摘要:

The articles in this section focus on a variety of biologic findings in the acute leukemias and their potential application to improvements in clinical care. Judith Karp (pp 3–9) describes the multiple examples of molecular mischief found in patients with myelodysplasia which produce perturbations in differentiation and cell cycle kinetics. Importantly, there is potential that some of the signal transduction and cell cycle kinetic changes might eventually be targets for pharmacologie intervention. There is enormous overlap between myelodysplasia and apparentde novoleukemia in adults, particularly in older patients, as evidenced by similarity in the karyotypes, expression of drug resistance genes (particularly P-glycoprotein), and a similar poor prognosis when treated with conventional chemotherapeutic approaches. Some patients with myelodysplasia by French-American-British morphologic criteria respond reasonably well to chemotherapy; clinical hints include a short antecedent hematologic disorder and the presence of cytogenetic findings—particularly t(8;21)—typical of acute myelogenous leukemia with better prognoses. Although there are recent provocative observations with the use of 5-azacytidine and amofostine in well established myelodysplasia, complete responses are virtually nonexistent and overall outcome remains very poor.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The myelodysplastic syndromes (MDS) are a family of disorders that are characterized by ineffective hematopoiesis and evolution to acute myelogenous leukemias (AMLs) that are strikingly refractory to current therapeutic approaches. A substantial proportion of these complex diseases arise in the setting of exposures to environmental or occupational toxins, including cytotoxic therapy for a prior malignancy or other disorder (secondary MDS/AML). On the genomic level, MDS is typified by losses and translocations involving certain key gene segments, with disruption of the normal structure and function of genes that control the balance of proliferation and differentiation in hematopoietic precursors. In addition, MDS cells display impaired responses to diverse cytokines in terms of activating signaling intermediaries that trigger both proliferation and differentiation, and the disruption of the normal flow of biochemical information along the pathways translates into ineffective multilineage hematopoiesis and bone marrow failure. MDS/AMLs provide a fertile testing ground for the development of novel agents and the concomitant molecular dissection of the mechanisms by which these agents induce growth inhibition, terminal differentiation, and eventual cell death.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Both autologous and allogeneic transplantation have been used to treat and cure patients with acute leukemia. An important component of the cure mediated by allogeneic transplantation comes from a graft-versus-tumor effect of the graft. The immunotherapeutic effect can be used to treat patients whose conditions relapse after allogeneic transplantation using donor leukocyte infusions. Research conducted in the areas of histocompatibility and stem cell biology have expanded the potential cellular sources for allogeneic transplantation, including matched unrelated marrow donors, unrelated cord blood, and allogeneic peripheral blood stem cells. Molecular studies in patients with leukemia have refined the assessments of minimal residual disease following therapy, including for patients who have undergone transplantation, and may provide an opportunity for intervention prior to overt relapse. The results of allogeneic and autologous transplantation preparative regimens, including the use of targeted radioimmunotherapy and individualized pharmacokinetics, may improve the effectiveness and lessen the toxicity of the treatment.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The use of highly sensitive and specific assays to detect residual disease in patients with acute leukemia should provide a basis for optimizing therapy and maximizing each patient's chance of cure. Strategies for detecting residual disease are based on biologic properties that allow acute leukemia cells to be distinguished from normal marrow cells. Techniques used to detect residual disease in acute leukemia include the reverse transcription-polymerase chain reaction, the polymerase chain reaction, fluorescencein situhybridization, and multiparameter flow cytometry. Contributions to the field published in the past year are reviewed in this article.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Granulocyte macrophage (GM)- and granulocyte colony-stimulating factors (G-CSF) are being used after chemotherapy for newly-diagnosed acute myelogenous leukemia (AML) in order to hasten neutrophil recovery, thereby decreasing morbidity and mortality. This review summarizes data pertinent to the accomplishment of these aims. The preponderance of evidence indicates that, while accelerating recovery, neither GM- nor G-CSF producibly decrease major morbidity or mortality, particularly in elderly patients. Although in several studies, patients have been pretreated with GM- or G-CSF to sensitive AML cells to subsequent chemotherapy, these studies have not demonstrated benefit. The review raises questions as to whether elderly patients entered on clinical traits are representative of AML in the elderly, suggests that in vitro and ex vivo studies are needed to identify whether patient might benefit from CSFs, and discusses new ways to use cytokines in AML,egin patients in complete remission.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The successful treatment of acute myeloid leukemia (AML) is hampered by the development of chemotherapy resistant disease. One molecular mechanism of pleiotropic resistance, typical multidrug resistance (MDR), has been recognized as an independent adverse prognostic factor in AML. Therefore, uniform laboratory assays are needed to evaluate the effect of MDR expression on the clinical outcome of strategies to overcome resistance. One approach has been to administer high-dose therapy with stem cell support. In elderly patients, less toxic treatment is required, while the results of induction treatment in this age group need further improvement. The use of hematopoietic growth factors may reduce treatment-associated morbidity and mortality, but does not consistently enhance cell death. MDR reversal with cyclosporin or PSC833 has shown promising results in Phase I/II trials.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Endocrine neoplasms are rare tumors that have traditionally been imaged with ultrasound, CT, magnetic resonance imaging, and angiography. Additional imaging modalities are now available. Endoscopic ultrasound is a new imaging approach to islet cell tumors of the pancreas, in which they typically appear round, homogeneous, and slightly hypoechoic compared with the pancreatic parenchyma. Carcinoid tumors can now be localized with111In octreotide scintigraphy, which binds to the somatostatin receptors in the tumor. Pheochromocytomas have a distinctive appearance on magnetic resonance imaging, but important advances have occurred using131I metaiodobenzylguanidine (MIBG).131I MIBG scanning has a high diagnostic accuracy in detecting pheochromocytoma, with sensitivity greater than 90%. The various tumors and recent advances in their imaging are discussed.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Neuroblastoma, a childhood neoplasm arising from neural crest cells, is characterized by a diversity of clinical behavior, ranging from spontaneous remission to rapid tumor progression and death. To some extent, outcome can be predicted by the stage of disease and age at diagnosis. The molecular events responsible for the variability in response to treatment and rate of tumor growth, however, remain largely unknown. Over the past decade, transformation-linked genetic changes have been identified in neuroblastoma tumors that have contributed to our understanding of tumor predisposition, metastasis, treatment responsiveness, and prognosis. This review discusses the recent advances in the understanding of neuroblastoma at the cellular and molecular levels, and the role that tumor biology plays in determining appropriate risk-based treatment for patients with neuroblastoma.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

