Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activated killer cells, unrestricted by major histocompatibility (MHC) antigens circulate in the peripheral blood of patients who have undergone autologous and allogeneic bone marrow transplant (BMT) and may contribute to the reduced risk of leukemic relapse observed after these procedures. Interleukin-2 (IL-2) in vitro augments this cytotoxicity and used therapeutically might thereby promote the eradication of minimal residual disease. In order to assess whether these effects on cytotoxicity can be reproduced in vivo, we studied changes in number, phenotype, and MHC unrestricted cytotoxicity of peripheral blood mononuclear cells obtained from patients with hematologic malignancy receiving IL-2 infusions. Patients with acute myeloid leukemia and multiple myeloma were treated after cytotoxic chemotherapy or autologous BMT. IL-2 infusions produced an initial lymphopenia, followed by a progressive recovery in mononuclear cell numbers and a rebound lymphocytosis after the termination of treatment. This affected all lymphocyte subsets; in particular CD25 (IL-2 receptor) positive cell numbers rose sevenfold. Cells with the ability to kill a natural killer (NK)-resistant, lymphokine activated killer cell (LAK)-sensitive target appeared in the circulation during 16 of 19 infusions and mean LAK activity rose from 5.9% to 15.5% during infusion (E:T ratio, 50:1; P less than .001). During IL-2 infusion, cells present in the peripheral blood inhibited the growth of myeloid leukemia blasts in agar after overnight co-culture. Depletion experiments showed that LAK activity was mediated by cells of both CD3- CD16+ (NK derived) and CD3+ CD16- (T derived) subsets. LAK precursor activity in peripheral blood also significantly increased during IL-2 infusion. Increases in major histocompatibility complex (MHC) unrestricted cytotoxicity can be produced by IL-2 infusions in vivo and may result in improved relapse-free survival following chemotherapy or BMT.
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PMID:Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo-radiotherapy for hematological malignancy. 280 69

Lymphocytes which appeared in the peripheral blood early (approximately 4 weeks) after complete bone marrow aplasia were studied in two groups of patients. Twenty-two allogeneic bone marrow transplant recipients and 12 acute nonlymphocytic leukemia patients (entering remission) were compared to 70 healthy control subjects studied during the same time interval. Studies performed included phenotyping T-cells using monoclonal antibodies and T-cell colony formation in response to phytohemagglutinin. The phenotypic profile for the two patient groups differed from each other and from that of the healthy controls. The total number of circulating cells reactive with OKT4 were significantly depressed in marrow graft recipients while only mildly, but significantly, depressed in leukemic patients. The number of circulating cells reactive with OKT8 were depressed in leukemic patients but were essentially normal in marrow graft recipients. The number of circulating cells reactive with OKla1 and OKT10 were significantly elevated in marrow graft recipients while significantly depressed in leukemic patients. The T4:T8 ratio was significantly depressed for marrow transplant recipients and significantly elevated for leukemic patients. T-cell colony formation in agarose without and with added interleukin-2 was decreased for both groups, more so for marrow graft recipients who virtually lacked the ability to make colonies without exogenous interleukin 2. These phenotypic and functional data suggest that T-cell reconstitution after bone marrow aplasia and profound lymphopenia takes quite different pathways for leukemic patients recovering from remission induction therapy and for recipients of bone marrow transplants. We were unable to correlate T-cell functional response in T-cell colony formation with the phenotypic profile of peripheral blood T-cells.
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PMID:T-cell phenotypic profile and colony formation during recovery from cytotoxic therapy-induced marrow aplasia. 393 27

