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Leukopenia prognosis during radiation therapy in patients with Hodgkin's disease.

The investigation goal of the present report is to use the early post-radiation peripheral blood DNA content changes during radiotherapy (RT) of cancer patients for the prognosis of the subsequent leukopenia value. Twenty-three primary patients with II-III stage Hodgkin's disease were treated at the linear accelerator of 15 Mev electrons by usual fractionation to total 40 Gy dose. The blood DNA content was fluorometrically determined by 4', 6-diamidino-2phenylindole before treatment, then 24 hrs after the 1st irradiation dose, in the middle and at the end of RT course. Retrospective analysis of obtained data demonstrated, that the first group of patients, having blood leukocyte levels above 3 x 10(9)/l at the end of RT, revealed an average blood DNA concentration decrease only after the middle of treatment course. The second group of patients, having at the end of RT severe leukopenia, showed an approximately twofold decrease of the DNA concentration after the first irradiation in 62% of cases. The biochemical change was not accompanied by a proportional decrease of the leukocytes amount. The DNA content fall, at the middle and at the end of RT course, was conditioned both by lymphocytes and granulocytes. These changes were not practically interfaced with plasma changes. Thus, a given biochemical criterium may be used as a sensitive index for the prognosis of leukopenia values after the RT beginning. Such a conclusion was confirmed by in vitro test-irradiation of blood specimens of primary patients with Hodgkin's disease. A significant correlation was found between the new index and the level of leukopenia of the patient's blood during post-treatment course.

Female↗

Transient leukopenia and anaphylatoxin production during granulocyte apheresis as treatment for ulcerative colitis.

It is well known that transient leukopenia due to activation of the alternative pathway of the complement system accompanies hemodialysis when cellulose acetate dialyzers are used. However, it has not been evaluated whether leukopenia also occurs during granulocyte apheresis (GCAP) as treatment for ulcerative colitis, in which an extracorporeal column is filled with cellulose acetate beads in order to remove circulating leukocytes. The aim of the present study was to evaluate whether transient leukopenia and activation of the alternative pathway of the complement system were observed during GCAP. In 8 patients undergoing GCAP weekly for 10 weeks, circulating leukocyte counts and plasma concentrations of C3a, a product of the activated alternative pathway of the complement system, were determined. GCAP elicited a rapid decline in the number of circulating leukocytes to 61.8 +/- 13.8% of the baseline value after 15 minutes of GCAP (P < 0.02). Thereafter, the number of circulating leukocytes returned to approximately baseline after 60 minutes. The baseline plasma C3a concentration was 123 +/- 61 ng/mL, and a significant increase to 425 +/- 123 ng/mL was observed after 15 minutes of GCAP (P < 0.02). The plasma C3a concentration reached 417 +/- 96 ng/mL after 60 minutes (P < 0.02). It thus follows that GCAP activates the alternative pathway of the complement system, resulting in anaphylatoxin production.

Adult↗

Splanchnic artery occlusion shock: vinblastine-induced leukopenia reduces tumour necrosis factor and thromboxane A2 formation, and increases survival rate.

This study was designed to assess the role of leukocytes in rats subjected to splanchnic artery occlusion for 45 min followed by reperfusion (SAO shock). Leukopenia was induced by an intravenous injection of vinblastine (1 mg/kg) 72 h before SAO shock. Survival rate (within 6 h), plasma levels of thromboxane B2 (TxB2), serum levels of tumour necrosis factor (TNF-alpha), and histological alteration of the intestinal tract were investigated. Control rats [white blood cells (WBC) = 10362 +/- 630/mm3] died within 2 h following ischaemia and reperfusion. Leukopenic (WBC = 1263 +/- 311/mm3) animals which underwent SAO shock survived more than 2 h and 50% of them were still alive after 6 h. Plasma TxB2 levels significantly increased in WBC count normal rats subjected to SAO shock (8.4 +/- 2.1 ng/ml), compared to sham animals (0.4 +/- 0.08 ng/ml); however SAO shock raised TxB2 levels significantly less (2.1 +/- 1.1 ng/ml) in leukopenic rats. Serum TNF-alpha, undetectable in sham-shocked rats (either with normal WBC count or without), rose up to 150 +/- 12 U/ml in shocked rate and to 45 +/- 5 U/ml (P < 0.01) in shocked animals with leukopenia. SAO shock induced a massive necrosis of the intestinal tract in rats with normal WBC count. Leukopenia prevented ileum necrosis in SAO shock. These data indicate that leukocytes play an important role in splanchnic artery occlusion and reperfusion.

