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)

Prophylaxis of the central nervous system against meningeal leukemia is a complex problem. There is no optimal solution that is universal for all patients. Instead, treatment must be individualized for the patient's age, prognostic group, and the concomitant systemic chemotherapy. Radiation, because of its CNS toxicity and potential carcinogenicity, is reserved for those in the highest risk groups. For these patients, 1,800 cGy cranial radiation plus intrathecal methotrexate during induction, consolidation, and maintenance therapy is recommended. For other patients, protection should be limited to systemic and intrathecal chemotherapy. Further studies are needed to compare the most effective intrathecal methotrexate prophylaxis with triple intrathecal drug therapy.
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PMID:Radiotherapy vs intrathecal chemotherapy for CNS prophylaxis in childhood ALL. 270 98

Bone-marrow transplantation has been used in patients with acute lymphoblastic leukaemia (ALL) thought to be at high risk of relapse if managed with chemotherapy. Data from 444 ALL patients with one or more high-risk features at diagnosis were analysed to evaluate outcome after HLA-identical bone-marrow transplantation during first or during second remission. The 4-year actuarial probability of leukaemia-free survival was 45% (95% confidence interval 36-54%) for transplants in first remission compared with 22% (15-29%) for those in second remission (p less than 0.0002). The 4-year probabilities of relapse were 26% (14-38%) and 56% (45-67%) respectively (p less than 0.0001). For high-risk ALL, transplantation in first remission had clearly superior results to transplantation in second remission. Further studies are needed to determine whether patients with high-risk ALL should receive transplants during first remission or should initially receive chemotherapy, with transplantation being reserved for patients who relapse.
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PMID:Bone-marrow transplantation in high-risk acute lymphoblastic leukaemia in first and second remission. 288 92

Granulocytopenia is the single most important risk factor for infection in patients with acute leukaemia. There are limitations to the effective prophylaxis of infection in granulocytopenic patients, but practical measures include the management of the patient in a private hospital room, the requirement of all medical personnel and visitors to wash their hands carefully and to wear masks, restricting the patient to a low-bacteria diet devoid of fresh fruit, vegetables and salads, and the administration of oral antimicrobial agents for gastrointestinal decontamination. When fever develops, empirical therapy with a combination of an aminoglycoside plus an antipseudomonal beta-lactam should be started promptly. A double beta-lactam combination of cefoperazone or ceftazidime plus piperacillin can be substituted if nephrotoxicity is a concern. The addition of empirical intravenous amphotericin may be useful in patients who remain febrile and granulocytopenic on broad-spectrum antibiotics, especially if surveillance cultures indicate fungal colonization. Amphotericin is also the most reliable agent for the treatment of established fungal infections. Acyclovir is not recommended for prophylaxis in acute leukaemia patients but should be reserved for the treatment of well-documented and clinically significant herpes simplex viral infections. During periods of remission, most patients with AML remain free of infection except when they become granulocytopenic again during intensification or consolidation chemotherapy. On the other hand, children with ALL in remission may experience frequent infections unrelated to granulocytopenia as a consequence of their maintenance chemotherapy. Pneumocystis carinii, varicella zoster, and other viruses are common pathogens. Trimethoprim-sulphamethoxazole is effective prophylaxis against Pneumocystis carinii pneumonia in patients with ALL, while intravenous acyclovir is the drug of choice for treatment of varicella zoster infection. Transfusion therapy in the acute leukaemia patient is guided by the patient's peripheral blood counts and degree of sensitization to blood products. Generally, packed red blood cells are given in order to maintain the haematocrit at greater than 30%, while random-donor platelets are administered to keep the platelet count at greater than 20 X 10(9)/l. If refractoriness to platelet transfusions develops, HLA-matched platelets from family members or selected unrelated donors can be used. Similarly, washed or filtered red blood cells may be given to patients with previous and recurrent non-haemolytic febrile reactions to red blood cell transfusions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Infection and transfusion therapy in acute leukaemia. 309 21