Three specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) strains Petaluma, TM1 and TM2, respectively were observed for over 8 years. Without showing any significant clinical signs of immunodeficiency syndrome (AIDS) for 8 years and 4 months of asymptomatic phase, the Petaluma-infected cat exhibited severe stomatitis/gingivitis, anorexia, emaciation, hematological and immunological disorders such as severe anemia, lymphopenia, thrombocytopenia, and decrease of CD4/CD8 ratio to 0.075, and finally died with hemoperitoneum at 8 years and 8 months post-infection. Histopathological studies revealed that the cat had systemic lymphoid atrophy and bone marrow disorders indicating acute myelocytic leukemia (aleukemic type). Plasma viral titer of the cat at AIDS phase was considerably high and anti-FIV antibody titer was slightly low as compared with the other FIV-infected cats. In addition, immunoblotting analysis using serially collected serum/plasma samples of these cats revealed that antibodies against FIV proteins were induced in all the infected cats, however in the Petaluma-infected cat anti-Gag antibodies disappeared during the asymptomatic period. These results suggested that plasma viral load and anti-FIV Gag antibody response correlated with disease progression, and supported FIV-infected cats as a suitable animal model of human AIDS.
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PMID:Eight-year observation and comparative study of specific pathogen-free cats experimentally infected with feline immunodeficiency virus (FIV) subtypes A and B: terminal acquired immunodeficiency syndrome in a cat infected with FIV petaluma strain. 956 Jul 79

Mutations that activate the N-ras oncogene are among the most frequently detected genetic alterations in human acute myeloid leukemias (AMLs), Philadelphia chromosome-negative myeloproliferative disorders (MPDs), and myelodysplastic syndromes (MDSs). However, because N-ras has not been shown to induce these disorders in an in vivo model, the role of N-ras in the evolution of myeloid leukemia is unclear. To investigate the potential of N-ras to induce myeloid leukemia, lethally irradiated mice were reconstituted with bone marrow (BM) cells infected with a retroviral vector carrying activated N-ras. Approximately 60% of these mice developed hematopoietic disorders, including severe MPDs resembling human chronic myelogenous leukemia (CML) or AML with differentiation (French-American-British [FAB] classification M2). Other reconstituted mice succumbed to hematopoietic defects that were pathologically similar to human MDSs. The latter disorders appeared to be due to a myeloid impairment that was demonstrated by enumeration of day-12 colony-forming units-spleen (CFU-S) and by in vitro colony assays. A high level of apoptosis associated with thymic atrophy and peripheral blood (PB) lymphopenia was also evident in N-ras reconstituted mice. Our results are consistent with a model in which antiproliferative effects are a primary consequence of N-ras mutations and secondary transforming events are necessary for the development of myeloid leukemia. This is the first report of an in vivo model for N-ras induced MPD and leukemia.
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PMID:Mutant N-ras induces myeloproliferative disorders and apoptosis in bone marrow repopulated mice. 1006 78

We present a case of tuberculous meningitis in a patient with acute myelogenous leukemia. The patient was in complete remission; he had persistent lymphopenia and CD4+ T lymphocytopenia. Diagnosis was complicated by the chronic and subacute nature of symptoms; some originally thought to be secondary to depression and chemotherapy related toxicity. Treatment was further complicated by the unusual phenomenon of paradoxical progression of disease while on appropriate therapy. This case illustrates the importance of consideration of mycobacteriosis in the differential diagnosis of chronic unexplained fever complicating treatment for acute leukemia. The natural history and essential aspects of diagnosis and treatment of CNS tuberculosis are reviewed. The clinical significance of unexplained CD4+ T lymphocytopenia and chronic lymphopenia in patients with leukemia is also discussed.
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PMID:Tuberculosis meningitis in a patient with acute myelogenous leukemia. 1019 37

IL-7 is produced by stromal cells and is the major lympho- and thymopoietic cytokine. IL-7 induces proliferation and differentiation of immature thymocytes, and protects thymocytes from apoptosis by induction of bcl-2 expression. The regulation of IL-7 production is poorly characterized, although down-regulation by transforming growth factor-beta (TGF-beta) has been described. We measured the serum levels of IL-7 before and after bone marrow transplant (BMT) in 32 children undergoing BMT for genetic diseases (severe combined immune deficiency (SCID) and thalassemia), aplastic anemia, and acute lymphoblastic and non-lymphoblastic leukemia (ALL and ANLL). Prior to BMT, the highest IL-7 levels were observed in patients with SCID and ALL, i.e. those patients with genetic or acquired lymphopenia. Patients with thalassemia and ANLL had normal levels of IL-7. Over the 8 weeks following BMT, the IL-7 levels of patients with SCID and ALL fell as the absolute lymphocyte count (ALC) increased. No detectable change in IL-7 levels was observed in the patients with thalassemia and ANLL. Levels of IL-7 were highest in the young infants with SCID compared to the age-matched controls. Together, the data demonstrate that serum levels of IL-7 in lymphopenic patients are inversely related to patient age and the absolute lymphocyte count (ALC). The inverse relationship to ALC suggests that there is either direct regulation of stromal production or more likely, binding of secreted IL-7 to lymphocytes expressing IL-7 receptors.
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PMID:Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count. 1023 Nov 40

