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

We review improvements achieved in the treatment of acute promyelocytic leukaemia (APL) over the last ten years. The combination of all- trans retinoic acid (ATRA) and conventional anthracycline-ARA-C chemotherapy (CT) has clearly demonstrated its superiority over CT alone (in terms of relapse and survival) in newly diagnosed APL. Combination treatment probably also reduces the incidence of initial failures, and complete remission (CR) rates greater than 90% are now regularly reported in large multicentre trials. Some randomized studies strongly suggest than prolonged maintenance treatment (for 1 or 2 years) with ATRA and low dose CT, and possibly very early introduction of anthracycline CT during induction treatment (i.e. not after ATRA) may reduce the incidence of relapse. With those treatments, the risk of relapse appears to be only 10-15%, although it remains greater in patients who initially have white blood cell counts (often associated with variant M(3)morphology, short bcr(3)isoform etc.) and patients with residual disease detectable by RT-PCR at the end of consolidation courses.ATRA syndrome remains the major side effect of ATRA treatment. It occurs in 10-15% of patients and is currently fatal in at least 10% of them. Rapid onset of CT and/or high dose steroids should improve its outcome.A sizeable proportion of APL patients who relapse after ATRA and CT can be durably salvaged by the same treatment followed by allogeneic or autologous stem cell transplantation, provided the transplant (in the autologous setting) is RT-PCR negative. Arsenic trioxide can induce CR in most APL patients refractory to ATRA and CT. It acts mainly by inducing apoptosis of APL cells. A place for arsenic trioxide earlier in the treatment of APL must currently be more precisely defined. Another issue in the treatment of APL is reducing the toxicity of first line treatment without increasing the relapse risk. Preliminary findings suggest that this could be achieved by consolidation CT using an anthracycline alone, without cytarabine.
Best Pract Res Clin Haematol 2001 Mar
PMID:Treatment of acute promyelocytic leukaemia. 1135 29

Clinical trials of colony-stimulating factors (CSFs) have been conducted for over 10 years. Initially, these agents, generally either granulocyte-macrophage (GM)- or granulocyte (G)-CSF, were hypothesized to reduce rates of major infection and/or death in the initial weeks after administration of chemotherapy. Although trials have consistently shown that both cytokines accelerate neutrophil recovery, only 1 out of 5-10 large randomized trials has reported that a decrease in major infection occurs as a result. While some of these trials have found that the use of cytokines lowers days in hospital, on antibiotics, or with fever, it is unclear whether the magnitude of these effects outweighs the expense currently entailed in CSF administration; indeed it appears that estimates of cost are themselves quite variable. The second major use of cytokines has been in priming acute myeloid leukaemia (AML) blasts to the cytotoxic actions of chemotherapy. Here again, the results of several randomized trials do not justify application of this strategy. It remains possible that there are subsets of AML patients who would benefit from priming. However, the identification of such patients might require years of accrual into clinical trials from which the majority of patients would not benefit. Future years may see trials of cytokines (e.g. pegylated recombinant human megakaryocytic growth and development factor +G- or GM-CSF) in patients in remission and as a means to increase the number of normal granulocytes that can be given to patients with infections. Further therapies may target cytokine receptors on AML blasts, to improve anti-leukaemia therapy.
Best Pract Res Clin Haematol 2001 Mar
PMID:Growth factors in acute myeloid leukaemia. 1135 30

After many years of hope and disillusionment, the possibility of utilizing immune-mediated approaches to control neoplastic clones has become a reality in various haematological malignancies. This is largely a consequence of the continuous advances in knowledge and the progressive development of more refined technologies that have led to a better understanding of the biology of the malignant cells and of the host immune system, to a more precise definition of disease entities and to the design of innovative therapeutic programmes. In this chapter, we will review different immunological strategies that have reached clinical practice in patients with acute myelogenous leukaemia (AML), the focus of this volume, and discuss pre-clinical developments that may in the near future translate into the design of new immunotherapeutic protocols for the management of AML. Treatment of AML with antibody directed therapy will also be discussed.
Best Pract Res Clin Haematol 2001 Mar
PMID:Developmental approaches in immunological control of acute myelogenous leukaemia. 1135 31

