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)

Four children with lymphoproliferative malignant disease, two with acute lymphocytic leukemia in remission and two with Hodgkin's disease, were treated with a Thymic Hormone, THF, for disseminated varicella infecition. It is suggested that THF increased significantly the number of peripheral blood lymphocytes and T-rosette forming lymphocytes in 3 out of 4 children, who developed the varicella at the time of impaired cellular immunity. On the other hand, in the fourth child, with Hodgkin's disease, who had a normal number of T-rosettes, a decreased absolute number of lymphocytes as well as T-rosettes was observed over a course of 14 days THF treatment, although the percent of T-cells has not changed significantly. All of the four children recovered, including the child who was at high risk, with a marked lymphopenia, severe bilateral pneumonitis, hepatitis secondary infected skin lesions and psudomonas sepsis. It is indicated that THF therapy may restore the depressed cellular immunity in immunosuppressed children with malignant disease, and has its value as a supportive immunotherapy in life-threatening disseminated varicella infection.
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PMID:Thymic hormone (THF) therapy in immunosuppressed children with lymphoproliferative neoplasia and generalized varicella. 26 20

Ten of 70 children (14%) with acute lymphoblastic leukemia developed severe interstitial pneumonitis within three weeks after induction of central nervous system prophylactic therapy. The clinical picture was characterized by fever, cough, progressive dyspnea, and hypoxemia with complete resolution in one to three weeks, except in one patient who died during the acute illness from respiratory failure. P. carinii organisms were found in the lung tissue of only one patient. The etiology of the pneumonitis in the other nine children was probably viral, acquired or activated during a period of lymphopenia and immunosuppression. The morbidity and potential mortality from the pneumonitis warrants early recognition by open lung biopsy and intensive supportive therapy.
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PMID:Acute respiratory illness in children with acute lymphoblastic leukemia. 30 Jul 96

In 56 children with acute lymphoblastic leukemia (ALL) T and B lymphocytes and immunoglobulins (IgG, IgM, and IgA) were studied before, during, and after therapy. At the time of diagnosis T lymphocytes were normal, the number of B lymphocytes was increased, and immunoglobulins usually were normal. Only two of 30 children had abnormally low immunoglobulin levels. Under therapy a progressive lymphopenia was observed. B cells were depressed most extensively. IgG and IgA levels showed a nadir during early treatment, i.e. after remission induction for IgG and 4-8 months after diagnosis for IgA. IgM was markedly elevated after meningosis prophylaxis. After cessation of therapy lymphocytes increased with an intense rebound of B cells. The recovery was not fully completed after one year free of therapy.
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PMID:[T and B lymphocytes before, during, and after cytostatic therapy of acute lymphoblastic leukemia (ALL) in children (author's transl)]. 30 85

Hereditary deficiency of adenosine deaminase (ADA) usually causes profound lymphopenia with severe combined immunodeficiency disease. Cells from patients with ADA deficiency contain less than normal, and sometimes undetectable, amounts of ADA catalytic activity and ADA protein. The molecular defects responsible for hereditary ADA deficiency are poorly understood. ADA messenger RNAs and their translation products have been characterized in seven human lymphoblast cell lines derived as follows: GM-130, GM-131, and GM-2184 from normal adults; GM-3043 from a partially ADA deficient, immunocompetent !Kung tribesman; GM-2606 from an ADA deficient, immunodeficient child; CCRF-CEM and HPB-ALL from leukemic children. ADA messenger (m)RNA was present in all lines and was polyadenylated. The ADA synthesized by in vitro translation of mRNA from each line reacted with antisera to normal human ADA and was of normal molecular size. There was no evidence that posttranslational processing of ADA occurred in normal, leukemic, or mutant lymphoblast lines. Relative levels of specific translatable mRNA paralleled levels of ADA protein in extracts of the three normal and two leukemic lines. However, unexpectedly high levels of ADA specific, translatable mRNA were found in the mutant GM-2606 and GM-3043 lines, amounting to three to four times those of the three normal lines. Differences in the amounts of ADA mRNA and rates of ADA synthesis appear to be of primary importance in maintaining the differences in ADA levels among lymphoblast lines with structurally normal ADA. ADA deficiency in at least two mutant cell lines is not caused by deficient levels of translatable mRNA, and unless there is some translational control of this mRNA, the characteristic cellular ADA deficiency is most likely secondary to synthesis and rapid degradation of a defective ADA protein.
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PMID:Adenosine deaminase messenger RNAs in lymphoblast cell lines derived from leukemic patients and patients with hereditary adenosine deaminase deficiency. 613 54

