Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deferoxamine (DFO) is an iron chelator that is known to inhibit acute non-lymphocytic leukemia cells in vitro. To explore the possibility that this drug has cytotoxic activity in vivo, rats were inoculated with a small lethal dose (10(2] of tumor cells from the transplantable BN acute myelogenous leukemia model. Animals were then treated with one of several regimens of bolus subcutaneous DFO: 10 mg/day x 5; 20 mg/day x 5; 10 mg/day x approximately 5 weeks; or no DFO. There were no consistently significant differences in survival between any of the DFO and untreated groups. Because the short plasma half-life of DFO was thought to be a potential reason for this lack of protection, a high molecular weight polymeric conjugate of DFO that is known to provide sustained intravascular drug levels was also studied. However, hydroxyethyl starch conjugated with DFO in amounts equivalent to 100 mg free drug (intraperitoneally for 5 days) also failed to have major impact on survival. These findings suggest that it may not be possible to achieve levels of this chelating agent in vivo that are cytotoxic for this disease.
 ...
PMID:Failure to alter the course of acute myelogenous leukemia in the rat with subcutaneous deferoxamine. 204 91

The majority of childhood acute leukemias can be classified as acute lymphoblastic leukemia and acute nonlymphocytic leukemia with light microscopy and cytochemical stains alone. However, myeloperoxidase-negative myeloblastic leukemias and megakaryoblastic leukemias, as well as some metastatic tumors, can mimic lymphoblastic leukemia when these cytologic examinations are used. Conversely, occasional cases of Sudan black B-positive ALL can be confused with myeloblastic leukemia. Thus, additional immunologic and sometimes further ultrastructural studies should complement the morphologic diagnosis of ALL. The significance of L1 and L2 subtypes of ALL is still controversial. Modern chemotherapy may have obscured any significance of this division. Future studies of lymphoblast morphology should center on biologic correlates of the L2 cytology. Little prognostic significance has been found for the morphologic variants of ALL, such as the granular and hand-mirror cell types. It is important not to confuse granular ALL with acute myeloblastic leukemia. Functional immunologic studies may help in delineating the cause of uropod formation in hand-mirror variant ALL.
 ...
PMID:Morphologic and cytochemical characteristics of childhood lymphoblastic leukemia. 222 93

The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach. 223 Nov 80

The in vitro incubation of NK cells with the lymphokine IL-2 stimulates the development of a population of activated cytotoxic lymphocytes (LAK cells). These activated cells have the capacity to recognize and kill a wide range of neoplastic cells. The cytotoxic activity of LAK cells does not appear to be directed against normal, non-neoplastic cells and we have recently examined the potential for using LAK cells as a method of purging bone marrow for autologous transplantation in patients with widespread neoplastic diseases. We have utilized an experimental system consisting of the incubation of LAK cells from inbred F344 rats and normal bone marrow and demonstrated that this procedure does not interfere with the ability of the treated bone marrow to reconstitute lethally-conditioned recipients. The frequency and rate of reconstitution is the same in treatment and control groups, including incubation periods that extend up to 18 hours. When RNK-16 leukemia cell line (a spontaneous large granular lymphocyte leukemia that is syngeneic to the F344 strain) is added to the incubation mixture, the LAK cells have the ability in vitro to recognize the neoplastic cells and prevent the transmission of the leukemia to naive animals following bone marrow transplantation. As expected from the in vitro LAK cytotoxic activity, these activated cells are capable of recognizing and eliminating a variety of neoplasms. To date we have tested three different hematopoietic tumor lines derived from the F344 strain and one that was induced in an unrelated BN strain. In each case, the F344 LAK cells demonstrated an ability to prevent the transmission of a fatal leukemia and significantly prolong the survival of animals that had received larger numbers of neoplastic cells. The tumor lines examined included the RNK-16 line (NK cells), the Dunning leukemia (monocyte-lymphoblastic leukemia), a T-lymphocyte lymphoma and the acute myelogenous leukemia of BN rats (BN AML). Comparison of the results of these purging experiments to those seen when control animals are injected with graded doses of the individual tumors indicate that the LAK cells are eliminating approximately 2-3 logs of neoplastic cells. The ability of LAK cells to kill a wide range of tumors without damage to the ability of the recipient stem cells to reconstitute the bone marrow may allow for an important application for this type of purging technique in patients with neoplasms for which specific immunological or chemical therapies do not exist.
 ...
PMID:Lymphokine-activated killer (LAK) cell purging of bone marrow. 230 77