Cytogenetic analysis has contributed greatly to our understanding of the nature of leukaemia and lymphoma. Study of these two groups of diseases has revealed general truths about the nature of the neoplastic process. Cytogenetic analysis has demonstrated that haematological neoplasms result from a somatic mutation occurring in a haemopoietic, lymphoid or multipotent stem cell. Complete remission has been related to disappearance of the clone of cells bearing the mutation whereas the occurrence of clonal evolution has often been found to be indicative of increasingly aggressive disease. Cytogenetic analysis of leukaemias and lymphomas has led to the discovery of numerous proto-oncogenes; these generally play a crucial role in proliferation and differentiation of normal cells with a perturbation of their function leading to neoplasia. In addition, cytogenetic evidence has suggested a role for loss of function of cancer-suppressing genes in haematological neoplasms. Cytogenetic analysis has also made major contributions to precise diagnosis and to the assigning of prognosis and, furthermore, by identifying good and poor prognostic groups has improved the management of patients. Good-prognosis patients have been spared unnecessary treatment and, conversely, more intensive treatment for some diseases associated with a cytogenetic abnormality that was previously indicative of a poor prognosis has improved the outcome for these patients.
Best Pract Res Clin Haematol 2001 Sep
PMID:Overview. Cytogenetic analysis in haematology. 1164 Aug 65

During the last three decades it has become apparent that the majority of cases of acute myeloid leukaemia (AML) are characterized by at least one of a variety of recurrent chromosomal abnormalities. These changes have been found in many instances to correlate closely with distinct morphological features and clinical characteristics, the molecular basis of which is becoming increasingly understood. Furthermore, diagnostic karyotype has been shown to be a key determinant of outcome in AML, with mounting evidence to support the notion that cytogenetic analysis can serve to identify biologically distinct subsets of disease that demand tailored therapeutic approaches. This has led to a rising trend towards routine cytogenetic and molecular characterization of newly diagnosed acute leukaemia, providing a framework for treatment stratification.
Best Pract Res Clin Haematol 2001 Sep
PMID:The clinical significance of cytogenetic abnormalities in acute myeloid leukaemia. 1164 Aug 67

Childhood myeloid leukaemias are a diverse collection of conditions. Although many are also seen in adults, some are peculiar to childhood. In childhood AML, as in adults, cytogenetic abnormalities are associated with specific clinical features and define prognostic groups. In infants under 1 year with AML, the incidence of 11q23 abnormalities is particularly high. The finding of identical 11q23 breakpoints in infant leukaemia as in therapy-related leukaemias suggests a role for in utero exposure to topoisomerase II inhibitors. There are a number of constitutional disorders that predispose children to develop AML, usually with a preceding myelodysplastic phase. Monosomy (or deletion of the long arm) of chromosome 7 is the most frequent chromosome abnormality in the bone marrow of such patients. Abnormalities of chromosome 7 are also common cytogenetic findings in all morphological subgroups of childhood myelodysplasia, either as a primary abnormality or associated with disease progression.
Best Pract Res Clin Haematol 2001 Sep
PMID:Childhood myeloid leukaemias. 1164 Aug 70

In acute lymphoblastic leukaemia (ALL) the karyotype provides important prognostic information which is beginning to have an impact on treatment. The most significant structural chromosomal changes include: the poor-risk abnormalities; t(9;22)(q34;q11), giving rise to the BCR/ABL fusion and rearrangements of the MLL gene; abnormalities previously designated as poor-risk; t(1;19)(q23;p13), producing the E2A/PBX1 and rearrangements of MYC with the immunoglobulin genes; and the probable good risk translocation t(12;21)(p13;q22), which results in the ETV6/AML1 fusion. These abnormalities occur most frequently in B-lineage leukaemias, while rearrangements of the T cell receptor genes are associated with T-lineage ALL. Abnormalities of the short arm of chromosome 9, in particular homozygous deletions involving the tumour suppressor gene (TSG) p16(INK4A), are associated with a poor outcome. Numerical chromosomal abnormalities are of particular importance in relation to prognosis. High hyperdiploidy (51-65 chromosomes) is associated with a good risk, whereas the outlook for patients with near haploidy (23-29 chromosomes) is extremely poor. In view of the introduction of risk-adjusted therapy into the UK childhood ALL treatment trials, an interphase FISH screening programme has been developed to reveal chromosomal abnormalities with prognostic significance in childhood ALL. Novel techniques in molecular cytogenetics are identifying new, cryptic abnormalities in small groups of patients which may lead to further improvements in future treatment protocols.
Best Pract Res Clin Haematol 2001 Sep
PMID:Acute lymphoblastic leukaemia. 1164 Aug 71