Animals↗

Analysis of the therapeutic effect of sodium copper chlorophyllin tablet in treating 60 cases of leukopenia.

OBJECTIVE: To evaluate the efficacy and safety of sodium copper chlorophyllin (trademarked as "Yebaike Tablet which is abbreviated as YBK in treating leukopenia. METHODS: One hundred and five patients with leukopenia caused by various factors were randomized into 3 groups. The 60 patients in the YBK group took orally YBK Tablets at the dose of 40 mg, three times per day, the 30 patients in the leucogen group were treated with Leucogen Tablets at the dose of 20 mg, three times per day, and the 15 patients in the placebo group were administered with vitamin C tablets 100 mg, three times per day. All the subjects were treated for 1 month. The change of peripheral leucocytes count after treatment and adverse drug reaction that occurred in patients were studied. RESULTS: In the 60 patients treated with YBK, the treatment proved to be markedly effective in 34 cases, effective in 17 and ineffective in 9, the total effective rate being 85%, which was significantly higher than that in the placebo group (26.7%, P < 0.01) and similar to that in the leucogen group (83.3%, P > 0.05). No adverse reaction was found in the treatment course. CONCLUSION: YBK can be used in the treatment of leukopenia caused by various factors, satisfactory in efficacy and safe in use.

Adolescent↗

Target organ toxicity and leukopenia in Fischer 344 rats given intravenous doses of vinblastine and desacetyl vinblastine.

The toxicity and leukopenia produced by vinblastine or desacetyl vinblastine were established in 1-month studies in rats. Groups of male Fischer 344 rats were given weekly intravenous doses of vinblastine or desacetyl vinblastine at doses of 0.08, 0.16, 0.32, 0.64, or 1.28 mg/kg. The target organ toxicity was similar for both compounds. Decreased cell production in the thymus, testes, and bone marrow was produced in the animals of the two highest dose groups for both compounds with the degree of severity greater in the highest dose group. All high dose rats (1.28 mg/kg) given desacetyl vinblastine and three rats given vinblastine died prior to study termination. Body weight loss was more pronounced in high dose rats given desacetyl vinblastine, but at lower doses there were no significant differences in body weight reduction for rats receiving either compound. Leukopenia occurred at all dose levels of 0.32 mg/kg and higher. During the first 2 weeks of the study, rats given 1.28 mg/kg of desacetyl vinblastine had a greater leukopenic response than rats given 1.28 mg/kg of vinblastine. It is concluded that both compounds produced similar target organ toxicity and leukopenia without deaths at doses of 0.32 and 0.64 mg/kg given once a week for 4 weeks. At the high dose (1.28 mg/kg) desacetyl vinblastine was more toxic than vinblastine resulting in greater mortality and body weight reduction.

Animals↗

Incidence and temporal pattern of anorexia, diarrhea, weight loss, and leukopenia in patients with cervical cancer treated with concurrent radiation therapy and weekly cisplatin: comparison with radiation therapy alone.

