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)

Chronically immunosuppressed individuals are susceptible to lymphoreticular tumors. Up to 15% of patients with congenital deficiencies such as ataxia=telangiectasia may develop malignancies, mainly high-grade B cell non=Hodgkin's lymphomas (NHLs). AIDS lymphomas are comprised of NHLs including Burkitt's lymphoma (BL) and primary cerebral lymphomas (PCLs). Almost 3% of all AIDS patients (2824 of 97,258 cases) developed NHL. Epstein-Barr virus (EBV) as a co-factor in AIDS lymphomagenesis has been studied: in 12 cases of 24 AIDS lymphomas EBV by DNA in situ hybridization was found. In an analysis of 6 primary cerebral lymphomas, .5 were positive for EBV DNA by Southern blotting. In Burkitt's lymphoma the characteristic genetic alteration affects the c-myc oncogene. In 1/3 of BL p53 mutations were found but none in the 43 NHLs suggesting that p53 mutations and c-myc activation act synergistically in the pathogenesis of these tumors. Cytotoxic agents dideoxyinosine, dideoxycytosine, and zidovudine may cause secondary neoplasia. 8 of 55 AIDS patients under zidovudine treatment developed high-grade lymphoma 23.8 months subsequently; recently doses were reduced. PCL was found in 21 of 90 patients. A 5.2 months survival was associated with combined treatment with cyclophosphamide, Oncovin (vincristine), methotrexate, etoposide, and cytosine arabinoside compared with 11.3 months with chemotherapy. Colony-stimulating factors (CSFs) alleviate drug-induced myelotoxicity and zidovudine-induced neutropenia, however, l8 of 11 patients receiving granulocyte-macrophage CSF developed hematological toxicity. Interleukine-2 produced by T-helper cells enhancing tumor cells cytotoxicity has been used in AIDS-associated cryptosporidial diarrhea and in 4 patients with AIDS lymphoma with modest response, but its stimulation of the HIV-infected substrate may increase viral proliferation.
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PMID:AIDS lymphomas. 161 63

The development of a new multidrug chemotherapy regimen for primary brain tumors was based upon the cellular heterogeneity within individual tumors, the Goldie-Coldman and Price-Goldie-Hill hypotheses, and known agonistic effects of certain drug combinations and sequences. Eight drugs (vincristine [VCR], hydroxyurea, procarbazine, CCNU, cisplatin, cytosine arabinoside [Ara-C] high-dose methylprednisolone, and either cyclophosphamide or dacarbazine) were administered within 12 hours in an attempt to minimize myelosuppression. Courses were repeated at 2- to 4-week intervals. The regimen was devised to include lipid and water soluble drugs, polar and nonpolar agents, phase-specific and cell-cycle independent agents, and antineoplastics with different mechanisms of action. More than 330 courses of the regimen were administered to 107 children with brain tumors whose tumor had recurred or had been incompletely resected at diagnosis. Tumor response according to protocol-specified criteria and independent review was evaluable in 78% of the patients. After just two cycles of chemotherapy and within a 4- to 6-week interval, 50% had an objective tumor response including 15.5% who had a complete response (CR). Nephrotoxicity and high-frequency hearing losses were noted after three to five courses of therapy in approximately half of the patients. Transfusions with red cells or platelets and use of antibiotics for fever and neutropenia were required in 10% to 25% of patients. The regimen appears satisfactory for preradiation chemotherapy in newly diagnosed patients with residual tumor after surgery, but it must be compared with standard therapeutic approaches in prospective controlled trials before its relative value can be established.
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PMID:Eight drugs in one day chemotherapy for brain tumors: experience in 107 children and rationale for preradiation chemotherapy. 304 Sep 19

