Gene/Protein Disease Symptom Drug Enzyme Compound
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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 concept that HLA-linked immune response genes may influence survival of patients with malignant disease has been investigated by performing HLA typing on a series of 150 patients with acute myelogenous leukemia. Patients with A1 and B8 and/or A2 and B12 survival longer than patients without either of these pairs of antigens in association. However, after correction of the statistical probability for the number of A and B locus combinations theoretically possible, these differences are not statistically significant. Clarification of this must await independent analysis of other series and more direct approaches to the study of immune response genes in man.
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PMID:HLA linked resistance factors and survival in acute myelogenous leukemia. 26 69

Frequencies of 25 HLA antigens in 526 Caucasian patients were compared to those in 629 healthy controls who were HLA-typed between September 1975 and February 1977. Haplotypes were compared for 711 patients and 549 controls typed between September 1974 and December 1976. Frequency deviations were found in those with ALL, AML, breast cancer, lymphoma and ovarian cancer, but only the increase in A29 in AML patients was statistically significant when corrected for the number of specificities. Interesting associations, when compared with earlier studies, include elevation of AW24 in both ALL and AML patients and increased B27 in ALL patients. Significant haplotype differences were increased A3-B8 and absence of A1-BW17 in ALL patients and increased A11-B5 and A2-BW40 as well as absence of A2-B5 in AML patients.
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PMID:HLA frequencies in cancer: a third study. 28 33

Seventy-nine Caucasians with acute myelogenous leukemia (AML) were genotyped to determine whether AML, the induction of remission or patient survival were associated with particular HLA phenotypes or haplotypes. HLA-B17 and B27 were increased in AML patients over 40 years of age. Combined analysis of four independent studies indicates that HLA-B17 is significantly but weakly associated with AML, relative risk = 1.48 (.01 less than P less than .025). The A1, B17 and Aw24, Bw35 haplotypes occurred more frequently in the AML group as compared to racial and geographic controls (uncorrected P = 0.0068 and 0.0098, respectively Fisher's Exact Test). Induction of remission occurred less frequently in patients with the B17 phenotype as compared to patients lacking this antigen (P = 0.047). Patient survival was associated with remission status (P = 0.002) but was not significantly associated with particular HLA phenotypes or haplotypes. These results indicate that a gene or genes in the HLA-B region of the major histocompatibility complex can influence susceptibility to AML and also the response to chemotherapy.
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PMID:HLA-B17 and the HLA-A1, B17 haplotype in acute myelogenous leukemia. 29 Nov 40

Short-term culture of acute myelogenous leukemia patient's remission lymphocytes with inactivated autologous leukemic blast cells plus allogeneic lymphocytes, generated effector T lymphocytes which were cytotoxic for the specific autologous blast cell in 11 of 14 patients studied. Experiments using Daudi and Molt 4 lymphoblastoid cell lines as third-party helper cell suggest that an HLA D locus incompatability is necessary to provide effective help in this system. Cold target inhibition experiments, crossover studies between pairs of patients, and experiments with allogeneic leukemic blast cells as priming stimulus suggest that the target antigen is only present on the specific autologous blast cell.
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PMID:Autologous leukemia-specific T-cell-mediated lymphocytotoxicity in patients with acute myelogenous leukemia. 30 61

A 22-yr-old man with acute myelocytic leukemia received a bone marrow transplant from a genotypically HLA-identical female sibling after cyclophosphamide preparation. He remained in complete remission for 18 mo, when he developed a chloroma in the perineum. The chloroma was treated with local radiotherapy. The chloroma recurred 8 mo later and was treated with radiotherapy followed by combination chemotherapy. At 34 mo after transplant, marrow relapse and chloroma were documented. The first chloroma contained host cells by fluorescent Y-chromatin body analyses of interphase nuclei. All metaphase cells and karyotypes from peripheral blood and marrow samples showed no evidence of host cells from 3 wk after transplant through the time of marrow relapse. Data from autosomal and sex chromosome studies indicate that the marrow relapse occurred in cells of donor origin. A new consistent chromosome abnormality [45, X, -X, t(8;21) (q22; q22)] was observed in a majority of donor cells. The patient received a second bone marrow transplant from the same donor after preparation with busulfan and cyclophosphamide and attained a complete remission with full hematologic engraftment.
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PMID:Cytogenetic evidence for recurrence of acute myelogenous leukemia after allogeneic bone marrow transplantation in donor hematopoietic cells. 35 3