Deoxyadenosine (AdR) appears to be central to the molecular events mediating immunodeficiency in children born with adenosine deaminase (ADA) deficiency but it is still uncertain whether lymphotoxicity is due to AdR directly inhibiting transmethylation reactions in which S-adenosylmethionine is the methyl group donor, or is due to phosphorylation of AdR to deoxyadenosine triphosphate (dATP) which then inhibits ribonucleotide reductase or is due to other mechanisms. Using AdR and the ADA inhibitor deoxycoformycin (dCF) and assessing cell viability, nucleoside incorporation into RNA and DNA, as well as measuring deoxyribonucleoside triphosphate (dNTP) concentrations and S-adenosylhomocysteine (SAH) hydrolase activity, we have studied various types of human lymphoid cells and demonstrated in them the relative importance of the above two mechanisms of AdR toxicity. Treatment of normal resting peripheral blood lymphocytes in culture with AdR and dCF resulted in impaired viability. Although elevated dATP levels as well as decreased SAH hydrolase activities were both observed, the failure of a known inhibitor of ribonucleotide reductase (hydroxyurea) to produce toxicity, and the inability of deoxycytidine (CdR) to achieve a rescue effect, point to another mechanism, possibly inhibition of trans-methylation or ATP depletion being the more likely causes of toxicity in resting lymphocytes. The same mechanism may well account for the rapid and severe lymphopenia in patients treated with dCF. On the other hand, in cultured lymphoblasts in the exponential phase of growth. AdR and dCF produced marked inhibition of growth and cell death both in a Thy-ALL line and in a c-ALL line, in the absence of significant inhibition of SAH hydrolase, but with a substantial elevation in dATP concentrations and depressed levels of the other dNTP. Minor toxicity occurred in a proliferating B lymphoblast line despite almost complete inactivation of SAH hydrolase. These observations indicate inhibition of ribonucleotide reductase as the more likely mechanism of toxicity in rapidly proliferating lymphocytes. Other T-cells actively synthesizing DNA, such as PHA-stimulated or MLC activated lymphocytes and T-lymphoid colony forming cells, are also likely to be affected by the same mechanism. Indeed in PHA-stimulated lymphocytes, deoxycytidine caused significant although incomplete rescue from toxicity due to dCF and AdR. In patients with ADA deficiency or treated with ADA inhibitors, both mechanisms could be operative. These observations are also relevant to the possible use of dCF and AdR as immunosuppressive agents and for the removal of T-cells or residual Thy-ALL blasts from bone marr
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PMID:Mechanisms of deoxyadenosine toxicity in human lymphoid cells in vitro: relevance to the therapeutic use of inhibitors of adenosine deaminase. 623 Oct 47

2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzyme elevations, and conjunctivitis. Lymphopenia occurred in all patients. The most serious adverse effects were acute tubular necrosis and central nervous system toxicity, which appeared to be dose related. In addition, two patients given the 0.75-mg/kg dose developed severe hepatic toxicity, although this could not be ascribed definitively to 2'-dCF. Antitumor activity was observed in eight patients, two of whom experienced a complete remission. Inhibition of lymphoblast adenosine deaminase activity was noted in the majority of cases and was observed at all doses. Antileukemic activity occurred at doses of 2'-dCF which were not associated with limiting toxicities. These results suggest that 2'-dCF is active against acute lymphoblastic leukemia and that a starting dose of 0.5 mg/kg/day be utilized in Phase II studies.
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PMID:Phase I study of 2'-deoxycoformycin in acute lymphoblastic leukemia. 697 90