OBJECTIVE: To investigate the temporal patterns of anorexia, diarrhea, weight loss, and leukopenia in chemoradiation therapy (CRT) for cervical cancer compared with radiation therapy (RT) alone. METHODS: Acute toxicities in 43 patients receiving RT alone and 40 patients receiving CRT were retrospectively analyzed. Patients were treated with a combination of external beam irradiation and high-dose rate intracavitary irradiation. Cisplatin was given once a week for 5 weeks concurrently with the external beam irradiation. CRT was divided into low-dose CRT group (cisplatin, 20-30 mg/m(2), n = 16) and high-dose CRT group (cisplatin, 35-40 mg/m(2), n = 24). Toxicities were evaluated before, every week up to 7 weeks during the cycle, and 12 weeks after initial irradiation, according to the National Cancer Institute Common Toxicity Criteria version 2. RESULTS: In the high-dose CRT group, anorexia during the first 5 weeks, leukopenia after 5 weeks, and weight loss after 3 weeks were significantly higher than those in the RT alone group. In the low-dose CRT group, anorexia between 1 and 2 weeks, leukopenia after 5 weeks, and weight loss between 3 and 4 weeks were significantly higher than those in the RT alone group. Diarrhea between 1 and 2 weeks in the high-dose CRT group (P = 0.037, P = 0.025) and between 2 and 3 weeks in the low-dose CRT group (P = 0.015, P = 0.036) was significantly lower compared with RT alone. CONCLUSION: These data can help us understand when patients are likely to develop maximal toxicities and to manage them with optimal timing.

Age Factors↗

Accelerated recovery from cyclophosphamide-induced leukopenia in mice administered a Japanese ethical herbal drug, Hochu-ekki-to.

The effect of a Japanese ethical herbal drug, Hochu-ekki-to (HOT), on recovery from leukopenia induced by cyclophosphamide (CY) was investigated. Daily oral administration of 1000 mg/kg HOT into CY-treated mice significantly prevented decrease of leukocyte numbers in the peripheral blood and accelerated recovery from leukopenia. Ginsenoside Rgl extracted from Ginseng radix, a major herb of HOT, was one of the active ingredients. HOT increased numbers of neutrophils and monocytes in the peripheral blood compared with CY-treated control. Moreover, HOT augmented the resistance against Pseudomonas aeruginosa infection. The number of colony-forming units in the spleen (CFU-S) also increased in HOT-treated mice. The frequencies of IL-3-, GM-CSF- and IFN-gamma-producing cells increased in the spleen, bone marrow, liver and IEL on HOT treatment, and HOT clearly augmented the expressions of IL-3, GM-CSF and IFN-gamma mRNA in the spleen, bone marrow, liver and IEL except IL-3 and IFN-gamma mRNA in the IEL. These results suggest that HOT enhances the production of hematopoietic lymphokines, stimulates the proliferation of hematopoietic progenitor cells and consequently accelerates recovery from leukopenia in CY-treated mice. Additionally, IFN-gamma which HOT-augmented the production may contribute the protective effect against the bacterial infection by activating of phagocyte cells.

Animals↗

Thrombocytopenia, leukopenia and abnormal liver function tests in the initial phase of tick-borne encephalitis.

One-hundred-seventy-five patients in whom bone marrow puncture had been performed at the Department of Infectious Diseases, University Medical Centre, Ljubljana, during the period from 1988 to 1992, were analysed in a retrospective study. In five out of these 175 patients, tick-borne encephalitis virus infection was confirmed by serological tests and in all of them bone marrow puncture was performed in the initial phase of the illness as part of diagnostic work-up in a patient with a febrile illness accompanied by leukopenia and thrombocytopenia. Bone marrow examination revealed minimal reactive changes or normal findings. In addition to leukopenia and thrombocytopenia, abnormal liver function tests were also found in four patients. All these patients later developed meningoencephalitis, i.e. they had clinically typical tick-borne encephalitis with biphasic course of the illness. In the initial phase of tick-borne encephalitis in addition to well-known leukopenia, thrombocytopenia and abnormal liver function tests may be found.

Adult↗

Do cancer patients with chemotherapy-induced leukopenia benefit from an antiseptic chlorhexidine-based oral rinse? A double-blind, block-randomized, controlled study.

