Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-seven patients receiving a standard cytosine arabinoside and daunorubicin regimen as induction of reinduction therapy of acute myelogenous leukemia were randomly assigned to receive lithium carbonate, 300 mg t.i.d., or no lithium. Treatment groups were comparable with respect to age and baseline granulocyte counts. All patients developed granulocyte nadirs below 100/cu mm. By actuarial analysis, the median duration of granulocytopenia, less than 1000/cu mm, was 16.0 days in the lithium group and 24.6 days in the no-lithium group, p = 0.013. The median duration of granulocytes less than 500/cu mm also favored the lithium group but only approached statistical significance: 14.0 days versus 20.5 days, p = 0.054. Lithium levels between 0.5 and 1.0 meq/liter were easily maintained in 11 of 12 patients receiving lithium, 300 mg t.i.d., and toxicity directly attributable to lithium was not observed. Despite the shortened duration of neutropenia, the incidence of infections and the rate of remission were not affected.
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PMID:Lithium and granulocytopenia during induction therapy of acute myelogenous leukemia. 28 86

The possible mechanisms of neutropenia associated with both human immunodeficiency virus (HIV) infection and drug treatment in adults are examined, and the current and investigational strategies for managing neutropenia are reviewed. Neutropenia associated with HIV arises from diverse mechanisms, including cellular immune dysfunction, direct effects on progenitor cells, humoral immune dysfunction, and vitamin deficiencies. Drug-induced neutropenia may be related to direct cytotoxic effects, immunologic mediators, and the effects of vitamin depletion on the bone marrow. Bone marrow toxicity in patients receiving zidovudine appears to be more frequent in those patients with advanced disease, low CD4 cell counts, a pretreatment anemia, low serum vitamin B12 levels, and low or low normal serum folic acid levels. Patients with AIDS also are at increased risk for adverse events associated with folate antagonists and sulfonamides compared with other patient populations. Lithium therapy has improved neutrophil counts in patients receiving zidovudine; however, the toxicities associated with use of lithium, combined with the lower dosages of zidovudine now recommended, may obviate its use. The use of colony-stimulating factors appears promising for increasing the number and function of circulating neutrophils. Although concomitant use of interferon alfa and zidovudine may result in a strong synergistic anti-HIV effect, dose-limiting neutropenia has been reported in patients receiving the combination. There are currently no controlled data assessing the effectiveness of intravenous immune globulin in the treatment of HIV-related or drug-related neutropenia. In evaluating neutropenia, the clinician must attempt to discern whether the neutropenia is more likely related to disease state(s) or drug therapies. Potential management strategies include modulation of the disease state, discontinuation or dose reduction of the offending agent, or administration of exogenous immune enhancer.
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PMID:Neutropenia in patients infected with human immunodeficiency virus. 203 44

Lithium utility and toxicity are reviewed. Lithium continues to be the most useful agent available for the prophylaxis and treatment of bipolar illness. Lithium augmentation of antidepressants is useful in treatment-resistant unipolar depression. Utility in other psychiatric disorders, such as schizoaffective, alcoholism, or aggressive behavior, is documented only when a significant affective component coexists. In internal medicine, lithium has proven useful in the prophylaxis of cluster headaches and in ameliorating chemotherapy-induced neutropenia. Other miscellaneous uses in both psychiatry and medicine have been anecdotally reported and are reviewed. However, the use of lithium may be limited by acute and chronic toxic side effects. Acute toxicity almost always manifests as central nervous system (CNS) dysfunction, and the degree of toxicity usually parallels the extent of CNS dysfunction. Chronic toxic manifestations effect cardiac, renal, and endocrine systems. In fetu exposure may be teratogenic.
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PMID:Lithium. 218 84

