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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The object of this study was to determine whether the "in vitro" parameters of medullary and blood granulopoiesis in patients with MDS, furnish information of either prognostic or diagnostic value. This study covered 94 patients with MDS. All patients were studied at the onset of disease. In order to identify the factors related to patients' survival, Cox Multiple Regression analysis was performed by the BMD P2L program. When analyzing by means of actuarial curves the survival probability of patients with benign development versus those of malignant development (those who developed ANLL), the significance between both groups was p = 0.0001. Different variables of patients included in this study were analyzed and all showed great significances. Fab: p = 0.0022, disease evolution: p = 0.0001 and presence of blastic aggregates: p = 0.0011. Cox's regression analysis revealed that the only predictable survival variable is the presence of blastic colonies and/or clusters. Accordingly, two groups were constructed: favourable and unfavourable. In the favourable group, 40% of the patients belonged to the RA group, while in the unfavourable group, 55% belonged to the RAEB group. This study shows the validity of the elaboration of prognostic groups in MDS according to the presence of blastic colonies and/or clusters in CFUGM medullary and/or peripheral cultures. The "in vitro" myeloid progenitors culture techniques may therefore be advantageously applied in these disorders for formulating a diagnosis and predicting the patient's short term evolution.
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PMID:The myelodysplastic syndrome: prognostic factors in relation to the "in vitro" clonogenic assay. 169 68

Initial interest in autologous blood stem cell transplants (ABSCT) in acute myeloid leukaemia (AML) was based on the postulate that there might be less malignant contamination than with bone marrow transplants. Although this remains presently uncertain, other advantages of ABSCT, such as a rapid haematopoietic recovery, were immediately recognized. In pilot studies, peripheral blood stem cells (PBSC) were collected after standard induction and consolidation courses of chemotherapy. The actuarial disease-free survival (DFS) and relapse rates (RR) at 2-3 years ranged from 28 to 39% and 57 to 60%, respectively. Recently, PBSC collection after high-dose cytarabine, with or without G-CSF, has been associated with DFS ranging from 47 to 57%. Thus, the timing of stem cell collection seems to be crucial in AML and it should be performed following an efficient in vivo purging but before the haematopoietic reserve is exhausted. Clinical results with ABSCT are similar to those seen after autologous bone marrow transplant (ABMT), although important issues such as potential contamination of stem cell collections and optimal timing of PBSC harvest remain to be clarified. Prospective randomized studies comparing ABMT and ABSCT are needed for definitive evaluation of the role of the source of stem cells in AML treatment.
Baillieres Best Pract Res Clin Haematol
PMID:Autologous peripheral blood stem cell transplantation for acute leukaemias. 1100 Sep 89

The modern characterization of acute myeloid leukaemia is a multidisciplinary process. It requires the integration of clinical information, morphology, cytochemistry, immunophenotyping, cytogenetic and molecular genetic diagnostic techniques. It is only by bringing all these modalities together that a clear picture of the disease can be presented. This initial work-up provides essential prognostic information of benefit to the patient. The selection of treatment and the monitoring of treatment response are dependent on the findings at the time of diagnosis.
Best Pract Res Clin Haematol 2001 Mar
PMID:Laboratory diagnosis of acute myeloid leukaemia. 1135 21

Acquired chromosome aberrations are present in the marrow of most patients with acute myeloid leukaemia (AML) at diagnosis. Cytogenetically, AML is a very heterogeneous disease with over 160 structural chromosome abnormalities observed recurrently to date. Molecular dissection of many reciprocal translocations and inversions has resulted in cloning of the genes involved in leukaemogenesis. Some recurrent aberrations and the resulting gene rearrangements, namely inv(16)/t(16;16) and CBFbeta- MYH11, t(8;21) and CBFA2-CBFA2T1, t(15;17) and PML-RARalpha, and rearrangements of band 11q23 and the MLL gene, are now used to help define distinct disease entities within AML in the new World Health Organization classification of haematological malignancies. Moreover, cytogenetic abnormalities, whether molecularly characterized or not, are among the most important, independent prognostic factors in AML, and are being used in the management of AML patients. This review presents current information on chromosome abnormalities in AML, and on associations between karyotype and clinical characteristics and outcome of AML patients.
Best Pract Res Clin Haematol 2001 Mar
PMID:Clinical importance of cytogenetics in acute myeloid leukaemia. 1135 22

Elucidation of the molecular genetic basis of leukaemias has relied on the cloning and characterization of recurring chromosomal translocations. A common theme in acute myeloid leukaemia (AML) associated with balanced reciprocal translocations is the involvement of transcription factors as one or both of the fusion partners. Transcription factors commonly involved in chromosomal translocations include core binding factor (CBF), retinoic acid receptor alpha (RARalpha), ETS family of transcription factors and homeobox gene (HOX) family members. In addition, the recruitment of transcriptional co-activators and co-repressors by these transcription factors suggests that these proteins also may play a critical role in leukaemogenesis. In support of this hypothesis' at least three fusions associated with leukaemias and involving transcriptional co-activators CBP and p300 have been recently cloned. However expression of transcription factor fusion proteins is not sufficient to induce a leukaemic phenotype, as evidenced in part by the long latencies required for disease development in the murine models of the disease. An emerging paradigm is the co-operation between constitutively activated tyrosine kinase molecules, such as FLT3, and transcription factor fusions in the pathogenesis of AML. In such a model, the activated tyrosine kinase confers proliferation and/or anti-apoptotic activity to the hematopoietic cells, while the transcription factor fusion impairs normal differentiation pathways with limited effect on cellular proliferation.
Best Pract Res Clin Haematol 2001 Mar
PMID:Molecular genetics of acute myeloid leukaemia. 1135 23