Over the past 9 years there has been a remarkable increase in the use of peripheral blood stem cells (PBSC) for allogeneic transplantation, primarily for matched sibling transplants but also increasingly for unrelated donor transplantation. In 1999 over 50% of all sibling transplants and over 25% of unrelated donor transplants reported to the European Group for Blood and Marrow Transplantation (EBMT) used PBSC. The major reason for this increasing use of PBSC relates to the rapid haemopoietic recovery seen which mirrors the advantages of using PBSC in autologous transplantation. This improvement in engraftment is a consequence of the larger number of stem cells that can be collected from G-CSF-mobilized peripheral blood compared to bone marrow. Evidence from randomized trials now shows a survival advantage for the use of PBSC in patients with advanced leukaemia. The reason for this improved survival appears primarily to relate to a reduced risk of transplant-related mortality and, possibly, a reduced risk of relapse, However, these randomized studies have also confirmed that there is an increased risk of chronic graft-versus-host disease associated with PBSC transplantation and further follow-up is required to determine the long-term impact on outcome.
Best Pract Res Clin Haematol 2001 Dec
PMID:Allogeneic transplantation using peripheral blood stem cells. 1192 16

Allogeneic stem cell transplantation (SCT) has become the treatment of choice for some patients with haematological malignancies, allowing dose escalation of chemo-radiotherapy beyond the limits imposed by bone marrow toxicity. However, it is now apparent that dose escalation alone does not eradicate the malignancy in many cases and that an associated immune-mediated graft-versus-malignancy effect may be equally important. Its presence is supported by the following observations: anecdotal reports that patients with relapsed leukaemia following SCT may re-enter remission after withdrawal of immunosuppressive drugs; the lower risk of relapse associated with the development of graft-versus-host-disease (GVHD); and an increased risk of relapse in patients receiving syngeneic transplants or T-cell depleted allogeneic marrow grafts. More directly compelling evidence has been provided by the efficacy of donor lymphocyte infusions, particularly for relapsed chronic-phase CML. Issues that remain to be resolved include the precise nature of the effector cells and their target antigens, the best strategies for separating graft-versus-malignancy from GVHD, the role of adjuvant chemotherapy/cytokines, and the role of non-myeloablative transplantation.
Best Pract Res Clin Haematol 2001 Dec
PMID:Exploiting graft-versus-tumour responses using donor leukocyte infusions. 1192 18

This chapter describes the current role of unrelated donor stem cell transplantation (UD-SCT) in the management of leukaemia. The available data are scant and incomplete and there are few randomized studies comparing UD-SCT with alternative therapies. Patients with many of the leukaemias require prolonged follow-up after allogeneic SCT to determine whether they are cured; the registry-based comparisons that have been initiated reflect the results achievable some years ago and may not help us in deciding what is best in 2001. In addition, new therapies such as ST1571, even though the long-term outcome of patients treated with this agent is uncertain, may affect which patients with chronic myeloid leukaemia we decide to recommend for transplant. The focus here is on acute and chronic myeloid leukaemia, acute lymphoblastic leukaemia and chronic lymphocytic leukaemia, as well as the myelodysplastic syndromes. Patient selection, conditioning strategies, comparison with other therapies, timing of transplant and the major causes of treatment failure are discussed, and there is an exploration of where improvement will come from.
Best Pract Res Clin Haematol 2001 Dec
PMID:Allogeneic transplantation for leukaemia using unrelated donors. 1192 22


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