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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interleukins comprise a class of hormones that have a definite known secondary and tertiary structure under physiologic conditions. The interleukin-2 is the leader in T cell differentiation. The interleukin-2 acts via interaction with high affinity, cell bound receptors (IL-2R). High affinity IL-2 receptors are constructed by cooperative binding of IL-2 to both the low affinity (55-Kd chain) and intermediate affinity (75-Kd chain) binding sites. The light (55-Kd) chain of these heterodimeric receptors is identified by monoclonal antibodies as TAC antigen. A soluble form of these receptors is released in the serum and it can be assayed by ELISA. Extraordinarily high levels of IL-2R are characteristic of hairy cell leukaemia. Smaller increases of IL-2R have been reported in other haematological conditions as well as in other disorders including AIDS, organ transplantation etc. Moreover, we have recently demonstrated that IL-2R is elevated in lung cancer.
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PMID:[The interleukin-2 receptor]. 188 56

In a search for mechanisms of potential graft-versus-leukaemia (GVL) activity after allogeneic bone marrow transplantation (BMT), peripheral lymphocytes from five patients (four chronic myeloid leukaemia, one acute lymphoblastic leukaemia) 24-39 days post-transplant were precultured with pretransplant host leukaemia cells and then cloned by limiting dilution with interleukin-2 (IL-2). Clones obtained were exclusively CD3+ CD56-, carried the alpha/beta form of the T cell receptor for antigen, and were mostly (88% of 138) CD4+. None of 143 clones, including CD8+ clones, convincingly lysed host pretransplant cells, although 35 (24.5%) manifested lytic potential in lectin-mediated cytotoxicity assays. Measuring the proliferative responses of 118 of these clones in the presence of exogenous IL-2 revealed that a small number of clones reacted more strongly to host leukaemia than to unrelated leukaemias or B lymphoblastoid cell lines. In the two cases tested, the donor's untransplanted lymphocytes cloned under the same conditions as post-transplant cells did not generate any clones reacting preferentially with host leukaemia cells. These results may suggest that some T cells appearing shortly after allogeneic BMT could potentially mediate anti-leukaemia activity not associated with cytolysis of target cells.
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PMID:Cytotoxic and proliferative functions of T lymphocyte clones derived very shortly after allogeneic bone marrow transplantation. 193 51

We determined nine immune function parameters at diagnosis in patients with myelodysplastic syndromes (MDS) and correlated the results with the FAB classification and prognosis by univariate and multivariate analyses. Patients with refractory anaemia (RA) and refractory anaemia with ring sideroblasts (RAS) tended to have a higher CD4/CD8 ratio and a lower amount of gamma-globulins and soluble interleukin-2 receptors in serum in comparison to those suffering from the other three subgroups of MDS. FAB classification, neutrophil and CD8+ T-cell number had the best discriminatory capacity for predicting survival less than 1 year, and FAB classification, neutrophil number and serum TNF levels were predictors for conversion to acute leukaemia. The frequent occurrence of infections, on the other hand, could be better predicted by the absolute numbers of neutrophils and CD4+ cells and by the skin test score.
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PMID:Immune function parameters at diagnosis in patients with myelodysplastic syndromes: correlation with the FAB classification and prognosis. 195 86

To help understand host-tumor relationships in adult acute lymphoblastic leukemia (ALL) and to better define potential indications for interleukin-2 (IL-2) treatment in this disease, the relationship between the susceptibility of leukemia cells of 22 patients with ALL to lysis by allogeneic lymphokine-activated killer (LAK) cells and characteristics of the leukemia was studied. Lymphocytes were activated in the presence of 1000 U/ml recombinant IL-2 for 5 days. The lysis of ALL cells was studied by the release of 51Cr. The average lysis of ALL cells by control, unactivated lymphocytes was 1.2 +/- 2.4% and by LAK cells 8.9 +/- 8.6%. The susceptibility of leukemic cells to lysis did not correlate with the expression of lymphoid or myeloid differentiation markers or expression of the adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3). Leukemic cells of the FAB I2 subtype were significantly more resistant to lysis than those of the other subtypes (average lysis 1.4 +/- 3.0% versus 12.3 +/- 8.2%, p = 0.003). The susceptibility to lysis did not correlate with the other initial characteristics of the leukemia. The 11 patients in whom 8% or more of leukemic cells were lysed by allogeneic LAK cells survived significantly longer than the 11 patients whose blast cells were less susceptible to lysis (p = 0.04). It is concluded that IL-2 treatment might be of benefit in adult ALL, particularly in non-L2 FAB subtypes and during complete remission to possibly delay relapse and prolong survival.
Leukemia 1991 Nov
PMID:Susceptibility of adult acute lymphoblastic leukemia blasts to lysis by lymphokine-activated killer cells. 196 Oct 38

