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)

Treatment with the monoclonal antibody OKT3 specific for the CD3 complex associated with the T cell antigen receptor can reverse acute rejection of human renal allografts. However, efficacy of anti-CD3 antibodies for treatment of patients with acute graft-versus-host disease after marrow transplantation has not been established. The dose-limiting side effects resulting from T cell activation induced by some anti-CD3 antibodies in vivo have discouraged their use for this application. We now report a phase I-II study of GVHD treatment with the anti-CD3 antibody BC3, a monoclonal murine IgG2b that, unlike OKT3, does not activate T cells. Fourteen patients were treated with BC3 after progression of acute GVHD despite treatment with cyclosporine and corticosteroids, and three patients received BC3 as primary treatment for GVHD. BC3 was administered at a dose of 0.1 or 0.2 mg/kg/day for seven or eight days. Five patients achieved complete resolution of GVHD, eight patients had partial improvement, two patients had no change, and two patients had progression of GVHD on therapy. Responses were sustained in 8 of 13 patients. Mild chills, fever, hypertension, and chest discomfort occurred in various combinations following 6 of 17 (35%) initial infusions of BC3 and following 4 of 99 (4%) subsequent infusions. In each instance it was possible to continue BC3 therapy without adjusting the dose or treatment schedule. In each patient treated, the absolute count of peripheral blood lymphocytes decreased transiently but returned to baseline within 22 hr after the first infusion. Circulating T cells had surface CD3 molecules saturated by the infused antibody in all but one patient. Four patients survived longer than one year after treatment with antibody BC3, and 13 patients died of infection or organ failure. Administration of the nonmitogenic anti-CD3 antibody BC3 was associated with improvement in the clinical manifestations of GVHD with minimal acute toxicity. Efficacy of antibody treatment did not depend on depletion of circulating T cells. Therefore, antibody BC3 may be achieving therapeutic immunosuppression by modulating T cell function. Controlled studies in patients treated earlier in the course of GVHD should determine whether antibody BC3 can improve survival.
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PMID:Treatment of acute graft-versus-host disease with a nonmitogenic anti-CD3 monoclonal antibody. 144 Aug 52

Bacterial infection is a common complication after allogeneic bone marrow transplantation. It is related to the toxic effects of the conditioning regimen on mucosal surfaces, to bone marrow aplasia and to the prolonged lymphopenia with immune deficiency that lasts for several weeks after bone marrow transplantation. We have performed a prospective randomized study comparing two methods of prophylaxis. Group I (OA) received a combination of ofloxacin 400 mg/day and amoxicillin 20 g/day; group II (VTC) received the oral nonabsorbable antibiotics vancomycin 450 mg/day, tobramycin 450 mg/day and colistin 4.5.10(6) units daily, from day -15 to 15 days after discharge from laminar air flow (LAF) rooms. All patients were nursed in LAF rooms with a strict isolation procedure and sterile water and food. They were evaluated daily for clinical symptoms, and bacterial culture samples were taken from the throat, stools and blood twice weekly. Forty-four patients were randomized, 22 entered in group I (OA) and 22 in group II (VTC). There were no differences between the two groups in age (mean 33 years, range 11-54), sex, diagnosis and mean duration of agranulocytosis (21.8 days, range 10-49). Seven patients were excluded because of the selection of a resistant bacteria, 5 were in group I (OA), and 2 were in group II (VTC). The mean duration of fever was 9.2 +/- 7.1 days in group I (OA) and 13.7 +/- 6.8 days in group II (VTC; p = 0.05). There were no significant differences between the two groups in graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prophylaxis of bacterial infections after bone marrow transplantation. A randomized prospective study comparing oral broad-spectrum nonabsorbable antibiotics (vancomycin-tobramycin-colistin) to absorbable antibiotics (ofloxacin-amoxicillin). 204 63

Immunologic reconstitution was studied in 24 patients who underwent bone marrow transplantation, 17 allogenic and 7 autologous. The GVHD prophylaxis consisted of methotrexate and prednisone. The complete immune evaluation was to be carried out prior to transplantation at 1, 2, 3, 6, 9, 12 months after BMT and subsequently every 6 months up to 4 years. The investigated immunological parameters included total lymphocyte count, B-lymphocytes, T3-, T4-, T8-lymphocytes, T4/T8 ratio, natural killer cell activity, ADCC, lymphocyte blastogenic response and serum-IgG, -IgA, -IgM. Absolute lymphocyte count, B-lymphocytes, T3-lymphocytes recovered to normal levels after 6 months. T4-lymphocytes decreased significantly during the first 180 days posttransplant. T8-lymphocytes increased after 6 months to values higher than normal and the T4/T8 ratio decreased significantly and continued below 0.8 for 48 months. Patients without and with GVHD had low lymphocyte response to PHA and Con A for the first 6 months.
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PMID:Immunoreconstitution after human bone marrow transplantation. 248 Mar 1

