Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High dose chemotherapy with the support of autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cells (PBPC) has been increasingly used in a variety of haematological and epithelial cancers over the last decade. The rationale of this approach is to overcome the chemotherapy resistance of tumour cells by increasing the dose of cytotoxic drugs. However, the clinical benefit of dose-intensification has been difficult to prove. Almost all studies of ABMT have been done without randomised comparisons with the standard form of therapy for a specific condition. From an economic perspective, the cost of ABMT has been steadily decreasing with improvements in supportive care primarily. Still, current ABMT cost estimates range from $US70 000 to $US150 000 for each uncomplicated procedure. Despite the lack of compelling evidence in support of dose-intensification, ABMT has become a default standard of care after relapse for many patients with lymphoma or leukaemia. We used a decision analysis model to estimate the cost effectiveness of the timing of ABMT in relapsed Hodgkin's disease. The model illustrates the difficulty of using available clinical trial data when follow-up of promising early reports is not available. The model showed that in most situations the optimal strategy is ABMT in second relapse despite growing consensus that immediate ABMT is the treatment of choice. ABMT for women with high-risk or early metastatic breast cancer is one of the most controversial areas in clinical oncology. In the US, several ongoing major randomised trials are addressing the role of ABMT in breast cancer. Using a Markov process we found that ABMT is the preferred strategy under almost all assumptions. The size of the benefit and cost effectiveness of ABMT varied markedly depending on the assumptions made. The model does not supplant the need for randomised trials that concurrently measure efficacy, quality of life, and resource utilisation. However, such analyses point out the critical areas where costs could be cut substantially without effecting efficacy. Drawing conclusions about the cost effectiveness of ABMT for all conditions is hampered by the lack of randomised comparisons of efficacy. Concurrent economic appraisals of selected phase III comparative trials should be considered since the supportive care costs associated with ABMT appear to be stabilising. However, the most important point is that randomised trials are the only mechanism for estimating the therapeutic effect of high dose chemotherapy.
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PMID:Cost-effective use of autologous bone marrow transplantation: few answers, many questions, and suggestions for future assessments. 1014 37

Three cases of typhlitis occurring during autologous blood stem cell transplantation (ABSCT) for metastatic breast cancer are described. Typhlitis is a rare complication of neutropenia and has uncommonly been reported in the autologous transplant setting. Although it has been most commonly described in children with leukemia, typhlitis has increasingly been reported in adult leukemias and in association with neutropenia secondary to chemotherapy for a number of solid tumors. Only five previous cases of typhlitis in the setting of ABSCT have been described. Whereas diarrhea and fever are common toxicities associated with high-dose chemotherapy, it is likely that many cases of typhlitis go unrecognized. Bone Marrow Transplantation (2000) 25, 321-326.
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PMID:Typhlitis complicating autologous blood stem cell transplantation for breast cancer. 1067 6

Oral cyclophosphamide is well tolerated and effective. Published data support its use as part of adjuvant and metastatic breast cancer treatment regimens. Cyclophosphamide has generally been administered at a higher dose intensity when given orally compared with intravenous infusion. However, there is currently no evidence that oral cyclophosphamide is either more toxic or more or less effective than an equivalent dose of intravenous cyclophosphamide. There is evidence in both the adjuvant and metastatic settings that classical oral cyclophosphamide-methotrexate-fluorouracil (CMF) is more effective than intravenous CMF, possibly because of the greater dose intensity of classical CMF. Prolonged administration of oral cyclophosphamide up to high cumulative doses is associated with an elevated risk of a secondary leukaemia. The rates of chemotherapy-related amenorrhoea with oral cyclophosphamide are directly related to the total dose of cyclophosphamide administered and the patient's age. With the growing availability of other oral cytotoxic agents with demonstrated effectiveness in breast cancer, it is likely that oral cyclophosphamide will be incorporated once again into regimens for both metastatic and adjuvant treatment.
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PMID:Oral alkylating agents for breast cancer therapy. 1071 35

