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)

Short courses of cytosine arabinoside (Ara-C), cyclophosphamide, and L-asparaginase were given to seven children with newly diagnosed acute lymphocytic leukemia, who had failed to remit on standard remission induction therapy. These 4-day courses of Ara-C and cyclophophamide followed by 4 days of L-asparaginase were repeated at 3- to 4-week intervals for two or four courses. Complete remission occurred in six patients. The median duration of remission was 94+ days, on various maintenance regimens. The most serious side effect was neutropenia. This combination of these three drugs appears to be effective remission-induction therapy for children with ALL with unfavorable prognostic features.
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PMID:Combination chemotherapy for children with acute lymphocytic leukemia who fail to respond to standard remission-induction therapy. 105 44

Case report of a 24 year old female patient with ALL that developed pulmonary invasive aspergillosis during aplastic phase of induction chemotherapy. She was treated with antibiotics and amphotericin B. After recovering from neutropenia, she developed a mycetoma in the inferior lobe of the right lung, which required lobectomy. Nine months after surgery the patient is well, in complete remission of ALL and with no evidence of infection. One month after lobectomy, chemotherapy had been reintroduced. Attention should be called to this form of therapy of Aspergillosis, as a successful way to eradicate this fungal infection that responds poorly to antifungal drugs currently used.
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PMID:[Surgical treatment of fungal bolus in acute lymphoid leukemia]. 134 Mar 69

Of 6,099 children treated for malignancy, 16 (ages 3.5 to 18 years) developed acute appendicitis between 1962 and 1989. Fourteen had leukemia (ALL 10, AML 4). One each had rhabdomyosarcoma and Ewing's sarcoma. Active malignancy at diagnosis was noted in 10, 4 of whom had severe neutropenia (absolute neutrophil count less than 500/mm3). Of all the leukemics (2,794/6,099), abdominal pain during induction was a frequent complaint. The incidence of appendicitis, however, was low (0.5%). Nine of the 16 patients presented classically, facilitating prompt diagnosis and treatment. Six diagnoses were delayed. Three of these patients presented atypically with vague, nonlocalized pain, abdominal distention, lack of abdominal guarding, fever, dehydration, diarrhea, and unusual symptoms such as upper gastrointestinal bleeding. In each of these 6 patients the appendix was ruptured. Delays led to complications and deaths. Three patients required perioperative transfusions to treat excessive bleeding and two patients with ruptured appendicitis developed wound abscesses. Two patients died; in one, ruptured appendix was diagnosed only at autopsy. The other patient died of uncontrolled sepsis. Typhlitis occurring during induction chemotherapy may present similarly and is the main differential diagnosis. Typhlitis will usually improve with medical treatment alone. Nausea and vomiting (13/16), right lower quadrant pain (13/16), guarding (14/16), tachycardia (12/16), fever (10/16), and rebound tenderness (10/16) were the most frequent signs and symptoms of appendicitis. Persistent localized abdominal pain and guarding, lack of improvement with medical treatment, clinical deterioration, and the development of a mass were our indications for laparotomy. Despite major improvements in therapy, there is still a 37.5% error rate in our ability to accurately diagnose appendicitis in pediatric cancer patients.
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PMID:Acute appendicitis in children with leukemia and other malignancies: still a diagnostic dilemma. 152 62

Granulocyte/Macrophage Colony Stimulating Factor (GM-CSF) stimulates the production as well as the function of myeloid cells, i.e. granulocytes and macrophages. Proliferative effects are exerted on the level of the multipotent as well as the unipotent progenitor cell. Functional effects on mature phagocytes comprise bactericidal and tumoricidal mechanisms including induction of cytokine release. GM-CSF receptors are present on normal hematopoietic progenitors as well as on mature granulocytes, on leukemic cells and some non-hematopoietic cells. Alteration of the GM-CSF gene has been associated with distinct features of AML and ALL. The glycosilated molecule is produced by various hemolymphopoietic and possibly non-hematopoietic cells, amongst whom T-lymphocytes and marrow stroma may be most relevant for myelopoiesis. The regulation of gene expression is exerted on both transcriptional and posttranscriptional levels of gene expression. GM-CSF production may play a role in steady state as well as in stress hematopoiesis. In vivo application of GM-CSF leads to a marked increase of phagocytes, in particular granulocytes. GM-CSF reduces the duration of neutropenia following aplasiogenic and ablative therapy. GM-CSF may possibly be helpful in the treatment of victims of radiation accidents and in patients with acquired neutropenias and glykogenosis IB. The curative potential for the underlying malignant disease is to be investigated in the present cooperative european Ewing's sarcoma study.
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PMID:The granulocyte/macrophage-colony stimulating factor (GM-CSF): basic science and clinical application. 194 37

