Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our previous study, we found that serum beta 2-microglobulin (beta 2M) levels were elevated in the active, but not in the inactive, phase of adult T-cell leukemia (ATL), suggesting a correlation between the beta 2M level and the clinical severity of this disease. In this study we examined the mechanisms underlying the elevation of serum beta 2M levels in ATL. First, the production of beta 2M by ATL cells was investigated in vitro. High levels of beta 2M were detected in the conditioned culture medium (CM) of ATL cells from seven out of nine patients. Second, we assessed the effects of the CM on the release of beta 2M by three human cell lines unrelated to ATL (NCTC 2544, Chang liver, and L 132; originating from the skin, the liver, and the fetal lung, respectively). Most of the CM definitely promoted beta 2M production by these cell lines. beta 2M production by the cell lines was markedly promoted by exogenous interferon-gamma (IFN-gamma), a well-known potent inducer of class I HLA antigen expression. We then investigated whether an antibody directed against IFN-gamma could attenuate the activity of three ATL CM. The anti-IFN-gamma antibody reduced the stimulatory activity of the CM to 28-65% of the original level, but did not affect basal beta 2M production by these cell lines. These data suggest that there are at least two mechanisms causing the elevation of serum beta 2M levels in ATL; direct production by tumor cells, and production by non-malignant cells that is mediated via humoral factors secreted by the ATL cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Possible mechanisms for the elevation of serum beta 2-microglobulin levels in adult T-cell leukemia. 151 Nov 67

Bone marrow transplantation from an HLA-identical sibling is increasingly used as a curative therapy for patients with hemopoietic stem cell disorders including acute leukemia, chronic myelogenous leukemia and severe aplastic anemia. Between March 1983 and March 1991, we performed 86 cases of allogeneic bone marrow transplantation (BMT) for the patients with hemopoietic stem cell disorders: 25 acute myelogenous leukemia (AML); 15 acute lymphoblastic leukemia (ALL); 20 chronic myelogenous leukemia (CML); and 26 severe aplastic anemia (SAA). Ten out of 25 AML are in disease free survival (DFS). The causes of death were recurrence of leukemia (12), acute GVHD (3), sepsis (1) and veno-occlusive disease (1). Nine of 15 ALL are in unmaintained remission. Thirteen out of 20 CML are in DFS. Among 26 SAA, 21 are enjoying DFS, but 1 died of engraftment failure, 3 of graft rejection followed by cytomegalovirus (1) and aspergillus pneumonia (1). Comparing the survival between standard [less than or equal to CR1: 9/14 (64%)] and high risk [greater than or equal to CR1: 1/11 (9%)] AML, our data suggest that preparative regimen for high risk AML was not potent enough to eradicate the minimal residual disease in advanced AML. Although our cases are limited and the follow-up period is short, our result of ALL [overall: CCR (60%), standard risk (adult less than or equal to CR1, children less than or equal to CR2; 8/11 (73%) and high risk; 1/4 (25%)] and CML [overall: 65%, CP; 9/10 (90%), AP; 4/6 (67%), BP; 0/4 (0%)] are optimistic. It is of our interest that the incidence of death related with IP (1/33: 3%) and with AGVHD 94/33: 12%) were much less than that of other's observation but the explanation for this still remains to be clear.
 ...
PMID:Allogeneic bone marrow transplantation for the patients with hemopoietic stem cell disorders: CUMC experience. 151 32

Leukaemia and its associated therapy result in pathophysiological peculiarities relevant to anaesthesia. Leukaemic patients suffer from anaemia, coagulation disorders, and the consequences of immunosuppression. In addition, some patients show infiltrations of the oropharynx, potentially resulting in difficult intubation and/or pharyngeal haemorrhage. Mediastinal masses can induce complete airway obstruction during general anaesthesia. Patients with a white blood cell count (WBC) greater than 100,000/mm3 (hyperleukocytosis) can suffer from the leukostasis syndrome with acute respiratory failure as well as cerebral vascular occlusions and bleeding due to increased blood viscosity and disturbed microvascular perfusion. Since this syndrome may be triggered by surgery, the WBC should be reduced prior to general anaesthesia in patients with hyperleukocytosis. To avoid development of the leukostasis syndrome, transfusion of packed red cells should be restricted in these patients. Hyperleukocytosis can simulate in-vitro hypoxaemia due to the excessive oxygen consumption of the mass of leukaemic blood cells during routine blood gas analysis. Therapy of leukaemia can lead to the tumor-lysis syndrome with hyperuricaemia, hyperphosphataemia, hyperkalaemia, hypocalcaemia, and hypoglycaemia, and may induce acute renal failure. Since drug interactions have only been evaluated for the combination of two or three drugs, interactions of cytotoxic agents with anaesthetics can hardly be predicted because of the large number of drugs simultaneously administered to leukaemic patients. The heart and lungs are target organs for the acute or chronic side effects of cytotoxic drugs, resulting in non-cardiogenic pulmonary oedema (e.g., cytosine-arabinoside), lung fibrosis (e.g., bleomycin), or arrhythmias and cardiac failure (e.g., adriamycin). The severity of these side effects depends on pre-existing organ disease and only in part on drug dosage. Only HLA- and CMV-compatible blood components should be administered to leukaemic patients. Hyperleukocytosis and the first days of cytotoxic treatment represent relative contraindications to general anaesthesia.
 ...
PMID:[Pathophysiologic and anesthesiologic characteristics of patients with leukemia]. 152 54