Several clinical trials have demonstrated that granulocyte colony-stimulating factor (G-CSF) accelerates the recovery of neutropenia in chemotherapy-induced bone marrow suppression. In this report, we describe a 46-year-old female with glioblastoma multiforme who developed interstitial pneumonia due to administration of G-CSF during the phase of immunochemoradiotherapy-induced neutropenia. Thirty-three days after starting immunochemoradiotherapy (ACNU, VCR, IFN -beta, radiation), she developed neutropenia (1,000/microliters). Administration of G-CSF at doses of 125-250 micrograms/day led to an increase of peripheral neutrophil counts. Eleven days later, the patient developed sudden severe respiratory failure and cyanosis with worsening of lung shadows. Blood gas levels on room air were PaO2 49.3mmHg, PaCO2 28.0mmHg, and pH 7.46. At this time, her neutrophil count had risen to 26,080/microliters. LDH and alpha - HBD had also increased to 1,439 IU/l and 1,117IU/l respectively. Chest radiograph and CT scan demonstrated interstitial pneumonia. After treatment with methyl prednisolone, her respiratory symptoms were gradually resolved. A number of side-effects have been reported with granulocyte-macrophage colony-stimulating factor (GM-CSF). These include fluid retention with pericardial and pleural effusion, fever, bone pain, fatigue, and rash. This report also suggests that G-CSF might be a cause of interstitial pneumonia during the phase of immunochemoradiotherapy-induced neutropenia.
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PMID:[A case report of interstitial pneumonia caused by granulocyte colony-stimulating factor]. 750 62

EMA/CO (etoposide-methotrexate-actinomycin D and Cytoxan-Oncovin) is an effective and well-tolerated chemotherapy regimen for the treatment of high-risk gestational trophoblastic disease. However, it is associated with significant neutropenia often requiring dose reductions and treatment delays. We describe the use of granulocyte colony-stimulating factor (G-CSF) in three patients in order to maintain the treatment schedule. A subcutaneous injection of 5 micrograms/kg/day was administered on Days 3-6 and 9-14 of each chemotherapy cycle. No patients had any adverse effects and all received full chemotherapy doses without any treatment delay. The addition of G-CSF to the EMA/CO regimen may benefit patients by achieving dose intensity in the treatment of high-risk gestational trophoblastic disease.
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PMID:A novel strategy using G-CSF to support EMA/CO for high-risk gestational trophoblastic disease. 752 41

Ten cases of newly diagnosed pediatric B cell non-Hodgkin's lymphoma or acute lymphoblastic leukemia (B-NHL, stage I & II 6 cases, stage III & IV 2 cases/ALL 2 cases) experienced during the last 7 years (1987-1994) were treated by BLK88 protocol, which consisted of HD-CPM (1,200 mg/m2), and HD-MTX (1,000 mg/m2) with VCR, ADR, and/or AraC combination, and CNS prophylaxis by triple intrathecal injection. The therapy duration was 24 weeks for B-NHL (36 weeks for B-ALL). The results showed that while one of the six cases in stage I & II relapsed, and other 4 cases of stage III & IV B-NHL/ALL remained in complete remission. On the other hand, all of the four cases in stage III & IV in historical controls had relapsed. Neutropenia and liver dysfunction were observed during therapy, but they were tolerable. We conclude that BLK88 is a very useful protocol for B-NHL/ALL in childhood.
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PMID:[Chemotherapy for B lymphoid malignancy in childhood--results in BLK88 protocol]. 884 99

Records from 653 patients treated between 1991 and 1998 in the Oncology Practice Patterns Study (OPPS) were analyzed to determine contemporary chemotherapy delivery patterns in patients with intermediate-grade non-Hodgkin's lymphoma (NHL). Of the 653 patient records reviewed, 90 (14%) omitted an anthracycline or mitoxantrone (Novantrone) from primary therapy. Among patients receiving CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) or CNOP (cyclophosphamide, mitoxantrone, vincristine, prednisone), 134 (27%) of 492 received an average relative dose intensity of less than 80% of the literature-referenced dose, due either to an inadequate planned or delivered dose. Of 181 advanced-stage patients with responsive disease, 28 (15%) failed to receive at least six treatment cycles. Overall, 283 (43%) of 653 patients potentially received suboptimal chemotherapy due either to choice of regimen or chemotherapy delivered. Patient age > or = 65 years and cardiac comorbidity appeared to have the greatest influence on a physician's decision regarding chemotherapy administration. Among the 492 patients who received CHOP or CNOP, 235 (48%) experienced a delay or reduction in chemotherapy dose (usually neutropenia-related), 100 (20%) developed mucositis, and 116 (24%) were hospitalized for febrile neutropenia. Growth factor was administered to 261 patients (53%), and its primary prophylactic use was associated with a significant reduction in the incidence of hospitalizations for febrile neutropenia in all patient subgroups receiving appropriate chemotherapeutic dose intensity (P = .02). This assessment of chemotherapy delivery to patients with intermediate-grade NHL showed significant variation from current standards. Further analysis of factors influencing chemotherapy delivery might improve therapeutic outcomes.
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PMID:Patterns of chemotherapy administration in patients with intermediate-grade non-Hodgkin's lymphoma. 1170 59

