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)

Low doses of endotoxin were administered to normal and acute anc chronic myeloid leukaemic subjects. Temperature, leucocyte count, blood colony stimulating activity and the number of circulating colony forming units were monitored. All subjects acquired fever while the leucocyte count remained unaltered. Blood CSA rose sharply in 6 normal individuals, but failed to increase in 4 acute leukaemic patients and in 2 patients with CML in blast crisis. 2 patients with CML in the chronic stage increased their blood CSA comparable to normal individuals. The number of circulating colony forming units rose following endotoxin with a peak at 30 min and declined subsequently. 4 patients with acute leukaemia showed no increase of circulating colony formers.
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PMID:Endotoxin-induced colony stimulating activity in normal and myeloid leukaemic subjects. 31 73

A combination of cyclosporine (CSA) and methylprednisolone (MP) was used as graft-versus-host disease (GVHD) prophylaxis in 25 patients age 11-47 years (median 27 years) who received HLA-compatible sibling marrow transplants after myeloablative therapy for leukemia, myelodysplasia or lymphoma. CSA was initiated at 3 mg/kg/day in two divided doses, and the dose was adjusted to maintain a trough whole blood h.p.l.c. concentration between 200 and 800 ng/ml. While on i.v. CSA, the dose of CSA was increased for 10 of the 25 patients. The actuarial rate of grades II-IV acute GVHD was 37%. Those patients who developed moderate to severe GVHD had a significantly higher early mortality than those who did not (56% vs 12%, p = 0.02). There was a significant association between the development of acute GVHD and a mean week 2 CSA trough concentration less than 250 ng/ml. Life threatening regimen-related toxicities in the first 100 days included capillary leak syndrome, acute pancreatitis and small bowel perforation. Although the combination of CSA and MP in this dosing schedule was active in preventing acute GVHD, nephrotoxicity remained a problem, and outcome was limited by the inability to achieve the target CSA trough concentration in a substantial proportion of patients.
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PMID:Cyclosporine and methylprednisolone after allogeneic marrow transplantation: association between low cyclosporine concentration and risk of acute graft-versus-host disease. 187 93

In adult leukemic marrow recipients of HLA identical sibling marrow, 23 patients were randomized to T cell depletion and 25 received cyclosporin (CSA) and four doses of methotrexate (MTX) to prevent graft-versus-host disease (GVHD). Anti-CD8 and anti-CD6 antibodies plus complement depleted 95.3 +/- 5.8% (mean +/- SE) CD3 cells. All patients engrafted except one who died early. Patients receiving T cell-depleted marrow had a faster time to 0.2 x 10(9) WBC/l (p less than 0.001), but required more erythrocyte units (p = 0.03). Platelet transfusions, infections and time in hospital did not differ. The incidence of grade II-III acute GVHD was 23% following T cell depletion and 12% for those receiving CSA + MTX. Chronic GVHD occurred in 51% and 23% in the two groups, respectively (p = 0.06). Recipients of T cell-depleted marrow who developed grade I-III acute GVHD received more T cells compared to those without acute GVHD (p = 0.02). The major cause of death in both groups was relapse, the cumulative incidence of which, at 4 years, was 39% in the recipients of T cell-depleted marrow and 54% in the CSA + MTX group. The 3-year actuarial leukemia-free survival was 42% and 44% in the two respective groups.
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PMID:Prevention of graft-versus-host disease with T cell depletion or cyclosporin and methotrexate. A randomized trial in adult leukemic marrow recipients. 205 58