The authors investigated cellular and humoral immunity in 53 children over 3 years of age suffering from acute lymphoblastic leukemia. The children had remission lasting from 6 to 120 months and were followed up for 7-14 years after the diagnosis was made. The treatment was performed according to programs of polychemotherapy practiced in 1981-1988. In November of 1995 42 children were alive, 15 had the disease for 10 years. Lymphocytopenia (absolute number of T-cells and B-cells fell 3-5 and 2-3-fold, respectively) was reported in all the examinees both in early remission and later (6-12, 24-60, 60 and more months since the disease onset). In early remission there was a significant reduction in the serum IgG, IgA and IgM. In children with ALL lethal outcome serum IgM and absolute number of E-RFCa dropped in early remission more significantly indicating deep drug-induced depression of lymphocytopoiesis. After 5 years of treatment the pool of peripheral T-lymphocytes and T/B lymphocyte proportion changed for the best, though their absolute number was subnormal. Serum IgG, IgA and circulating immune complexes were 1.3-1.5 times higher than normal which may be explained by gastrointestinal pathology and food allergy in the majority of children treated.
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PMID:[Retrospective evaluation of blood immunologic parameters in the course of remission of acute lymphoblastic leukemia in children]. 875 51

The fluorescence-activated cell sorter (FACS) was utilized to phenotype lymphocyte compartments in children receiving intensive chemotherapy for acute lymphoblastic leukemia (ALL). Sixteen patients (eight males and eight females) of diverse ages, risks of relapse, and within weeks 7-53 of maintenance/continuation chemotherapy treatment were arbitrarily selected for study. All 16 patients had profound B cell lymphopenia. In contrast, T cell numbers were often normal or marginally low, and accounted for up to 98% of the lymphocyte populations. No abnormality in T cell phenotypes could be demonstrated. Due to the highly skewed B/T lymphocyte ratios in these ALL patients, the absolute white blood cell counts and lymphocyte percentages were not predictive of the underlying B cell lymphopenia. Patients were also tested for serum immunoglobulin levels and most had abnormally low IgG and IgM. None of four patients immunized with the 1996-1997 influenza virus vaccine seroconverted to at least two vaccine antigens as compared to 10 of 10 healthy, age-matched controls. In total, these data highlight for the first time the profound abnormality of the B/T lymphocyte ratio in patients during treatment for ALL, and argue for consideration of B cell-targeted immunotherapy.
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PMID:Profound abnormality of the B/T lymphocyte ratio during chemotherapy for pediatric acute lymphoblastic leukemia. 955 22

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

The objective of this study was to examine the incidence and characteristics of Ara-C-related fever and the frequency and severity of infections after single-drug, high-dose Ara-C treatment (HDAC) in children treated for acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). A retrospective review was performed of 169 courses of HDAC administered to 57 patients (age 1.8-17.8 years). Procalcitonin values (PCT) were analyzed in a subgroup of 16 patients. Fever during HDAC occurred in 113 of 169 (67%) cases. C-reactive protein (CRP) was elevated in the febrile patients (median 38 mg/L [range 3-150]). PCT was elevated (>0.5 ng/mL) during HDAC in 4 of the 16 evaluated patients. Corticosteroids could inhibit fever (P < 0.001). Myelosuppression after HDAC was prominent: 99% developed neutropenia (<0.5 x 10/L) and 92% thrombocytopenia (<25 x 10/L). An early lymphopenia (median 0.1 x 10/L [range 0.01-0.68]) was seen during the first week. G-CSF was used after 12 of the 169 HDAC courses. A febrile episode occurred after 93 of the 169 (55%) HDAC courses, with no need for intensive care and no deaths. The incidence of viridans streptococcal septicemia was 2 of the 169 cases. Ara-C fever is common, and evaluation with inflammation markers is complicated by the fact that HDAC can induce a moderate release of both CRP and PCT. Profound neutropenia and lymphopenia are causative factors for the high incidence of infections, but the risk of life-threatening complications after HDAC in children in remission of lymphoid malignancies is low, even without prophylactic use of colony-stimulating factors.
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PMID:Ara-C fever and infections after high-dose ara-C treatment in pediatric lymphoid malignancies. 1601 25


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