Rhesus peripheral blood mononuclear cells (PBMC) fail to demonstrate natural killer (NK) activity against the human T-cell lines CEM, CEM x 174, or SUP-T1. However, these cell lines could act as NK-sensitive target cells if they were pulsed with heat-inactivated, whole simian immunodeficiency virus (SIV). The ability of these SIV-pulsed T-cell lines to act as NK-sensitive target cells was directly related to the relative density of CD4 on their surface. Target cell generation was inhibited by preincubation of cell lines with CD4 monoclonal antibody (MAb) with specificity for the SIV binding site. In addition, NK activity was seen against target cells that had been prepared with human immunodeficiency virus type 1 (HIV-1) gp120, nonglycosylated gp120, env A of feline leukemia virus (FeLV), and simian type D retrovirus (SRV). Addition of leupeptin to target cells prior to SIV pulsing did not result in a significant decrease in cytotoxic activity, suggesting that processing is not required for the generation of target cells. The cells that mediate NK activity are nonadherent, do not form rosettes with AET-treated sheep red blood cells (SRBC), and are phenotypically CD16+ and CD8+. NK activity of SIV-infected macaques was significantly decreased against both K562 cells and SIV-pulsed target cells as compared with uninfected animals. However, treatment of PBMC with interleukin-2 (IL-2) resulted in a partial restoration of NK activity.
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PMID:Natural killer cell activity of rhesus macaques against retrovirus-pulsed CD4+ target cells. 197 94

A case of acute adult T-cell leukemia-lymphoma (ATLL) was observed in northeast Italy, presenting with fever, lymphadenomegaly, splenomegaly, hypercalcemia and renal failure. Leukaemic cells were morphologically typical, expressed a T-cell CD4+ phenotype, did not display any helper functions, and grew in vitro under supply of exogenous interleukin-2. Antibodies to human T-cell lymphotropic virus (HTLV-I) were found in the serum, and the virus was isolated from leukaemic cells. The family members who could be tested were seronegative. The patient had never travelled outside Italy, had never received blood transfusions and did not belong to any known categories at risk of viral disease transmission. Present knowledge of the epidemiology of HTLV-I infection warns that other cases of HTLV-I induced disease are expected to occur outside already recognised endemic areas. This case suggests that untraceable, presumably short-term exposures can also account for HTLV-I transmission.
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PMID:HTLV-I positive adult T-cell leukaemia-lymphoma: report of a typical case from Italy. 198 Apr 80

Immunotherapy with recombinant human Interleukin-2 (rhIL-2) was given to nine patients in first complete remission from acute myeloid leukaemia (AML). Five patients relapsed. The median time to relapse after commencing rhIL-2 was 26 weeks (range 2-44). Four patients were studied at relapse. The morphological and cytochemical features at relapse and presentation were similar. Cytogenetic analysis at relapse in patients 1 and 3 showed a normal karyotype. At relapse, patient 4 had the abnormality 46,XY, t(2;3). Patient 2 had the chromosomal abnormality t(8;21) at presentation and relapse. Patients 3 and 4 with M5 AML relapsed rapidly at 2 and 9 weeks after starting rhIL-2 treatment. Relapse leukaemia cells had features normally associated with lymphoid development. Patient 3 was TdT positive, with rearranged immunoglobulin genes, and a proportion of cells expressing the CD7 antigen; patient 4 also expressed the CD7 antigen. Relapse leukaemic cells from three of four patients expressed the alpha chain of the IL-2 receptor as assessed by flow cytometry. After overnight incubation and removal of T-lymphocytes the proportion of cells from these patients expressing the alpha chain increased from 15% to 61% (P less than 0.01). Using tritiated thymidine uptake to assess cell proliferation, two of three patients who expressed the IL-2 receptor alpha chain proliferated in response to 1000 u/ml of rhIL-2 in vitro, with a stimulation index greater than 1.95 (P less than 0.05). Following rhIL-2 immunotherapy for AML, relapse cells may express an inducible form of the alpha chain of the IL-2 receptor, which can mediate a proliferative response. It is possible that rhIL-2 when administered to AML patients in remission, may induce relapse. This may be a particular risk in patients with the M5 subtype.
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PMID:Acute myeloid leukaemia relapsing following interleukin-2 treatment expresses the alpha chain of the interleukin-2 receptor. 195 99