Regulation of haemopoiesis in the marrow of patients with myelodysplastic syndromes (MDS) was evaluated by assaying (1) the production of haemopoietic regulators acting upon multipotent and committed progenitors by MDS marrow cells, and (2) the responsiveness of MDS marrow progenitors to stimulation with granulocyte colony-stimulating factor (G-CSF). The levels of multipotent progenitor cell colony-stimulating activity (CFU-GEMMCSA) in 7 d bone marrow-conditioned medium (BMCM) from MDS patients were markedly reduced as compared to controls. MDS BMCM also exhibited reduced levels of burst-promoting activity (BPA) for primitive erythroid (BFU-E) progenitors. Both CFU-GEMMCSA and BPA detected in BMCM were completely neutralized by antibodies directed against interleukin-3. MDS BMCM exhibited markedly reduced levels of murine-active CSA. This activity was partially neutralized by anti-CSF-1 antibodies. Levels of regulators in BMCM of refractory anaemia (RA), sideroblastic anaemia. RA with excess blasts, and chronic myelomonocyte leukaemia were virtually the same. CFU-GEMM and BFU-E growth in MDS marrow (n = 9) was markedly reduced. A 5-fold saturating dose of G-CSF induced an approximately 2-fold increase in CFU-GEMM in four of eight MDS and a 1.5-fold increase of BFU-E in five of nine MDS, but not in control (n = 5) marrow cell cultures. Impaired haemopoiesis in MDS marrow may be related to abnormalities both in regulator production by marrow accessory cells and in regulator responsiveness of multipotent and committed progenitors.
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PMID:Regulatory abnormalities in the marrow of patients with myelodysplastic syndromes. 247 8

Thy 1.2+ cells of L8313 leukemia bearing mice were previously shown to produce granulocyte macrophage colony stimulating activity (GM-CSA) and interleukin-3 (IL-3). Cell lines with the Thy 1.2+ phenotype were established from spleen cells of the leukemic mice, and were designated STIL-3 C5 and STIL-3 D10. They produced and released GM-CSA and IL-3 activities in culture supernatant. C5 cells were phenotypically Thy 1.2+ and Lyt 2.1+ with rearrangement of the T-cell receptor beta chain gene also being identified. D10 was Thy 1.2+ and L3T4+ with T-cell receptor beta chain gene rearrangement not detectable. Since the same sized rearranged bands were observed between C5 and L8313 leukemic mouse spleen cells, it is indicated that C5 cells are derived from the leukemic cells. Inoculation of these cells into mice induced granulocytosis. These results indicated that L8313, which was thought to be a "granulocytic leukemia", is actually a T-cell leukemia, whose granulocytosis is a leukemoid reaction induced by normal hemopoietic cells responding to the hemopoietic stimulating factors, GM-CSA and IL-3, produced by the leukemic T cells. Thus, L8313 should be known as a T-cell leukemia associated with granulocytosis.
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PMID:Establishment of a hemopoietic stimulating factor producing murine leukemia cell lines: pathogenesis of granulocytosis in L8313 bearing mice. 290 47

In conclusion, a culture system is now available that reproducibly facilitates the development of megakaryocyte colonies and the emergence of megakaryocytes within multilineage colonies. The assay is dependent upon the use of human plasma and a source of exogeneous MEG-CSA. Patients with perturbed hemopoiesis plasma may contain activities able to replace exogeneous MEG-CSA. This system can therefore be used to evaluate MEG-CSA activities. In addition it is now feasible to study blast populations of patients with leukemia characterized by a megakaryocyte phenotype.
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PMID:Human megakaryocytopoiesis in cell culture. 390 Oct 29

Sera from patients with aplastic anemia and amegakaryocytic thrombocytopenia contain an activity that stimulates megakaryocyte colony formation in vitro. We have assayed this megakaryocyte colony-stimulating activity (Meg-CSA) in sera of four patients receiving intensive antileukemic chemotherapy to determine whether the appearance of Meg-CSA is a physiologic response to the suppression of megakaryocytopoiesis. Three of the four patients were receiving consolidation or late intensification therapy for acute myoblastic leukemia (AML) in remission. The fourth was receiving induction therapy for de novo AML. During all or part of four chemotherapeutic cycles, serial Meg-CSA levels were assessed and correlated with the corresponding peripheral platelet counts. All courses of cytotoxic chemotherapy resulted in increases in serum Meg-CSA comparable to activity levels present in sera from patients with aplastic anemia. Two of the three patients studied during the early postchemotherapy interval manifested initial serum Meg-CSA elevations seven days before their thrombocytopenic nadirs when platelet counts were still between 100,000/mm3 and 140,000/mm3. Bone marrow recovery from chemotherapy was characterized by a decrease in serum Meg-CSA to pretherapy levels that occurred concurrently with the rise in platelet count to normal. These observations support the hypothesis that Meg-CSA is a physiologic humoral regulator of megakaryocytopoiesis elaborated in response to the depletion of either bone marrow megakaryocytes or megakaryocyte progenitor cells.
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PMID:Human serum megakaryocyte colony-stimulating activity increases in response to intensive cytotoxic chemotherapy. 633 51

