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At least 505 records · Page 28Linked to original sources
PubMed1998

The importance of CD34+/CD33- cells in platelet engraftment after intensive therapy for cancer patients given peripheral blood stem cell rescue.

The study was designed to determine whether the number of CD34+/CD33- cells given at autologous peripheral blood stem cell (PBSC) rescue after intensive therapy for cancer was a better predictor of platelet engraftment than the total number of CD34+ cells infused. Comparison between the total number of CD34+ cells/kg infused with the number of CD34+/CD33- cells/kg infused showed that, generally, 2 x 10(6) total CD34+ cells contained 1.38 x 10(6) CD34+/CD33- cells. There was poor correlation between the number of CD34+/CD33- and CD34+/CD33+ cells in the graft (r = 0.332). Engraftment times for platelets and neutrophils were evaluated in 68 patients. There was no significant difference between the times for platelets to reach >25 x 10(9)/l or neutrophils to reach >0.5 x 10(9)/l among patients who received > or <2 x 10(6) total CD34+ cells or > or <1.38 x 10(6) CD34+/CD33- cells although the latter was consistently the better predictor. Platelet recovery to >50 x 10(9)/l and >100 x 10(9)/l was delayed significantly in patients who received <1.38 x 10(6) CD34+/CD33-/kg infused (P < 0.02 and P < 0.05, respectively). The number of CD34+/CD33- cells/kg infused was a stronger predictor of platelet recovery than the total number of CD34+ cells infused (P < 0.05 for platelets >50 or >100 x 10(9)/l). Although platelet recovery was delayed significantly in patients who had <4 x 10(4) granulocyte-macrophage colony-forming units (CFU-GM)/kg infused, the time delay between receipt of PBSCs and availability of the colony counts limits the use of this assay to patients who do not require stem cells to be given immediately. Our data suggest that the number of CD34+/CD33- cells given at PBSC rescue provide information about the quality of the graft necessary for long-term platelet engraftment. However, since the percentage of CD34+/CD33- cells shows considerable inter-patient variation, measurement of this cell population may be important in patients who experience poor stem cell mobilization or when a target dose of 2 x 10(6) total CD34+ cells/kg is not achieved.

Adolescent↗
PubMed1999

Field cancerization, clonality, and epithelial stem cells: the spread of mutated clones in epithelial sheets.

There has been considerable debate about the origin of human tumours, whether they arise from a single cell and are clonal populations or whether there needs to be some sort of co-operativity between cells for the neoplastic process to begin. Current theories subscribe to the clonal view, where a series of mutations in one cell begins a process of selection and clonal evolution leading to the development of the malignant phenotype. This review approaches this problem by asking how mutated clones, once established, spread through tissues before becoming overtly invasive. While there is substantial evidence in favour of independent origins of each tumour from a unique mutated clone, there are instances where such clones expand and remain cohesive, often involving a large area of tissue. The main example is the movement of mutated clonal crypts through the colorectal epithelium, by the process of crypt fission. In passing, the clonal architecture of early, pre-invasive lesions is examined, often with some surprising results.

Animals↗
PubMed2002

Gli and hedgehog in cancer: tumours, embryos and stem cells.

Do tumours arise from stem cells, or are they derived from more differentiated cells that, for some reason, begin to recapitulate developmental programmes? Inappropriate activation of the Sonic hedgehog-Gli signalling pathway occurs in several types of tumour, including those of the brain and the skin. Studies in these and other systems suggest that inappropriate function of the Gli transcription factors in stem or precursor cells might lead to the onset of a tumorigenic programme and that these factors are prime targets for anticancer therapies.

Animals↗
PubMed1999

The multiple organ dysfunction syndrome in cancer patients undergoing hematopoietic stem cell transplantation.