A total of 239 patients with chronic myeloid leukaemia (CML) in chronic phase awaiting bone marrow transplantation (BMT) from an HLA-identical sibling donor were randomized to receive, as part of their conditioning, splenic irradiation (SI+) or no splenic irradiation (SI-). There was no difference between the SI+ and SI- groups regarding the distribution of age, sex, donor/recipient sex combination and blood counts at diagnosis and at BMT. Survival, leukaemia-free survival (LFS), incidence of transplant-related mortality, incidence of rejection and probability of relapse do not differ between the 117 SI+ and the 118 SI- patients at a median follow-up time of 2.5 years (minimum 0.5 years). LFS at 30 months is 56% (SE 5%) for the SI+ and 51% (SE 6%) for the SI- group (p = 0.65). LFS is better for younger patients (less than 25 years), for patients without T cell depletion and for those with a low white blood cell count at diagnosis (less than 30 x 10(9)/l) (p less than 0.05). It is worst for male recipients of a female marrow (p less than 0.05). The incidence of graft-versus-host disease grade greater than or equal to II was higher in the SI+ group, though not significantly. We conclude that routine splenic irradiation prior to BMT for patients with CML is of no benefit and should not be used as a routine procedure.
 ...
PMID:No advantage for patients who receive splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia: results of a prospective randomized study. 152 4

The association of graft-versus-host disease (GVHD) with lower relapse rates following allogeneic bone marrow transplantation (BMT) in humans led us to analyse post HLA-identical BMT derived anti-host cytotoxic T cells (CTL) for their putative anti-leukemic activity. To establish whether graft-versus-host (GVH) and graft-versus-leukemia (GVL) activities are separate, CTL lines were generated at different time points post-BMT from three patients suffering from acute GVHD. These CTL lines, which exhibited lysis of host normal lymphocytes and neoplastic cells, were analysed at the clonal level. Three functionally different types of clones were characterized: clones directed at host specific minor Histocompatibility (mH) antigens which are shared by patient's peripheral blood lymphocytes (PBL) and leukemic cells; clones recognizing only host PBL but not host leukemic cells; and putative GVL clones directed at patient's neoplastic cells only. These data could explain the long controversies on dissection of GVH and GVL activities. Our results demonstrate that GVH and GVL activities can be dissected, while non-separable effector cells which exhibit both activities do exist as well.
 ...
PMID:In vitro separation of host specific graft-versus-host and graft-versus-leukemia cytotoxic T cell activities. 152 8

This study was undertaken to ascertain the frequency of compatible sibling donors for individuals requiring bone marrow transplantation (BMT) in Ireland. During the study period 1984-89, a total of 392 patients were HLA typed. Of these, 218 (55.6%) had a compatible sibling donor. Among the latter there were 4 degrees of compatibility: 168 (42.9%) were HLA-A,B,DR identical MLC unreactive: three (0.8%) were HLA-A,B,DR identical MLC reactive: 12 (3.0%) were HLA-A,B,DR identical (no MLC performed) and 35 (8.9%) were HLA-A, B identical (no DR or MLC performed). The leukaemias and aplastic anaemia comprised 82.9% of all requests. The majority of patients with acute myeloid leukaemia (64.4%), acute lymphoblastic leukaemia (51.2%), chronic myeloid leukaemia (73.9%) and aplastic anaemia (77.3%) had a potential sibling donor. Subsequently 144 of these patients had an allogeneic BMT, 79.9% of which were for patients with leukaemia (acute and chronic). This study found that there was a higher probability of finding a donor within the family than reported in most series. A clear relationship was demonstrated between family size and the likelihood of obtaining a HLA-identical sibling donor.
 ...
PMID:Probability of finding a compatible sibling donor for bone marrow transplantation in Ireland. 153 37

The results of pretransplant mixed leukocyte culture (MLC) assays were compared to subsequent risk of graft-versus-host disease (GVHD) in 783 patients receiving marrow transplants from HLA genotypically identical sibling donors. The mean MLC response observed between 1303 normal HLA identical sibling pairs was 0.0 +/- 4.2% RR. The donor anti-recipient MLC reaction, an in vitro response that presumably might be relevant to GVHD, was significantly increased (greater than mean + 2 sd) in 83 (10.6%) of the cases, most often in patients in relapse at the time of testing. No association was found, however, between this increased donor anti-recipient MLC reactivity pretransplant and the incidence or severity of subsequent acute or chronic GVHD. These data suggest that the increased MLC responses sometimes observed between leukemia patients and their HLA identical sibling donors prior to marrow transplantation do not represent genetic differences capable of causing GVHD.
 ...
PMID:Mixed leukocyte culture reactivity and graft-versus-host disease in HLA-identical marrow transplantation for leukemia. 843 17