The purpose of this study was to determine the efficacy of salvage chemotherapy with, P-IMVP-16/CBDCA, consisting of carboplatin (CBDCA), etoposide (VP-16), ifosfamide (IFM), and methotrexate (MTX), for patients with aggressive non-Hodgkin's lymphoma (NHL) who had previously received CHOP [a regimen of cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisolone], as first-line chemotherapy. The 45 consecutively enrolled patients received methylprednisolone (mPSL) 1000 mg per body for 3 d (from day 1 to day 3), IFM 1000 mg/m(2) for 5 d (from day 1 to day 5), MTX 30 mg/m(2) on day 3 and day 10, VP-16 80 mg/m(2) for 3 d (from day 1 to day 3), and CBDCA 300 mg/m(2) on day 1, with granulocyte colony-stimulating factor every 21 d. Patients 70 yr of age or older were given 75% of the standard dose. The response rate [complete response (CR) plus partial response (PR)] was 55.6% (25/45), including 12 (26.7%) CR and 13 (28.9%) PR. The overall survival rate for the 45 patients was 31.1% at 1 yr and 17.3% at 2 yr. The failure-free survival rate for the 45 patients was 6.7% at 1 yr and 4.4% at 2 yr. The survival rate for the 25 responders was 48.0% at 1 yr and 24.0% at 2 yr, and the survival rate for the 20 non-responders was 10.0% at 1 yr (P<0.001). Multivariate analysis demonstrated that prior chemotherapy (reduced-dose CHOP for age 70 yr or older) and the number of cases of extranodal involvement (>1) were significant unfavorable factors for overall survival. Although the major toxicity was neutropenia, no patient died of infection related to neutropenia. Non-hematological adverse effects were predominantly mild and tolerable. Unfortunately, the clinical outcome with P-IMVP-16/CBDCA was unfavorable, possibly because the study comprised consecutive patients who had received identified intensive chemotherapy, such as biweekly CHOP. Salvage chemotherapy with P-IMVP-16/CBDCA is not sufficient to cure relapsed or refractory aggressive NHL. Aggressive NHL should be cured by first-line chemotherapy with or without hematopoietic stem cell transplantation.
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PMID:A prospective study of P-IMVP-16/CBDCA: a novel salvage chemotherapy for patients with aggressive non-Hodgkin's lymphoma who had previously received CHOP therapy as first-line chemotherapy. 1222 93

The aim of this study is to verify the feasibility and the clinical activity of a new CHOP-like schedule (ACOD) with a fractionated days 1 and 8 administration in elderly patients. This regimen was chosen in the attempt to allow a sufficient dose intensity (DI) of each drug with better compliance. Fifty-two patients, (74 years, median age), with diffuse large B cell non-Hodgkin's lymphoma were retrospectively evaluated. Patients received ADM 25 mg/sqm, CTX 500 mg/sqm, VCR 1.2 mg/sqm (max 2 mg intravenously) days 1 and 8 and PDN 50 mg orally, days 1-8. Results showed that 54% of patients reached a complete remission, 21% a partial remission with an overall response rate of 75%. Two-thirds of the patients received at least 70% of the planned dose of cyclophosphamide and doxorubicin and 50% of vincristine and prednisone. The median duration of follow up was 12.6 months (range 0.7-61.4). The estimated median OS was 15.2 months (95%CI = [11.6, not estimable]); the estimated median PFS was 5.7 months (95%CI = [5.12, not estimable]). After 2 years, the proportion of patients alive was 47% (95%CI = 34-64%) and the proportion of patients free from progression was 39% (95%CI = 27-57%). Grade 3-4 leukopenia was observed in 61% of patients with 11% of febrile neutropenia. In conclusion, the ACOD chemotherapy regimen seems safe and feasible in elderly patients. This schedule allowed a sufficient DI of chemotherapic agents with clinical results very similar to those recorded with the standard CHOP regimen in young adults.
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PMID:ACOD, a modified CHOP regimen for elderly patients with aggressive non-Hodgkin's lymphoma. 1280 17

