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)

Ninety-seven patients with aggressive malignant lymphoma (ML) were treated with an intensive and sequential chemotherapy (protocol LNH-80). There were 42 patients with intermediate grade ML, 53 patients with high-grade ML, and two patients with true histiocytic ML. Most of the patients were in advanced stage: 21 stage III and 61 stage IV. The LNH-80 protocol schedule comprised three phases: (1) induction with three courses of an intensified CHOP-Bleo (cyclophosphamide, doxorubicin, vindesine, methylprednisolone, and bleomycin); (2) consolidation with cytarabine, followed by high-dose methotrexate and folinic acid rescue, then asparaginase; and (3) final intensification with two courses of CVAP-Bleo (cyclophosphamide, teniposide, cytarabine, methylprednisolone, and bleomycin). CNS prophylaxis included one injection of methotrexate during each induction course and the drugs of the consolidation phase. In cases of initial CNS localization, cranial radiotherapy was added. Eighty-four patients (87%) went into complete remission (CR), 18 (21%) of whom relapsed, usually during the phase of treatment or within 6 months of completing chemotherapy. Sixty-three patients are alive with an overall median follow-up of 24 months. The median survival time and the median disease-free survival have not been reached, and the survival curve seems to have plateaued at above 60%. There was no statistical difference between intermediate-grade ML (CR 90%, relapse 18%) and high-grade ML (CR 84%, relapse 24%). The toxicity of this treatment is mainly encountered during the induction phase: almost all patients had short-term neutropenia, less than 0.500 g/L in 57, with a documented infection in 25. Overall treatment-related mortality was 6%, with four patients dying during the induction phase.
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PMID:Intensive and sequential combination chemotherapy for aggressive malignant lymphomas (protocol LNH-80). 241 66

Myelosuppression is often the major limiting factor that prevents timely administration of cytotoxic chemotherapeutic agents, particularly in chemoresponsive malignancies. A study was designed to assess the role of GM-CSF in preventing myelosuppression in patients with intermediate-grade non-Hodgkin's lymphoma receiving combination chemotherapy (Cyclophosphamide, Vincristine, Prednisone and Epirubicin or Mitozantrone, +/- Bleomycin). A total of 24 patients were entered and data collated from 20 of them are amenable to analysis. All patients received the first chemotherapy cycle without GM-CSF and the second with GM-CSF (250 mg/m2 subcutaneously twice daily for 5 days commencing on the 5th day following chemotherapy). By entering only those patients who had suffered myelosuppression following chemotherapy, an internal control was established. GM-CSF administration significantly reduced the degree of neutropenia and leucopenia. The mean nadir white blood cell (WBC) and absolute neutrophil counts (ANC) were 2.88 x 10(9)/L and 0.97 x 10(9)/L in cycle 1 as compared to 5.95 x 10(9)/L and 2.92 x 10(9)/L respectively, in cycle 2 (p = 0.05 and 0.02, respectively). Eight patients (40%) had febrile neutropenias and 13 patients (65%) experienced a treatment delay by a median of 8 days during cycle 1. Six patients (30%) had febrile neutropenias and 2 patients (10%) had a treatment delay of 3 days during cycle 2. Reversible toxicity was seen in the majority of patients: bone pains (60%), skin rashes (35%), arthralgias (25%), and altered taste sensation (10%). No patient developed the capillary leak syndrome. This study demonstrates the efficacy of GM-CSF in preventing chemotherapy-induced myelosuppression.
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PMID:A phase II study of recombinant granulocyte macrophage colony stimulating factor in patients with non-Hodgkin's lymphoma. 795 Sep 23