Patients undergoing cancer chemotherapy frequently suffer from mucositis, particularly if they become leukopenic (leucocytes <1000/microL). To identify a possible benefit from antiseptic rinsing of the oral cavity, 47 patients were randomized to rinse either with a chlorhexidine-based product (chlorhexidine concentration 0.3%; N=24) or with an amine-stannous fluoride combination (control group; N=23). Patients were asked to rinse three times a day for 30s from the beginning of chemotherapy until the end of leukopenia. Before rinsing, as well as during and after leukopenia, aerobic and anaerobic bacteria in the oral cavity were counted. At the same time, the patients were assessed for mucositis. In the chlorhexidine-based group, a significant decrease of the aerobic (P=0.042) and anaerobic (P=0.008) bacterial flora was identified. In the control group, the numbers of aerobic and anaerobic bacteria remained unchanged (P>0.05). Fifteen patients in the chlorhexidine-based group had a C-reactive protein (CRP) increase >50mg/L, compared with only eight patients in the control group [odds ratio: 3.13, confidence interval (CI) 0.82-12.39]. Nine patients in the chlorhexidine-based group but only two patients in the control group developed severe mucositis. This difference was statistically significant with an odds ratio of 6.30 (CI: 1.02-49.67). As not all of the 47 patients developed severe leukopenia, a separate analysis was carried out for patients with <1000 leucocytes/microL for a minimum of three days. The results of the microbial counts were very similar, with a clear reduction in the chlorhexidine group and no major alterations in the control group. Twelve of 15 patients in the chlorhexidine-based group had a CRP >50mg/L whereas only eight of 15 patients did so in the control group, which can be regarded as a slightly elevated risk for a CRP increase in the former group. Seven of 15 patients developed severe mucositis in the chlorhexidine-based group, but only two of 15 patients in the control group. These differences were not significant, but patients treated with chlorhexidine-based product seemed to have more problems with inflammation of the oral mucous membranes, resulting in an elevated mucositis score and a CRP increase. Other parameters such as body temperature or application of antibiotics did not differ between the two groups. We conclude that treatment with the chlorhexidine-based product did not provide a clinical benefit for cancer chemotherapy patients. On the contrary, the risk of mucositis and clinical sequelae seems to be enhanced, although the counts of micro-organisms on the oral mucous membranes are significantly reduced.

Adolescent↗

Selenate- and selenomethionine-induced leukopenia in ICR female mice.

The investigations reported here were conducted to gain a better understanding of the comparative toxicity of selenium. Sodium selenate and selenomethionine were administered to young adult ICR female mice. Peripheral leukocyte counts and ratios of agranulocyte (Ag) to granulocyte (G) leukocytes were determined from blood that was collected at regularly scheduled intervals. Data indicated that both forms of selenium induced a transient yet marked decrease in the number of circulating leukocytes (leukopenia) following serial injections (2 mg Se/kg/injection). The leukopenia was more extensive and of a greater duration for selenomethionine-treated mice. For selenate-injected animals the Ag/G ratio increased sharply while the ratio shift for selenomethionine-injected mice was significantly less. Data are interpreted in regard to the different possible modes of action of selenate and selenomethionine on peripheral leukocytes causing leukopenia and the variable Ag/G ratio values.

Animals↗

Spurious automated leukopenia due to in vitro granulocyte aggregation.

A patient with spurious automated leukopenia secondary to in vitro aggregation of neutrophils is evaluated. The primary importance of this transient phenomenon is the potential generation of unnecessary clinical investigation and diagnostic expense. The cause of this phenomenon is not related to time, temperature, or type of anticoagulant. The true leukocyte count is obtained easily by diluted manual leukocyte counts. Presence of granulocyte aggregates on anticoagulated blood smears should suggest spurious leukopenia, and smears of anticoagulated blood should be examined in patients with unexplained leukopenia.

Anticoagulants↗

Granulocyte colony-stimulating factor for gastrointestinal perforation in patients with leukopenia.