The presence of two distinct T-cell receptors (TCR) alpha/beta and gamma/delta dimers as well as of the activated T cells was analysed in peripheral blood mononuclear cells from seventeen recipients of allogeneic bone marrow transplants for leukemia and for severe aplastic anemia. Nine of seventeen recipients expressed an elevated percentage of T cells bearing TCR gamma/delta receptors in their peripheral blood. Seven out of nine cases having elevated gamma/delta positive cells showed chronic graft-versus-host (GVH) disease; one patient was treated with Cyclosporin A, and one patient was asymptomatic. In the twelve patients with GVH or other clinical symptoms, activated T cells (CD3+/HLA-DR+) were elevated indicating an autoreactive or alloreactive cell population. Our results confirmed earlier in vitro data showing that TCR-gamma/delta-bearing lymphocytes may be an activated T-cell population, and this T cell subset might be involved in mediating GVH disease, or in prolonging immunodeficiency after transplantation.
Leukemia 1992
PMID:TCR gamma/delta bearing lymphocytes in peripheral blood of allogenic bone marrow transplanted patients. 153 60

Recent studies performed in Seattle, USA have suggested that pretransplant assignment of high or low donor alloreactivity may predict acute graft-versus-host disease (aGvHD) after allogeneic HLA identical marrow transplantation for acute leukaemia. The effect of such pretransplant assignment was studied in a Scandinavian population of 114 consecutive transplantations for acute and chronic leukaemias in 1st remission (n = 74) or chronic phase (n = 40) performed between 1975 and 1989. The selected cut-off value for discriminating between donors of high and low responding capacity (DRC) was based on distribution plots of results from the pretransplant mixed lymphocyte culture (MLC) and chosen as the median value (80% normalized response). Then 57 donors were assigned with high DRC and 57 donors assigned with low DRC. Kaplan-Meier estimates of the probability of patients to develop Grade II or higher aGvHD in receipt of high or low responder donor transplants were compared by univariant analysis. The patients in first remission or chronic phase transplanted with bone marrow from donors assigned as high or low responders had a 36.1% and 10.6% risk for aGvHD, respectively, a difference found to be significant by log rank test (chi-squared = 10.1, d.f. = 1, P = 0.0015). Subsequent studies of the cellular and humoral requirements for this predictive response of donor cells, by blocking with cytokine specific antibodies, addition of excess of recombinant human cytokines and scanning of lymphocyte subsets during the response, showed that the response against pool cells mostly depended upon IL-2 responding cells with the phenotype CD3+, CD4+, CD8-, CD25+, CD16-. It is concluded that prospective studies of alloreactivity as a risk factor should be performed to confirm the above findings.
 ...
PMID:A study of donor alloreactivity, which may predict acute graft-versus-host disease in HLA identical bone marrow transplantations for early leukaemia. 153 90

We have followed for 33 months the changes that occurred in natural killer (NK) cell numbers and activity in a patient (A) with hairy cell leukaemia (HCL), using a single cell assay and a microcytotoxicity assay. The composition of the peripheral blood mononuclear cell population and malignant cell phenotype were also analysed. During this period he received treatment with interferon and his grossly enlarged spleen was removed. Four further patients were also studied, two were splenectomized and all had received treatment with interferon. In four of the five patients studied there was an apparent link between low NK activity and presence of a tumour-infiltrated spleen, and in the fifth patient, who was aleukemic and had no splenomegaly, NK function was related to disease activity. There was no correlation between NK activity and the number of target binding (TB) cells in these five patients. IFN had little direct effect on overall NK activity, but the proportion of killing cells among TB cells was increased. Three patients showed binding of several cells to a single target. Further analysis revealed that in the patients most of the TB cells were not CD56-positive NK cells, in contrast to TB cells from normal subjects. In patient A a large proportion (84%) of TB cells were identified as malignant cells and in patient E 15% of TB cells were malignant cells. The phenotype of the malignant cells was: CD19+, HLA-DR+ and CD25(Tac)+, except for patient A. In this patient the hairy cells were positive for the NK marker CD56 as well as the monocyte marker CD14. Furthermore, a change occurred in phenotype as only later samples carried CD25. It is concluded that the level of NK function correlates closely with disease activity in HCL and that competitive target cell binding by malignant cells may be one cause of depressed NK-cell function in hairy cell leukaemia.
 ...
PMID:Natural killer cell function and malignant cell phenotype in hairy cell leukaemia. 153 17


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