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PubMedDate not supplied

[Dose-effect relation in therapy of cytostatic-induced leukopenia with lithium carbonate].

Lithium is used increasingly for attenuation of chemotherapy induced leukopenia in infants and adolescents. Thus, pharmacological data are needed. The purpose of this study was to give recommendations for oral dosage yielding efficient serum levels. Furthermore, two methods of serum level determination were compared. Flame emission photometry using microsamples gave results comparable to atomic absorption photometry. The correlation of oral dose and serum level was investigated in a phase I study. A wide range of serum levels related to an identical oral dose was found. Therefore, frequent serum level determinations are needed to realize efficacy and to avoid toxicity. The correlation between increasing serum levels and leucocyte count was investigated in the first part of a phase II study. No significance was found; i.e. a linear progressing dose-effect relation does not exist. The time course of leukocyte count was analysed for two different serum level groups in the second part of the phase II study. A significant correlation was found in the group with a serum level greater 0,7 mmol/l.

Adult↗
PubMed1958

A comparison of the effects on the Shwartzman phenomenon of leukopenia produced by nitrogen mustard and by whole body irradiation.

The effect of leukopenia on the susceptibility of rabbits to the localized Shwartzman reaction was studied in those receiving whole body irradiation and nitrogen mustard respectively. Of animals receiving nitrogen mustard in which the total polymorphonuclear leukocyte count was less than 100 cells/c.mm. only 17 per cent developed positive local Shwartzman reactions whereas 75 per cent of irradiated animals with total polymorphonuclear leukocyte counts less than 100 cells/c.mm. had positive reactions. A local Shwartzman reaction occurred in 60 of 71 control rabbits (85 per cent). Animals of both the treated groups showed positive Shwartzman reactions at a time when their total polymorphonuclear leukocyte counts were less than 500 cells/c.mm. From the findings, it is concluded (a) that the presence of normal numbers of circulating polymorphonuclear leukocytes is not an obligatory prerequisite condition to the localized hemorrhagic necrosis of the Shwartzman phenomenon, and (b) the mechanisms of action of nitrogen mustard and whole body irradiation on body tissues differ in relation to the Shwartzman reaction.

Animals↗
PubMed1961

Studies on bacteriemia. V. The effect of simultaneous leukopenia and reticuloendothelial blockade on the early blood stream clearance of staphylococci and Escherichia coli.

Observations are presented on the course of experimental bacteriemia in rabbits modified by thorotrast reticuloendothelial "blockade" and mechlorethamine induced leukopenia, given singly and together. The production of severe granulocytopenia did not impair the clearance of staphylococci from the blood stream and did not enhance the impairment of clearance produced by thorotrast reticuloendothelial "blockade." Neither severe granulocytopenia nor thorotrast blockade alone produced consistent impairment in the removal of circulating E. coli from the blood stream, whereas when these conditions were present together, the early phases of clearance in these animals were virtually prevented. These results indicate that the host mechanisms operative in the control of bacteriemia differ for staphylococci and E. coli. It is suggested that the fate of bacteria within polymorphonuclear leukocytes may in part determine the importance of these cells in the removal of bacteria from the blood stream.

Animals↗
PubMed2001

Clearance of human herpesvirus 8 from blood and regression of leukopenia-associated aggressive classic Kaposi's sarcoma during interferon-alpha therapy: a case report.

A human immunodeficiency virus-negative woman with severe classic Kaposi's sarcoma, idiopathic leukopenia, and massive spread of human herpesvirus 8 (HHV-8) in circulating cells showed stable disease remission in response to systemic interferon-alpha treatment that was accompanied by increased CD3(+) and CD4(+) T cell numbers and complete clearance of HHV-8 from the circulation. These results suggest a direct relationship between HHV-8 clearance from blood and regression of Kaposi's sarcoma and are consistent with the in vitro inhibitory effects of interferon-alpha on HHV-8 infection.

Antiviral Agents↗
PubMed1999

Retrovirus-mediated gene transfer of the human multidrug resistance-associated protein into hematopoietic cells protects mice from chemotherapy-induced leukopenia.