The occurrence of delayed neutropenia following rituximab is poorly defined and of unknown cause. We hypothesized it may be related to perturbations of stromal derived factor-1 (SDF-1) and granulocyte homeostasis. Late-onset neutropenia (LON) was investigated in 130 patients with untreated aggressive B-cell lymphoma receiving DA-EPOCH (dose-adjusted etoposide, prednisone, Oncovin [vincristine], cyclophosphamide, and hydroxydaunorubicin) chemotherapy with or without rituximab. All patients were in remission and had no known causes for neutropenia. LON occurred in 6 (8%) of 76 patients receiving rituximab and 0 of 54 patients not receiving rituximab (P = .04). The median onset was 175 days (range, 77-204 days) after treatment with a median duration of 14 days (range, 11-16 days). In a subset of 24 patients, a significant correlation was found between rapid B-cell recovery and granulocyte decline over the 6-month recovery period (R = -0.53; P = .04). Rapid B-cell recovery directly correlated with prerecovery SDF-1 levels (R = 0.65; P = .015) and SDF-1 decline (R = -0.67; P = .013) after recovery. Our results suggest that early B-cell lymphopoiesis is important for B-cell recovery following rituximab, and that perturbation of SDF-1 during B-cell recovery retards neutrophil egress from the bone marrow. These findings illustrate the dual role of SDF-1 in human B-cell and granulocyte homeostasis.
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PMID:B-cell recovery following rituximab-based therapy is associated with perturbations in stromal derived factor-1 and granulocyte homeostasis. 1571 16

From 1999 to 2002, 20 patients with aggressive non-Hodgkin lymphoma, among 28 who failed autologous peripheral blood progenitor cell transplantation, were rescued with cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisone (CHOP)/rituximab (RTX) and granulocyte-macrophage colony-stimulating factor (GM-CSF). RTX was administered twice during each course of chemotherapy, before CHOP and after GM-CSF. This cytokine was given to increase the antibody-dependent cell-mediated cytotoxicity and to reduce the leukopenia on the basis of our preliminary data, which suggested that this cytokine can upregulate CD20 expression. The relevant (World Health Organization grade 3-4) toxicity mainly consisted of myelosuppression (neutropenia in 60% of patients). Fifteen patients achieved complete remission (CR) or had a partial response, with an overall response rate of 75% (60% CR and 15% partial response). Six of the 12 patients who achieved CR relapsed: 2 died of progressive disease, 1 died of infectious complications after allogeneic transplantation, and 3 are alive in second CR. Eight patients showed progressive disease: 5 died of progressive disease, 1 of secondary acute leukemia, and 1 of infectious complications after allogeneic transplantation, whereas 1 is alive in second CR. At last follow-up, 10 patients are alive, 6 of whom are in complete continuous remission, with a median follow-up of 31 months (range, 3-51 months). The projected 4-year progression-free survival is 31.4%, and the 4-year overall survival is 50%. This new association (RTX, CHOP, and GM-CSF) was feasible in approximately 70% of patients; the overall toxicity was manageable. The good response rate and the promising outcome observed in this subset of patients could be explained by the possible increased synergy between chemotherapy, RTX, and GM-CSF, which should be explored in further studies.
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PMID:A new schedule of CHOP/rituximab plus granulocyte-macrophage colony-stimulating factor is an effective rescue for patients with aggressive lymphoma failing autologous stem cell transplantation. 1604 13


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