Bone marrow (BM) morphology was studied in patients who underwent bone marrow transplantation (BMT) for severe aplastic anaemia (SAA) and acute myeloid leukaemia (AML). Four patients with SAA had marrow transplanted from HLA-identical siblings after conditioning with cyclophosphamide (CY); three cases of AML were treated with allogeneic BMT. The medullary material was generally obtained by aspiration, but treated so as to preserve its architecture; fresh, postvital preparations were particularly useful for this purpose. In SAA, the bone marrow before transplantation showed dense infiltrates composed of macrophages and other inflammatory cells; after BMT, repopulation started at the periphery of the infiltrates, when they were not totally destroyed by CY. Granulocytic repopulation generally preceded erythropoiesis, which always occurred by way of typical erythroblastic reticulocytopoietic islands. Marked but transient dyserythropoiesis was found in two cases; in one of them, it was considered as drug-dependent. Both in SAA and in AML, but more so in the latter, a marked and sometimes imposing macrophagic hyperplasia was found after transplantation. Many macrophages were actively engulfing erythrocytes and nucleated cells. This last type appeared prominent in rejection episodes.
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PMID:Transplantation haemopoiesis. Morphological bone marrow studies after allogeneic marrow transplantation in man for severe aplastic anaemia and acute leukaemia. 39 Apr 94

In nonmalignant disease, there have been two mechanisms implicated in the association of HLA antigens with disease. In ankylosing spondylitis, evidence is accumulating for cross tolerance between a bacterial antigen and the HLA-B27 antigen; while in the autoimmune diseases, the involvement of an abnormal immune response gene, associated with A1/B8 haplotype, is strongly suspected. The same haplotype has also been associated with recovery from hepatitis B infection and survival of patients with Hodgkin's disease and acute myeloid leukaemia. At present, there are no techniques to study directly immune response genes in man and so these observations are still strictly academic. However, with increasing interest in the use of immunotherapy in cancer and the demonstration in mice that the major histocompatibility system may be the site of action of soluble mediators of immune memory, understanding the mechanisms of action of the HLA associated resistance factors may enable a more rational approach to immunotherapy in man.
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PMID:The HLA system and immunological defence against cancer: a review. 63 42

The outcome of sixty-four patients with acute leukemia in first remission who had been treated with either bone marrow transplantation (BMT) or conventional chemotherapy was retrospectively evaluated (a median follow-up of 37 months). Among them, 26 patients (age range; 14-42 years) received allogeneic BMT from HLA-identical siblings and 38 patients (age range; 13-43 years) who had no HLA-identical donors undertook the continued combination chemotherapy. Kaplan-Meier product-limit estimate of actuarial survival of acute myelogenous leukemia (AML) patients was 48.9% for the BMT group and 15.7% for the chemotherapy group (p = not significant, NS). For acute lymphoblastic leukemia (ALL) patients, the survival following BMT was 80.2% and was significantly higher than that of the chemotherapy group of 33.3% (p < 0.05). The disease-free survival of AML and ALL for the BMT group was 34.3% and 36.5%, respectively, which was higher than that of the chemotherapy group (16.7% and 23.4%, respectively (p = NS)). These findings in our Japanese single institution study suggested that BMT may be the treatment of choice for adult patients with acute leukemia in first remission if they had suitable donors and that more effective therapeutic regimens were necessary for patients without compatible donors in order to obtain the longer remission duration.
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PMID:Comparison of the survivals between bone marrow transplantation and chemotherapy for acute leukemia in first remission--a Japanese single institution study. 129 Sep 60

Most recent progress in the treatment of leukemia and choice of therapies for obtaining "cure" from leukemia are discussed. Chemotherapy can now provide about 40% long term survival in acute myeloblastic leukemia (AML) and about 20% disease-free survival in acute lymphoblastic leukemia (ALL) of adults. Bone marrow transplantation (BMT) should be applied for the patients at risk in those leukemias (Cytogenetic abnormalities for AML and prognostic factors in ALL). In CML patients, BMT offers the only cure. Update result of interferon (IFN) therapy for CML is still a matter of controversy. Ex vivo treatment of autologous cells with IFN or drugs may be beneficial for CML patients without HLA identical donor.
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PMID:[Recent advances in the chemotherapy of leukemias]. 138 49

Allogeneic bone marrow transplantation (BMT) has been associated with a graft-vs.-leukemia (GVL) reactivity. Since T cell depletion of the bone marrow graft has decreased the risk of graft-vs.-host disease (GVHD), but has been associated with higher rates of leukemia relapse, GVL reactivity is probably caused by donor-derived T lymphocytes. Previously, we demonstrated that minor histocompatibility (mH) antigen-specific cytotoxic T lymphocyte (CTL) clones, generated from patients after BMT, are capable of major histocompatibility complex-(MHC) restricted lysis of (clonogenic) myeloid leukemic cells. Here, we investigated whether donor-derived leukemia-specific CTL clones can be generated in vitro, before BMT, using irradiated leukemic cells from a patient with acute myeloid leukemia as stimulator cells, and peripheral blood or bone marrow from the HLA genotypically identical sibling donor as responder cells. Several CTL lines were generated that showed specific lysis (> 50%) of the recipient leukemic cells in a 51Cr-release assay. Two of these CTL lines were cloned by limiting dilution in the presence of the irradiated recipient cells. Multiple leukemia-reactive, HLA class I and II-restricted clones with various specificities could be established. These alloreactive, antileukemic CTL clones may cause GVL reactivity after BMT, and may be used as adjuvant immunotherapy in the treatment of leukemia.
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PMID:Generation of leukemia-reactive cytotoxic T lymphocyte clones from the HLA-identical bone marrow donor of a patient with leukemia. 140 74


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