The role of operation for anorectal infections associated with perineal gangrene and cellulitis in children with myelo-suppression from cancer chemotherapy is unclear. We evaluated anorectal/perineal infections caused by Pseudomonas aeruginosa in 16 children with malignant diseases seen over 27 years. In 12 of 16 patients, leukemia was the underlying malignancy (ALL 10, AML 2), and in 13 of 16, severe neutropenia (absolute neutrophil count less than 500/mm3) was present at diagnosis. Cultures of the lesions showed multiple organisms in 14 of 16 patients with Escherichia coli, Klebsiella species, and Enterococcus being the most frequent coexisting organisms. All positive blood cultures grew P aeruginosa exclusively. Of three patients with necrotizing infections, two had complete resolution with medical treatment alone; the other patient who developed this problem while on terminal care died. In none of the 16 patients was a major operation (debridement or diversion) performed. Five patients died, three of whom were considered terminally ill when the anorectal infections occurred. Four of the five deaths occurred before 1974. Since then, only 1 of 7 patients died. Excluding the three terminally ill patients, the success rate of medical therapy alone is 85% (11/13). The antibiotic regimen should include an aminoglycoside in synergistic combination with anti-Pseudomonas penicillin. These results suggest that operative management may have no role in the management of anorectal infections caused by P aeruginosa in children with cancer.
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PMID:Management of anorectal/perineal infections caused by Pseudomonas aeruginosa in children with malignant diseases. 205 13

In an open study, 42 venous Port-A-Cath systems (PAC) were implanted in 40 patients with AML (12), ALL/AUL (11), NHL with bone marrow infiltration (8), Hodgkin's lymphoma (3), solid tumors (5) and severe aplastic anemia (1). Mean duration of system use was 212 days. The cumulated duration of use of all systems was 8.883 days. 1,627 blood samples were taken from the PAC. Blood sampling was possible on 8,696 of 8,883 days of cumulated access (98%). A total of 522 blood transfusions were administrated. Fifty-two episodes of neutropenia (granulocyte counts less than 0.5 x 10(9)/l) with a mean duration of 17 days were observed in the group of the 23 patients with acute leukemias. A total of 25 complications were registered. The incidence was 2.8/1,000 days of access. Twelve complications were regarded as severe. Venous thrombosis was observed in 3 cases. In addition, there were 2 disruptions of the catheter, 1 disconnection, 1 looping and 4 local infections. The rate of systemic infection could not be accurately estimated because the catheter was always left in place and antibiotic treatment was started immediately in case of fever with or without bacteriemia. The overall rate of catheter-related complications in patients with acute leukemia was not higher than in patients with solid tumors.
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PMID:Use of a fully implantable drug delivery system in the treatment of acute leukemias and disseminated lymphomas. 224 62

Intracellular thioguanine nucleotides (6-TGN) are the major cytotoxic metabolites of mercaptopurine (6-MP). Red blood cell (RBC) 6-TGN concentrations were measured in a group of 120 consecutive children with lymphoblastic leukemia (ALL) to assess interpatient variability and its clinical importance. Assays were performed after at least 2 months 6-MP maintanance chemotherapy and a minimum 7 days unattenuated protocol dose of 75 mg/m2. Observed 6-TGN concentrations ranged from 126 to 832 pmol/8 x 10(8) RBCs (median, 275). There was a correlation between 6-TGN and neutropenia 14 days postassay (rs = .51; P less than .0005), and an inverse correlation between 6-TGN and the length of time uninterrupted full protocol dose was tolerated without neutropenia (rs = -.3; P less than .01). After a median follow-up of 49 months, 19 children had relapsed, of whom 17 (89%) had 6-TGN concentrations below the group median (log-rank chi 2 = 11.9; P less than .001). Multivariate analysis using Cox's proportional hazards regression showed the 6-TGN effect on disease control to be independent of diagnostic WBC count, sex, age, immunological cell type, French-American-British (FAB) type, variation in other antineoplastic therapy, and duration of remission at the time of 6-TGN assay. Children with ALL taking the same dose of 6-MP show great variability in its measurable cytotoxic effect, and this variability is apparently important in predicting treatment outcome.
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PMID:Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukemia. 258 22