Suppression of hematopoiesis is far too often the main consequence of antineoplastic therapy, such that the developing degree of myelosuppression and/or thrombocytopenia are usually the rate-limiting steps to adjuvant therapy. This communication reports the results of studies designed to investigate the capability of lithium to accelerate in vivo hematopoietic recovery following exposure to vinblastine sulfate (VB). Male mice (144 BC3F1) received VB (4 mg/kg/b.w.) i.v. Twenty-four h following VB, 72 mice received 35 micrograms m/animal, ultra-pure lithium carbonate (Li2CO3) i.p. Another 72 mice received either VB or phosphate buffered saline as controls. Beginning 24 h later and continuing on days 2, 5, 7, 9, 12, 21 and 28, three mice from each group were randomly sacrificed and their hematological parameters analyzed. Bone marrow and splenic granulocyte-macrophage progenitor cells (CFU-gm) and megakaryocyte progenitor cells (CFU-meg) content were evaluated. Lithium was unable to prevent the onset of either neutropenia or thrombocytopenia; however, lithium was successful in restoring normal white blood cell and platelet values earlier than the VB control group, thus significantly reducing the period of drug-induced neutropenia and thrombocytopenia. This lithium-enhanced hematopoiesis was measured by an accelerated recovery in both marrow and splenic CFU-gm and CFU-meg compared to controls. These data demonstrate the efficacy of lithium to accelerate hematopoietic recovery following exposure to cytotoxic antineoplastic drugs.
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PMID:Lithium and hematopoietic toxicity. II. Acceleration in vivo of murine hematopoietic progenitor cells (CFU-gm and CFU-meg) following treatment with vinblastine sulfate. 357 50

The literature as well as the author's data of this topic are reviewed. Lithium stimulates myelopoesis in vitro, especially via CSF-production. This effect is associated with a modulation of cyclic nucleotides. Lithium stimulates leukemic cell lines too. However, according to epidemiological data lithium does not play an etiological role in leukemia. Furthermore, lithium does not stimulate several tumor cell lines in culture. The effect of cytostatic drugs as well as remission rates are not lessened by lithium. In spite of increased production the functions of the granulocytes are not impaired. Because of the wide range of serum level variation serum level determinations are mandatory. To treat hematological disorders a serum level between 0.7 and 1.2 mmol/l should be achieved. Flame emission photometry and atomic absorption photometry are equivalent methods for determination of the serum level. CNS, thyroid gland, kidney, electrolyte balance, gastrointestinal tract have to be monitored for side effects. Lithium therapy has not be given in pregnancy and to breast feeding mothers. In neutropenia with increased susceptibility to infections lithium therapy including serum level monitoring can be given. Lithium reduces leukopenia and infections following cytotoxic chemotherapy for solid tumors. Current pediatric studies are investigating whether patients with chemotherapy induced neutropenia benefit from this effect in terms of increased and prolonged remission rates.
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PMID:[Lithium in the therapy of hematologic diseases in childhood]. 385 36

Lithium administration has been shown to attenuate the leukopenia associated with systemic chemotherapy. The results of a randomized trial of lithium in 45 patients with small cell lung cancer who received combination chemotherapy and radiation therapy are reported. Patients randomized to receive lithium were started on 300 mg three times daily for 18 days of every 21 day chemotherapy cycle. Patients who received lithium experienced significantly less mid-cycle leukocyte and neutrophil count depression and spent fewer days with leukopenia and neutropenia than control patients regardless of age or extent of disease. Patients who received lithium spent fewer days hospitalized and fewer days with fever in the presence of severe neutropenia than control patients. The cumulative risk of fever with signs of infection was greater in control patients regardless of age, disease extent or the presence of marrow involvement. Patients who were given lithium received significantly more chemotherapy than control patients. Patient survival was greatest in those with limited disease, in complete responders and in those who received more than 75 percent of their induction chemotherapy although it did not differ between the two study groups. The majority of patients required either reduction or discontinuation of lithium. Those who received lithium continuously demonstrated a higher objective response rate and longer survival than either patients in whom the lithium had to be discontinued or those randomized to the control group. Infection was an important cause of death in the control group and cardiovascular event occurred frequently in the lithium group, but the major cause of death in this patient population remains progressive malignant disease.
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PMID:Lithium carbonate in patients with small cell lung cancer receiving combination chemotherapy. 626 91

