated levels of certain cell cycle control/marker proteins (CCNB1, CCNB2, CCND1, CCNA2, CDC2, CDC25, Ki67, USP22). Consequently, these cancer cells would acquire metastasis-enabling anoikis-resistance aneuploid phenotype with aberrant cell cycle control. A functionally complementary role of multiple cooperating oncogenic pathways and the essential role of Polycomb Group (PcG) protein chromatin silencing pathway in emergence of the stem cell cancer phenotype is highlighted.

Aneuploidy↗
PubMed1996

[High-dose therapy of cancer with CD34 positive cells as stem cell support].

In this article we report our initial clinical experiences in connection with immunomagnetic isolated CD34-positive cells from peripheral blood progenitor cells. Six patients, five with breast cancer and one with non-Hodgkin's lymphoma, were mobilized by chemotherapy and G-CSF (5ug/kg). CD34-positive cells were isolated by means of immunomagnetic beads (Dynalbeads) and Isolex 300 Cell Separator (Baxter, USA). Mean purity of isolated CD34-positive cells was 97% (94.7-99.7) and mean yield was 54% (35-68). Three patients were treated with high dose therapy followed by reinfusion of CD34-positive cells as stem cell support. Recovery of neutrophils (> 0.5 x 10(9) leucocytes/liter) occurred at day 8, 11 and 13 and of platelets (> 20 x 10(9) platelets/litre) at day 9,14 and 32. It is concluded that immunomagnetic isolated CD34-positive cells give high purity and yield. Although use of CD34-positive cells reduces the content of contaminating tumour cells in the graft, breast cancer cells were still detectable in two out of five CD34-positive cell products.

Antigens, CD34↗
PubMed2003

High dose chemotherapy and stem cell support in the treatment of germ cell cancer.

PURPOSE: The current status of high dose chemotherapy with autologous stem cell support in patients with germ cell cancer is reviewed. MATERIALS AND METHODS: Advanced germ cell cancer can be cured in most patients using chemotherapy with or without surgery. A small fraction of patients fail to achieve a marker remission, have residual viable carcinoma at post-chemotherapy surgery or have relapse after remission. Phase II trials suggest that autologous stem cell support is more active than standard dose chemotherapy in patients with relapse. A comprehensive literature review, focusing on trials published in the last decade, is followed by a discussion of current trials and recommendations for the use of autologous stem cell support in germ cell cancer. RESULTS: In early trials about 15% of patients with multiple relapsed and refractory disease had durable remission with high dose carboplatin and etoposide. Most regimens now add high dose cyclophosphamide or ifosfamide to carboplatin and etoposide. Together with the use of autologous stem cell support in less heavily-pretreated patients, these regimens have produced durable remissions in 40% to 50% of patients. Multivariate analyses led to the identification of prognostic factors at diagnosis and predictive factors during therapy which were associated with a low rate of durable remission. Ongoing randomized trials of autologous stem cell support early in relapse or as part of initial therapy are designed to study and validate further these prognostic factors. CONCLUSIONS: For patients with poor risk presenting features, the role of autologous stem cell support has not been proven and awaits the results of an ongoing United States intergroup trial. Patients with residual cancer at post-chemotherapy surgery may have a substantial risk of relapse despite additional cycles of the same drugs used to achieve marker remission. For select patients in this category alternatives to additional cycles of the original chemotherapy may include established second line regimens or autologous stem cell support. The role of autologous stem cell support for germ cell tumor in relapse may be challenged by the future discovery of new agents for these diseases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Progression of cancer.

Carcinoma constitution originates in the hetero duplication mitoses which divide non-maturable stem cells into two different types of daughter cells: maturable and non-maturable cancerous stem cells. Throughout the progression of such mitoses the organoid continuity of the cancer depends only on the non-maturable daughter stem cells, not on the maturable ones. This type of cancer can be considered non-progressive or to be in the incubation stage, as it only enables cancer tissue to preserve its organoid continuity without allowing progressive growth. However, when an occasional mitotic phase of the hetero-duplication mitotic progression undergoes genuine cell-phase duplication mitosis, this non-progressive or incubation stage of cancer is converted to a progressive type of cancer. This conversion is dependent on the reappearance of the complete mitotic condition of the mitotic maturation promoting system (MMPS) containing an abnormal supplement. Thus, a thorough investigation of the abnormal supplement and the reappearance of the complete mitotical condition is an essential part of research efforts to prevent and eradicate cancer.

Cell Division↗
PubMed2000

Mobilization of peripheral blood stem cells in high-risk breast cancer patients using G-CSF after standard dose docetaxel.

Chemotherapy, in addition to recombinant growth factors, has been effective in mobilizing stem cells. Unfortunately, the use of chemotherapy for this purpose has resulted in profound myelosuppression and increased morbidity. Docetaxel, the single most active agent in the treatment of advanced breast cancer, was evaluated for its potential to mobilize stem cells when given at conventional doses followed by granulocyte colony-stimulating factor (G-CSF). Sixteen high-risk breast cancer patients were mobilized with a regimen consisting of docetaxel (100 mg/m2) followed by daily G-CSF (10 microg/kg), beginning 72 h after the docetaxel, and continuing until completion of the apheresis. The median white blood cell count (WBC) nadir was 1,000/microl (range 500 to 4000/microl ) occurring a median of 6 days (range 4 to 9 days) after the docetaxel. No patient experienced a neutropenic febrile episode due to the mobilization regimen. The median time interval for initiating the apheresis was 8 days (range 6 to 11 days) following the docetaxel. The median number of apheresis was 2 (range 1 to 3) in each patient. Stem cell recovery as measured by the CD34 cell count x 10(6)/kg was a median of 5.2 (range 1.4 to 15.1). A significant correlation was found between CFU-GM, BFU-E, and CFU-GEMM/kg and CD34 cells/kg (r = 0.891, 0.945, and 0.749, respectively, p < 0.001). When our results were compared to a matched cohort receiving G-CSF alone, the docetaxel group demonstrated a superior CD34 cells/kg yield (p = <0.001). Following myeloablative chemotherapy consisting of thiotepa and cyclophosphamide with or without carboplatinum, the hematopoetic recovery determined by an absolute neutrophil count (ANC) of greater than 500/microl and an unsupported platelet count of > or =20,000/microl for 48 h, was a median of 10 days (range 9 to 14 days) and 10 days (range 8 to 30 days), respectively. The results demonstrate that conventional dose docetaxel, combined with G-CSF, is an effective mobilization regimen with minimal toxicity in high-risk breast cancer patients.