OBJECTIVE: Leukopenia in the setting of widespread infection may predispose to sepsis, which is associated with a poor prognosis. Granulocyte colony-stimulating factor (G-CSF), which restores polymorphonuclear leukocyte function and count, has been shown to have protective effects in animal models of sepsis and burns. The aim of this retrospective study was to determine whether G-CSF can reduce the morbidity and mortality gastrointestinal perforation with leukopenia. PATIENTS AND METHODS: The studied subjects were 31 patients who had reduced leukocyte and neutrophil counts before undergoing surgery for gastrointestinal perforation, including six gastroduodenal, nine small intestinal, and 16 colonic perforations from 1986 to 1994. The patients were divided into two groups: a G-CSF(+) group (n = 8) that received G-CSF subcutaneously (150 microgram/day) during the perioperative period, and a G-CSF(-) group which did not. MAIN RESULTS: No significant difference was found in the preoperative and operative factors of the two groups. The postoperative increase in the leukocyte and polymorphonuclear cell counts of the G-CSF(+) group was significantly higher than that of the G-CSF(-) group (p <0.01). Renal, hepatic, and gastrointestinal insufficiency was significantly less common in the G-CSF(+) group than in the G-CSF(-) group. The mean number of organs that failed was reduced from 4.00 +/- 2.50 in the G-CSF(-) group to 1.88 +/- 2.03 in the G-CSF(+) group. One of the eight patients who received G-CSF died of sepsis because of panperitonitis. In contrast, in the G-CSF(-) group, 15 of 23 patients died of sepsis because of panperitonitis. The cause-specific survival rate of the G-CSF(+) group was better than that of the G-CSF(-) group (p <0.05). CONCLUSION: These results suggested that G-CSF reduced the morbidity and mortality of gastrointestinal perforation in patients with leukopenia and encouraged a prospective randomized study in future.

Aged↗

Leukopenia and granulocytopenia after oxacillin therapy.

Two cases of granulocytopenia and leukopenia developing after high-dosage oxacillin therapy given intravenously are described. One patient developed leukopenia and granulocytopenia after 17 days of therapy. The conditions were reversible when oxacillin therapy was discontinued. In the other case, the adverse reaction developed within 48 hours after therapy began and the patient died from heart failure. Leukopenia and granulocytopenia as adverse effects of oxacillin therapy should be kept in mind, especially when high dosages are used.

Adolescent↗

Leukopenia, hypoxemia, and complement activation during a single hemoperfusion.

White blood cell count, acid-base balance, PO2, and complement function in five uremic patients undergoing a single hemoperfusion employing activated charcoal coated with methacrylate were studied. After 20 min on hemoperfusion, a marked leukopenia [ranging from 6,080 +/- 526 to 3,740 +/- 1,124 (p less than 0.02)] and hypoxemia [ranging from 106 +/- 13.8 to 80.2 +/- 11.9 mm Hg (p less than 0.02)] were observed. At the same time, total hemolytic complement decreased from 135 +/- 15.7 to 123 +/- 14.7 U/ml (p less than 0.001) and alternative pathway activity from 38.1 +/- 5.1 to 33.1 +/- 6.7 U/ml (p less than 0.005). C3 and B cleavage fragments were detected in the samples tested, thus demonstrating the activation of the complement alternative pathway. After 60 min, the different parameters tended to increase but did not reach the baseline levels. A direct correlation between the degree of leukopenia and the reduction of PO2 throughout the hemoperfusion period was found. pH PCO2, and HCO-3 did not change throughout the hemoperfusion period. The results demonstrate that complement activation, leukopenia, and hypoxemia occur during hemoperfusion.

Acid-Base Equilibrium↗

Haemostatic and fibrinolytic parameters in septic patients with leukopenia or leukocytosis.