Acute graft-versus-host disease (aGVHD) of the liver was studied with fine-needle aspiration biopsies of thirty-four bone marrow transplant recipients. White cell differentials of liver FNABs and simultaneously taken blood samples were performed, and the increment and corrected increment methods were used to quantitate the inflammatory reaction in the liver. Biopsies taken before transplantation were used as the baseline. During aGVHD, the percentage of lymphoid cells and monocytes increased in the liver. The appearance of immunological blasts, together with a high proportion of activated lymphocytes in the FNABs, were typical findings during aGVHD. In patients with apparent prolonged liver graft-versus-host disease small lymphocytes were the predominating cell type. After initiating corticosteroid treatment, the number of blasts and the proportion of activated lymphocytes decreased. There was no significant difference in the proportions of CD4- and CD8-positive lymphoid cells in FNABs during or after aGVHD.
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PMID:Monitoring of bone marrow transplant recipient liver by fine-needle aspiration biopsy. 259 86

The purpose of this paper is to demonstrate the effect of the transfusion of blood received 1500 rad exposure upon the immune response in 14 patients underwent various type of cardiac surgery. 13 patients received known amounts banked blood and irradiated fresh blood, while one patient received a lot of amounts of banked and irradiated and non-irradiated fresh blood. The authors studied the numbers of lymphocytes as well as lymphocyte subsets such as pan-T cells, B cells, helper/inducer T cells (TH/I), cytotoxic/suppressor T cells (Tc/s), active T cells, natural killer (NK) cells and NK cell activity during two weeks after surgeries. In all 14 patients, pan-T lymphocytes decreased markedly in a few days after surgeries, but increased to higher levels on the eight postoperative day than the levels preoperatively. TH/I and TC/S lymphocytes changed on the similar pattern as pan-T lymphocytes. Active T and B cells did not change significantly in two weeks. The number and activity of NK cells gave the lowest levels on the second postoperative day and did not recover to the preoperative levels in two weeks. One patient received non-irradiated fresh blood showed the similar immune response as other 13 patients, while he gave the lower levels than others did. This patient died of graft-versus-host disease (GVHD)-like syndrome on the 36th postoperative day. It may be thought that the transfusion of irradiated blood would prevent the host from GVHD and gave the better effects on the immune response than that of non-irradiated blood following open-heart surgeries.
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PMID:[The effects of transfusion of irradiated blood upon cellular immune response in patients underwent open heart surgery]. 260 Apr 70

Isolator-maintained CBH/Ola (Rtlc) rats were lethally irradiated and reconstituted with spleen and bone marrow cells from fully allogeneic WAG or Wistar (Rtlu) donors. Hematopoietically reconstituted rats were treated with cyclosporine (CsA)4 as prophylaxis for graft-versus-host disease (GVHD) for periods ranging from 6 to 26 weeks. Following the termination of CsA treatment GVH reactivity developed in all recipients of allogeneic cells regardless of the duration of immunosuppression. Approximately a third of the reconstituted rats survived the post-CsA period of GVH activity; these rats carried peripheral lymphocytes and spleen cells of donor strain origin and were specifically unresponsive to donor strain skin grafts. Surviving chimeras remained healthy for long periods (up to 18 months) after transplantation, although morbidity increased slightly for rats moved to normal animal house conditions. However, all chimeras had some degree of lymphopenia and showed diminished immunological responses to extraneous antigens and third-party skin grafts. Experiments to elucidate the mechanisms by which specific tolerance was maintained in chimeras indicated that neither the deletion of host-reactive lymphocytes from the graft nor an absence of host bone-marrow-derived "stimulator" cells was responsible. It was shown that the potential GVH reactivity of normal donor strain cells was specifically suppressed in vivo (in the chimera) and that this suppression could be transferred to secondary irradiated recipients by transferring chimeric spleen cells. Attempts to demonstrate a role for suppressor cells in the maintenance of the chimeric state yielded inconclusive results.
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PMID:The effect of limited courses of cyclosporine on survival and immunocompetence of allogeneic bone marrow chimeras. 293 20

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), frequently found in the acquired immune deficiency syndrome (AIDS), have been suspected of contributing to the latter immunodeficiency. The ability of normal HLA-identical sibling bone marrow to reconstitute an 8-month-old infant with severe combined immunodeficiency infected with these two viral agents is of interest. After presentation with severe mucocutaneous candidiasis, cavitary pulmonary disease, nodular cutaneous lesions, and hepatic abscesses containing acid-fast organisms, immunologic studies revealed lymphopenia, 1-3% T cells, and no lymphocyte responses to mitogens. Prior to transplantation, the infant's blood B lymphocytes grew spontaneously in culture, suggesting they were infected with EBV. Indeed, an appropriate antibody response to EBV was detected at 2 months post-transplantation. At 3 weeks postgrafting, neutropenia and cholestatic jaundice developed without other signs of graft versus host disease. Liver biopsy demonstrated CMV but no EBV by DNA hybridization. There was evidence of T- and B-cell function by 2 weeks postgrafting, including vigorous in vivo and in vitro responses to candida. Although the blood lymphocyte T4:T8 ratio was inverted at 2 weeks, it reverted to normal by 6 weeks post-transplantation. All clinical disease resolved by 8 months and karotyping revealed all T and B lymphocytes to be XX. Thus, despite infections with both CMV and EBV, complete immunologic reconstitution was achieved in this, the most severe of all genetically determined immunodeficiency conditions, arguing against these viruses having a major role in the failure of bone marrow transplantation in AIDS.
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PMID:Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections. 298 Nov 67