Gene therapy strategies employing the HSVtk/ganciclovir (GCV) suicide gene offer promising approaches towards the treatment of metastatic breast cancer. These include bystander effects on non-transduced tumor cells, lower systemic toxicity, and the possibility of inducing immunity against the tumor. Previously we have demonstrated the ability of the grp78 stress-inducible promoter to stimulate expression of reporter genes within the tumor microenvironment. However, experimental evidence demonstrating the ability of this promoter to activate therapeutic agents within the breast cancer environment causing tumor eradication is needed prior to clinical trials. In this report, we test the efficacy of the grp78 promoter in a retroviral system to drive the expression of the HSVtk suicide gene in a murine mammary adenocarcinoma cell line (TSA) in syngeneic, immune-competent hosts. Our results show that under glucose-starvation conditions in vitro, the expression of HSVtk and GCV induced cell death are enhanced in tumor cells in which the HSVtk gene is driven by the internal grp78 promoter compared to cells in which the Moloney murine leukemia virus LTR drives HSVtk. In in vivo studies, in tumors in which the HSVtk gene is driven by the grp78 promoter, GCV treatment causes complete tumor eradication, whereas tumors persist when the HSVtk gene is driven by the retroviral LTR. Our study suggests that the grp78 promoter may be useful to enhance the effectivity of therapeutic agents within a breast tumor. In addition, it is shown that immune memory is induced in syngeneic, immune-competent hosts. This new retroviral vector might therefore be useful for breast cancer gene therapy.
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PMID:Eradication of murine mammary adenocarcinoma through HSVtk expression directed by the glucose-starvation inducible grp78 promoter. 1075 83

Women over 65 years are underrepresented in Cancer and Leukemia Group B (CALGB) breast cancer trials of adjuvant chemotherapy. There is greater participation in older patients with metastatic breast cancer except when toxic regimens are involved. Studies of stage III and IV Hodgkin's disease have shown that patients over 60 years achieved lower response rates, more leucopenia and thrombocytopenia, the shortest median time to recurrence, and the shortest median survival time. In acute myeloid leukemia a series of trials confirmed the disparity between young patients and those over 60 years whose complete response rate seldom exceeds 50%. In an effort to reduce toxicity rather than enhance the cure rate, CALGB showed that administration of GM-CSF after intensive induction chemotherapy was of no benefit in patients over 60 years. The use of G-CSF in acute lymphoblastic leukemia reduced hematologic toxicity and improved clinical outcome.
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PMID:Age-Related Clinical Trials of CALGB. 1088 3

HER2 (neu, erbB-2), a receptor related to the human epidermal growth factor receptor, has now become more important as a predictive marker of treatment response. While the value and direction of the treatment/HER2 interaction may vary, depending on the agents, dose, or schedule of drug administration, there is little disagreement that HER2 testing is an important part of breast cancer evaluation. In 1998, trastuzumab (Herceptin) was approved for the treatment of HER2-positive metastatic breast cancer patients by the Food and Drug Administration of the USA. Patients with abnormal HER2 in their breast cancer cells (generally 2 or 3+ with the HercepTest, overexpression by other immunohistochemical assays or amplification by fluorescence in situ hybridization [FISH] assay) have demonstrated the greatest response to trastuzumab treatment. It is unclear which test (method, reagent, cut-off points, etc.) is best to use to evaluate HER2 for this purpose because parallel testing of the same cancers from patients who received trastuzumab has only recently been initiated and the data are limited. It is widely believed that breast cancers without HER2 alterations will not be responsive to trastuzumab, although a clinical trial to test this specific hypothesis has not been initiated. There are also concerns that clonal heterogeneity for HER2 within a tumor, or between primary and metastatic cancer foci, may affect treatment response; yet we do not currently evaluate these parameters. Consensus regarding the best methods, reagents, or cut-off points to define HER2 status for determining trastuzumab responsivity has not yet been reached. HER2 testing for other prognostic or predictive purposes, e.g. to determine whether patients are likely to respond to other agents, such as dose-intensive doxorubicin, may be less. Data from the Cancer and Leukemia Group B trial 8541 (companion 8869) suggest that, with proper controls in high-volume laboratories, many of the available methods produce comparable results.
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PMID:HER2--a discussion of testing approaches in the USA. 1152 14