Utilization of chemotherapy for the treatment of tumors is mainly limited by its hematological toxicity. Because of the low-level expression of drug resistance genes, transduction of hematopoietic progenitors with multidrug resistance 1 (MDR1) or multidrug resistance-associated protein (MRP) genes should provide protection from chemotherapeutic agent toxicity. Successful transfer of drug resistance genes into hematopoietic cells may allow the administration of higher doses of chemotherapy and, thus, increase regression of chemosensitive tumors. The interest in the use of MRP as an alternative to MDR1 for bone marrow protection lies in its different modulation. This would allow, in the same patient, the use of MDR1 reversal agents to decrease MDR1 tumor resistance without reversing bone marrow (BM) protection of the MRP-transduced hematopoietic cells, since MRP expression is not reversed by these agents. We have constructed MRP-containing retroviral vectors using the phosphoglycerate kinase promoter and generated ecotropic producer cells. Lethally irradiated mice were engrafted with BM cells transduced by coculture with MRP producer cells. Evidence of long-term (9 months) gene transfer was provided by PCR of peripheral blood from MRP-transduced mice. Southern blot analysis confirmed the integrity of the provirus in the MRP-transduced mice. Long-term MRP expression (>5 months) was detected by RT-PCR and fluorescence-activated cell sorting of blood from living mice. High-level expression of MRP in murine hematopoietic cells reduces doxorubicin-induced leukopenia and mortality. Furthermore, we show in vivo selection of MRP-transduced cells following doxorubicin administration, with better and more significant chemoprotection after the second chemotherapy cycle. These data indicate that MRP retroviral gene transfer may be useful for chemoprotection and selection.

ATP-Binding Cassette Transporters↗
PubMed2000

Cytokine responsiveness of mitogen-activated T cells derived from acute leukemia patients with chemotherapy-induced leukopenia.

The aim of the study was to characterize effects of exogenous cytokines on T lymphocytes derived from acute leukemia patients with chemotherapy-induced leukopenia. We investigated the cytokine responsiveness of long-term expanded CD4+ and CD8+ T cell clones and the effects of exogenous cytokines on anti-CD3-stimulated polyclonal T cell responses. After mitogenic activation in the presence of acute myelogenous leukemia (AML) blasts, most CD4+ and CD8+ clones proliferated in response to interleukin-2 (IL-2). Although a majority of the IL-2-responsive clones could also proliferate in the presence of exogenous IL-4, IL-7, IL-9, IL-10, IL-12, and IL-15, only IL-15 responses were equal to or exceeded the corresponding IL-2 responses. Exogenous cytokines were also added during T cell activation with phytohemagglutinin (PHA) + accessory leukemia cells derived from different AML patients, and all the cytokines then had divergent effects that depended on both differences between clones and differences between AML patients. However, for most of these T cell clone/AML blast combinations, IL-2 and IL-15 caused enhanced T cell proliferation. IL-2 and IL-15 also enhanced anti-CD3-stimulated polyclonal responses of nonexpanded T cells derived from cytopenic patients, whereas other cytokines had only minor effects. Our results demonstrate that cytokine-responsive T cells remain in the circulation during chemotherapy-induced cytopenia, and combination therapy including intensive chemotherapy and T cell-targeting cytokine therapy should, therefore, be possible in AML.

Clone Cells↗
PubMedDate not supplied

Long-term prophylaxis of infection by selective decontamination in leukopenia and in mechanical ventilation.

The autochthonous anaerobic bacterial flora in the mucosal layer of the gastrointestinal tract limits colonization by aerobic potential pathogens. This effect is called colonization resistance. Colonization of the digestive tract by potentially pathogenic microorganisms precedes infection in patients with leukopenia and in cases of mechanical ventilation and can be prevented by long-term administration of antimicrobial agents that spare the autochthonous anaerobic bacterial flora of the mucous membranes, a concept known as selective decontamination. Antimicrobial agents active against anaerobic flora reduce colonization resistance, permitting colonization by and overgrowth of potentially pathogenic microorganisms and possibly leading to infections with resistant microorganisms. A distinction can be made between antimicrobial agents that reduce colonization resistance and those that leave it intact by examining the effect of antimicrobial agents on aerobic intestinal flora of mice and humans.

Animals↗
PubMed1993

Ibopamine-induced reversible leukopenia during treatment for congestive heart failure.