In the past two decades, major improvements in antibiotics and other elements of supportive care have decreased the number and severity of complications of hematopoietic stem cell transplantation (HSCT). Despite these improvements, many subpopulations of transplant patients still have a significant morbidity and mortality. It is becoming increasingly clear that medical science does not have a good understanding of the pathophysiology of many of the common, potentially fatal complications in patients currently undergoing HSCT. As the mechanisms of these complications are subjected to increasingly more rigorous scrutiny, it is becoming clear that many of these complications are intimately connected one to another and are not isolated clinical disorders as previously thought. One hypothesis that can explain the close relationship between them is that most of the severe complications of HSCT are the result of a systemic inflammatory disorder that has escaped biologic control, an inflammatory process begun by the preparative regimen and perhaps added to by intercurrent infections, tumor cell death and other as yet unidentified stimuli (transfusions, medications?). If this is true, this syndrome would have many similarities with the multiple organ dysfunction syndrome (MODS) seen in critically ill non-transplant patients. As such, this hypothesis has two significant corollaries: (a) That looking for or empirically treating for a reversible organ specific cause of single organ dysfunction during HSCT (such as infectious pneumonia, intracranial hemorrhage, or acute infectious hepatitis) in any given patient is unlikely to be rewarding as the defect causing the organ dysfunction is often systemic at the time of its presentation, and (b) that MODS is the dose-limiting toxicity of our current preparative regimens, suggesting that when we understand its pathophysiology and develop therapies for MODS we will be able to escalate their intensity and, by doing so, cure more patients of their malignancy. Manipulation of the hemostatic system may prove to be one of these therapies, but there is little doubt that other interventions designed to modulate the inflammatory process will prove to be even more useful in this syndrome. Using the definitions of organ dysfunction outlined in this article, we can provide a basis for clinical monitoring of patients today and for use in interventional clinical trials in the future.

Hematopoietic Stem Cell Transplantation↗
PubMed2004

Prospective clinical evaluation of a LightCycler-mediated polymerase chain reaction assay, a nested-PCR assay and a galactomannan enzyme-linked immunosorbent assay for detection of invasive aspergillosis in neutropenic cancer patients and haematological stem cell transplant recipients.

Invasive aspergillosis (IA) is a considerable clinical problem in neutropenic patients with haematological malignancies but its diagnosis remains difficult. We prospectively evaluated a LightCycler polymerase chain reaction (PCR) assay, a nested-PCR assay and a galactomannan (GM) enzyme-linked immunosorbent assay (ELISA) to validate their significance in diagnosing IA. During 205 treatment episodes in 165 patients from six centres, a nested-PCR assay and GM testing was performed at regular intervals. Positive nested-PCR results were quantified by a LightCycler PCR assay. Patient episodes were stratified according to the 2002 European Organization for Research and Treatment of Cancer/Mycosis Study Group consensus criteria and the PCR and serology results were correlated with the clinical diagnostic classification. Sensitivity and specificity rates for the nested-PCR assay were up to 63.6% [95% confidence interval (CI): 30.8-89%) and 63.5% (95% CI: 53.4-72.7%) respectively, and 33.3% and 98.9% (95% CI: 7.5-70.1% and 94.2-99.9%) for GM respectively. The LightCycler PCR assay yielded positive results in 21.4%, lacking discrimination by quantification across the different clinical categories. In this prospective comparison, PCR was superior to GM with respect to sensitivity rates. In patients at high risk for IA, positive results for Aspergillus by PCR of blood samples are highly suggestive for IA and contribute to the diagnosis.

Adolescent↗
PubMed2004

Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients.

The recent advent of an improved commercial serum enzyme-linked immunosorbent assay (ELISA) for the detection of circulating galactomannan (GM), a major constituent of Aspergillus cell walls, has contributed to the diagnosis of invasive aspergillosis (IA) in many haematology and transplant centres. However, the optimal threshold for positivity remains a matter of debate. We prospectively evaluated the impact of lowering the cut-off in 124 neutropenic episodes with a high pretest probability for IA. Two new cut-off points, lower than previously accepted, are proposed: (a) a 'static' cut-off at 0.8 and (b) a 'dynamic' cut-off at 0.5. A single assay with an optical density (OD) index > or = 0.8 warrants the initiation of anti-Aspergillus therapy. A further lowering of the 'static' threshold seems not clinically feasible given the drop in positive predictive value (PPV). However, the demonstration of at least two sequential sera with an OD > or = 0.5 ('dynamic' threshold) increased the specificity and the PPV to 98.6% and the efficiency to 98%. Applying both cut-offs to a subgroup of 21 'possible' fungal infections further identified and upgraded six cases of IA. However, the clinical benefit of lower cut-offs (particularly for earlier diagnosis) depends upon the kinetics of antigenaemia and the intensity of serum sampling.

Adolescent↗
PubMed1988

Detection of small cell lung cancer bone marrow metastases by tumor stem cell assay.

