Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the treatment of patients with meningeal leukemia, conventional intrathecal methotrexate therapy followed by maintenance intrathecal methotrexate at intervals of 8 weeks has been shown superior to an intensive, unmaintained intrathecal methotrexate induction regimen, and to neuroaxis radiotherapy, tumor dose 2000-2500 rads. In each of the treatment regimens, all children completing proscribed therapy achieved complete CNS remission as judged by the return of CSF findings to normal. Median lengths of remission were: maintenance regimen 240 days; intensive induction regimen, 106 days; and radiotherapy, 216 days. Differences were of statistical significance between the maintenance regimen and the intensive regimen (p equal 0.001), and between the radiotherapy and intensive regimens (p equal 0.01). Maintenance intrathecal therapy appeared to affect favorably the duration of existing marrow remissions; the median time to marrow relapse for patients given maintenance therapy was significantly longer than for those given intensive induction therapy. Toxicity of the chemotherapy regimens was not prohibitive. Radiotherapy was associated with severe myelosuppression, interruptions of systemic therapy, and serious infections, which resulted in death in five children.
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PMID:Superiority of conventional intrathecal methotrexate therapy with maintenance over intensive intrathecal methotrexate therapy, unmaintained, or radiotherapy (2000-2500 rads tumor dose) in treatment for meningeal leukemia. 80 66

The toxicity and efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) is established in adults, but limited information is available on its use in children. The profound myelotoxicity induced by cisplatin (40 mg/m2 daily x 5) and etoposide (150 mg/m2 daily x 3) provides a model to test the clinical value of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric cancer patients; myelosuppression occurred (absolute neutrophil count [ANC] < 500/microL) during 99 of 118 (84%) courses given to 44 children with refractory solid tumors. Fifty-nine courses (50%) resulted in hospitalizations for fever. Subsequently, rhuGM-CSF was added to this treatment regimen to: (i) determine the dose-limiting toxicity of this agent in children; and (ii) to determine whether it can decrease the duration and severity of neurtropenia and attendant complications. Here we summarize and update our experience with this glycoprotein in children with relapsed solid tumors.
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PMID:Use of GM-CSF in children after high-dose chemotherapy. 130 84

We have studied the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in stimulating haematopoiesis of patients with chemotherapy-induced myelosuppression. Ten patients with various myeloid and lymphoid neoplasias were treated daily with a single subcutaneous dose of rhGM-CSF (5 micrograms/kg/day), for a period of 5-10 days, after receiving highly myelotoxic chemotherapy. The treatment increased the white blood cell count (WBC) in nine of ten patients, primarily because of an increase in the number of neutrophils. Increase in bone marrow myeloid precursor cells, and myeloid to erythroid cell rations accompanied the white-cell response. In spite of this, five patients demonstrated rapid platelet recoveries, and in two patients erythrocyte levels increased after GM-CSF treatment. No toxicity was encountered with the cytokine therapy. Although rhGM-CSF was shown to stimulate haematopoiesis in patients with chemotherapy-induced myelosuppression, additional studies are needed to assess whether the use of GM-CSF will reduce chemotherapy-associated morbidity and improve response rates and survival among patients with neoplasias.
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PMID:Effect of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy-induced myelosuppression. 134 Jan 91

Ten dogs were given mitoxantrone at a dose of 5 mg/m2 body surface area intravenously. Recombinant canine granulocyte colony-stimulating factor (rcG-CSF) was administered subcutaneously daily for 20 days after an infusion of mitoxantrone in five of these dogs to determine the effect of the hematopoietic growth factor on the duration and severity of myelosuppression. The median neutrophil counts dropped below normal (less than 3,000/uL) for 2 days in the dogs that received rcG-CSF, and for 5 days in the dogs that received only mitoxantrone. Four of five dogs not treated with rcG-CSF and none of those receiving rcG-CSF developed serious neutropenia (less than 1,500/uL). The neutrophil counts were significantly (P less than 0.05) higher in the rcG-CSF treated dogs at all time points except before the administration of the colony-stimulating factor, and the sixth day after the mitoxantrone was administered. These findings demonstrate that rcG-CSF is capable of reducing the duration and severity of mitoxantrone-induced myelosuppression.
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PMID:Use of recombinant canine granulocyte colony-stimulating factor to decrease myelosuppression associated with the administration of mitoxantrone in the dog. 137 55

