ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

As the overall long-term event-free survival rate in children with acute lymphoblastic leukemia approaches 80%, emphasis is being placed on risk-directed therapy so that patients are neither overtreated nor undertreated. It has become apparent that a risk assignment system based on primary genetic abnormalities is inadequate by itself. For example, leukemias with theMLL-AF4orBCR-ABLfusion gene are, in fact, heterogeneous diseases. Many require allogeneic hematopoietic stem-cell transplantation; some, if the patient is of favorable age and has a low presenting leukocyte count, can be cured with chemotherapy alone. Measurement of early responses to therapy and extent of minimal residual disease can greatly improve the accuracy of risk assessment. Consideration of the variable effects of therapy on the prognostic significance of specific genetic abnormalities is also important. Therefore,TEL-AML1fusion confers a favorable prognosis in some protocols of chemotherapy but not in others. Studies to identify genetic polymorphisms with pharmacokinetic and pharmacodynamic significance promise to guide further refinement of treatment strategies. This will allow maximization of anticancer effects without induction of unacceptable toxicity in individual patients.

ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The epidemiology of myelodysplasia, or myelodysplastic syndrome (MDS), is in evolution. As populations are aging and therapies for cancer are improving, the frequency of this disease is increasing. Recent population surveys and case-control studies are reviewed. Knowledge of the molecular pathogenesis and pathophysiology of MDS is advancing at a remarkable pace and new information on molecular events is presented. The treatment of MDS is complex and highly individualized. Although many patients are older and may have significant co-morbid disease or poor performance status, there are curative options with allogeneic transplantation for selected patients. The recent transplant publications are reviewed. Other investigative treatment approaches, including the use of new chemotherapy agents, growth factor combinations, and antithymocyte globulin appear promising and are reviewed.

ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

An understanding of the molecular biology of B-cell chronic lymphocytic leukemia (B-CLL) has led to the appreciation that several different B-cell diseases are represented under this name. Variability in the bcl-2 family of proteins,p53mutation, or the presence of various chromosomal abnormalities corresponds to variability of the clinical course of disease and response to therapy. Differential expression of cell surface adhesion molecules by B-CLL cells have also been shown to influence clinical outcome, as have the expression of immune regulatory molecules (eg, CD80, CD40R, CD27 and CD79b). Recent work studying immunoglobulin-heavy chain gene rearrangement postulates at least two subsets of B-CLL originating from different stages of B-cell development and following different clinical courses. The knowledge that B-CLL is the final consequence of many different molecular perturbations may allow the development of chemotherapies, immunotherapies, and gene therapies that target the specific molecular defect in a given case of B-CLL.

ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Conventional chemotherapeutic treatments of acute leukemias are often associated with life-threatening toxic effects due to a lack of specificity for hematopoietic cells. Monoclonal antibodies and fusion proteins that target antigens on leukemic blasts are being explored for their antileukemic effects and as a means of delivering chemotherapy or radiation directly to malignant cells. This approach might be safer and more effective than current non-specific chemotherapeutic agents. The cell surface antigens CD33 and CD45 are attractive targets. Although CD33 is expressed on acute myelocytic leukemic blast cells from about 90% of patients, normal hematopoietic stem cells lack this antigen, as do essentially all non-hematopoietic tissues. Anti-CD33 antibodies have been engineered to selectively target malignant myeloid and immature normal cells while sparing normal stem cells. Recently, anti-CD33 antibodies have also been used to deliver radiation or a cytotoxic agent directly to leukemic cells. The strategy for using CD45 as a target differs from CD33 in that it is expressed not only by the vast majority of leukemias, but also by normal stem cells. Therefore,131I-labeled anti-CD45 antibody has been used in combination with conventional preparative regimens for patients receiving marrow transplantation for acute leukemia. Because the receptor for granulocyte-macrophage colony-stimulating factor is expressed by most myeloid leukemias, fusion proteins consisting of granulocyte-macrophage colony-stimulating factor ligand associated with diphtheria toxin have been proposed as a means of delivering a toxic agent directly to leukemic cells. Both unconjugated and conjugated antibodies show significant promise in the treatment of acute myelocytic leukemia.

ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Modern chemotherapy can place most patients with acute leukemia into remission. Unfortunately, many of these patients will subsequently relapse. The study of minimal residual disease focuses on the detection of patients destined to relapse despite appearing to be in clinical remission. In addition, the research has demonstrated that some patients appear to co-exist with their leukemia for years, and this suggests a need to re-examine what it means to be “cured” of leukemia. We await trials testing the intervention of “molecular relapse.” Data appear to be sufficient to launch such trials in diseases such as pediatric acute lymphoblastic leukemia and the t(15;17) acute myeloid leukemia.

ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Parathyroid tumors are virtually always benign with an estimated incidence of parathyroid carcinoma causing hyperparathyroidism in only .017% of cases. Virtually all parathyroid neoplasms, including the rare parathyroid carcinoma, are functional and discussion of the management of parathyroid tumors is tantamount to the discussion of primary hyperparathyroidism. The biochemical diagnostic criteria with rare exception is definitive, and the key issue with this functional benign endocrine neoplasm is when to recommend operation and how to ensure optimal results in this curable disease. Patients symptomatic with nephrolithiasis, significant osteoporosis, bone pain, and in some cases constitutional symptoms should undergo a surgical therapy. Also, patients with markedly abnormal laboratory values including a calcium 12.0 mg/dL, or 24-hr urinary calcium >400 mg/day should be treated surgically. The sestamibi nuclear medicine scan has become the best tool available for imaging of abnormal parathyroid glands. This study is positive between 60% and 90% of initial operations and in between 40% and 70% of re-operations. For multi-gland parathyroid disease or hyperplasia, the sensitivity of this test is decreased. Understanding of the ectopic locations of parathyroid adenoma is of utmost importance in the conduct of the parathyroidectomy. For the rare patients with parathyroid carcinoma, aggressive surgical resection withen blocremoval of any adjacent invading structures is the best chance for cure leading to 10-year survival rates of 49%.

ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Adrenal tumors are very common, with the majority being non-hypersecretory and benign and less than 1% being malignant. Most primary adrenal tumors are sporadic, but may be associated with other endocrine and familial disorders, especially pheochromocytoma. All patients with “sporadic” pheochromocytoma should be screened for MEN-2 and Von Hippel-Lindau disease. As in many endocrine tumors, there are no uniform definitive histologic criteria to distinguish malignancy, which is dependent on the clinical behavior of the tumor and is accurately diagnosed in the presence of adjacent organ invasion, recurrence, or distant metastasis. Surgery remains the cornerstone and the treatment of choice for functional and primary malignant adrenal tumors, both for cure and palliation, with low morbidity and mortality.

ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Thyroid cancers are still the most common endocrine cancers. They are dominated by well-differentiated carcinomas, including papillary carcinoma, follicular carcinoma, and medullary thyroid carcinoma. Diagnosis is based on fine-needle aspiration cytologic examination. Recently, reverse transcription polymerase chain reaction for the detection of cancer-specific mRNA was shown to be a useful adjunct in both initial diagnosis and detection of recurrent disease. In addition, positron emission tomography has become a valuable tool for staging and surveillance of thyroid cancer. Given the gradual perfection of surgical technique and reduction in complication rates, near-total and total thyroidectomy should be offered to patients with well-differentiated carcinoma. For medullary thyroid carcinoma, near-total and total thyroidectomy with routine central and bilateral functional neck dissection are recommended. So far, no effective treatment exists for anaplastic thyroid carcinoma.

ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:1040-8746    

出版商:OVID    

年代:2000

数据来源: OVID