Reversible leukopenia was documented in an 81-year-old woman treated with adjunctive ibopamine 100 mg t.i.d. for chronic congestive heart failure. Her antecedent medical history included stable, mild renal function impairment, mitral regurgitation, atrial fibrillation, recurrent transient ischaemic attacks and cholelithiasis. The drugs concomitantly used were digoxin, isosorbide dinitrate, frusemide, urapidil and chlorthalidone in conjunction with oral potassium substitution. Upon withdrawal of ibopamine but continuation of all other drugs, the patient recovered from the blood dyscrasia within 5 days and showed resolution of symptoms. Measurements of protected isolation and selective intestinal decontamination were taken. No complications resulting from secondary infection occurred. After withdrawal of ibopamine and under continuation of all other concomitant medications her body weight continued to decrease during the following few days, her symptoms were alleviated and she was discharge to a nursing home.

Aged↗
PubMed1985

Virus-induced leukopenia: Colorado tick fever as a human model.

Eight patients with Colorado tick fever were studied to determine whether alterations in the production of granulopoietic stimulatory or inhibitory factors (or both) could be found in association with the leukopenic state of the disease. The studies demonstrate that in the patients with Colorado tick fever the mononuclear cell production of colony-stimulating factor is decreased and that there is an increase in circulating inhibitory factors in the serum of such patients. The depressed mononuclear cell colony-stimulating activity does not appear to be reversible by addition of either endotoxin or normal human serum. Characterization of these serum inhibitory factors may facilitate understanding of leukopenia in human disease.

Adult↗
PubMed2000

Niacin deficiency in rats increases the severity of ethylnitrosourea-induced anemia and leukopenia.

Many chemotherapeutic agents function by damaging the DNA of rapidly dividing cells, leading to side effects in the bone marrow, including anemia and leukopenia during chemotherapy and the development of secondary leukemias in the years following recovery from the original disease. We have created an animal model of alkylation-based chemotherapy, in nontumor-bearing rats, to investigate the effect of niacin deficiency on the side effects of chemotherapy [2 x 2 design, niacin-deficient (ND) vs. pair-fed (PF) control, and ethylnitrosourea (ENU) vs. vehicle control (C)]. Weanling Long-Evans rats were fed ND diet or PF niacin replete diet for 4 wk. ENU or C treatment started after 1 wk of feeding and consisted of 12 doses delivered by gavage, every other day. At 4 wk postweaning, niacin deficiency and ENU treatment ended, the rats were fed a high-quality control diet (AIN-93M) and the recovery of blood variables was monitored. ND alone decreased growth rate and caused anemia and neutrophilia. ENU treatment alone caused anemia, lymphopenia, neutropenia and an increase in circulating reticulocytes. In combination, ND and ENU treatment synergistically decreased hematocrit. ND prevented the ENU-induced increase in reticulocyte numbers observed in control rats. ND also increased the severity of ENU-induced lymphopenia. A combination of ND and ENU abolished the neutrophilia caused by ND alone. In summary, ND significantly increased the susceptibility of young Long-Evans rats to ENU-induced bone marrow suppression, suggesting that niacin-deficient cancer patients may benefit from supplementation.

Alkylating Agents↗
PubMedDate not supplied

Severe leukopenia and mild thrombocytopenia after chronic bromocriptine (CB-154) administration.

A 23-year-old woman was receiving bromocriptine (CB-154, 7.5-10 mg/day, for a hyperprolactinemic galactorrhea-amenorrhea syndrome. She also had insulin-dependent diabetes. After three months the bromocriptine therapy was stopped because she developed severe leukopenia (leukocyte counts about 1,800/cu mm) and mild thrombocytopenia (platelet count about 130,000/cu mm). Five months after stopping the bromocriptine therapy, the leukocyte count returned to normal (4,400/cu mm), as did the platelet count (238,000/cu mm). Prior to bromocriptine therapy, the patient's leukocyte and platelet counts ranged between 5,500 and 6,000/cu mm and 250,000 and 300,000/cu mm, respectively. While taking bromocriptine she was on insulin maintenance therapy and took no other drugs. Regular menses had returned and spontaneous galactorrhea had disappeared during bromocriptine therapy, and serum prolactin levels became normal. After stopping bromocriptine therapy the patient again became basally hyperprolactinemic and amenorrheic, with spontaneous galactorrhea. The article discusses possible mechanisms of this hematologic reaction.

Adult↗
PubMed1992

Ga-67 uptake unsuppressed by leukopenia and intense antibiotic therapy.

