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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beginning in 1895, with the discovery of x-rays, alpha and beta radiation, uranium, radium, thorium, and polonium, the fascinating story of the beginning of knowledge concerning the existence of ionizing radiation unfolds. This brief history of radiation and leukemia is divided into two main parts: the first 50 years, which deals with the confusion regarding radiation effects and the failure to clearly recognize that exposure to ionizing radiation may induce leukemia. The second part focuses on the last 60 years, when the radiation induction of leukemia was accepted and some progress achieved in understanding the clinical and pathophysiological characteristics of radiation-induced leukemia. Particular attention in this is paid to the effects of radiation on the survivors of Hiroshima and Nagasaki. The discussion in this section also covers some concepts of radiation-induced cell damage and ruminations on unanswered questions.
Best Pract Res Clin Haematol 2007 Mar
PMID:Radiation-induced leukemia: lessons from history. 1733 61

Consideration of potential donors for transplantation includes a rigorous assessment of the availability and HLA-match status of family members, and the identification of suitable unrelated donors when related donors are not available. Because HLA gene products provoke host-versus-graft and graft-versus-host alloimmune responses, HLA matching serves a critical preventive role in lowering risks of graft failure and graft-versus-host disease (GVHD). At the same time, graft-versus-leukemia effects associated with HLA mismatching may provide an immunological means to lower the recurrence of post-transplant disease in high-risk patients. The definition of a suitable allogeneic donor is ever changing, shaped not only by current typing technology for the known HLA genes but also by the specific transplant procedure. Increased safety of alternative donor hematopoietic cell transplantation (HCT) has been achieved in part through advances in the field of immunogenetics. Increased availability of HCT through the use of HLA-mismatched related and unrelated donors is feasible with a more complete understanding of permissible HLA mismatches and the role of NK-KIR genes in transplantation.
Best Pract Res Clin Haematol 2007 Jun
PMID:Risk assessment in haematopoietic stem cell transplantation: histocompatibility. 1744 54

Bone marrow (BM) has been used for many years as the unique source of progenitor cells for allogeneic transplantation. However, two other sources of progenitor cells, peripheral blood (PB) and umbilical cord (UC), are being increasingly used. The type of graft is one of the most important factors in determining the speed and robustness of the reconstitution after the transplant of monocytes, T lymphocytes, B lymphocytes, NK cells, and dendritic cells. This fact is of especial relevance since the most important reactions after allogeneic transplants - e.g. graft-versus-host disease (GVHD), graft-versus-leukaemia effect (GvL), achievement of full donor chimerism, and fight against infections - are strongly influenced by a rapid and robust reconstitution of these cells. For this reason, the choice of the type of graft for allogeneic transplantation will influence the clinical outcome.
Best Pract Res Clin Haematol 2007 Jun
PMID:Risk assessment in haematopoietic stem cell transplantation: stem cell source. 1744 61

Graft-versus-host disease (GvHD) is the major cause of transplant-related mortality and morbidity. As it is closely related to the major therapeutic principle, graft-versus-leukaemia (GvL) effect, risk assessment has to balance both risks depending on the pre-transplant status. This is clearly demonstrated when comparing the two major strategies for prevention of GvHD. While the majority of approaches aiming at T-cell depletion show efficacy in reducing acute and chronic GvHD and transplant-related mortality, T-cell depletion also affects graft-versus-leukaemia effects and thus results in a higher relapse rate. Thus, standard prophylaxis relying on calcineurin inhibitors frequently results in at least equivalent or even superior long-term disease-free survival, and the risk of relapse has to be considered when selecting regimens for prevention of GvHD. In addition to this general dilemma, drug-specific side-effects and risks have to be considered when selecting regimens for GvHD prevention and treatment.
Best Pract Res Clin Haematol 2007 Jun
PMID:Risk assessment in haematopoietic stem cell transplantation: GvHD prevention and treatment. 1744 62

After the introduction of cyclophosphamide and total body irradiation in the 1970s, a variety of conditioning regimens has been developed. However, none has proven to be superior. Fractionation of the irradiation results in less toxic side-effects, but the total dose has to be increased to obtain similar immunosuppressive effects. Data from randomized trials indicate that among patients with myeloid leukaemia, busulfan in combination with cyclophosphamide results in similar outcome, while a regimen containing total body irradiation is probably still the best for patients with acute lymphoblastic leukaemia. Busulfan treatment can be optimized by targeted steady-state concentration or with the use of intravenous preparations. Intensified regimens decrease the relapse incidence, but because of a higher mortality from transplant-related causes survival is unchanged. Reduced-intensity conditioning can reduce transplant-related mortality and offer otherwise ineligible patients a potentially curative treatment. Long-term results are unknown.
Best Pract Res Clin Haematol 2007 Jun
PMID:Risk assessment in haematopoietic stem cell transplantation: conditioning. 1744 63