One hundred and forty-seven consecutive patients with previously untreated high-intermedium and high clinical risk diffuse large cell lymphoma (DLCL) were included in a prospective clinical trial to evaluate the efficacy and toxicity of escalating doses of epirubicin compared to standard doses in the CEOP-Bleo (cyclophosphamide, epirubicin, vincristine and prednisone and bleomycin) regimen, 55% of the patients were > 60 years old and most patients had adverse prognostic factors at diagnosis. Complete response rates were similar in both groups (68% in the standard dose compared to 73% in the escalating arm, (p = 0.5). However, time to treatment failure (TFF) and overall survival were better after escalating doses. At 3-years TTF at a medial follow-up of 33.6 months was 76% in the patients whose received escalating dose statistical different to 37% of the patients whose received standard doses (p < .01). Overall survival was 81% in the escalated therapy arm which is statistical different to 40% of the patients treated with standard doses (p < .01). Toxicity was mild in both arms. Neutropenia, mucositis and cardiotoxicity were mild in the escalated dose arm and no severe complications were observed. All patients received the planned doses of all drugs. Patients > 60 years old had the same CR rate, TTF and overall survival as younger patients. In conclusion it seems that the dose of epirubicin can be increased in combination chemotherapy regimens with safety and only mild toxicity. The CR rate was not superior compared to the standard dose but the TTF and overall survival were better. Longer follow-up periods are required in order to determine if the cure rate can also be improved. Older patients can also benefit because they also tolerated the increase in epirubicin without severe side effects and also improved their outcome. The use of more aggressive regimens with increase in dose intensity may be the treatment of choice for more patients poor prognosis, with DLCL provided there is no increase in toxicity. In this respect the use of epirubicin in higher doses/appears to be useful.
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PMID:Dose escalation of epirubicin in the CEOP-BLEO regimen: a controlled clinical trial comparing standard doses for the treatment of diffuse large cell lymphoma. 916 42

In a previous study of prevalidation, a standard operating procedure (SOP) for two independent in vitro tests (human and mouse) had been developed, to evaluate the potential hematotoxicity of xenobiotics from their direct and the adverse effects on granulocyte-macrophages (CFU-GM). A predictive model to calculate the human maximum tolerated dose (MTD) was set up, by adjusting a mouse-derived MTD for the differential interspecies sensitivity. In this paper, we describe an international blind trial designed to apply this model to the clinical neutropenia, by testing 20 drugs, including 14 antineoplastics (Cytosar-U, 5-Fluorouracil, Myleran, Thioguanine, Fludarabine, Bleomycin, Methotrexate, Gemcitabine, Carmustine, Etoposide, Teniposide, Cytoxan, Taxol, Adriamycin); two antivirals (Retrovir, Zovirax,); three drugs for other therapeutic indications (Cyclosporin, Thorazine, Indocin); and one pesticide (Lindane). The results confirmed that the SOP developed generates reproducible IC90 values with both human and murine GM-CFU. For 10 drugs (Adriamycin, Bleomycin, Etoposide, Fludarabine, 5-Fluorouracil, Myleran, Taxol, Teniposide, Thioguanine, and Thorazine), IC90 values were found within the range of the actual drug doses tested (defined as the actual IC90). For the other 10 drugs (Carmustine, Cyclosporin, Cytosar-U, Cytoxan, Gemcitabine, Indocin, Lindane, Methotrexate, Retrovir, and Zovirax) extrapolation on the regression curve out of the range of the actual doses tested was required to derive IC90 values (extrapolated IC90). The model correctly predicted the human MTD for 10 drugs out of 10 that had "actual IC90 values" and 7 drugs out of 10 for those having only an extrapolated IC90. Two of the incorrect predictions (Gemcitabine and Zovirax) were within 6-fold of the correct MTD, instead of the 4-fold range required by the model, whereas the prediction with Cytosar-U was approximately 10-fold in error. A possible explanation for the failure in the prediction of these three drugs, which are pyrimidine analogs, is discussed. We concluded that our model correctly predicted the human MTD for 20 drugs out of 23, since the other three drugs (Topotecan, PZA, and Flavopiridol) were tested in the prevalidation study. The high percentage of predicitivity (87%), as well as the reproducibility of the SOP testing, confirm that the model can be considered scientifically validated in this study, suggesting promising applications to other areas of research in developing validated hematotoxicological in vitro methods.
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PMID:Application of the CFU-GM assay to predict acute drug-induced neutropenia: an international blind trial to validate a prediction model for the maximum tolerated dose (MTD) of myelosuppressive xenobiotics. 1288 91