To evaluate the possible additive leukocyte count-enhancing properties of lithium and oxymetholone, patients (1-21 years old) were randomized to receive lithium or lithium plus oxymetholone after chemotherapy. Seventy-one trials with lithium, 63 with both drugs, and 79 in the control group, were compared. White blood cell count and neutrophil nadirs were better in both treatment groups than in the controls (p = 0.001) but an additive effect of oxymetholone above and over lithium alone was seen only in patients under 15 years old (p = 0.05). The median duration of severe neutropenia (absolute neutrophil count less than 1000/cm3) was 6.2 days/patient in the control group but only 4.5 days/patient and 3.8 days/patient in the lithium and lithium plus oxymetholone groups, respectively (p = 0.0001). Both the lithium and lithium plus oxymetholone treatments had a modest platelet-sparing effect (p = 0.03). No difference in the hemoglobin nadirs was observed in the three groups. While the majority of the patients lost weight in the control and lithium-treated group, the patients on oxymetholone gained weight (median 1.25 kg) p = 0.00001. Lithium reduces the period of neutropenia after chemotherapy during which the patients may acquire infection. The addition of oxymetholone does not substantially lessen myelosuppression in most patients but improves the patients' appetite and weight.
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PMID:Effect of lithium carbonate plus oxymetholone vs. lithium alone on chemotherapy-induced myelosuppression. 640 52

Lithium carbonate ameliorates neutropenia associated with cancer chemotherapy. The effect of lithium on platelet suppression has not, however, been well established. In the present study, five patients with ovarian carcinoma received daily lithium during alternate cycles of treatment with hexamethylmelamine, cyclophosphamide, adriamycin, and cis-platinum. Analysis of myelosuppression was performed on 24 paired consecutive cycles given at identical doses, one with and one without lithium. During lithium cycles, nadir leukocyte, neutrophil, and platelet counts were significantly higher (P less than 0.01, less than 0.01, less than 0.05 respectively) and the interval between treatments was shorter (P less than 0.01). One patient who has received 11 cycles of chemotherapy continues to receive 100% doses owing to the beneficial effect of lithium on chemotherapy-induced thrombocytopenia. Lithium was poorly tolerated by some patients because of either tremor or nausea and vomiting, in spite of nontoxic serum lithium levels. The amelioration of drug-induced platelet suppression as well as neutrophil suppression noted in this study suggests that lithium's effect on hematopoiesis is not limited to stimulation of neutrophil production. The ability of lithium to decrease chemotherapy-induced myelosuppression suggests that lithium administration may facilitate escalation of chemotherapy doses in selected patients.
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PMID:The effect of lithium carbonate on chemotherapy-induced neutropenia and thrombocytopenia. 642 95

The effects of lithium carbonate on leukocyte functions in a case of chronic benign neutropenia are presented. Lithium was able to induce leukocytosis and to bring about increases in chemotaxis, marrow granulocyte reserve test and phagocytosis. After lithium interruption, leukocyte functions returned to initial values. Some hypotheses are advanced to account for lithium action.
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PMID:Effects of lithium carbonate on leukocyte functions in chronic benign neutropenia. 644 26

Lithium (Li) is a known stimulator of steady-state granulopoiesis, influencing both pluripotential (CFUS) and granulocyte-macrophage committed stem cell (CFUGM) populations. Li has therefore been suggested to be an effective agent to reduce the neutropenia that often is seen after either cytotoxic chemotherapy or radiotherapy protocols. In this report, we have examined bone marrow and spleen cells for their recovery patterns of CFUS, CFUGM, CFUE, BFUE and 59Fe-incorporation, along with the usual peripheral blood indices (packed red cell volume, WBC and differential) from mice administered Li after receiving 200 rad whole body irradiation. Li increased granulopoietic recovery as measured by significant elevations in both marrow and spleen derived CFUGM compared to those values obtained from radiation controls. Significant elevation in the WBC, consisting mainly of neutrophils, was also observed. Bone marrow and splenic derived erythroid stem cells (CFUE, BFUE) and % 59Fe-incorporation measured from peripheral blood, femur and spleen were all slightly reduced, but not to a significant degree to alter the packed red cell volume. The CFUS populations from both irradiated groups (control and Li-treated) were depressed when compared to normal non-irr controls and this degree of suppression was greater in the Li-treated group. These results document the ability of Li to stimulate the recovery of granulopoiesis after radiation-induced hematopoietic injury and suggest Li may be useful in ameliorating the neutropenia that can often develop after routine radiotherapy protocols.
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PMID:Lithium stimulates the recovery of granulopoiesis following acute radiation injury. 661 90


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