Induction of leukocytopenia by cytotoxic drugs protects against the generalized Shwartzman reaction induced by endotoxin. To elucidate the relationship between leukocyte number and in haemostatic and fibrinolytic disturbances in human sepsis, we studied 32 septic patients with abnormal leukocyte counts. Twenty patients had sepsis in the setting of leukopenia after chemotherapy for haematological malignancies. Twelve patients with leukocytosis developed sepsis associated with benign disorders. Concentrations of thrombin-antithrombin III complex (TAT), plasminogen activator inhibitor-1 (PAI-1) and plasma thrombomodulin (TM) in the leukocytosis group of (12.0 +/- 11.0, 40.2 +/- 27.0 and 5.5 +/- 2.3 ng/ml, respectively) were significantly elevated compared to the leukopenia group of (3.8 +/- 2.3, 18.0 +/- 15.0 and 3.1 +/- 1.0 ng/ml, respectively) and controls (3.3 +/- 0.4, 10.5 +/- 5.3, 3.0 +/- 0.5 ng/ml, respectively). On the other hand, there were no significant differences in these values between leukopenia group and controls. Thus leucocytes may play important roles in thrombin generation, PAI-1 release and injury to endothelial cells.

Adult↗

Increase in total blood leukocyte count following intranasal administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits with cyclophosphamide-induced leukopenia.

We investigated the effects of intranasal (i.n.) administration of recombinant human granulocyte colony-stimulating factors (rhG-CSF) on the total count of leukocytes in peripheral blood (total blood leukocyte count) of rabbits with leukopenia who received cyclophosphamide (CPA). When CPA (30 mg/kg per d) was administered intravenously, the total blood leukocyte count decreased to levels below 5000/microliters approximately 4 d after the initiation of CPA multiple dosing. The decreased level of the total blood leukocyte count was maintained throughout the period of CPA dosing. RhG-CSF was given once a day for 3 d in CPA-treated rabbits via i.n. administration of aqueous preparations containing rhG-CSF with or without alpha-cyclodextrin (alpha-CyD). The total blood leukocyte count increased from levels below 5000/microliters to the normal physiological level following i.n. administration of rhG-CSF preparation and reduced the period of leukopenia induced by CPA. The coadministration of rhG-CSF and alpha-CyD was more effective in increasing the total blood leukocyte count. It is suggested that i.n. administration of rhG-CSF is promising for reducing the risk of cytotoxic chemotherapy (CPA)-induced leukopenia as an adverse side effect.

Administration, Intranasal↗

European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.9.2. Haematological complications. Leukopenia.

GUIDELINE: Because leukopenia is relatively common after kidney transplantation, regular screening and careful evaluation of its causes are recommended. Azathioprine and mycophenolate mofetil may lead to leukopenia. The combination of allopurinol and azathioprine should be avoided. Leukopenia is often associated with viral infections.

Azathioprine↗

[Clinical analysis of curative effect of rhG-CSF on chemotherapy-induced leukopenia in cancer patients].

Myelosupression is the major dose-limiting toxicity in most chemotherapeutic drugs. To evaluate the curative effect of a domestic product of rhG-CSF on chemotherapy-induced leukopenia, 132 patients with malignancies were enrolled, including 80 patients with lung cancer, 35 patients with breast cancer, 10 patients with nasopharyngeal carcinoma, 3 patients with non-Hodgkin's lymphoma, 2 patients with gastric carcinoma and 2 patients with bone metastasis. Total of 528 cycles of chemotherapy were performed. The results showed that according the grade of leukopenia, the different daily doses of the domestic product of rhG-CSF were administered: 75 micro g/d for 3 days, 150 micro g/d for 4 days and 300 micro g/d for 5 days, in grade I-II, grade III and grade IV groups, respectively, the times of recovery to normal level of white blood cells were 2.5, 4.2 and 7 days in 3 groups, respectively. In conclusion, The Chinese product of rhG-CSF shortened the duration of leukopenia and accelerated the hematologic recovery, which shows only slight side effects, so that patients receive the optimal doses of chemotherapy and completed the planned schedule on time.

Adolescent↗