Adult↗
PubMed1994

[Ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer].

This is a report of 45-year-old man with advanced nonseminomatous germ cell tumor (stage IIIB2: embryonal carcinoma, yolk sac tumor, seminoma), who had relapse after PVB (cisplatin, vinblastine, bleomycin) chemotherapy. Peripheral blood stem cells (PBSCs) were taken by two consecutive apheresis using a CS-3000 blood separator after high-dose chemotherapy of cytarabine and mitoxantrone. In total, 6.4 x 10(5)/kg of granulocytic cells (CFU-GM) was collected. He was treated with ultra high-dose chemotherapy consisting of carboplatin (800 mg/m2), etoposide (1,000 mg/m2) and cyclophosphamide (100 mg/kg) from day 1, followed by peripheral blood stem cell autotransplantation (PBSCT) on day 9. We transfused 2.4 x 10(5)/kg CFU-GM, which was enough number of stem cells for safe PBSCT. No serious side effects or complications were encountered. The patient achieved partial remission for more than two months. However, he died of respiratory dysfunction caused by metastatic lung cancer 5 months later. It was thought that ultra high-dose chemotherapy with PBSCT might be a new therapy for refractory testicular cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Infection in patients with neutropenia that undergo an autologous peripheral blood stem cell transplant due to breast cancer].

BACKGROUND: The extent and duration of neutropenia and the characteristics of the underlying disease are determinant factors for the prognosis of febrile syndromes. Despite the fact that traditionally the peripheral blood stem cell transplantation (PBSCT) were considered to cause high risk neutropenia, in all probability the neutropenia observed in the PBSCT in some solid tumours could be considered moderate risk. Febrile episodes in patients with these characteristics were evaluated. METHODS: We prospectively analysed 132 autologus PBSCT in patients with breast cancer (1994-1999). Conditioning regime: STAMP V. Antibacterial prophylaxis: ofloxacin (400 mg/12 hrs PO). Classification of the febrile syndrome: bacteremia, microbiologically documented infection withut bacteremia, clinical infection and a fever of unknown origin. RESULTS: 122 patients had a fever (92%), mean age: 45 years (range: 27-61). There were 32 (26%) bacteremias, 13 (11%) microbiologically documented infections without bacteremia and 54 (44%) clinical infections. The mean number of days with a neutrophil count of <1x109/1 was 14 (range: 11-20). In the 74 patients (61%) that had a granulocyte colony stimulating factor (G-CSF), the mean number of days to reach a 0,5x109/I neutrophil count (7,6) and the average number of days in hospital (26) were significantly less. There was a main infectious point in 80 patients (65%): the most frequent being oropharynx in 33 cases (46%) and digestive in 29 cases (41%). 48 gram negative (GN) 29 gram positive (GP) bacteria were isolated (71% of the GN's were resistant to ofloxacin). Between 1997-1999 the GN/GP ratio was 2,3. There were no deaths related to the infection. CONCLUSIONS: Given the excellent evolution of our patients we can consider their neutropenia to be moderate or low risk, and they are a long way from the death rates caused by infections published by other types of hemopoietic transplants. The predominance of GN over the last few years and their limited sensitivity to quinolones means that their prophylactic use in these patients should be reconsidered.

Acyclovir↗
PubMed2005

Identification of bronchioalveolar stem cells in normal lung and lung cancer.

Injury models have suggested that the lung contains anatomically and functionally distinct epithelial stem cell populations. We have isolated such a regional pulmonary stem cell population, termed bronchioalveolar stem cells (BASCs). Identified at the bronchioalveolar duct junction, BASCs were resistant to bronchiolar and alveolar damage and proliferated during epithelial cell renewal in vivo. BASCs exhibited self-renewal and were multipotent in clonal assays, highlighting their stem cell properties. Furthermore, BASCs expanded in response to oncogenic K-ras in culture and in precursors of lung tumors in vivo. These data support the hypothesis that BASCs are a stem cell population that maintains the bronchiolar Clara cells and alveolar cells of the distal lung and that their transformed counterparts give rise to adenocarcinoma. Although bronchiolar cells and alveolar cells are proposed to be the precursor cells of adenocarcinoma, this work points to BASCs as the putative cells of origin for this subtype of lung cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2004

Getting at the root and stem of brain tumors.

Brain tumors are among the most aggressive and intractable types of cancer. Recent studies indicate that brain tumor cells resemble neural stem cells in terms of phenotype, signaling, and behavior in vitro. In light of these similarities, it has been suggested that brain tumors arise from stem cells, that they co-opt stem cell strategies for self-renewal, and even that they contain "cancer stem cells" that are critical for tumor maintenance. We will examine these possibilities and discuss their implications for the understanding and treatment of brain tumors.

Animals↗