Detection of small cell lung cancer (SCLC) bone marrow (BM) metastases has a prognostic implication in itself and a therapeutic interest in the setting of autologous bone marrow transplantation. In a prospective study involving 68 bone marrow samples, we compared SCLC detection results obtained using a tumor stem cell assay and those obtained using conventional morphology by light microscopy. In agar, tumoral cells were stimulated either by Salmon's conditioned medium or by epidermal growth factor (EGF). Tumoral clonogeneic cells were detected in 11 cases, although 7 of these were considered negative when investigated by light microscopy. On the contrary, metastases were detected by morphology in 8 instances where no growing colonies were revealed by tumor stem cell assay. The choice of stimulating factor did not seem critical since the number of colonies was similar in all the cases. We conclude that the tumor stem cell assay is useful in the detection of small cell lung cancer bone marrow metastases, particularly in cases where these metastases have failed to be recognized through light microscopy investigation. However, the sensitivity of this assay is low and should be complemented by other techniques such as immunodetection.

Bone Marrow Cells↗
PubMed1997

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in breast cancer.

Since 1981 we have conducted four studies of the treatment of metastatic and postoperative high-risk breast cancer with high-dose chemotherapy supported by autologous hematopoietic stem-cell transplantation (AHSCT). Study I, involving 56 metastatic cancer patients, proved that induction chemotherapy produces a lasting complete response (CR) in only a few cases despite the achievement of a CR rate higher than that expected from standard chemotherapy. Study II was designed to examine consolidation chemotherapy in metastatic cancer patients responding to induction chemotherapy. At a median follow-up of 26 months (range 2-66), consolidation therapy produced a 5-year progression-free survival rate of 27.1% in 30 patients showing a CR or a partial response to induction therapy and 58.6% in 13 patients showing a CR to consolidation therapy. No treatment-related death occurred during study II. The same regimen used in study I was employed for 58 postoperative high-risk patients in study III. The 10-year disease-free survival rate recorded for patients with > or = 10 positive axillary lymph nodes was significantly higher (P < 0.05) in the AHSCT-supported chemotherapy group than in the conventional chemotherapy group. A double high-dose regimen was adopted for 21 postoperative high-risk patients in study IV. The 3-year disease-free survival rate recorded for 9 patients with > or = 10 positive axillary lymph nodes was 71.4% at a median follow-up of 25 (range 8-45) months. No treatment-related death occurred during study IV. Peripheral blood stem-cell transplantation shortened the duration of bone marrow suppression more effectively than did bone marrow transplantation, thereby optimizing high-dose chemotherapy.

Adult↗
PubMed2003

Nonmyeloablative allogeneic hematopoietic stem cell transplantation for metastatic breast cancer.

Previously, there was very little interest in investigating allogeneic hematopoietic stem cell transplantation (alloHSCT) in breast cancer because of the significant morbidity and mortality associated with this procedure, as well as the disappointing results observed in clinical trials with high-dose chemotherapy and autologous hematopoietic stem cell transplantation in advanced breast cancer. However, the development of nonmyeloablative (reduced-intensity) conditioning regimens, which have less treatment-related mortality but preserve the T cell-mediated graft-versus-tumor (GVT) effect, has led to the investigation of nonmyeloablative alloHSCT in diseases that had not previously been considered for conventional alloHSCT, including metastatic breast cancer. Laboratory data demonstrate that T cell-mediated responses to breast cancer that inhibit tumor growth are possible and provide the rationale to pursue allogeneic adoptive cellular therapy as a strategy to eliminate breast cancer. Early reports of nonmyeloablative alloHSCT indicate that a clinical GVT effect against breast cancer does exist. The responses appear to be dependent on the development of complete donor lymphoid chimerism, and responses may be delayed. The results from these initial trials must be interpreted cautiously. It is unlikely that nonmyeloablative alloHSCT by itself will result in complete eradication of metastatic breast cancer; however, it may serve as a therapeutic platform to enhance the effects of currently available immunotherapies (eg, trastuzumab administration) and complement existing cytotoxic therapies. Well-designed studies will be necessary to determine the clinical efficacy of nonmyeloablative alloHSCT as adoptive cellular therapy in metastatic breast cancer.

Adoptive Transfer↗
PubMed2003

Umbilical-cord blood transplantation for the treatment of cancer.

Haematopoietic stem-cell transplantation is used to treat many haematological cancers, but is limited by the lack of suitable bone-marrow donors, the risk of graft-versus-host disease (GVHD) and slow immune reconstitution. Umbilical-cord blood is an alternative source of haematopoietic stem cells that has recently been tested in both child and adult cancer patients. These studies have identified several advantages to umbilical-cord cell transplantation, including a lower incidence of GVHD. Umbilical-cord blood is therefore a promising alternative to bone-marrow-derived stem cells.

Bone Marrow Transplantation↗