Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adoptive immunotherapy with transfusion of donor lymphocytes in allogeneic stem cell chimeras has been successful in the treatment of recurrent chronic myelogenous leukaemia (CML) and some patients with acute myeloid leukaemia (AML). The hypothesis that the graft-vs-leukaemia effect (GVL) is promoted by leukaemia-derived dendritic cells has been supported by the concurrent treatment of patients with cytokines that are known to induce differentiation of leukaemia cells towards dendritic cells. In combination with donor lymphocyte transfusions, treatment with interferon-alpha and granulocyte-macrophage colony-stimulating factor has been studied in patients with recurrent CML and AML, and pre-emptively in patients with high-risk AML. Long-term remissions have been observed in cytokine-treated patients, indicating the beneficial effect of cytokine stimulation of GVL reactions. This is likely to be due to differentiation of leukaemia progenitor cells towards dendritic cells in vivo.
Best Pract Res Clin Haematol 2004 Sep
PMID:In-vivo generation of leukaemia-derived dendritic cells. 1549 15

Allogeneic bone marrow transplantation as a cure for leukaemia and lymphoma is limited by the development of graft-vs-host disease (GVHD), an immunological reaction of the donor's T lymphocytes against the host's normal tissues. One therapeutic option to treat GVHD is the transfer of 'suicide' genes into the donor's T lymphocytes to render them susceptible to prodrug administration. This procedure should permit the elimination of unwanted T lymphocytes in GVHD. The main genes proposed for such a strategy will be described in this chapter, together with the advantages and limitations found during preclinical and clinical studies to date.
Best Pract Res Clin Haematol 2004 Sep
PMID:Suicide gene therapy and the control of graft-vs-host disease. 1549 16

Around 20% of children affected by B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) still experience a recurrence of the disease after diagnosis, despite a significant improvement in the cure rate (80%). Moreover, standard therapies have high and often unacceptable acute and chronic organ toxicity, with an increased risk for secondary malignancies. Therefore, new strategies are needed to improve overall survival and decrease treatment-associated morbidity. Recent in-vitro and in-vivo studies have demonstrated that CD40 engagement improves tumour immunogenicity and, consequently, generates a strong antitumour immune response. The CD40-CD40 ligand (CD40L) system is of pivotal importance in the immune response via interactions between T cells and antigen-presenting cells. The general aim of this chapter is to review the feasibility of developing cellular strategies to increase childhood BCP-ALL immunogenicity, and the potential use of CD40L as a new strategy to induce an antileukaemia immune response in BCP-ALL.
Best Pract Res Clin Haematol 2004 Sep
PMID:Potential use of CD40 ligand for immunotherapy of childhood B-cell precursor acute lymphoblastic leukaemia. 1549 17

Adoptive immune cell therapy represents one of the most promising fields of investigation in allogeneic haematopoietic stem cell transplantation (allo-HSCT). Preliminary studies indicate that adoptive immune cell therapy can be used to restore the immunocompetence of allo-HSCT recipients towards widespread pathogens in the early post-transplant period. These strategies can be of fundamental importance in patients given a T-cell-depleted allograft, a type of transplant that has been performed increasingly over the last few years. A few seminal studies have recently documented that prevention/treatment of Epstein-Barr-virus-related lymphoproliferative disorders, human cytomegalovirus disease and invasive aspergillosis can be obtained through infusion of pathogen-specific T-cell lines or clones. Several efforts are also being directed towards the identification of strategies capable of selecting and/or strengthening specific graft-vs-leukaemia responses. In this regard, strategies of ex-vivo generation and expansion of clones or cell lines, specifically or preferentially leukaemia reactive, have been developed.
Best Pract Res Clin Haematol 2004 Sep
PMID:Innovative approaches of adoptive immune cell therapy in paediatric recipients of haematopoietic stem cell transplantation. 1549 18

We report 6 children, aged 4.5- 16 years, with acute lymphoblastic leukaemia with back pain, exacerbated by walking as the first symptom of disease. Collapse of the vertebral bodies at multiple levels was shown on imaging. The presented group had good prognosis. In densitometric examination of BMD (bone mineral density) was observed loss in the thoracic and lumbar vertebrae in 5 out of 6 children. Chemotherapy resulted in decrease of pain and spontaneous remodelling of the vertebrae.
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PMID:[Vertebral compression fractures--the first manifestations of acute lymphoblastic leukemia of childhood]. 1595

