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)

The present study investigated the susceptibility of human leukemia cells to allogeneic lymphocytes with lymphokine-activated killer (LAK) activity from normal donors and autologous LAK activity from patients in complete remission. LAK activity was generated from peripheral-blood mononuclear cells cultured for 6 days with 1,000 U/ml recombinant interleukin-2 (IL-2). Cytotoxicity was evaluated using a standard 4-hour chromium release assay. Susceptibility of leukemic cells to LAK was defined on the basis of the mean Cr release in 52 samples of normal bone marrow cells. Using allogeneic LAK, we examined leukemic cells from bone marrow or peripheral blood of 252 patients [102 with acute myeloid leukemia (AML), 99 with acute lymphoblastic leukemia (ALL), 13 with chronic myelogenous leukemia in blast crisis (CML-BC) and 38 with chronic leukemias of various types]. A significant lysis could be detected in 62% of all leukemias tested (in 68% of AML, 60% ALL, 92% CML-BC, 39% chronic leukemias). The mean chromium release (effector-to-target cell ratio 50:1) was 28.8 +/- 13.5% for LAK-sensitive leukemias versus 5.2 +/- 3.2% for resistant leukemias. We observed a distinct susceptibility of various leukemia subtypes. LAK cytotoxicity against autologous leukemia cells was examined in 40 leukemia patients in complete remission (24 AML, 16 ALL). 63% of the patients developed a significant cytotoxicity against their autologous leukemia cells. Regarding mean Cr releases, the efficiency of allogeneic LAK activity of normal donors did not differ significantly from that of autologous LAK activity of patients in complete remission against the same leukemic target cells. Analysis of our data revealed that examinations with allogeneic LAK activity make it possible to predict whether patients will develop significant in vitro killing of their autologous leukemia cells during complete remission. These results may be of particular importance in determining which patients could benefit from immunologic therapy modalities and in scheduling immunotherapy. Further clinical studies are necessary to ascertain the clinical significance of therapeutic approaches with IL-2 or adoptive cellular immunotherapy combined with IL-2 for treatment of human leukemia.
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PMID:Susceptibility of human leukemia to allogeneic and autologous lymphokine-activated killer cell activity: analysis of 252 samples. 139

Immunological parameters were evaluated in patients treated with cytokine-mediated immunotherapy (CMI) consisting of low doses of recombinant human interferon alpha 2a (rIFN alpha) and recombinant human interleukin-2 (rIL-2) administered either concomitantly or sequentially by subcutaneous self-injections in an outpatient setting. Twenty-six patients with hematological malignancies and 2 metastatic melanoma patients in a progressive stage were enrolled in this clinical trial. Of the 26 patients, 24 were at a stage of minimal residual disease, including 14 patients who had received autologous bone marrow transplantation (ABMT) 2-5 months previously, 7 chronic myelogenous leukemia (CML) and 3 acute myeloid leukemia (AML) patients. Two patients (1 CML and 1 mult. myeloma) were treated at a stage of progressive disease. Non-MHC-restricted cytotoxicity directed against natural-killer(NK)-resistant (Daudi) and NK-sensitive (K562) target cells was assessed before, during and after CMI, either in fresh peripheral blood samples (spontaneous activity) or after in vitro rIL-2 activation (induced activity). Spontaneous killing activity was low prior to treatment, but increased upon termination of treatment in 10/15 evaluated cycels. rIL-2-activated cytotoxicity in vitro was markedly elevated in 8/12 and 6/8 patients after one and two cycles, respectively, of sequential treatment, as well as in 3/8 CML and 5/6 patients after one and two cycles, respectively, of concomitant treatment. Activation of the T cell mitogenic response was demonstrated in 6/9 patients after concomitant CMI, while no such effect was observed throughout a sequential treatment in lymphoma and leukemia patients after ABMT. Although a direct correlation between immune stimulation and the in vivo antitumor response cannot yet be determined, our clinical observations support a beneficial therapeutic effect in a substantial number of patients. These results indicated that the ambulatory CMI protocol of rIL-2 and rIFN alpha could stimulate the host defense immune system and may be helpful in mediating the in vivo antitumor response in patients with minimal residual disease.
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PMID:Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-alpha 2a and interleukin-2. 139 43