Excellent response rates are now achieved with modern chemoimmunotherapeutic approaches in chronic lymphocytic leukaemia (CLL), but the disease remains incurable. Younger patients and those with adverse prognostic factors will die from their disease, and are therefore candidates for clinical trials investigating the potential role of haematopoietic stem-cell transplantation (SCT) in the management of their disease. Autologous SCT is feasible and safe, but there is a high incidence of subsequent relapse. Myeloablative allogeneic SCT is associated with high treatment-related morbidity and mortality but few late relapses. Attempts to exploit the graft-versus-leukaemia effect of allogeneic donor cells but to reduce the toxicity are being explored in studies of reduced-intensity conditioning allogeneic SCT in CLL. With many potential treatments available, appropriate patient selection and the timing of SCT in the management of CLL remain controversial and the focus of ongoing clinical trials.
Best Pract Res Clin Haematol 2007 Sep
PMID:Stem-cell transplantation in chronic lymphocytic leukaemia. 1770 37

Chronic lymphocytic leukemia (CLL) is a common leukemia with a highly variable natural history. A subset of patients with high-risk CLL rapidly progress to develop symptomatic disease requiring treatment. Over-represented in this group are those who have a deletion of 17p13.1, the chromosomal location of the tumor suppressor gene P53. Of all prognostic factors examined in CLL, del(17p13.1) has a superior predictive value for poor response to conventional therapy. In this article we review the current published data on prognostic factors relevant to treatment in CLL. We next provide therapeutic recommendations for patients with del(17p13.1) that are available to oncologists in general practice. Chemoimmunotherapy, alemtuzumab, or high-dose corticosteroids are all effective as initial therapy for these patients, but progression is generally rapid. If allogeneic immune therapy is to be considered, it should be approached as part of initial or first salvage therapy. The investigational agent flavopiridol has also demonstrated clinical activity in this subset of patients. Identification of small molecules and new treatment approaches for patients with del(17p13.1) is a major focus of several investigators. Selection of therapy based on high-risk genomic features represents an appropriate treatment approach supported by currently available published data.
Best Pract Res Clin Haematol 2007 Sep
PMID:Novel agents and strategies for treatment of p53-defective chronic lymphocytic leukemia. 1770 39

Gene therapy for patients with hematologic malignancies, particularly chronic lymphocytic leukemia (CLL), have focused on transducing primary leukemia cells with a virus vector to express immune-stimulating genes which can induce and propagate a productive and clinically significant immune response against the malignant cells. A variety of replication-defective vectors has been studied to transduce genes for cytokines and function-associated surface molecules. Active vaccines have been developed in vitro, and their activity has been confirmed in clinical trials. Ongoing work aims to optimize this strategy and to identify the appropriate and optimal patient groups in which to apply vaccine therapy. Clinical trials also have provided insight into unexpected alternative mechanisms through which these strategies might provide a clinical benefit.
Best Pract Res Clin Haematol 2007 Sep
PMID:Gene therapy and active immune therapy of hematologic malignancies. 1770 40

Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically, and this subgroup shows a remarkable heterogeneity of genetic mutations at the molecular level and an intermediate response to therapy. The finding of recurrent cytogenetic abnormalities has influenced, in a primary way, the understanding and treatment of leukemias. Yet "normal karyotype AML" lacks such obvious abnormalities, but has a variety of prognostically important genetic abnormalities. Thus, the presence of a FLT3-ITD (internal tandem duplication), MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1 mRNAs confer a poor prognosis, and an increased risk of relapse. In contrast, the presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with lower relapse rates and improved survival. Although resistance to treatment is associated with specific mutations, the degree to which the leukemia resembles a stem cell in its functional properties may provide greater protection from the effects of treatment. Although usually all of the circulating leukemia cells are cleared following treatment, a small residual population of leukemic cells in the bone marrow persists, making this disease hard to eradicate. Increased understanding of the biological consequences of at least some of these mutations in "normal karyotype AML" is leading to more targeted approaches to develop more effective treatments for this disease.
Best Pract Res Clin Haematol 2008 Mar
PMID:Is it important to decipher the heterogeneity of "normal karyotype AML"? 1834 11

Vascular endothelial cells are an exposed target tissue for immune-mediated injury during graft-versus-host disease (GVHD). However, widespread endothelial death resulting in multi-organ failure similar to that in hyperacute solid-organ transplant rejection is not observed during GVHD. The rather mild endothelial injury seen in histological samples from affected skin biopsies contrasts with severe epithelial injury observed sometimes simultaneously. The elucidation of the mechanisms that influence endothelial susceptibility to immune-mediated injury would explain this paradox and may help to separate GVHD from the beneficial graft-versus-leukaemia effect. Transplant-associated microangiopathy, veno-occlusive disease and accelerated arteriosclerosis are vascular injury syndromes that occur after allogeneic stem-cell transplantation. Biomarkers are needed to identify individuals at risk of developing these complications. Treatments that have been found to be particularly effective for these specific endothelial injury syndromes need to be tested in larger clinical trials.
Best Pract Res Clin Haematol 2008 Jun
PMID:Vascular endothelium and graft-versus-host disease. 1850 81


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