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

Today, 80% of paediatric patients with acute lymphoblastic leukaemia (ALL) can be cured. To reduce the rate of relapses, but also to limit treatment morbidity, risk-adapted treatment has been attempted after identifying the most specific prognostic factors. In addition to clinical factors (e.g. age, WBC), the immunophenotype and cytogenetic results, the early in vivo treatment response as determined by cytology had evolved as the most important predictor for relapse. The lack of specificity of most prognostic factors stimulated the search for more relevant parameters. Detection of minimal residual disease (MRD) at defined time points by identifying clone-specific T-cell receptor- (TCR) or immunoglobulin (Ig) gene rearrangements can provide new, highly specific prognostic information which allows definition of new risk groups. The high sensitivity of the method is a prerequisite for applying treatment reduction in patients with fast clearance of leukaemia. Persistent disease is an indication for treatment modification and intensification. Logistics and quality control are demanding but are essential for the introduction of this new technology into clinical practice.
Best Pract Res Clin Haematol 2002 Dec
PMID:New treatment strategies in childhood acute lymphoblastic leukaemia. 1261 73

Until recently, progress in the treatment of patients with Ph(+) acute lymphoblastic leukaemia (ALL) has been limited, and long-term survival, even with high-dose intensified chemotherapy, is rare. Allogeneic stem cell transplantation is potentially curative, but treatment-related mortality and rate of disease recurrence are substantial. With the advent of the ABL-selective tyrosine kinase inhibitor STI571 (imatinib mesylate, Glivec), it has become apparent that the understanding of crucial leukaemogenic pathways at the molecular level can lead to the development of specific and selective agents. In recent clinical trials, imatinib has demonstrated significant anti-leukaemic efficacy in patients with advanced Ph(+) ALL, in conjunction with a remarkably favourable safety profile. Clinical resistance to imatinib develops rapidly, highlighting the limitations of using imatinib as a single agent; however, the value of imatinib as an element of treatment has become apparent. Resistance mechanisms have already been identified that will enable the development of rational strategies to prevent or overcome resistance. On the basis of available clinical results, combinations of imatinib with established anti-leukaemic agents, as well as with novel, molecularly targeted treatment modalities, will need to be evaluated in advanced Ph(+) ALL. Incorporation of imatinib in the first-line treatment of de novo Ph(+) ALL and in the setting of minimal residual disease is a promising therapeutic approach which is currently being studied in clinical trials. Better understanding of targeted therapies, including strategies based on recruitment of host immune functions, as well as the prudent use of active chemotherapy agents, may eventually improve the outlook for patients with Ph(+) ALL.
Best Pract Res Clin Haematol 2002 Dec
PMID:Imatinib in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia: current status and evolving concepts. 1261 75

The evidence that hairy cells are activated clonal late B cells is presented. The largely non-specific (i.e. not confined to hairy-cell leukaemia) chromosome and genetic abnormalities are then described. Next, the features of malignant-cell activation are considered, including the distinctive morphology of hairy cells and their expression of activation-related antigens and activated adhesion receptors. Also, signalling and cytokine production are discussed in the context of malignant-cell activation. It is then demonstrated that many of the distinctive clinicopathological features of hairy-cell leukaemia can be explained in terms of the interaction of the activated malignant cells with other types of cell and tissue matrix. Finally, the biological basis of the hairy cell's unusually high sensitivity to IFN-alpha and nucleoside analogues is discussed.
Best Pract Res Clin Haematol 2003 Mar
PMID:The biology of hairy cells. 1267 Apr 61

Hairy-cell leukaemia is an indolent lymphoproliferative malignancy characterized by infiltration of the bone marrow, liver, spleen, and occasionally lymph nodes with a malignant B cell with hair-like cytoplasmic projections. This involvement leads to splenomegaly with secondary consumption of red cells, platelets and neutrophils as well as other complications of an enlarged spleen, including infarction-or-rarely rupture. The common haematological complications of anaemia, neutropenia and thrombocytopenia are due not only to the enlarged spleen but probably also to hairy cells in the bone marrow inducing cytokine-mediated suppression of haematopoiesis. Hepatic involvement, although frequent, only occasionally leads to liver dysfunction. Infections are a major cause of morbidity and mortality in patients with hairy-cell leukaemia, presumably owing to neutropenia and monocytopenia in these patients. The infections seen may be due to unusual pathogens, including Mycobacterium and Listeria. Autoimmune disease, including polyarthitis and vasculitis, occurs frequently and does not correlate with the severity of the disease. Other rare complications include bone involvement, meningitis and ascites. A wide range of secondary malignancies have been reported in patients with hairy-cell leukaemia, but it is still unclear whether the incidence is increased and whether they are related to the disease or treatment.
Best Pract Res Clin Haematol 2003 Mar
PMID:Clinical manifestations and infectious complications of hairy-cell leukaemia. 1267 Apr 63