Eight cell lines were established from patients with adult T-cell leukemia, and from normal adults, by cocultivation with human T-cell leukemia virus type I(HTLV-I)-producer cell lines in the presence of interleukin-2. All of these cell lines harbored HTLV-I and showed T-cell markers CD2, CD3 and CD4, but not B-cell markers. Unexpectedly, all eight cell lines expressed a myeloid marker CD13 and three of the eight lines also expressed another myeloid marker CD33. Dual staining showed the simultaneous expression of CD3 and CD13 on the same cells. Thus, evidence was obtained for the expression of myeloid antigens on HTLV-I-harboring T cells.
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PMID:Simultaneous expression of T-cell and myeloid cell phenotypes in eight newly established HTLV-I-positive T-cell lines. 142 1

Recent investigations in animal models of human lymphoid and myeloid leukemia suggest that induction of immune-mediated antitumor effects is feasible at the stage of minimal residual disease (MRD) using allogeneic immunocompetent lymphocytes following initial reconstitution with T cell depletion and/or activation of reconstituting syngeneic or allogeneic immune cells by recombinant interleukin-2 (rIL2). Pilot clinical trials in patients with leukemias and lymphomas at high risk to relapse following autologous bone marrow transplantation (BMT) suggest that beneficial antitumor effects may be achieved at the stage of MRD by home immunotherapy as soon as hematopoietic reconstitution occurs using rIL2 (Cetus) and alpha interferon (Roferon A) (Hoffmann LaRoche). Although results obtained from our open trial seem encouraging, prospective randomized trials and longer observation periods are needed in order to confirm immune-mediated antitumor effects in conjunction with autologous BMT in patients with malignant hematological disorders at high risk to relapse. Likewise, it seems that amplification of anti-leukemia effects following allogeneic BMT is feasible by post-transplant infusion of donor's peripheral blood lymphocytes for prevention and/or treatment of relapse.
Leukemia 1992 Nov
PMID:Immunotherapy of minimal residual disease in conjunction with autologous and allogeneic bone marrow transplantation (BMT). 143 23

Interleukin-2 receptors are composed of at least two polypeptide chains of alpha (55KD) and beta (75KD). The IL-2R beta chain is an essential component of the functional receptor for signal transduction of IL-2. We previously reported the distribution of IL-2R subunits among peripheral blood mononuclear cells. We here present some data regarding the expression of IL-2R subunits on various hemopoietic malignant cells. Fresh leukemic cells obtained from adult T cell leukemia patients expressed both alpha and beta chains, and leukemic cells derived from some patients with T cell leukemia, B cell leukemia or myeloid leukemia expressed the alpha and/or beta chain of IL-2R. The IL-2R beta chain on these leukemic cells were demonstrated to be functional for cell growth signaling. IL-2R alpha and beta chains should be tumor markers.
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PMID:[The expression of IL-2 receptor subunits on various leukemic cells]. 144 19

Lymphokine activated killer cells have potent antitumor effect both in vitro and in vivo. They have been reported to suppress bone marrow (BM) progenitor cell activity (PCA) in vitro, thus raising concern about the feasibility of their use after autologous bone marrow transplantation. The present study was carried out to evaluate the effect of LAK cells on BM engraftment in a syngeneic BMT setting in mice. LAK cells supplemented with or without exogenous interleukin-2 therapy did not impair the hematopoietic reconstitution or survival of mice undergoing BMT. LAK cells also did not reduce the PCA of the engrafted BM. LAK cell therapy did not cause graft-versus-host disease. Finally, LAK cells supplemented with IL-2 therapy improved the graft-versus-leukemia effect. These findings suggest that LAK cells plus IL-2 therapy after BMT does not impede hematopoiesis and should be evaluated as an adjuvant therapy with the aim of eradication of minimal residual disease after autologous BMT.
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PMID:Lymphokine-activated killer cells in autologous bone marrow transplantation. Evidence against inhibition of engraftment in vivo. 146 68

