ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder characterized by the (9:22) translocation and resultant production of the constitutively activated bcr-abl tyrosine kinase. Characterized clinically by marked myeloid proliferation, it invariably terminates in an acute leukemia. Interferon-based regimens and stem cell transplantations are the standard therapeutic options, with stem cell transplantation being the only curative therapy. As therapy for CML improves, molecular methods of monitoring response will become integrated in patient treatment. Through rational drug development, STI571, a bcr-abl tyrosine kinase inhibitor, has emerged as targeted therapy that offers new hope for expanded treatment options for patients with CML.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Acute progranulocytic leukemia (APL) is characterized by unique biologic and clinical features. Understanding of these unique features has resulted in dramatic improvements in therapy for patients with APL. Current therapy with all-trans-retinoic acid (ATRA) plus an anthracycline with or without cytosine-arabinoside has yielded complete response rates of 85% or greater and long-term disease-free survival rates of 70% or greater. Arsenic trioxide has also surfaced as an effective induction therapy for relapsed APL. Further progress in the care of patients with APL awaits better definition of optimal schedules for ATRA plus chemotherapy, the role of arsenic trioxide, the use of current molecular monitoring for minimal residual disease, optimal therapy for minimal residual disease, and improved methods to address complications of APL including early hemorrhagic deaths and ATRA toxicities.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The vast majority of adults with acute lymphoblastic leukemia (ALL) now achieve remission with current intensive chemotherapy regimens. Nevertheless, most adults with ALL will eventually relapse and die of their disease. Specific clinical and molecular-cytogenetic prognostic factors have been identified that are beginning to provide insights for the development of risk-adapted management strategies that appear to improve survival for several high-risk patient groups, including those with mature B-cell ALL and B-lineage ALL patients with a Philadelphia chromosome. We review standard and some recently described prognostic factors in adult ALL, describe current therapy based on a risk-adapted approach, and look toward the future with a brief discussion of novel, targeted treatments that could be incorporated into postremission strategies to improve survival for adults with ALL.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Markers of anticancer drug resistance are predictive of treatment response and outcome in patients with acute myeloid leukemia. Immunologic detection of the drug efflux pumps, P-glycoprotein (Pgp) and multidrug resistance–associated protein 1 (MRP1), correlate with functional assays of drug resistance. These accumulation defects also appear operable in acute lymphoblastic leukemia. Many of the efflux pumps identified share significant structural homology with the large superfamily of ATP–binding cassette transporters. Other markers such as lung-resistance protein, bcl-2, and breast cancer–resistance protein, have been described in acute myeloid leukemia patients although their pathophysiology and clinical relevance are less clear and the methodology for their quantification are not well standardized. Preclinical studies have shown that small molecules capable of reversing efflux can restore drug sensitivity in resistant tumor models. Although initial clinical studies were limited by both potency and specificity of the reverser, later studies with more effective reversers have in many instances been limited by pharmacokinetic interactions exacerbating the clinical toxicities of chemotherapy. Although one large randomized study has demonstrated a proven survival advantage without increased toxicity using cyclosporine, the inconsistent results with other modulators raise doubt as to the utility and overall strategy of using drug efflux blockers in patients with established Pgp overexpression. Many of these patients have additional resistance mechanisms, and achieving meaningful clinical responses will likely require more complex clinical strategies. Preventing or delaying development of drug resistance in chemosensitive patients represents another therapeutic strategy to be tested.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