Patients with poor and intermediate prognosis metastatic germ-cell tumours (MGCTs) are at a significant risk of relapse after standard platinum-based chemotherapy. Novel treatment regimens are required to improve survival. Dose intense, alternating combinations of drugs with known activity in germ-cell tumours represents one approach. In all, 43 patients with IGCCCG intermediate/poor prognosis MGCT were treated with a dose intense regimen alternating bleomycin, vincristine, cisplatin (BOP) with bleomycin, etoposide, cisplatin (BEP) to a maximum of three cycles. Data were collected on the maintenance of dose intensity, toxicity, response, progression-free (PFS) and overall survival (OS). The complete response rate was 58%; a further 7% of patients being rendered disease free by resection of viable residual tumour. With a median follow-up of more than 4 years in surviving patients, 3-year OS and PFS rates of 81% (95% CI: 66-91%) and 72% (95% CI: 56-83%) are seen, respectively. Bleomycin, vincristine, cisplatin (BOP)/bleomycin, etoposide, cisplatin (BEP) was well tolerated, with 86% of patients completing all planned courses. Toxicity was predominantly haematological with common toxicity criteria grade III neutropenia in 90% of patients. Cisplatin neuropathy and bleomycin-induced pulmonary toxicity represented the most significant nonhaematological toxicity. Bleomycin, vincristine, cisplatin (BOP)/bleomycin, etoposide, cisplatin (BEP) represents a practicable, well-tolerated, dose intense chemotherapy regimen with significant activity in intermediate and poor prognosis MGCT.
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PMID:Bleomycin, vincristine, cisplatin/bleomycin, etoposide, cisplatin chemotherapy: an alternating, dose intense regimen producing promising results in untreated patients with intermediate or poor prognosis malignant germ-cell tumours. 1476 Mar 71

ABVD remains a standard chemotherapy for Hodgkin Lymphoma (HL) despite many efforts to demonstrate the superiority of other regimens. Bleomycin was proven marginally active in this combination (J Clin Oncol 22:1532-3, 2004) but adding significant toxicity. Response to ABVD is often slow and relapse rate of 20-30% is a concern. ABVD has never been directly compared to CHOP, the other global standard for other lymphomas that is composed of agents certainly active in HL. Current study is an update on our initial report of 2004 (Blood 104, 2004). In addition to extending the follow-up, we compared outcome after CHOP in a pilot series of previously untreated patients with a retrospective results of ABVD therapy at our institution. CR/CRu rates were 88 and 62% for CHOP and ABVD, respectively. In CHOP CS III/IV group, more patients had at least three risk factors (80%) than in ABVD CS III-IV group (40%). In contrast to ABVD, there were no deaths in CHOP group, but EFS was inferior. This might result from a higher risk level in CHOP patients. Toxicity of both regimens was mild: grade 3/4 leukopenia in 9%, grade 1/2/3 peripheral neuropathy in 6% of ABVD patients, and grade 3/4 neutropenia in 7% of CHOP patients. In conclusion, CHOP-21 is an active and low-toxic regimen in HL with risk factors. A prospective comparison of CHOP with a standard chemotherapy in a randomized study will be justified.
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PMID:CHOP-21 for unfavorable Hodgkin's lymphoma. An exploratory study. 1931 2

A combination of Adriamycin (a.k.a. Doxorubicin), Bleomycin, Vinblastine, and Dacarbazine (ABVD) is the most commonly used chemotherapy regime for Hodgkin lymphoma. This highly effective treatment is associated with a significant risk of neutropenia. Various strategies are adopted to counter this commonly encountered problem, including dose modification, use of colony stimulating factors, and prophylactic or therapeutic use of antibiotics. Data to support these approaches is somewhat controversial, and in keeping with the paucity of definitive evidence, there is a wide disparity in the management of neutropenia in patients receiving ABVD chemotherapy. This paper summarizes the evidence for managing ABVD-related neutropenia during the treatment of Hodgkin lymphoma.
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PMID:Neutropenia and Neutropenic Complications in ABVD Chemotherapy for Hodgkin Lymphoma. 2168 49

A retrospective study was performed to evaluate response rate, time to progression, and toxicity of a bleomycin and cytosine arabinoside (Bleo/Cytarabine) combination protocol for dogs with relapsed lymphoma (LSA). Dogs diagnosed with LSA and previously treated with chemotherapy were included in the study. A total of 20 dogs met the inclusion criteria, and 19 were evaluable for response. Bleomycin was administered subcutaneously on days 1 and 8 and cytosine arabinoside was administered subcutaneously on days 1-5 of a 21-day cycle. The median number of chemotherapy drugs given prior to the administration of Bleo/Cytarabine was 8.5. A total of 23 cycles of Bleo/Cytarabine were administered. The overall response rate was 36.8% (7 of 19 dogs had a partial response). The median time to progression was 15 days. Three dogs developed grade 3 thrombocytopenia and one dog had a grade 4 neutropenia. Bleo/Cytarabine had minor activity when used as a rescue therapy for pretreated LSA patients.
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PMID:Combination of Bleomycin and Cytosine Arabinoside Chemotherapy for Relapsed Canine Lymphoma. 2955 12