Eighty consecutive patients were transplanted with human leukocyte antigen (HLA)-identical sibling marrow for acute myelogenous leukemia (AML, N = 29), acute lymphoid leukemia (ALL, N = 23), or chronic myelogenous leukemia (CML, N = 28). Donor marrow was depleted of lymphocytes using counterflow centrifugation. Median age of the recipients was 31 years. Pretransplant conditioning consisted of cyclophosphamide and fractionated total body irradiation (TBI) with a low (4.1 +/- 0.3 cGy/min) or high (13.1 +/- 1.6 cGy/min) midline average dose rate. In 43 patients, cytosine-arabinoside or anthracyclines were added to the conditioning regimen. Immunoprophylaxis posttransplant consisted of methotrexate (MTX) alone, cyclosporine A (CsA) in combination with MTX, or CsA alone; two patients received no immunoprophylaxis at all. Graft failure occurred in 4 of 77 evaluable patients (5%). The probability of acute graft-versus-host disease (GVHD) greater than or equal to grade 2 at day 100 after transplantation was 15%. The projected 3-year estimate of extensive chronic GVHD was 12%. Only three patients died of cytomegalovirus-interstitial pneumonitis. The projected 3-year probability of relapse was 30% (95% confidence interval [CI], range 8% to 53%) in transplants for AML in first complete remission (CR1), 35% (95% CI, 1% to 69%) after transplantation for ALL in CR1, and 38% (95% CI, 2% to 74%) after transplantation for CML in first chronic phase (CP1). The projected 3-year probability of leukemia-free survival (LFS) was 56% (95% CI, 35% to 77%) after transplantation for AML-CR1, 42% (95% CI, 16% to 69%) in patients transplanted for ALL-CR1, and 49% (95% CI, 18% to 80%) after transplantation for CML-CP1. After transplantation for AML-CR1, ALL-CR1, or CML-CP1, the median follow-up time for leukemia-free survivors was 31+, 30+, and 21+ months, respectively. Probabilities of relapse, survival, and LFS in AML-CR1 and ALL-CR1 transplants were comparable with those reported in recipients of untreated grafts. In patients transplanted for CML-CP1, probability of relapse was higher and probability of LFS was lower than in recipients of untreated grafts. In transplants for leukemia in CR1 and CP1, preparative regimen and immunoprophylaxis posttransplant were not associated significantly with the probability of acute GVHD greater than or equal to grade 2, extensive chronic GVHD, relapse, survival, or LFS. In bone marrow transplantation for leukemia, counterflow centrifugation is a useful technique for the prevention of GVHD.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Allogeneic bone marrow transplantation for leukemia with marrow grafts depleted of lymphocytes by counterflow centrifugation. 231 Aug 32

In a study of 55 patients with either acute lymphoid leukemia (ALL; 25 cases) or acute myeloid leukemia (AML; 30 cases), paraffin-embedded bone marrow particle sections were examined with a panel of monoclonal and polyclonal antibodies reactive toward lymphoid and myeloid-associated antigens, using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. All cases were previously classified according to the French-American-British (FAB) Co-operative Group, and cases of ALL were immunophenotyped by flow cytometry. Results indicated that myeloid-associated antibodies (Mac 387, KP 1 [CD68], antielastase, antilactoferrin, and antilysozyme) did not react with any case of ALL, M1-AML, or M6-AML, whereas at least one of these antibodies reacted with 20 of 21 (95%) cases of M2, M3, M4, and M5-AML. Anti-glycophorin C marked cases of M6-AML, whereas anti-CD3 labeled T-cell ALL. None of the antibodies tested specifically identified cases of B-cell ALL. The authors conclude that use of a selected panel of antibodies on paraffin-embedded bone marrow particle sections may be of value in the diagnosis and immunophenotypic classification of many cases of acute leukemias.
 ...
PMID:Immunophenotyping of acute leukemias using paraffin-embedded tissue sections. 232 81

The ultrastructural, light microscopical and immunological features of twelve cases of acute childhood leukemia are described. Nine cases were unclassifiable by light microscopy, morphology and cytochemistry, and three were difficult to classify because of a low percentage of Sudan-Black B positive blasts. By means of electron microscopy (including peroxidase cytochemistry), two main groups were seen: 1. Acute myeloid leukemia, in which could be distinguished a) a more differentiated myeloid leukemia, b) a leukemia with megakaryoblastic involvement and c) a minimally differentiated acute myeloid leukemia with granules present and 2. lymphoblastic leukemia. One case could not be classified. The first group included two possible cases of a hybrid leukemia with CD19 or CD10 positivity as well as ultrastructural peroxidase activity. We conclude that electron microscopy aids to further classification of minimally differentiated and hybrid acute leukemias.
 ...
PMID:Electron microscopy: a contribution to further classification of acute unclassifiable childhood leukemia. 235 May 92