The authors describe a patient with myelofibrosis who showed intense Ga-67 uptake in spite of being severely leukopenic and receiving large amounts of antibiotics. They conclude that false-negative results associated with leukopenia or intensive antibiotic treatment may not always be correct.

Abscess↗
PubMedDate not supplied

Leukopenia in non-septic burn patients receiving topical 1% silver sulfadiazine cream therapy: a survey.

The cause of early postburn leukopenia (EPBL) is unknown. The evidence suggests that treating burn wounds with 1% silver sulfadiazine cream (SSD) is contributory, but that other factors exist, possibly including burn stress. Differences of opinion exist as to whether SSD applications to the wounds of non-septic burn patients should be discontinued if EPBL develops. A survey of opinion in 101 North American burn treatment facilities and a review of the literature show a strengthening of the perception that EPBL, whether caused by SSD or not, holds little risk for the burn patient. The majority of burn patients are now being assigned to treatment strategies in which the onset of EPBL requires discontinuance of SSD only at WBC counts lower than 2,000/cu mm or not at all. This is significantly lower (p less than .02) than the mean of the values recorded in the literature. There is now substantial experience with continuing the SSD therapy in this setting regardless of the WBC count. No complications are reported therefrom.

Administration, Topical↗
PubMed1976

Acute leukopenia as an allergic reaction to silver sulfadiazine in burn patients.

Of 68 burn patients at the University of Wisoncsin Burn Center treated with silver sulfadiazine cream over 2 years, two (about 3%) developed fever and marked leukopenia. The symptoms disappeared 1-2 days after discontinuation of the cream. The two cases are described and possible mechanisms of allergic response to this agent are discussed.

Acute Disease↗
PubMed1995

Granulocyte colony stimulating factor in the treatment of alcohol abuse, leukopenia, and pneumococcal sepsis.

A 32-year-old woman was admitted with alcoholism, leukopenia, and pneumococcal sepsis (ALPS). Standard treatment consists of antibiotics, vitamin replacement, and intensive care unit support. Even with this treatment, the mortality rate is exceedingly high. In addition to standard therapy, this patient received subcutaneously 300 micrograms granulocyte colony stimulating factor (G-CSF) daily. Initial white blood cell count was 700 microL; by day 4 it had increased to 11,400 microL. She had a prolonged hospital course but was discharged in good condition 6 weeks after admission. G-CSF may be warranted in treating ALPS.

Adult↗
PubMed2003

The successful use of topical tacrolimus treatment for a chronic actinic dermatitis patient with complications of idiopathic leukopenia.

Chronic actinic dermatitis (CAD) is a photosensitivity disorder marked by severe eczematous lesions on exposed areas. Although associations with contact dermatitis, atopic dermatitis, and human immunodeficiency virus (HIV) have been suggested, its pathogenesis remains unknown. CAD is often refractory, and systemic administration of cyclosporin A has been the treatment of choice. Recently, topical tacrolimus therapy has been reported to be effective. We report the efficacy of topical tacrolimus treatment in a CAD patient who also had the complication of idiopathic leukopenia. A phototest showed marked suppression of erythema formation in the skin pre-treated with tacrolimus before UVB radiation but not in the skin treated after the irradiation. Therefore, it is suggested that tacrolimus may prevent UV-B induced erythema by suppressing a very early phase of the inflammatory process in CAD.

Administration, Cutaneous↗
PubMed1991

On the pathogenesis of anaemia and leukopenia in filarial (Litomosoides carinii) infection of Mastomys natalensis.

Mastomys natalensis infected with the filarial parasite Litomosoides carinii show anaemia and leukopenia. Alterations start with the onset of microfilaraemia. Anaemia is temporally macrocytic (up to 80 days after infection), subsequently normocytic and hypochromic, accompanied by reticulocytosis. Increased intravascular haemolysis (i) and functional disorders of the haemopoetic system (ii) are involved in the pathogenesis. i: Circulating erythrocytes showed increased osmofragility. Hypoglycaemia demonstrated in parasitaemic animals may be one reason. ii: Histological and electron microscopical investigations of the bone marrow revealed markedly enhanced haemopoiesis in infected animals. However, a high proportion of cells was found pathologically altered already beginning in the late prepatency and increasing in the further course of infection. Thus, dyshaemopoiesis may result in the production of morphologically and functionally aberrant cells which are rapidly eliminated by the MPS which is highly activated in L. carinii infected M. natalensis.

Anemia↗