The study was aimed to evaluate the feasibility of dose-intensive chemotherapy given on a weekly basis for 12 weeks. Seventeen [7 with limited disease (LD) and 10 with extensive disease (ED)] previously untreated patients with small-cell lung cancer (SCLC) were treated with the cisplatin, vincristine, doxorubicin, and etoposide (CODE) regimen. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given to eight patients for the purpose of increasing the dose intensity. Overall response rate was 88%, with a 29% complete response. The median survival times were greater than 20.5 months for LD patients and 8.1 months for ED patients. Overall actual dose intensity was 88% of planned protocol. The major toxicity was myelosuppression. Fifteen patients (88%) had grade 3 or 4 leukopenia. Other problems were weight loss and worsening of performance status during the treatment. RhG-CSF significantly reduced leukopenic nadirs and shortened the neutropenic period. Our preliminary results indicate that 12 cycles of the CODE regimen on a weekly schedule is effective for SCLC, but is also associated with significant toxicity.
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PMID:Weekly dose-intensive chemotherapy in patients with small-cell lung cancer: a pilot study. 137 63

Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a polypeptide hormone produced through recombinant DNA technologies in glycosylated (yeast or mammalian expression systems) or nonglycosylated (Escherichia coli expression system) form. It is a multilineage haematopoietin which stimulates proliferation and differentiation of bone marrow myeloid progenitors and increases peripheral white blood cell counts when administered systemically. Treatment is generally well tolerated, although mild to moderate flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be problematic in occasional patients. rGM-CSF accelerates recovery of peripheral neutrophil counts after bone marrow transplantation, and results of a placebo-controlled randomised trial correlate this with reduced infectious episodes and shortened length of hospitalisation in patients with lymphoid malignancies. A substantial number of patients with graft failure after bone marrow transplantation also respond to rGM-CSF. The duration of myelosuppression secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which has permitted investigation of antineoplastic dose-intensity escalation. In some haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically useful increases in peripheral blood granulocyte counts, although the effect is generally not sustained after drug withdrawal. The potential for rGM-CSF to stimulate proliferation of the abnormal clone in myelodysplasia and in acute myelogenous leukaemia following induction therapy is of concern. Available data suggest, however, that with appropriate monitoring and exclusion of high-risk patients this serious potential risk can be avoided, and that myelopoiesis is enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating factors are a new therapeutic modality; hence many aspects of their use remain to be clarified. Nonetheless, as one of a small group of novel agents rGM-CSF has major potential in the management of myelosuppression secondary to cytoreductive therapy with or without bone marrow transplantation, and in amelioration of disturbed myelopoiesis. It represents an important application of biotechnology to a difficult area of therapeutics.
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PMID:Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). A review of its pharmacological properties and prospective role in the management of myelosuppression. 137 18

Anemia and neutropenia are common complications of HIV infection. Antiretroviral therapy with zidovudine exacerbates bone marrow suppression by inhibiting proliferation of blood cell progenitor cells. In addition, treatment for opportunistic infections or malignancies can involve the use of myelosuppressive drugs. As a consequence, severe anemia and neutropenia can result, thereby limiting the utilization of antiretroviral drugs. Since antiretroviral therapy can increase survival, drugs that ameliorate myelosuppression are important adjuncts in the treatment of HIV-infected patients. Three hematopoietic growth factors are effective in the treatment of anemia or neutropenia. In four placebo-controlled trials, erythropoietin (EPO) at doses up to 600 U/kg/wk decreased mean transfusion requirements by 37%, increased mean hematocrit by 4.5% and corrected anemia in the majority of patients receiving zidovudine over a 12-week period. In a separate study, granulocyte colony-stimulating factor (G-CSF) corrected leukopenia and isolated neutrophil defects in 22 patients with AIDS without altering HIV expression. When erythropoietin was added to the regimen, combined G-CSF and EPO corrected both anemia and leukopenia and lessened subsequent zidovudine toxicity. Similarly, granulocyte macrophage-colony-stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In controlled and uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, and antineoplastic therapy. New combinations of hematopoietic stimulants are being used to decrease the toxicity from combination antiretroviral therapy with alpha interferon and cytotoxic chemotherapy in the treatment of AIDS-related malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematopoietic growth factors as adjuncts to antiretroviral therapy. 138 Feb 56