We studied the clinical and biologic features of 10 cases of acute leukemia that met standard French-American-British (FAB) criteria for acute myeloid leukemia (AML) but in which the blast cells also expressed the T-cell-associated CD2 surface antigen. All cases had greater than 3% myeloperoxidase and Sudan black B-positive leukemic blasts, and blasts from seven cases contained Auer rods. Reactivity of the cells with a panel of monoclonal antibodies (MAbs) indicated that leukemic cells in all cases expressed myeloid-associated (CD11b, CD13) surface antigens, further supporting the diagnosis of AML. However, blasts from every patient coexpressed the T-cell-associated surface CD2 and CD7 as well as cytoplasmic CD3 antigens. Blasts from five patients expressed surface CD25, whereas blasts from only one expressed surface CD3. Five patients had rearranged T-cell receptor beta-chain genes, whereas only three had rearranged T-cell receptor gamma-chain genes. This pattern of lineage-related gene expression appears to define a distinct subtype of AML with T-lymphoid features (CD2+ AML) and could reflect either aberrant gene expression in leukemic blasts or transformation of a pluripotent stem cell having a flexible pattern of gene expression. Clinically, these 10 patients presented at an older age with a higher leukocyte count and a higher frequency of lymphadenopathy than did children whose blast cells were characteristic of myeloid leukemia. Patients with CD2+ AML also had poorer responses to remission induction therapy (50% v 80% entered complete remission, P = .05). However, each of the five children who failed induction chemotherapy on AML protocols had a striking response to drug combinations usually reserved for lymphoid leukemia. We conclude that this leukemia with mixed lymphoid and myeloid characteristics is a distinct biologic and clinical entity.
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PMID:Acute myeloid leukemia with T-lymphoid features: a distinct biologic and clinical entity. 326 Nov 83

A panel of 19 monoclonal antibodies (McAb) and the enzyme terminal transferase (TdT) have been applied to the characterization of poorly differentiated blasts from 50 patients with chronic granulocytic leukaemia (CGL) and myelofibrosis in blast crisis (BC), acute myelofibrosis and undifferentiated leukaemia. These cells were also extensively studied by transmission electron microscopy (TEM) (see Polli et al, 1985a). McAb against platelet glycoproteins (GP) showed a high specificity for megakaryoblasts, in particular those reactive with the GPIIb/IIIa complex (J15) and GPIIIa (C15 and C17), which were positive in a higher proportion of blasts than the McAb to GPIb (AN51 and FMC25). Findings with these anti-platelet McAb paralleled those of the platelet-peroxidase (PPO) reaction in 76% of cases studied simultaneously. The PPO reaction was always positive in cases in which two or more of the McAb were reactive with the blast cells. The differences observed suggest, nevertheless, that PPO is more sensitive for megakaryoblasts than the McAb and that this TEM technique should be reserved for cases which are negative with the platelet specific McAb. Of the McAb against myeloid antigens used in this series OKM1 was positive in 50% of cases but the others failed to demonstrate early features of differentiation in myeloblasts and monoblasts. In only three cases were erythroid precursors demonstrated by TEM and these were the only ones reactive with a McAb to glycophorin-A (LICR LON/R10). TdT and the McAb J5 helped in the identification of lymphoblasts which were seen as a 'pure' proliferation in 23% of CGL-BC and as part of blast cell mixtures in another 17% of cases. The McAb reactive to haemopoietic precursor cells (RFB1, FMC8 and OKIa), on the other hand, were of no practical value for the classification of blast cell types. The lineage specificity of several of the McAb used in this study, confirmed by TEM, suggest that these reagents are valuable tools for the characterization of immature blast cells.
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PMID:Characterization of blast cells in chronic granulocytic leukaemia in transformation, acute myelofibrosis and undifferentiated leukaemia. II. Studies with monoclonal antibodies and terminal transferase. 388 37

Lymphosarcoma cell leukemia has been used to refer to three related clinical syndromes. As originally described, it refers to the invasion of peripheral blood by poorly-differentiated lymphocytic lymphoma. Blood involvement occurs in 10 to 70 percent of patients with poorly-differentiated lymphocytic lymphoma, depending on the methods and criteria used to define leukemic phase, but it may have little impact on the clinical course of such patients. Second, lymphosarcoma cell leukemia can describe a variant of chronic lymphocytic leukemia, presenting clinically without lymphoma. Although not all hematologists recognize this as a distinct entity, others believe that such patients have a poorer prognosis than those with typical chronic lymphocytic leukemia. In the absence of a lymph node biopsy diagnostic of poorly-differentiated lymphocytic lymphoma, the diagnosis of lymphosarcoma cell leukemia should be reserved for cases demonstrating immunologic features of poorly-differentiated lymphocytic lymphoma, namely bright surface immunoglobulin immunofluorescence, normal capping, and low mouse red cell rosette formation. Finally, lymphosarcoma cell leukemia has been used to describe the invasion of blood by other types of lymphoma, including large cell, lymphoblastic, and Burkitt's lymphoma, although these are better designated as the particular lymphoma in leukemic phase. When abnormal cells appear in the blood samples of patients with lymphoma, acute myelogenous leukemia must also always be considered, particularly in patients who have received substantial prior chemotherapy or irradiation.
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PMID:Lymphosarcoma cell leukemia and other non-Hodgkin's lymphomas in leukemic phase. 634 32

