摘要:

High-dose cyclophosphamide was developed as a conditioning regimen for allogeneic bone marrow transplantation. Later, it was discovered that high-dose cyclophosphamide spares early hematopoietic stem cells because of their relatively high levels of the enzyme aldehyde dehydrogenase; thus, high-dose cyclophosphamide is a potent immunosuppressive agent, but nonmyeloablative. Recent reports demonstrate that high-dose cyclophosphamide without bone marrow transplantation induces durable treatment-free remissions in severe aplastic anemia and a variety of other autoimmune disorders; however, there is lingering concern about the safety of this approach.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Multiple myeloma is incurable with standard chemotherapy. Autologous transplantation appears to offer a modest survival advantage over standard dose chemotherapy, but most patients subsequently relapse. Through the induction of graft-versus-tumor activity, allogeneic bone marrow transplantation can lead to long-term disease-free survival, and cure in some patients with myeloma. Transplant-related mortality after allogeneic bone marrow transplantation is high. Many patients are ineligible for this approach because of advanced age, comorbid illnesses, and extensive previous chemotherapy. Ongoing investigations endeavor to reduce regimen-related mortality through nonmyeloablative preparative regimens while maintaining immunologic antitumor activity through donor lymphocytes, which have significant graft-versus-myeloma activity. Early reports demonstrate lower rates of transplant related mortality; however, graft-versus-host disease rates are high and can preclude the administration of graded donor lymphocyte infusions, which may optimize the therapeutic index of graft-versus-host reactivity.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Autologous stem cell transplantation using marrow or peripheral blood is routinely used to consolidate patients with acute myelocytic leukemia in complete remission. The situation is less clear for adult acute lymphocytic leukemia in which results achieved with all strategies are disappointing.In acute myelocytic leukemia, autografts should be done in patients with good and standard risk factors. Patients with high-risk acute myelocytic leukemia defined by poor cytogenetics or failure to achieve remission with the first induction course, should proceed to allogeneic stem cell transplantation with the best available human leukocyte antigen-identical donor (family or unrelated), and the nature of the conditioning regimen (myelo-ablative or non–myelo-ablative) should be decided in relation to age, and the patient's clinical condition. Results of autografting in acute myelocytic leukemia rely strongly on the quality of the graft. Higher doses of infused stem cells translate into lower relapse rates. Marrow purging with cyclophosphamide derivatives also diminishes the relapse incidence. Autologous stem cell transplantations using peripheral blood are presently preferred to marrow as the source of stem cells, but an aggressive priorin vivopurge (high-dose consolidation course(s) before cytaphereses) is then mandatory. In good-risk acute myelocytic leukemia, autografting is superior to high-dose ARA-C; in standard-risk acute myelocytic leukemia, both are supposedly equivalent. There is no prospective randomized study testing the two approaches in the good–standard-risk population. We presently test the combination of marrow and blood both purged by mafosfamide.In adult acute lymphocytic leukemia, good-risk patients get the best benefit from autografting over conventional chemotherapy. Maintenance chemotherapy after transplant is likely to bring benefit.Research in progress aims at facilitating access of the largest number of patients to autografting and at introducing posttransplant immunomodulation maneuvers such as tumor vaccination.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Human leukocyte antigen-matched sibling donor umbilical cord blood transplantation, or 0–2 human leukocyte antigen mismatched unrelated donor umbilical cord blood, is now considered an acceptable alternative to the use of bone marrow as a source for hematopoietic stem cells for pediatric hematopoietic stem cell transplantation, and is being investigated in adults. Major advantages of umbilical cord blood include the speed of availability compared with unrelated donor bone marrow, and tolerance of 1–2 human leukocyte antigen mismatch, which offers the opportunity to extend the donor pool. Umbilical cord blood transplantation is associated with durable engraftment and low incidence of severe graft-versus-host disease, even in the 1–2 human leukocyte antigen mismatched setting. Clinical experience has established the importance of graft cell dose in determining engraftment and survival in unrelated donor umbilical cord blood transplantation. More recently, the influence of human leukocyte antigen on outcome has become apparent. This review outlines the state of the art of umbilical cord blood transplantation, with emphasis on practical considerations in umbilical cord blood selection, and describes current research directions for this hematopoietic stem cell source.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Intensive therapy and autologous stem cell transplantation represent the standard of care in most patients whose Hodgkin disease has not been cured with conventional chemotherapy. With more prolonged follow-up of autografted patients, the problems with autologous stem cell transplantation are clear. In particular, recurrent disease and late transplant-related complications limit the effectiveness of this approach. A number of autologous stem cell transplantation studies have reported prognostic factors that will help identify patients at high risk for relapse. Several new approaches for decreasing recurrence rates are discussed, including novel immune strategies and re-evaluation of allogeneic stem cell transplantation. Although the risk of secondary malignancy and other causes of late morbidity and mortality after autologous stem cell transplantation is relatively low, current studies contribute to understanding of the pathogenesis of these complications and may diminish their impact in the future.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The wealth of data in basic science and translational research may often represent a conundrum for clinical oncologists, who need to selectively consider this abundant information and translate it into therapeutic decisions. For the sake of simplicity, we have classified the multiplicity of genetic abnormalities in five repertoires that are rapidly assessable and useful for stratification in clinical trials: allelic imbalance, aberrant promoter methylation, gene mRNA overexpression, microtubule alterations, and polymorphisms. Allelic imbalance refers to chromosomal instability, which is a major feature of cancer, and innovative techniques used in colorectal cancer should also be implemented in lung cancer. Epigenetic changes (variations in transcription levels) have been extensively studied in non–small cell lung cancer. Methylation techniques have shown that these epigenetic changes commonly occur at the same frequency in numerous genes, both well-known (FHIT,APC,p16) and recently discovered (TMS1,RASSF1) in non–small cell lung cancer and in breast cancer. Innovative techniques like quantitative polymerase chain reaction can determine gene expression profiles, mainly overexpression of mRNAs, which may be related to resistance to specific cytotoxic drugs. In the near future, we hope these profiles can be used to individualize chemotherapy. Multiple microtubule alterations related to overexpression of different genes can also be used to predict response to taxanes andVincaalkaloids. Finally, the assessment of polymorphisms could enable us to understand their functional consequences in chemotherapy response.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