During the past few years there has been an explosion of knowledge in nonablative allogeneic stem cell transplantation. This approach to transplantation relies more on the creation of “immunologic space” for engraftment rather than the more traditional approach of creating “physical space” by the application of either intensive radiation or chemical therapy. Nonablative allogeneic stem cell transplantation holds the promise of allowing powerful alloimmune responses to eradicate disease processes while minimizing the initial treatment-related morbidity and mortality, and it appears to be the necessary enabling platform by which to apply allogeneic cellular therapy. Intuitively, this approach should broaden the eligibility for potentially curative allogeneic transplantation in various disease categories, reduce initial hospitalization costs, and at the same time have a positive impact on quality of life. We review the current published data relating to this approach including the underlying principles, the preparative regimen, disease indications, preliminary results in hematologic and solid malignancies, and certain correlative immunologic evaluations.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Parathyroidectomy provides effective treatment for primary and secondary hyperparathyroidism with a predictable response of symptoms related to hypercalcemia and elevated parathyroid hormone. Calcium and vitamin D supplementation has reduced the need for parathyroidectomy in dialysis patients with secondary hyperparathyroidism. However, surgery continues to be the only effective treatment of primary hyperparathyroidism. Potential nonoperative treatments for hyperparathyroidism have included the use of estrogen replacement, bisphosphonates, and a new class of drugs known as calcimimetics. Hormone replacement therapy with estrogen has been reported to improve cortical bone density in postmenopausal women with asymptomatic or mildly symptomatic primary hyperparathyroidism. Calcimimetic agents are a new class of drugs that increase the sensitivity of the calcium receptor to ionized calcium. Initial studies have shown that calcimimetics can acutely lower parathyroid hormone levels in patients with primary and secondary hyperparathyroidism. These drugs are currently being evaluated in phase II clinical trials. Ultimately, these medical modalities will need to be compared to parathyroidectomy in randomized controlled clinical trials.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Radioiodine has been shown to reduce recurrences and improve survival in well-differentiated thyroid cancer. To maximize the effectiveness of radioiodine therapy, patients are first treated by total thyroidectomy and then allowed to become hypothyroid. The elevation of thyroid-stimulating hormone, or thyrotropin (TSH), that occurs with hypothyroidism stimulates uptake of radioiodine in normal and cancerous thyroid tissues. A recent advance has been the introduction of recombinant human TSH (rhTSH), which is administered intramuscularly prior to testing with radioiodine. Phase III trials have demonstrated that rhTSH stimulates both uptake in and production of thyroglobulin by thyroid cells and the results are comparable to those of hypothyroid protocols in the majority of patients. Patients prefer the rhTSH protocol because they continue to ingest exogenous thyroid hormone and the symptoms of hypothyroidism are avoided. The rhTSH protocol is preferable in patients with pituitary dysfunction and in those who cannot tolerate hypothyroidism. RhTSH can also allow treatment of patients who have not had an adequate thyroidectomy and who are poor candidates for reoperation.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Familial thyroid cancer can arise from parafollicular cells (familial medullary thyroid cancer) or from follicular cells (familial nonmedullary thyroid cancer). Familial medullary thyroid cancer may occur in isolation or as part of multiple endocrine neoplasia (MEN) type II syndromes. Genetic testing for aRETmutation on chromosome 10 is used to identify new family members who are gene carriers. Total thyroidectomy should be used in gene carriers without clinical disease before age 6 in medullary thyroid cancer and MEN type IIA, and as soon as the diagnosis is made in MEN type IIB after the first year of life. Those with clinical disease should have at least a bilateral central neck dissection. Modified radical neck dissection is recommended for patients when the primary tumor is 1.5 cm. A normal postoperative serum calcitonin level suggests that the operation has been curative. Physicians need to be aware of ethical and lifestyle issues related to patients with familial disease and their family members. Familial nonmedullary thyroid cancer occurs as a discrete entity or as part of other family cancer syndromes such as Gardner syndrome, Cowden disease, and other rare syndromes. Familial nonmedullary thyroid cancer almost exclusively includes patients with papillary or Hurthle cell cancers. These families appear to have more benign thyroid conditions. The gene (or genes) for familial papillary thyroid cancer is yet to be identified, whereas that for some Hurthle cells (TCO) has been mapped to chromosome 19p13.2. Familial nonmedullary thyroid cancer is somewhat more aggressive than its sporadic counterpart, but is less aggressive than medullary thyroid cancer. Total thyroidectomy and central neck dissection followed by radioactive iodine ablation and thyroid hormone suppression appear to be the most effective therapy.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Pancreatic endocrine tumors are rare but have long held a fascination for clinicians because of the physiologic derangements that they can cause, and the dramatic corrections that can be achieved by appropriate management. In the year reviewed in this article, the literature again demonstrated the ongoing interest and research in this area. In particular, the areas of gastrinoma, insulinoma, and multiple endocrine neoplasia type 1 have received careful attention.

ISSN:1040-8746    

出版商:OVID    

年代:2001

数据来源: OVID