Osteoporosis is increasingly being seen in young people. The primitive forms are relatively rare, but the secondary forms--particularly in long-term corticosteroid therapy--are a relevant problem given the much longer survival in chronic diseases such as cystic fibrosis, chronic renal insufficiency, leukaemia, and Duchenne muscular dystrophy. Controlled, prospective studies to evaluate the results of prevention and therapy in children are still lacking. The basis of therapy is the correct daily intake of calcium and the use of vitamin D (or active metabolites). This helps the growing skeleton to restore its equilibrium in many cases. Restraining the long-term use of corticosteroids to the minimum effective dose and shorter duration is essential. In severe cases, particularly in the presence of fractures, bisphosphonates can be remarkably effective. In some cases, such as idiopathic juvenile osteoporosis, the rule is spontaneous resolution, and the advisability of an aggressive drug therapy is discussed.
Best Pract Res Clin Rheumatol 2005 Dec
PMID:How to manage osteoporosis in children. 1630 Nov 93

An important problem in the treatment of children with acute lymphoblastic leukaemia (ALL) is pre-existent or acquired resistance to structurally and functionally unrelated chemotherapeutic compounds. Various cellular mechanisms can give rise to multidrug resistance (MDR). Best studied is the transmembrane protein-mediated efflux of cytotoxic compounds that leads to decreased cellular drug accumulation and toxicity. Several MDR-related efflux pumps have been characterised, including P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), breast cancer resistance protein (BCRP) and lung resistance protein (LRP). P-gp expression and/or activity has been associated with unfavourable outcome in paediatric ALL patients, whereas MRP1 and BCRP do not seem to play a major role. LRP might contribute to drug resistance in B-lineage ALL, but larger studies are needed to confirm these results. The present review summarises the current knowledge concerning multidrug resistance-related proteins and focuses on the clinical relevance and prognostic value of these efflux pumps in childhood ALL.
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PMID:Prognostic significance of multidrug resistance-related proteins in childhood acute lymphoblastic leukaemia. 1632 33

Identification of genes responsible for rare familial cases of cancer provides genetic and biochemical insight into the mechanisms of carcinogenesis at work in the more common, sporadic occurrences of the corresponding malignancy. Hematopoietic malignancy is no exception, and considerable evidence substantiates the role of genetic factors in the risk for leukemia. In a few instances, leukemia runs in families as a single gene, Mendelian disorder. Only a few genes conferring heritable risk for leukemia are known, however, and most are responsible for bone marrow failure syndromes. Thus, the identification of additional genetic risk factors for leukemia represents both a challenge and an opportunity. The high frequency of leukemia and transient leukemia in Down syndrome is beginning to yield the secrets of its unique clinical properties. The apparent phenomenon of anticipation (a declining of age of onset with each passing generation) in familial forms of bone marrow failure and leukemia is now affirmed through its association with mutations in genes responsible for maintaining telomere length. And, for the majority of leukemia cases, as with other common diseases that are not under the influence of a single, major gene, but rather result from the additive interactions of complex genetic and environmental factors, common variants in metabolic enzymes, and other genes awaiting discovery, are being teased out.
Best Pract Res Clin Haematol 2006
PMID:Familial leukemia. 1651 24

The graft-versus-leukemia effect following allogeneic stem cell transplantation (SCT) reduces the incidence of leukemic relapse and establishes that effector cells can eliminate or at least contain resistant leukemic stem cells. Natural killer cells also appear to play a role in directly lowering the rate of relapse following allogeneic SCT in patients with acute myeloid leukemia. To date, however, effective prevention of leukemic relapse by autologous immune effector cells has not been demonstrated. This article examines some of the challenges that limit autologous antileukemia immunity as well as some possible immunotherapeutic approaches that may help control leukemic relapse following autologous SCT.
Best Pract Res Clin Haematol 2006
PMID:Autologous immune strategies to reduce the risk of leukemic relapse: consideration for IL-15. 1651 25

The history of the treatment of childhood leukemia from 1950 to the present is reviewed here. Particular emphasis is placed on the 'Total Therapy' studies conducted at St Jude Children's Research Hospital in Memphis, Tennessee. Under the guidance of Donald Pinkel, MD, the first medical director of St Jude, variations in chemotherapy and craniospinal irradiation were tried, and by Study XV, begun in 2000, a 4-year event-free survival of 92+/-7% had been achieved. Strengths and weaknesses in the current treatment of childhood leukemia are discussed as well as possibilities for the future.
Best Pract Res Clin Haematol 2006
PMID:History of the treatment of childhood ALL: a paradigm for cancer cure. 1651 33


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