Three patients with breast cancer with poor prognosis were treated with high-dose chemotherapy (HD-CT) and peripheral blood stem cell transplantation (PBSCT) as adjuvant treatment. After radical mastectomy, the consolidation chemotherapy with Adriamycin 50 mg/m2, Cyclophosphamide 1,000 mg/m2, Vincristine 1.0 mg/m2 and Methotrexate 200 mg/m2 with Leucovorin rescue was started. Recombinant human granulocyte colony stimulating factor (rhG-CSF) was also added for early recovery from myelosuppression. This combination chemotherapy was given every 3 weeks for 3 courses, and after the 2nd and 3rd courses, peripheral blood stem cells (PBSC) were collected and cryopreserved. HD-CT with Cyclophosphamide 2,000 mg/m2/day, Thio-TEPA 200 mg/m2/day, and Etoposide 300 mg/m2/day, were administered for 3 consecutive days, and after 48 hours of last doses, frozen-thawed PBSC (6.4-8.9 x 10(4)/kg of CFU-GM) were administered. rhG-CSF was also added. HD-CT and PBSCT were well tolerated, recovery from myelosuppression of the HD-CT was very quick and no serious side effects were observed.
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PMID:[High-dose adjuvant chemotherapy with peripheral blood stem cell transplantation for breast cancer with poor prognosis--a pilot study]. 138 71

In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m2, etoposide 120-150 mg/m2 and ifosfamide 1.2 g/m2 for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died of Clostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/microliters and a thrombocyte nadir of 47,000/microliters. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m2, etoposide 150 mg/m2 and ifosfamide 1.6 g/m2 five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 micrograms/kg on days 6-15. Acute toxicity was severe with a white blood cell nadir of 300/microliters and thrombocyte nadir of 11,000/microliters. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure and Aspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m2, etoposide 200 mg/m2 and ifosfamide 1.6 g/m2 for 5 days and GM-CSF 10 micrograms kg-1 day-1 on days 6-15 s.c.
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PMID:Cisplatin/etoposide/ifosfamide stepwise dose escalation with concomitant granulocyte/macrophage-colony-stimulating factor for patients with far-advanced testicular carcinoma. 166 92

In three consecutive pilot studies the effect of recombinant human granulocyte/macrophage-colony-stimulating factor (rhGM-CSF) on haematopoetic recovery after chemotherapy in patients with small-cell lung cancer was investigated. In study I, 20 patients received AIO chemotherapy (A, Adriamycin 25 mg/m2 on days 1 + 2; I, ifosfamide 2 g/m2 on days 1-5; O, vincristine 2 mg on day 1) at 4-week intervals either with or without rhGM-CSF (250 micrograms/m2 sc) from day 8 until recovery of leucocytes. Neither the degree nor the duration of myelosuppression was markedly influenced by rhGM-CSF. Suggesting that these disappointing results were caused by the late onset of GM-CSF application, in the following study we shortened chemotherapy to 3 days and started with GM-CSF on day 4. The main objective of this study was to test whether the earlier administration of GM-CSF allowed treatment intervals to be reduced or the dose to be escalated. After 10 patients had received a starting dose of AIO (A, 50 mg/m2 on day 1; I, 2 g/m2 on days 1-3; 0,2 mg on day 1) alternating with cisplatin (90 mg/m2 on day 1) and etoposide (150 mg/m2 on days 1-3), the dose of ifosfamide and etoposide was escalated to 2.5 g/m2 on days 1-3 and 200 mg/m2 on days 1-3 in the next 10 patients. Treatment was given at 2-week intervals when leucocytes were greater than 3500/mm3 and thrombocytes were greater than 100,000 mm3 on day 14. At each dose level patients were randomized to receive either rhGM-CSF 250 micrograms/m2 s.c. on days 4-12 or no GM-CSF. In this study, rhGM-CSF markedly shortened the duration of leukopenia. Reinstitution of chemotherapy on day 15 was possible at dose level 1 in 1/4 patients without and in 3/4 patients with GM-CSF, and at dose level 2 in 0/5 patients without and in 5/5 patients with GM-CSF. However, the degree of myelosuppression was not improved by GM-CSF. In a third study we tried to apply rhGM-CSF simultaneously with chemotherapy. After 3 patients had received GM-CSF starting on day 1 concurrent to AIO chemotherapy, we noticed an increase of myelosuppression with prolonged neutropenia and thrombocytopenia and stopped this investigation. Considering all patients included in these three consecutive pilot studies, there is no difference in response rates and survival between patients with and without rhGM-CSF treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of rhGM-CSF on haematopoietic reconstitution after chemotherapy in small-cell lung cancer. 166 93


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