The search for a simple, sensitive test to reliably determine prognosis and predict response to therapy in patients with cancer is an important area of translational research. In this issue of Clinical Cancer Research, Hayes et al. (Clin. Cancer Res., 7: 601-604, 2001) report the results of an ancillary Cancer and Leukemia Group B protocol designed to determine whether the circulating extracellular domain of HER-2/neu (ECD-HER-2) was indicative of prognosis or predictive of response to therapy in women with metastatic breast cancer. Results were drawn from a sample of 242 patients of whom 89 had elevated values of the protein. These women had been enrolled in a variety of Cancer and Leukemia Group B protocols evaluating either the efficacy of dose in the use of megestrol acetate as second-line hormonal treatment or in patients enrolled into several chemotherapeutic protocols, many containing doxorubicin. They report that patients with pretreatment elevation of ECD-HER-2 had a worse prognosis than those who did not, but that there was no convincing correlation of elevated ECD-HER-2 with response to either endocrine or chemotherapy. Although the small number of patients and the retrospective study design allows one to draw only tentative conclusions, this report raises several important issues for the conduct of translational research and points to several new hypotheses for future testing.
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PMID:The prognostic and predictive values of ECD-HER-2. 1155 82

Absolute lymphocyte count (ALC) recovery correlates with survival after autologous hematopoietic stem cell transplantation (AHSCT) for patients with multiple myeloma, non-Hodgkin's lymphoma, and metastatic breast cancer. The role of ALC recovery in relationship to clinical outcome after AHSCT in patients with acute myelogenous leukemia is unknown. We analyzed 45 patients who underwent AHSCT at Mayo Clinic, Rochester, Minnesota between 1990 and 2000. The ALC threshold was selected at 500 cells/microl on day 15 post-AHSCT based on our previous studies. Thirty-two females and 13 males were included in the study with a median age of 45 years (range 12-75). The median follow-up was 14 months with a maximum of 129 months. The median overall and leukemia-free survival were significantly better for the 23 patients with ALC at day 15 > or =500 cells/microl compared with 22 patients with ALC <500 cells/microl (not yet reached vs 10 months, P < 0.0009; 105 vs 9 months, P < 0.0008, respectively). In conclusion, ALC > or =500 cells/microl on day 15 post-AHSCT is associated with better survival in acute myelogenous leukemia and requires further studies.
Leukemia 2002 Jul
PMID:Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia. 1209 55

High-dose chemotherapy combined with autologous stem cell support has improved response rates in high-risk and metastatic breast cancer, but has failed to improve long-term survival. Breast cancer has a tendency to metastasize to the bone marrow, and live tumor cells are known to circulate in the peripheral blood of breast cancer patients. Sensitive immunohistochemical, culture-based, and reverse transcriptase polymerase chain reaction (RT-PCR)-based methods have shown that about 50% of histologically normal stem cell grafts from breast cancer patients are contaminated with occult tumor cells, which may cause or contribute to tumor recurrences. Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) inactivates a wide range of leukemia and lymphoma cells and is well tolerated by normal hematopoietic stem and progenitor cells. Unfortunately, most solid tumor cells (including breast cancer cells) are only moderately sensitive or refractory to MC540-PDT. We report here that if MC540-PDT is followed by a 1-h incubation with the alkyl-lysophospholipid, Edelfosine (ET-18-OCH(3)), the depletion of murine and human breast cancer cells is greatly enhanced whereas the recovery of normal hematopoietic stem and progenitor cells is only minimally degraded. When used under conditions that reduce CD34-positive human bone marrow cells only 5.1-fold, and murine and human granulocyte/macrophage progenitors 6.8- and 3-fold, respectively, combination purging with MC540-PDT and Edelfosine depletes murine (Mm5MT) and human (MDA-MB-435S) breast cancer cells >17,000- and >125,000-fold, respectively. These data suggest that combination purging with MC540-PDT and Edelfosine may offer a simple, safe and effective method for the ex vivo purging of autologous stem cell grafts from breast cancer patients.
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PMID:Anti-tumor effect of Merocyanine 540-mediated photochemotherapy combined with Edelfosine: potential implications for the ex vivo purging of hematopoietic stem cell grafts from breast cancer patients. 1246 4

A kindred with familial leukemia is described in which three members are affected by leukemia in three consecutive generations. One of these members had Philadelphia positive chronic myeloid leukemia (CML) and other two had precursor B acute lymphoblasticleukemia (ALL)--Philadelphia negative. All three of them shared a common haplotype A2, B55, Cw3. In addition, another member sharing same haplotype developed metastatic breast cancer. Phenomenon of anticipation is demonstrated in the affected family members. Possible causes of genetic susceptibility to leukemia especially the association of Cw3 with familial leukemia are discussed.
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PMID:Association of familial leukemia with HLA Cw3: is it real? 1268 50


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