We report the case history of a boy with juvenile chronic arthritis, complicated by amyloidosis, who was treated with chlorambucil. He later developed an acute leukaemia and died. The published reports of malignancies developing in children following the use of this drug are reviewed and it was seen from these that cytotoxic drugs should be reserved for treating the life threatening complications of non-malignant diseases of childhood.
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PMID:Acute leukaemia related to chlorambucil therapy for juvenile chronic arthritis. 653 14

By the concurrent use of scanning electron microscopy (SEM) and time lapse cinematography the interdependence of cellular shape and motility was visualized for leukemia cells and for normal and malignant epithelial cells. During the different modes of motility (stationary without net translocation of the whole cell, and locomotion), the cells display a distinct configuration. This allows the interpretation of static images in terms usually reserved for the description of activities of living cells. The ability of cells to change shape is of special importance when they migrate in the body. Irrespective of nature and origin, these cells must continuously adapt their configuration to the structural elements which they encounter in their pathways. The existence of such an adaptability could be shown by time lapse films for leukemia cells and for cells of the V2 rabbit carcinoma moving in mesenteries of rat and rabbit, respectively.
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PMID:Shape and motility, two interdependent features. 696 96

ALL is characterized by small to medium sized leukaemic blasts with a rather low grade of cell-to-cell variability. The nucleocytoplasmic ratio is high with just a small cytoplasmic rim in many cases. The cytoplasm tends to be moderately basophilic. Usually, though not in each instance, it is agranular and free of vacuoles. The chromatin is more condensed than in AML and the nucleoli tend to be indistinct. The FAB classification of haematological malignancies separates ALL into three categories: ALL L1, L2, and L3. However, just the identification of the L3 variant is of major importance. The L3 cells are medium sized to large and are characterized by intensely basophilic and moderately abundant cytoplasm with prominent cytoplasmic vacuolation in the bone marrow but not necessarily in the peripheral blood. According to our experience there is a high but not universal correlation of the L3 phenotype as defined by morphology with the immunologically defined B-ALL with surface expression of immunoglobulins. Until recently, acute leukaemias proving negative for all cytochemical tests especially for the PAS reaction and for the focal type of acid phosphatase, were termed 'acute undifferentiated leukaemia' (AUL). However, this morphological/cytochemical diagnosis may be confused with the immunological diagnosis of unclassifiable leukaemia. Since almost any of these cases can be recognized as ALL or AML by immunology, the term AUL should be reserved for cases which can be classified neither by morphology/cytochemistry nor by immunology. The morphological and cytochemical distinction of ALL from poorly differentiated AML remains a problem, especially if the FAB criteria for distinguishing ALL from AML by cytochemistry (3% of the blasts positive for peroxidase) are applied rigidly. A small but significant percentage of poorly differentiated leukaemias have less than 3% of the blasts positive for peroxidase and the myeloid nature of the leukaemia can be identified by cytochemistry. The absence of blasts being positive for peroxidase is no reliable indicator for the lymphatic nature of a leukaemia, even if the PAS reaction is typical for ALL. The morphological diagnosis of ALL needs confirmation by immunology in each instance.
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PMID:Morphology and cytochemistry of acute lymphoblastic leukaemia. 780 1

Cell death can occur by two basically different processes. The original term, necrosis, is now reserved for the generally destructive series of events which include the release of lysosomal enzymes and loss of cell membrane integrity. In contrast, mild treatment with cell damaging agents, or withdrawal of growth factors, may result in a characteristic form of degradation of cellular DNA which is associated with cell death that has morphology known as apoptosis. In this study human leukemia cells were exposed to agents or conditions previously reported to cause necrosis or apoptosis, monitored by detection of DNA "ladders," and the integrity of cellular DNA was determined on Southern blots. Nuclear DNA was distinguished from mitochondrial DNA by use of probes specific for nuclear genes or for mitochondrial DNA. When HL60, K562, MOLT4, or U937 cells were exposed to conditions which resulted in necrosis, mitochondrial DNA was damaged at approximately the same rate as nuclear DNA, but in apoptosis mtDNA was not degraded. Thus, the ratio of the relative (to untreated cells) abundance of mitochondrial DNA measured by a probe for 16S mitochondrial ribosomal RNA on Southern blots, to the relative abundance of DNA of any nuclear gene, was 1 or less in necrosis, but rose to values greater than 2 in apoptosis. It is concluded that the comparison of the degree of fragmentation of mitochondrial and nuclear DNA provides a quantitative way of distinguishing necrosis from apoptosis.
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PMID:Resistance of mitochondrial DNA to degradation characterizes the apoptotic but not the necrotic mode of human leukemia cell death. 836 46


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