The introduction of alpha interferon in 1984 initiated a new and exciting turnaround in the treatment of hairy-cell leukemia. Until that time splenectomy was the only known effective therapy for this disease. Interferon proved to benefit hairy-cell leukemia patients with active disease, whether or not they had undergone prior splenectomy. However, most interferon-induced responses were partial and were of relatively short duration. Purine analogues such as cladribine and pentostatin have since been found to be more effective than alpha interferon and, therefore, have now replaced interferon as first-line therapy for hairy-cell leukemia. At the present time, interferon has a relatively limited role in the treatment of hairy-cell leukemia and it is reserved for a group of selected patients who have failed nucleoside analogue therapy. In this chapter, we discuss the efficacy of interferon and its response duration, toxicity and possible mechanism of action in patients with hairy-cell leukemia.
Best Pract Res Clin Haematol 2003 Mar
PMID:Interferon in the treatment of hairy-cell leukemia. 1267 Apr 66

Hairy-cell leukaemia cells have a low rate of growth but an even lower rate of apoptosis. Accordingly, this malignancy is an excellent model for studying the effects of drugs on the pathways of apoptosis independently of cell proliferation. The remarkable effectiveness of 2-chlorodeoxyadenosine in hairy-cell leukaemia affirms the feasibility of developing drugs that can destroy even non-proliferating malignant cells. The major nucleotide metabolite of 2-chlorodeoxyadenosine accumulates selectively in lymphocytes and co-activates two key apoptosis-regulating enzymes: poly(ADP-ribose) polymerase and Apaf-1/caspase-9. The ability of 2-chlorodeoxyadenosine to induce durable remissions in hairy-cell leukaemia may also be attributable to its effects on lymphocytes and monocytes in the microenvironment, although this latter effect remains to be proven experimentally.
Best Pract Res Clin Haematol 2003 Mar
PMID:Hairy-cell leukaemia as a model for drug development. 1267 Apr 67

Pentostatin (2'-deoxycoformycin; Nipent), a potent inhibitor of adenosine deaminase, is a purine nucleoside analogue that is highly effective in the treatment of hairy-cell leukemia. This agent is capable of inducing durable complete remissions in the majority of patients, and is capable of re-inducing a complete remission in many of the patients who have relapsed. Pentostatin appears to have changed the natural history of this disease. Long-term follow-up studies suggest that patients with hairy-cell leukemia who are induced into complete remission have a projected survival comparable to age-matched controls. While purine nucleoside analogues induce profound T-cell dysfunction and longstanding immunosuppression, the incidence of secondary malignancies is apparently not increased. Infections still pose a threat to these patients, and effective strategies for treating this disease that do not further compromise the immune system are needed. Patients with this disease should be encouraged to participate in ongoing clinical trials to better define the optimal treatment regimen. New studies should explore the combination of pentostatin and rituxan in treating the typical form of hairy-cell leukemia, and the incorporation of new agents for those with the rare variant form of this disease.
Best Pract Res Clin Haematol 2003 Mar
PMID:Pentostatin in the treatment of hairy-cell leukemia. 1267 Apr 68

Cladribine, a purine nucleoside analogue, is a safe and effective treatment for patients with hairy-cell leukaemia. It is administered at a dose of 0.09 mg/kg daily as a continuous intravenous infusion over 7 days. This chapter discusses the history, rationale, chemical structure and mechanism of action of cladribine. The indications for therapy and guidelines for clinical usage are reviewed. The response of hairy-cell leukaemia to cladribine, the acute and chronic complications and the risk for second malignancies are summarized. The chapter concludes with a section on salvage therapy.
Best Pract Res Clin Haematol 2003 Mar
PMID:Cladribine in the treatment of hairy-cell leukaemia. 1267 Apr 69

Evaluation of cell morphology is usually sufficient to diagnose acute promyelocytic leukaemia (APL). In this chapter we discuss the features of classical hypergranular APL, the APL variant, hyperbasophilic promyelocytic leukaemia, APL with basophil-like granules, acute eosinophilic leukaemia with PML/RARalpha positivity and the morphology of APL cells lacking t(15;17). In addition to morphological examination, cytochemical investigations (peroxidase chloroacetate-esterase, etc.) may help further in defining the cytology of leukaemic cells in APL.
Best Pract Res Clin Haematol 2003 Sep
PMID:Morphological and cytochemical characteristics of leukaemic promyelocytes. 1293 55

Recent progress has demonstrated that acute myelogenous leukaemia (AML) can be classified by chromosomal aberrations and leukaemia-specific molecular gene rearrangements into homogeneous biological subgroups. However, descriptive epidemiological reports on AML consider the disease as a single entity. Acute promyelocytic leukaemia (APL) is an example of a truly unique AML subtype that has an easy-to-recognize morphology associated uniformly with distinct chromosomal and gene rearrangement aberration. Thus, APL is amenable to epidemiological studies as a model of human AML with a specific and well-characterized chromosomal and molecular abnormality. This chapter shows that epidemiological characteristics of APL are different from those of non-APL AML using data from the Los Angeles tumour registry and other sources. The principal distinct APL epidemiological features that so far have been described are the constant incidence with age after age 20, equal incidence in males and females and higher frequency among patients originating in Latin America. The APL-specific PML/RARalpha gene rearrangement is different in Latinos and non-Latinos. Therapy-related APL has the same response to treatment and outcome as de novo APL. It is therefore likely that aetiological factors for APL are different from those of other AML subtypes. So far no environmental and/or occupational risk factors have been found for APL. Future molecular studies of the APL-specific fusion gene combined with epidemiological and environmental investigations might lead to better understanding of specific aetiological factors in APL patients.
Best Pract Res Clin Haematol 2003 Sep
PMID:The epidemiology of acute promyelocytic leukaemia. 1293 56


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