Early immune reconstitution after intensive chemotherapy for acute myelogenous leukemia (AML) occurs after 2-4 weeks of cytopenia, but T cell reconstitute is usually completed after several months. Interleukin-7 (IL-7) is a T cell growth factor involved in the late immune reconstitution, but its function during the early period of cytopenia has not been investigated. In the present study, we found that patients with untreated AML had decreased IL-7 serum levels, and induction chemotherapy had divergent effects on these levels. In contrast, patients in complete remission (CR) had intermediate levels immediately before consolidation therapy, and these levels decreased significantly when the patients developed therapy-induced cytopenia. Systemic IL-7 levels showed only minor increases during febrile neutropenia. Furthermore, IL-7 enhanced in vitro proliferative responses of polyclonal T cells derived from cytopenic patients, and the majority of circulating clonogenic CD4(+) and CD8(+) T cells from cytopenic patients could respond to both IL-2 and IL-7. To conclude, patients with untreated AML and severe chemotherapy-induced leukopenia (1) differ from other patients with CD4(+) T lymphopenia in that they show decreased IL-7 serum levels, and (2) the detection of circulating IL7-responsive T cells indicates that variations in systemic IL-7 levels are functionally important and contribute to an additional qualitative T cell defect in these severely T lymphopenic patients.
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PMID:Interleukin-7 (IL-7) in patients receiving intensive chemotherapy for acute myelogenous leukemia: studies of systemic IL-7 Levels and IL-7 responsiveness of circulating T lymphocytes. 1243 86

IgA deficiency is a relatively common congenital immunodeficiency in children. It can either be asymptomatic or lead to frequent infections, most often of the sinuses and lungs. Intensive chemotherapy for acute leukemia is also profoundly immunosuppressive and can be complicated with life-threatening infections, usually associated with neutropenia and prolonged lymphopenia in the post-bone marrow transplant setting. Isolated, acquired immunoglobulin deficiency that occurs during treatment has been described but is usually transient. In this report, the authors describe a patient with infant acute myelogenous leukemia with acquired, persistent IgA deficiency.
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PMID:Isolated IgA deficiency after chemotherapy for acute myelogenous leukemia in an infant. 1463 25

Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.
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PMID:An indolent case of severe acute respiratory syndrome. 1469 7

Proteasome inhibitors, a novel class of chemotherapeutic agents, enhance the antitumor efficacy of anthracyclines in vitro and in vivo. We therefore sought to determine the maximum tolerated dose (MTD) and dose-limiting toxicities of bortezomib and pegylated liposomal doxorubicin (PegLD). Bortezomib was given on days 1, 4, 8, and 11 from 0.90 to 1.50 mg/m2 and PegLD on day 4 at 30 mg/m2 to 42 patients with advanced hematologic malignancies. Grade 3 or 4 toxicities in at least 10% of patients included thrombocytopenia, lymphopenia, neutropenia, fatigue, pneumonia, peripheral neuropathy, febrile neutropenia, and diarrhea. The MTD based on cycle 1 was 1.50 and 30 mg/m2 of bortezomib and PegLD, respectively. However, due to frequent dose reductions and delays at this level, 1.30 and 30 mg/m2 are recommended for further study. Pharmacokinetic and pharmacodynamic studies did not find significant drug interactions between these agents. Antitumor activity was seen against multiple myeloma, with 8 of 22 evaluable patients having a complete response (CR) or near-CR, including several with anthracycline-refractory disease, and another 8 having partial responses (PRs). One patient with relapsed/refractory T-cell non-Hodgkin lymphoma (NHL) achieved a CR, whereas 2 patients each with acute myeloid leukemia and B-cell NHL had PRs. Bortezomib/PegLD was safely administered in this study with promising antitumor activity, supporting further testing of this regimen.
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PMID:Phase 1 trial of the proteasome inhibitor bortezomib and pegylated liposomal doxorubicin in patients with advanced hematologic malignancies. 1562 43


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