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)

Etoposide has been used in the treatment of a wide variety of neoplasms, including small cell lung cancer. Kaposi's sarcoma, testicular cancer, acute leukemia, and lymphoma. Its current therapeutic use is limited by myelosuppression, particularly neutropenia. Pharmacodynamic studies of etoposide show that this toxicity can be modeled using a modified Hill equation, and that the dose intensity of etoposide can be successfully increased by adaptive control using this model. Significant influences on the degree of myelosuppression include pretreatment leukocyte count, performance status, extent of prior erythrocyte transfusions, and serum albumin level. In the past 5 years, interest has developed in a distinct subset of acute nonlymphocytic leukemia that is associated with prior exposure to etoposide. This syndrome has been described in several studies, and is characterized by the lack of a preleukemic phase, M4 or M5 morphology, and distinct translocations involving the chromosome 11q23 region.
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PMID:New perspectives on the toxicity of etoposide. 149 30

Since January 1988, 91 children with ANLL have been treated with a polychemotherapy regimen containing Mitoxantrone (MTZ), excluding other anthracyclines. Induction consisted of Ara-C, MTZ, and VP 16. Consolidation lasted 6 weeks with Vincristine, MTZ, Ara-C and 6-thioguanine (6TG), and was followed by 2 intensification courses combining High-dose Ara-C with respectively MTZ or VP 16. Maintenance therapy associated 6TG, Ara-C and MTZ up to a cumulative dose of 150 mg/m2. 91 patients are evaluable: 70 (76.9%) achieved complete remission, 59 (64.8%) after induction alone. There were 7 early deaths, 5 deaths in complete remission, and 17 relapses. Major toxic side effects were observed during the consolidation phase, mainly infectious complications, and the median duration of neutropenia was 82 days in this phase, leading to decrease the MTZ dose from 10 to 8 mg/m2. The event-free survival at three years is 38%. Cardiac toxicity is presently absent in children without previous cardiopathy.
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PMID:Mitoxantrone and high dose Ara-C for the treatment of ANLL in childhood: a pilot study of the EORTC CLCG (EORTC 58 872). 157 44

Carboplatin (CBDCA) is a second-generation platinum drug that has been shown to be useful when used as a continuous infusion in treatment of refractory adult leukemia. We report on the effectiveness of continuous infusion CBDCA, 300 mg/m2/d x 5 days, as evaluated in nine patients with secondary acute nonlymphocytic leukemia (ANLL) (seven previous myelodysplastic syndrome and two treatment-associated ANLL), three ANLL patients in first relapse, six refractory ANLL, and nine patients with blastic phase of chronic myelogenous leukemia (BP-CML). All patients were considered assessable. The response rate was 44% (eight complete remissions [CRs], four partial remissions [PRs]). Median duration of postchemotherapy neutropenia was 36 days (range, 18 to 45). Therapy was well tolerated, and toxicity was mainly hematologic and nondose-limiting. Despite prolonged neutropenia, severe infections were rarely seen, and most patients were managed as outpatients. Twelve patients had nausea and vomiting, two had symptomatic hypomagnesemia, and one patient showed reversible ototoxicity. Because of substantial antileukemic activity and unusual extrahematologic toxicity, CBDCA appears to be an effective second-line agent in the treatment of ANLL and should be considered for upgrading to first-line treatment regimens.
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PMID:A phase II clinical trial of carboplatin infusion in high-risk acute nonlymphoblastic leukemia. 198 71

We evaluated the courses of 115 consecutive cases of pediatric acute leukemia treated with induction chemotherapy. Seventy-two patients developed fever associated with neutropenia; 15 developed systemic fungal infections. We reviewed multiple demographic and treatment characteristics of these patients in an attempt to identify potential risk factors for the development of invasive fungal disease (IFD). Risk factors identified in a univariate analysis included duration of neutropenia after first fever (P less than .0001), diagnosis of acute nonlymphocytic leukemia (ANLL) (P = .003), onset of fever and neutropenia within 5 days of starting induction chemotherapy (P = .009), and multiple (greater than one) surveillance culture sites positive for fungal organisms (P = .02). In a multiple logistic regression analysis, duration of neutropenia (P less than .001) remained a significant risk factor. The study group of patients had a significantly higher risk of fungal infections than a matched group of leukemia patients developing fever with neutropenia due to postremission consolidation chemotherapy (P = .003). In the first 48 patients, 14 (29%) developed IFD. In the subsequent patients (n = 24), intravenous miconazole (5 mg/kg every 8 hours) was begun at the time of the first fever. One of the 24 patients (4%) given miconazole developed IFD. The use of miconazole was a negative risk factor for the development of IFD in univariate (P = .01) and multivariate (P = .05) analysis. We conclude that pediatric leukemia patients who develop fever associated with neutropenia during induction chemotherapy are at high risk for developing IFD. The role of intravenous miconazole at the time of the first fever in this group deserves further study.
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PMID:Invasive fungal disease in pediatric acute leukemia patients with fever and neutropenia during induction chemotherapy: a multivariate analysis of risk factors. 229 71