Marrow transplantation is now preferred treatment, if the patient has a suitable identical twin or HLA-identical sibling donor, for aplastic anemia, acute myelogenous or lymphoblastic leukemia that has relapsed once, and is commonly employed for the treatment of acute myelogenous leukemia in the first remission, for chronic myelogenous leukemia in the chronic phase, and for certain congenital disorders. The results of transplantation from HLA-nonidentical donors appears promising, but the follow-up is short at this time. The low incidence of relapse or nonrelapse mortality beyond the first 3-5 years with follow-up now to almost 20 years from transplantation signifies that surviving patients are cured of their disease and are likely to have survival similar to the normal population thereafter. They will probably lead normal productive lives in society. These data support applying criteria for insurance candidacy of patients who have survived more than 5 years from marrow transplantation which are similar to criteria applied to other normal individuals.
 ...
PMID:Long-term results of bone marrow transplantation for leukemia or aplastic anemia. 235 90

The Southeastern Cancer Study Group conducted a phase I-II trial of sequentially administered 5-azacitidine and amsacrine in patients with refractory adult acute leukemia from September 1980 to March 1983. The 5-azacitidine was administered by continuous iv infusion on Days 1-4 at doses ranging from 112 to 200 mg/m2/day, while amsacrine was given at doses ranging from 75 to 150 mg/m2/day on Days 5-8. The doses of 5-azacitidine and amsacrine were alternately escalated through six dose levels during the phase I portion of the trial. Of 128 patients entered, 102 (80%) were evaluable for response. Remission was achieved in 13 of 80 evaluable patients with acute myeloid leukemia, in one of 12 evaluable patients with acute lymphoid leukemia, and in none of 11 patients with blastic transformation of chronic granulocytic leukemia. Three remissions occurred in patients with acute myeloid leukemia who were refractory to initial induction chemotherapy with cytarabine and anthracycline combination chemotherapy. Remissions were relatively durable, lasting a median of 28 weeks in the 13 patients with refractory acute myeloid leukemia (range, 14-54 weeks). Toxic effects included universal severe myelosuppression, hyperbilirubinemia at a frequency and severity similar to those seen with amsacrine used as a single agent, moderately severe stomatitis and diarrhea, three incidents of amsacrine-related cardiac dysrhythmia, and a single case of probable drug-related cardiomyopathy. This combination has activity in the treatment of myeloid leukemia, which is primarily resistant to cytarabine and anthracyclines, and could have a role in primary management.
 ...
PMID:Sequentially administered 5-azacitidine and amsacrine in refractory adult acute leukemia: a phase I-II trial of the Southeastern Cancer Study Group. 241 Jan 19

Hematological and cytogenetic characteristics of 75 cases of therapy-related acute non lymphoid leukemia (t-ANLL) occurring in Hodgkin's disease (HD) are analysed in this multi-institution study. Combined radio and chemotherapy had been given in 88 per cent of patients, either as adjuvant (44 per cent) or as salvage modality (44 per cent). Radiotherapy alone and chemotherapy alone had been given in 3 per cent and 9 per cent respectively. Eighty per cent of patients were in remission of HD and 71 per cent off-therapy while developing leukemia. The median latent time from remission of HD to leukemia was 34 months. The myeloblastic variety of leukemia accounted for 43 per cent of total cases; the myelomonocytic and monocytic for 17 per cent and 4 per cent, the promyelocytic and erythroblastic variants for 5 per cent and 7 per cent of t-ANLL. Twenty four per cent of cases were unclassifiable; one of these was TdT-positive. Dysplastic features of erythrocytic line were invariably present with circulating erythroblasts; defects of granulocytes, circulating megathrombocytes and micromegakaryocytes were also present. Bone marrow hypoplasia and marked fibrosis were documented in 47 per cent and 30 per cent of cases. Preleukemia heralded overt leukemia in 73 per cent of cases; 37 per cent had refractory anemia with no excess of blasts; 16 per cent of preleukemias were unclassifiable. Cytogenetics revealed chromosome abnormalities in 83 per cent of cases; 72 per cent presented chromosome 5 and/or 7 monosomy or partial deletion (5q- or 7q-) of the long arm (94 per cent in the combined modality therapy group). In 3 cases, a pure monosomy 7 was observed; in none 5q-alone. Response rate to conventional therapy was 14 per cent; low and high-dose cytarabine were of little benefit. Long-term CR (28 + and 16 + months) was achieved in 2 cases with allogeneic bone marrow transplantation (BMT) as first-line therapy. A better knowledge of t-ANLL in HD and new therapies, including BMT, may improve the prognosis of this late complication of intensive HD treatment.
 ...
PMID:Treatment-related leukemia in Hodgkin's disease: a multi-institution study on 75 cases. 243 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>