Adherent lymphokine activated killer (ALAK) cells are a subpopulation of activated natural killer (NK) cells with MHC unrestricted antitumour activity distinguished by their propensity to adhere to plastic in the presence of interleukin-2 (IL-2). We generated ALAK cells from seven patients with chronic myeloid leukaemia (CML) following Campath-1-depleted bone marrow transplantation (BMT). Five had relapsed and were in chronic phase, one had cytogenetic evidence of relapse and one had prior evidence of cytogenetic relapse but was in complete remission at time of study. Phenotypically the ALAK cells included both CD56+/CD3- NK cells and CD56-/CD3+ T cells. The CD3- subpopulation were studied cytogenetically and their functional activity tested in a 4 h 51Cr release cytotoxicity assay using the pretransplant leukaemia cells as targets. Cytogenetic studies showed that the ALAK cells from six patients were Ph negative, and where donor and recipient were sex mismatched, ALAK cells were exclusively of donor origin. In one patient ALAK cells were Ph positive and of recipient origin in eight of nine metaphases. In the 51Cr release assay the ALAK cells showed significant lysis of the pretransplant leukaemia in five of the seven patients tested. These data indicate that in CML patients who relapse post-BMT the NK cells are usually of donor origin but may be recipient-derived. In most patients these ALAK cells have antileukaemic activity in vitro.
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PMID:Origin and function of adherent lymphokine activated killer cells in patients with chronic myeloid leukaemia who relapse following bone marrow transplantation. 199 98

Serum interleukin-2 (IL-2), soluble IL-2 receptors (sIL-2R) and tumor necrosis factor-alfa (TNF-alpha) levels were determined in 66 previously untreated consecutive patients with acute myeloid leukemia (AML) and in 22 normal volunteers. The following mean (+/- SE) values were observed in patients and controls, respectively: 35 +/- 14.7 (range 0.5-500) and 0.7 +/- 0.02 (0.5-0.8 U/ml for IL-2 (p = 0.001); 1622 +/- 289 (110-10,600) and 422 +/- 30 (207-666) U/ml for sIL-2R (p = 0.0001); 1247 +/- 196 (218-4672) and 152 +/- 11 (75-308) pg/ml for TNF-alpha (p = 0.0001). With respect to the FAB classification system, we found a significantly different distribution of serum IL-2 mean values in distinct subcategories, i.e. 3.4 +/- 1.9 U/ml in M1-M2-M3 and 42.4 +/- 20.4 U/ml in M4-M5 subgroups, respectively (p = 0.01), whereas sIL-2R and TNF-alpha levels were 1144 +/- 322 U/ml and 1120 +/- 317 pg/ml in M1-M2-M3 patients and 1945 +/- 317 U/ml and 1270 +/- 259 pg/ml in the M4-M5 group. A significantly positive correlation between TNF-alpha and sIL-2R (r = 0.53; p = 0.002) was also detected in the M4-M5 group. Sixty-three out of 66 patients received an intensive chemotherapy program. Univariate analysis showed that age and sIL-2R greater than 2000 U/ml significantly affected both complete remission rate and overall survival, whereas by multivariate analysis, age was the only independent variable significantly influencing survival. These data confirm recent in vitro evidence suggesting the role of IL-2, sIL-2R, and TNF-alpha in the control of normal hematopoiesis and leukemogenesis. Since the availability of recombinant cytokines for clinical use in AML, it is crucial to understand their spectrum of interaction in order to select the appropriate combination for in vivo administration.
Leukemia 1991 Jan
PMID:Serum interleukin-2 (IL-2), soluble IL-2 receptors and tumor necrosis factor-alfa levels are significantly increased in acute myeloid leukemia patients. 199 55

The clinical significance of pleural effusion was assessed in 24 children with unresectable abdominal small non-cleaved cell lymphoma (St. Jude Stage III). Patients were consecutively enrolled and treated on a regimen including high dose fractionated cyclophosphamide and co-ordinated high dose methotrexate and cytarabine. The overall results were excellent, with 20 of 24 patients alive and event-free at a median follow-up of 4 years. Only one of the patients who lacked pleural effusion has relapsed (testicular), even though many had massive disease. In contrast, three of seven patients with pleural effusion have failed treatment (p = 0.02) and subsequently died. Two measures of tumor burden, serum lactic dehydrogenase and, in a subset of patients, interleukin-2-receptor levels, were significantly higher in patients with pleural effusion (p = 0.002 and p = 0.05, respectively). These findings suggest that unresectable abdominal small non-cleaved cell lymphoma associated with pleural effusion should be up-staged and that these patients should receive more intensive chemotherapy.
Leukemia 1991 Jan
PMID:Pleural effusion is associated with a poor treatment outcome in stage III small non-cleaved cell lymphoma. 199 58


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