The role of mucositis in infectious complications in the patient with cancer is poorly understood. Consequently, neither the presence nor the severity of mucositis is routinely considered in the selection of specific antibacterial agents for the initial empirical therapy of the febrile cancer patient. In a study of children receiving remission induction chemotherapy for acute nonlymphocytic leukemia, the number of febrile days correlated more closely with the degree of mucositis than with the number of days of neutropenia. Oral mucositis appears to predispose cancer patients to systemic infections with alpha-hemolytic streptococci, Capnocytophaga, and Candida species. Overall, studies of single-drug versus combination therapy for the initial empirical therapy of febrile, neutropenic cancer patients indicate that monotherapy approaches the efficacy of combination therapy, although combination therapy may be preferred for certain cohorts of cancer patients. A concern that is closely related to the issue of combination therapy versus monotherapy is the need for vancomycin in the initial empirical regimen. Vancomycin appears to be the consensus drug of choice for patients with known gram-positive bacterial infections pending antibiotic susceptibility testing; however, there is disagreement as to whether the increased activity of vancomycin against gram-positive bacteria outweighs its expense and potential toxicity for inclusion in the initial empirical regimen. There is an explicit need for continued support of basic and clinical research to address these concerns.
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PMID:Combination and single-agent empirical antibacterial therapy for febrile cancer patients with neutropenia and mucositis. 234 88

A 40-year-old white woman with acute nonlymphocytic leukemia, which relapsed despite bone marrow transplantation and various chemotherapeutic regimens, developed fever and neutropenia. Her fever was unresponsive to broad-spectrum antibiotics, and on hospital day 53 she developed purpuric macules with necrotic centers on her left hand and forearm. Frozen sections of lesional skin were stained with Grocott's methenamine-silver and showed hyphae consistent with a species of Aspergillus; culture of the skin biopsy specimen yielded a pure culture of Aspergillus flavus. Localization of the emboli to the left upper extremity was subsequently explained by magnetic resonance imaging scan of the chest demonstrating invasion of the left subclavian artery by a pulmonary aspergilloma.
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PMID:Unilateral cutaneous emboli of Aspergillus. 239 39

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.
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PMID:Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study. 247 58

Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies.
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PMID:A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. 259 40

The toxicity, pharmacokinetics, and hematologic effects of granulocyte-macrophage colony-stimulating (GM-CSF) were studied in a phase I/II trial of 16 patients with myelodysplastic syndrome (MDS). The GM-CSF was administered subcutaneously (SC) daily so as to achieve prolonged blood levels and to establish an outpatient treatment regimen. Four dose levels were administered for ten days: 0.3 microgram/kg/d (three patients), 1.0 microgram/kg/d (three), 3.0 micrograms/kg/d (four), and 10.0 micrograms/kg/d (six). The most common toxicities were fever and a flu-like syndrome, which were dose-dependent. The maximum-tolerated dose was 10.0 micrograms/kg/d, which induced severe rigors (two patients), fever greater than 40 degrees C (one), severe bronchospasm (one), and WBC 60,000 (one). In one patient, refractory anemia with excess blasts in transformation (RAEB-T) progressed to acute nonlymphocytic leukemia after two doses of GM-CSF, and the patient died of leukemia that did not respond to chemotherapy. After doses of 3.0 and 10.0 micrograms/kg, serum GM-CSF levels peaked at 3.8 to 6.3 hours, and persisted for 14 and 24 hours, respectively. Circulating granulocytes (neutrophils and bands) increased in a dose-dependent manner, as 11 of 13 patients who received greater than or equal to 1.0 microgram/kg/d responded with a two- to 194-fold increase. Although the neutrophils usually returned to pretreatment levels shortly after stopping GM-CSF, two patients continue to exhibit an elevation of neutrophils for 6 months. Dose-related increases in circulating monocytes and eosinophils were also noted. Transient increases in platelet and reticulocyte counts were observed in two and three patients, respectively. Five of the 16 patients later received maintenance GM-CSF at 3 micrograms/kg/d for 2 to 9 weeks. All showed a dramatic increase in neutrophils after 2 weeks. Thereafter, despite continued therapy, the neutrophil count in four patients declined markedly. In conclusion, GM-CSF is well tolerated by the SC route and induces striking, but usually temporary, improvement in the neutropenia of MDS. Larger prospective phase III trials will determine the duration of hematologic responses and the impact on infection, morbidity, and mortality.
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PMID:Subcutaneous granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome: toxicity, pharmacokinetics, and hematological effects. 265 78

Busulfan 16 mg/kg and cyclophosphamide 120 mg/kg were used as conditioning prior to allogeneic marrow transplantation in 50 adult patients with acute nonlymphocytic leukemia (ANLL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML). A standard risk group of 20 patients included those with acute leukemia in remission and CML in chronic phase. A high-risk group of 30 patients included individuals with refractory acute leukemia, acute leukemia in relapse, acute leukemia following preleukemia, and CML in accelerated and blastic phase. Complete remission and sustained complete engraftment were achieved in all evaluable patients. The duration of aplasia was remarkably short (median of 8 days), resulting in a low infection rate during the period of neutropenia, a reduced need for blood product support, and a short length of hospital stay. Three-year actuarial relapse-free survival in both standard-risk (88.9% +/- 10.5%) and high-risk (50.5% +/- 9.6%) groups compares favorably with that reported with total body irradiation (TBI) containing regimens.
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PMID:Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. 331 Dec 3


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