Thirty-four children after multiple relapse or with refractory acute lymphoblastic leukemia were treated with two novel combinations of high-dose cytosine arabinoside, methotrexate, asparaginase, vincristine, and prednisone. The first combination was given to 19 patients. Oncolytic response and marrow hypoplasia was achieved in all. There were four early infectious deaths. Thirteen of the remaining 15 (87%) in whom the response to therapy could be evaluated achieved complete remission. Two achieved good partial remissions. The median duration of complete remission and survival on study was 8 and 10 months, respectively. The four proven and three suspected fungal infections seen in the initial 19 patients was the major toxicity observed. The therapy was modified in the last 15 patients to retain efficacy while reducing the period of neutropenia from a median of 28 to 22 days. No deep-seated fungal infections were seen in these patients. Twelve (80%) achieved a complete remission. Three had an oncolytic response without achieving remission. Eighty-three percent of the 30 evaluable patients, or 74% of all patients entered on study, achieved remission. It is anticipated that the therapy described here will not only achieve another remission in the majority of patients with advanced ALL but that the patients will be able to proceed to alternate therapies with potentially more durable benefit.
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PMID:Reinduction therapy for advanced or refractory acute lymphoblastic leukemia of childhood. 264 73

The studies reviewed herein support the precept that "systemic dose-intensity" (i.e., systemic exposure) may be more informative than "administered dose-intensity" for certain anticancer drugs. This does not mean that the administered dose-intensity should be ignored; in fact these data indicate the importance of documenting and assessing administered dose-intensity as an initial step toward identifying those situations where systemic dose-intensity may be most important. The studies described in this review were selected as representative examples of successful clinical pharmacodynamic studies; other published examples include vincristine AUC versus severity of neurotoxicity, etoposide systemic exposure versus leukopenia, red cell concentration of mercaptopurine metabolites versus neutropenia in children with ALL, and ARA-CTP retention in leukemic blasts versus clinical response in acute non-lymphocytic leukemia. As is the case with other types of clinical trials in cancer patients, there are also examples of negative pharmacodynamic studies (i.e., no relationship found between concentration and effects). There are several possible reasons for such negative findings, including the lack of such a relationship for some drugs, measuring the inappropriate drug moiety (e.g., failure to measure all active metabolites), measuring drug concentrations in the wrong biological fluid, evaluating systemic exposure over too narrow a range (i.e., all patients have either sub- or supra-therapeutic systemic exposure), selecting inappropriate sampling times or pharmacokinetic parameters, inadequately assessing drug toxicity or response, or simply studying an inadequate number of patients or patients with drug-resistant cancers. Therefore, negative findings in some pharmacodynamic studies should not deter the investigation of other drugs and/or other malignant diseases, just as negative therapeutic trials do not preclude subsequent clinical trials in oncology. Also, finding a relation between systemic exposure and drug toxicity, in the absence of a clear relation to antitumor effects, is potentially of great clinical utility. Such data should allow more objective escalation of drug dosages in individual patients, to ensure maximum dose-intensity while avoiding host toxicity. Obviously, if such dose escalation could be guided by more easily measured patient characteristics (e.g., age, weight, CrCl, shoe size, etc.), then using drug concentrations in individual patients might be obviated.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacodynamics of anticancer drugs: a basis for extending the concept of dose-intensity. 328 32

The effect of folic acid supplements on 6-mercaptopurine remission maintenance therapy in lymphoblastic leukaemia (ALL) was investigated in a retrospective longitudinal study of 10 children. Red cell concentrations of 6-thioguanine nucleotide, a cytotoxic metabolite of 6-mercaptopurine, were measured and the peripheral neutrophil count was used as an index of myelosuppression. During the control period of the study there were significant correlations between 6-mercaptopurine dose and 6-thioguanine nucleotide concentration (rs = 0.59, P less than 0.0005) and between 6-thioguanine nucleotide concentration and the peripheral neutrophil count at 14 days (rs = 0.58, P less than 0.0005). These relationships were absent when the same children were subsequently taking folate supplements. Also when taking folate supplements the children tolerated significantly more 6-mercaptopurine (P less than 0.005) for a significantly longer time (P less than 0.005) before neutropenia developed. There was no significant difference in red cell 6-thioguanine nucleotide concentration in the absence and presence of folate supplements. These findings suggest that folate supplements may interfere with remission maintenance therapy in ALL.
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PMID:The effect of folate supplements on 6-mercaptopurine remission maintenance therapy in childhood leukaemia. 345 41


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