The prognosis between subgroups of patients with acute myeloid leukaemia (AML) may range considerably. Haematological, genetic and clinical analysis has provided possibilities for defining the heterogeneity of prognosis. This furnishes clinically relevant insights into the probability of treatment response and survival in individual cases of AML and it provides a lead in treatment management.
Best Pract Res Clin Haematol 2001 Mar
PMID:Prognostic factors in acute myeloid leukaemia. 1135 24

Acute myeloid leukaemia (AML) is characterized by a block in differentiation and an unregulated proliferation of myeloid progenitor cells. While the cause of AML in children is unknown, risk factors that have been identified include exposure to toxins such as ethanol, pesticides and dietary topoisomerase II inhibitors, prior chemotherapy with alkylating agents or topoisomerase II inhibitors, constitutional disorders such as Down's syndrome and type I neurofibromatosis, and haematopoietic failure syndromes such as Fanconi anaemia and severe congenital neutropenia. With intensified chemotherapy including high-dose Ara-C, followed in many cases by bone marrow transplantation, and with improvements in supportive care, current survival rates approach 50%. Future advances in paediatric AML will include better risk stratification to determine optimal treatment and targeted cytotoxic therapy.
Best Pract Res Clin Haematol 2001 Mar
PMID:Acute myeloid leukaemia in children. 1135 25

The survival of AML in younger patients has improved in the last 20 years, as a consequence of a more intensive approach to treatment. Seventy-five to eighty percent of patients will enter complete remission, so the main challenge is to prevent relapse. Several trials have assessed the value of allogeneic or autologous transplantation. When these trials have been assessed by careful statistical methods, the advantage of transplant overall is difficult to detect. Intensive consolidation can deliver a similar survival, of which high-dose Ara-C has been widely adopted, but other intensive schedules appear equivalent. It is not known how many treatment courses are required. Patients are at differing risks of relapse which may influence the choice of treatment. In trials where a risk profile is available, and where a donor versus no-donor analysis is performed, there appears to be little robust evidence to support transplant in good or poor risk disease, although the experience in the latter groups is not unanimous. Standard risk patients may be the subgroup who deliver survival benefit, but since chemotherapy continues to improve, there remains some uncertainty. It is possible that technical improvements in transplantation, such as peripheral blood as a source of stem cells, may remove this uncertainty.
Best Pract Res Clin Haematol 2001 Mar
PMID:Treatment of acute myeloid leukaemia in younger patients. 1135 26

Secondary leukaemias are common, accounting for more than 40% of all patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). A clinical history of exposure to haematotoxins or radiation is helpful; however, many older patients are diagnosed with leukaemia with no antecedent history of exposure. These patients' disease show a remarkably similar phenotype to classic therapy-related leukaemia. The specific cytogenetic abnormalities common to MDS, alkylating-agent-related AML and poor-prognosis AML (3q-, -5, 5q-, -7, 7q-, +8, +9, 11q-, 12p-, -18, -19,20q-, +21, t(1;7), t(2;11)), probably reflect a common pathogenesis distinct from that of other de novo AMLs, although the pathogenetic pathway has yet to be elucidated. Possibly, tumour suppressor genes are implicated and genomic instability may be a cause of multiple unbalanced chromosomal translocations or deletions. Typically, these patients are either elderly or have a history of exposure to alkylating agents or environmental exposure 5-7 years prior to diagnosis. Another distinct entity affects the mixed lineage leukaemia (MLL) gene located on 11q23. These account for about 3% of patients with therapy-related leukaemia and have a short latency period from exposure, usually to an inhibitor of topoisomerase II. Other therapy-related patients with t(8:21), inv16 or t(15;17) translocations should be treated as any other de novo AML with similar cytogenetics. In summary, the major prognostic factor is related to the pathogenetic mechanisms of the leukaemia. Cytogenetics and molecular features are a better predictor of outcome than patient history. Patients should receive standard induction therapy. However, the long-term outcome is relatively poor; the best results being obtained among patients undergoing allogeneic transplantation.
Best Pract Res Clin Haematol 2001 Mar
PMID:Biology and therapy of secondary leukaemias. 1135 27

Undertreatment of the older patients with acute myeloid leukaemia (AML) can explain, in part, their inferior outcome when compared with that of younger patients. Corresponding to the benefit to patients under the age of 60 from high-dose Ara-C there are also dose effects in those over 60 years old, in particular for daunorubicin in the induction treatment, and for the quantity in terms of duration of postremission treatment. The use of these effects can partly overcome the mostly unfavourable disease biology seen in older age AML patients, which is expressed by the absence of favourable and the over-representation of adverse chromosomal abnormalities as well as by the expression of drug resistance. We recommend an adequate dosage of 60 mg/m(2)daunorubicin for 3 days in combination with standard dose Ara-C and 6-thioguanine given for induction and consolidation, followed by a prolonged monthly maintenance chemotherapy for a duration of at least 1 year. Further improvements in supportive care may help in delivering additional anti-leukaemic cytotoxicity. As a novel approach, non-myeloablative preparative regimens may open up the field of allogeneic transplantation for older patients with AML. Given that the actual median age in this disease is more than 60 years the management of older age AML remains as the major challenge.
Best Pract Res Clin Haematol 2001 Mar
PMID:Acute myeloid leukaemia (AML): treatment of the older patient. 1135 28


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