One hundred and nineteen patients with leukaemia have received CSA as prophylaxis against acute GVHD following sibling MHC matched (84) or family member mismatched bone marrow transplants (35). four recipients of matched transplants (3%) died of acute GVHD, a marked improvement on our previous results using methotrexate (26 patients; 27% died of GVHD). Thirty-five patients received mismatched transplants, 15 were under the age of 20 years and eight are alive and in remission, the longest survivor being one at 2 1/2 years after transplant.
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PMID:Cyclosporin A following matched and mismatched family allogeneic bone marrow transplants. 634 98

It is apparent from the accompanying Table 9 and Figure 5, that transplantation offers an improved survival in AML. The use of CSA has made possible the technique of a mis-matched transplant, but as yet an unrelated donor has not been used. It may be that tolerance is more easily established with a one haplotype mis-match than with a completely unrelated person who may, nevertheless, be HLA identical. Clearly this would be an exciting project for the future, provided that all problems concerning relapse of disease and GvHD are overcome, and will also probably depend upon improvements in tissue typing techniques. (table; see text) Certainly we would now recommend this form of treatment to all patients under 40 years of age, in first remission from AML. Patients above this age, have responded less well and have been prone to more complications. We do not as yet know whether a complete remission is essential prior to embarking on a graft; certainly a few patients have been in early relapse, and this does not seem to have necessarily produced a poor outcome. Florid relapse at the present time is a definite contra-indication and no patients have been grafted in this situation. It will be noted that results for acute lymphoblastic leukaemia and chronic granulocytic leukaemia are bad. The first group were grafted early in the programme, but the number of relapses was extremely high and was accompanied in many circumstances by interstitial pneumonitis. Transplantation in chronic granulocytic leukaemia, a disease in which the prognosis has not improved for the past 20 years, has also not been successful except in one syngeneic graft. Two of the three deaths were in previously treated patients, one in blast transformation, but the third was virtually untreated and GvHD was a very serious problem indeed. Other reports of grafting for CGL have been discouraging except in twins. All these deaths occurred early. Whether this therapeutic approach will remain a treatment of choice remains to be seen, but we are very encouraged by our progress so far, although much work remains to be done.
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PMID:Bone marrow transplantation in acute myeloid leukaemia. 676 73

With very few exceptions, it has not been possible to grow human myeloid cells for long periods in culture. We have recently developed techniques enabling the long-term in vitro propagation of normal immature myeloid cells from fresh foetal cord blood and monocytes from normal adult peripheral blood, and have utilized these procedures to initiate cultures of fresh peripheral blood leukocytes from leukemic donors. In four of 26 leukemic samples tested, leukocyte replication beyond that obtained in control cultures was observed, and in one of these HL-92, derived from the peripheral blood of a patient with acute myelomonocytic leukemia, the culture has continued to replicate slowly for over 2 years under the special growth conditions. Morphological, cytochemical, immunological and functional studies show that the culture consists predominantly of immature myeloid cells (myeloblasts through to myelocytes) but also contains some mature neutrophils and monocytes. At least a portion of HL-92 cells express Fc and complement receptors, contain histacompatibility locus antigens, including HLA-DR, and release GM-CSA, low levels of PGE and lysozyme. HL-92 cells can be induced with DMSO or RA to differentiate into mature neutrophils (an increase from 20 to 70% of the cell population) as determined by morphology, by an increase in phagocytic cells, and superoxide anion production. Fresh leukocytes from the patient's bone marrow appeared to have a diploid karyotype. However a consistent chromosomal abnormality observed in HL-92 was a deletion in the long arm of chromosome 11 [del(11)(q23)]. This is consistent with recent observations in monocytic leukemia. Since the few other established human myeloid cell lines have various chromosomal abnormalities, and some respond to differentiation inducers, while others do not, there appears to be no detectable common chromosome change required either for in vitro growth of myeloid cells or their response to inducers of differentiation. These cell lines and the application of the techniques described here for the growth of myeloid cells from other leukemic or normal sources should be helpful in the study of normal and leukemic myeloid cell growth and differentiation.
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PMID:Establishment, characterization and differentiation induction of a new human diploid myelomonocytic cell line (HL-92) derived from a patient with acute myelomonocytic leukemia. 696 Dec 68


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