There continues to be controversy regarding the optimal evaluation and treatment of adrenal tumors. Magnetic resonance imaging, metaiodobenzylguanidine scan, single-photon emission tomography imaging, endoscopic ultrasound, and radiolabeled somatostatin analogues are just a few of the newer imaging techniques being investigated to improve our ability to obtain a specific diagnosis of an adrenal mass. Although the diagnosis and treatment of pheochromocytomas are relatively straightforward, the evaluation and treatment of incidentally discovered adrenal masses is less clear-cut. The management of an incidentaloma is guided by two principle considerations: whether the tumor has hormonal activity, and its malignant potential. In addition to diagnostic advances, refinements continue to be made regarding surgical management of these lesions. Laparoscopic adrenalectomy is fast becoming the procedure of choice for benign-appearing adrenal masses with appropriate indications for operative removal.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Chemotherapy was considered the standard for treatment of neuroendocrine tumors during the 1970s and 1980s. During the 1980s both interferon alfa and somatostatin analogue therapies were developed and significantly improved the clinical management of malignant neuroendocrine tumors. Surgery remains the cornerstone of treatment and should always be considered in patients with neuroendocrine tumors, even if a cure is not possible. Tumor reduction is always of beneficial value for patients undergoing medical treatment. Since the introduction of biotherapy, no real breakthrough in medical treatment has come forward, but new insights into tumor biology will probably improve therapeutic regimens in the near future. Somatostatin subtype receptor determination in tumor tissues and development of subtype-specific analogues for therapy are two new approaches. The gene for multiple neoplasia type I was cloned recently, and it will increase our understanding of the development of neuroendocrine tumors and give new insights into tumor pathophysiology. The current medical treatment of neuroendocrine tumors is based on chemotherapy for the more highly proliferating tumors, such as malignant endocrine pancreatic tumors and foregut carcinoids, whereas biotherapy, including interferon alfa and somatostatin analogues, is used in slow-growing neoplasms such as midgut carcinoids. These treatments can be supplemented by liver embolizations and chemoembolization to reduce the masses in the liver. When these treatments fail, tumor-targeted irradiation can be attempted, such as131I-MIBG (metaiodobenzylguanidine) and90Y DOTA (1,4,7,10-tetraazacyclododecane-N,NI,NII,NIII-tetraaceticacid)-octreotide. The treatment of neuroendocrine gut and pancreatic tumors necessitates a multimodal approach, and more effective medical treatment is being developed.

ISSN:1040-8746    

出版商:OVID    

年代:1998

数据来源: OVID