The soluble Interleukin-2 Receptor (sIL-2R) serum levels were assessed in 42 patients with Hairy-Cell Leukemia (HCL) at diagnosis and after alpha-Interferon therapy and correlated with spleen size, peripheral hematological values, hairy cell index (HCI) and clinical response. Serum sIL-2R levels were significantly increased in all HCL patients, particularly in those with a higher HCI (> 0.50) and in non-splenectomized patients. Among the 26 HCL patients who were studied before and after 12 months of alpha-IFN treatment, 16 normalized the sIL-2R level and 10 did not. Our findings suggest that sIL-2R levels in HCL patients correlate with the splenic and bone marrow tumor burden as assessed by HCI. In addition patients with low levels of sIL-2R at diagnosis appear to have a better chance of achieving a good clinical response.
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PMID:Serum soluble interleukin-2 receptor levels in hairy cell leukemia: correlation with clinical and hematological parameters and with alpha-interferon treatment. 147 20

Although the application of biological therapy for solid tumors with cytokines and adoptively transferred activated lymphocytes has received substantial attention, this approach has not been actively explored in treatment of hematopoietic neoplasms. This review will address the possibilities of interleukin-2 (IL-2) and IL-2 activated natural killer (NK) cells and T cells in antileukemia reactivity and therapy. The new approaches to optimal activation and generation of oncolytic cells, selective propagation of lymphocyte subsets, and the role of adhesion molecules in antileukemia cytotoxicity will also be addressed. We trust that this article will be conducive to the development of new directions in leukemia research and treatment.
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PMID:Role of interleukin-2 activated MHC-nonrestricted lymphocytes in antileukemia activity and therapy. 147 26

Our studies on the susceptibility of fresh noncultured leukemia cells to interleukin-2 (IL-2)-induced lymphokine-activated killer (LAK) cells have shown that about two thirds of the leukemias are susceptible to the LAK-cell-mediated cytolysis. Analysis of 214 acute leukemias revealed considerable variation in the degree of cytotoxicity achieved. Cytolysis was substantially lower in fresh noncultured acute leukemia samples than in K562 and Daudi cell lines (mean Cr-release 21.0 +/- 16.0% versus 69.2 +/- 6.6% and 70.8 +/- 7.9%). Augmentation of susceptibility to LAK-cell lysis is desirable in connection with therapeutic application of IL-2-induced effector mechanisms. We observed a relationship between the LAK-cell susceptibility of leukemia cells and their spontaneous proliferation rate, which is significantly higher in LAK-cell-sensitive than in LAK-cell-resistant leukemias. It was therefore considered useful to examine the possibility of augmenting LAK-cell sensitivity by proliferation induction. These studies demonstrate that incubation of blast cells from acute myeloid leukemia (AML) and chronic myelogenous leukemia in myeloid blast crisis (CML-BC) with recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) significantly augments LAK-cell susceptibility and that this is associated with an increased cell proliferation.
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PMID:GM-CSF-mediated proliferation induction improves the susceptibility of leukemia cells to lymphokine-activated killer cells. 149 16

Interleukin-2 (IL-2) and interferon-beta (IFN-beta) have demonstrated activity against lymphoid malignancies, presumably mediated by the augmentation of lymphokine-activated killer (LAK) cell and natural killer (NK) cell activity. There is in vitro and in vivo evidence to suggest that the combination of IL-2 and IFN-beta is synergistic. The Cancer and Leukemia Group B (CALGB) conducted a randomized phase II trial of IL-2 with or without IFN-beta in 49 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL). Overall toxicity was severe, with 17 patients experiencing life-threatening toxicity. Three patients had treatment-related deaths. Responses were noted in seven patients (17%). There were no meaningful differences between treatment arms in toxicity profile, response rate, or modulation of in vivo NK and LAK activity. We conclude that IL-2 with or without IFN-beta is not effective therapy for NHL in the doses and schedule used in this study.
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PMID:A phase II study of recombinant interleukin-2 with or without recombinant interferon-beta in non-Hodgkin's lymphoma. A study of the Cancer and Leukemia Group B. 150 52


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