We report four cases of Omenn's syndrome (OS), an autosomal recessive disease characterized by early erythrodermia, protracted diarrhea, severe infections, lymphadenopathy, hepatosplenomegaly, failure to thrive, and leukocytosis with marked eosinophilia. The immunological investigations revealed B lymphopenia with increased levels of serum IgE and marked depression of T-cell activation, not restored by the addition of exogenous interleukin 2 (IL-2). IL-2 and interferon-gamma (IFN-gamma) production in vitro were very low or absent. One patient was treated with HLA-identical bone marrow transplant with a complete remission of the clinical picture and the immunological defect. The infant died of graft versus host disease 4 months after the graft. For the remaining three infants the outcome was also fatal within the first year of life. In conclusion, OS should be considered a severe combined immunodeficiency disease with peculiar clinical, immunological, and histological findings.
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PMID:Clinical and immunological findings in four infants with Omenn's syndrome: a form of severe combined immunodeficiency with phenotypically normal T cells, elevated IgE, and eosinophilia. 311 64

The infectious complications of bone marrow transplantation were reviewed in 43 adults, 22 of whom received transplants from HLA-matched donors without T-cell depletion and 21 of whom received donor marrow pretreated with the murine anti-T-cell monoclonal antibody CT-2 and complement. Recipients of HLA-mismatched, T-cell-depleted transplants had a higher rate of bacteremia (1.33 compared with 0.64 per patient, p = 0.05) and especially systemic fungal infections (0.92 compared with 0.14 per patient, p less than 0.001) than recipients of transplants from HLA-identical donors without T-cell depletion; two thirds of these infections occurred during the granulocytopenic period early after transplantation. Recipients of HLA-identical but T-cell-depleted transplants also had significantly more systemic fungal infections (0.77 per patient, p less than 0.001). T-cell depletion was associated with delayed engraftment, more prolonged granulocytopenia, and more severe lymphopenia and was shown by stepwise multivariate regression analysis to be the most powerful predictor of systemic fungal infection (r = 0.512, p less than 0.0001). Whereas ex-vivo T-cell depletion may reduce the risk of severe graft-versus-host disease, it may predispose the patient to infection, especially with fungi.
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PMID:Infectious complications in adults with bone marrow transplantation and T-cell depletion of donor marrow. Increased susceptibility to fungal infections. 351 42

We tested whether the in vivo infusion of recombinant, soluble CTLA4 fused with Ig heavy chains, as a surrogate ligand used to block CD28/CTLA4 T-cell costimulation, could prevent efficient T-cell activation and thereby reduce graft-versus-host disease (GVHD). Lethally irradiated B10.BR recipients of major histocompatibility complex disparate C57BL/6 donor grafts received intraperitoneal injections of human CTLA4-Ig (hCTLA4-Ig) or murine CTLA4-Ig (mCTLA4-Ig) in various doses and schedules beginning on day -1 or day 0 of bone marrow transplantation (BMT). In all five experiments, recipients of CTLA4-Ig had a significantly higher actuarial survival rate compared to mice injected with an irrelevant antibody control (L6) or saline alone. Survival rates in recipients of hL6 or PBS were 0% at 29 to 45 days post-BMT. In recipients of CTLA4-Ig, survival rates were as high as 63% mice surviving 3 months post-BMT. However, protection was somewhat variable and recipients of CTLA4-Ig were not GVHD-free by body weight, clinical appearance, and histopathologic examination. There were no significant differences in the survival rates in comparing injection dose, injection duration, or species of CTLA4-Ig (hCTLA4-Ig v mCTLA4-Ig). Splenic and peripheral blood flow cytometry studies of long-term hCTLA4-Ig-injected survivors showed a significant peripheral B-cell and CD4+ T-cell lymphopenia, consistent with GVHD. A kinetic study of splenic reconstitution was performed in mice that received hCTLA4-Ig and showed that mature splenic localized CD8+ T-cell repopulation was not significantly different in recipients of hCTLA4-Ig compared with hL6, despite the significant increase in actuarial survival rate in that experiment. These data suggest that the beneficial effect of hCTLA4-Ig on survival is not mediated by interfering with mature donor-derived T-cell repopulation post-BMT. Neither hCTLA4-Ig nor mCTLA4-Ig interfered with hematopoietic recovery post-BMT. We conclude that CTLA4-Ig (most likely in combination with other agents) may represent an important new modality for GVHD prevention.
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PMID:In vivo blockade of CD28/CTLA4: B7/BB1 interaction with CTLA4-Ig reduces lethal murine graft-versus-host disease across the major histocompatibility complex barrier in mice. 751 23


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