For many years, surgery has been considered the best treatment modality for resectable nonsmall cell lung cancer. However, survival has not increased over the last few decades. The reported 5-year survival rates for the early stages (stage I and II) show failures of 35 to 65%. Therefore, a combined modality approach has been taken in patients with N2(lymph node) disease to improve results. These adjuvant treatments, consisting of chemotherapy, radiotherapy, or both, have yielded mixed responses. Adjuvant radiation therapy alone has shown a decrease in local recurrence but no significant improvement in survival. Randomized trials of adjuvant chemotherapy have shown mixed results, and large, randomized trials are currently being evaluated. Combinations of radiation and chemotherapy in the adjuvant setting have failed to show a survival benefit so far.In the neoadjuvant setting, chemotherapy has aroused great attention because it has significantly improved survival in patients with locally advanced nonsmall cell lung cancer (N2disease). This result led to the use of neoadjuvant chemotherapy in early-stage lung cancer. Multinational and multi-institutional studies have been initiated recently. In the future, researchers will have clear insight into the effects of the classical chemotherapy regimen as induction therapy in the early stages of nonsmall cell lung cancer.Tyrosine kinase inhibitors, antisense therapies, and antiangiogenesis therapies are the most promising developments of the last few years. Implementation of these agents is expected to have great impact on the survival in patients with nonsmall cell lung cancer.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Among all cancers, lung cancer has the highest rate of mortality in the western world, both in men and women. The poor lung cancer survival rates argue powerfully for new approaches to control this disease, such as chemoprevention, which has been defined as the use of agents that reverse, suppress, or prevent lung carcinogenesis. Over 80% of lung cancers are attributed to tobacco and carcinogens from cigarette smoke, which unquestionably links nicotine addiction and lung cancer. Epidemiologic studies show that not more than 15% of heavy smokers will ultimately develop lung cancer. That 85% of heavy smokers will not develop lung cancer points to differences in susceptibility. Diet and genetically determined factors seem to play an important role in modulating individual susceptibility and are closely linked to the chemoprevention approach. Despite encouraging data from experimental and epidemiologic studies, the evidence for a positive effect in the human situation is still controversial. However, recent developments in molecular biology and increased insight in lung carcinogenesis have led to the potential of more specifically targeted intervention and optimism for new, successful chemopreventive approaches.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Platinum-based combination and single-agent chemotherapy have become accepted as treatments for locally advanced and metastatic nonsmall cell lung cancer as a consequence of improved survival, quality of life, and symptom control compared with best supportive care. However, it is clear that a therapeutic plateau has been reached with current combinations requiring a re-evaluation of strategies to improve clinical outcomes. Dose intensification may offer one way in which to achieve better results, as may extension of the duration of treatment. The evidence suggests that dose intensification is a useful tool, and that its use in combination with markers of treatment duration and cumulative dose may help to maximize results from current active drug combinations.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Approximately one third of all patients with nonsmall cell lung cancer (NSCLC) are over the age of seventy. Elderly patients tolerate chemotherapy poorly because of impaired organ function and comorbidities. For this reason, these patients are often not considered eligible for aggressive cisplatin-based chemotherapy. A multidimensional geriatric evaluation is important to plan appropriate treatments. At present, there are no indications for adjuvant and neoadjuvant chemotherapy. Combined chemoradiotherapy in locally advanced disease increases toxicity and seems determine no survival advantage as compared with radiation therapy alone. In advanced disease, single-agent vinorelbine proves to be active and well-tolerated, and compared with best supportive care, improves survival and perhaps quality of life. Gemcitabine is active and also well tolerated. Taxanes are in advanced phase of evaluation. A phase III randomized trial showed that polychemotherapy with gemcitabine and vinorelbine does not improve any outcome as compared with single-agent chemotherapy with vinorelbine or gemcitabine. In clinical practice, single-agent chemotherapy should remain the standard treatment. The choice of the drug should be based on the toxicity profile of each drug and type of comorbid conditions. In the near future, new therapeutic strategies and biologic agents could improve present results.

ISSN:1040-8746    

出版商:OVID    

年代:2002

数据来源: OVID