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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The multilineage hematopoietic effects of IL-3 appear to be most important for its clinical use comprising especially leucocyte and platelet responses. This was demonstrated to be dose dependent characterising doses of 250 to 500 micrograms/m2/day subcutaneously as hematopoietic effective and well tolerable. Since preclinical data suggest synergism between IL-3 and GM-CSF hematopoietic effects of their sequential administration were evaluated in 15 patients with preserved hematopoietic function. An enhanced stimulation of megakaryopoiesis combined with more pronounced stimulation of granulopoiesis than IL-3 alone could be demonstrated. The cytokine combination of IL-3 and GM-CSF was thus used during chemotherapy induced myelosuppression. Data indicates beyond the known amelioration of myelosuppression by GM-CSF additional chances to enhance platelet recovery which can be of important clinical impact.
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PMID:Interleukin-3 and granulocyte-macrophage colony-stimulating factor in combination: clinical implication. 130 86

The efficiency of GM-CSF to reduce myelosuppression after chemotherapy depends on the schedule of administration and the dose of chemotherapy. If conventional chemotherapy doses are given, a seven to ten day administration starting one day after the end of chemotherapy is able to reduce both degree and duration of leucopenia. A later onset is less effective, an earlier one aggravates leuco- and thrombocytopenia. The reduction of myelosuppression is accompanied by a reduction of infection rates and hospitalisation of patients due to these complications. If high-dose chemotherapy is given, GM-CSF does not markedly affect nadir values for leuco- and thrombocytes, but still shortens the duration of leucopenia. This effect is consistently seen after the initial cycles of chemotherapy, but seems to be less pronounced in later cycles. Thus, the growth factor administration allows a treatment intensification mainly by shortening of treatment intervals. Whether these modifications will improve the prognosis of patients with solid tumors is currently being investigated in small cell lung cancer in a German multicenter randomized trial.
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PMID:Experience with GM-CSF in the treatment of solid tumors. 133 37

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

Hematopoietic stem cells circulate in the peripheral blood. These cells can be collected by apheresis techniques either in the unperturbed state, after mobilization following the administration of cytokines like G-CSF or GM-CSF, or during the phase of early blood count recovery following chemotherapy-induced myelosuppression. The number of cells collected following mobilization is greater than that obtained after apheresis in the unperturbed state. There are, however, qualitative differences between unperturbed and mobilized cells. Chemotherapy related mobilization can be potentially dangerous in that severe myelosuppression necessary to achieve mobilization can have serious consequences. There are no controlled studies that evaluate the relative merits of each method of collection. Regardless of the techniques employed peripheral blood stem cells can reliably accelerate hematologic recovery after potentially myeloblative therapy and provide an alternative to bone marrow support.
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PMID:Peripheral blood stem cell mobilization by cytokines. 136 99

Three hematopoietic growth factors, erythropoietin, GM-CSF, and G-CSF, have all been evaluated in the context of HIV infection. Recombinant human Epo is currently licensed for therapy of anemia related to zidovudine and is well tolerated in this patient population. Although myelosuppression can clearly be overcome using recombinant human GM-CSF or G-CSF in HIV-infected hosts, the clinical benefits for such patients are still not determined. It is likely that these growth factor therapies will allow for delivery of certain important myelosuppressive medications that otherwise could not be tolerated. Improvements in virological quantitation in vivo should help settle the controversies regarding modulation of HIV replication caused by cytokine treatment. The clinical use of hematopoietic growth factors in HIV disease requires further study with regard to the optimization of increases in blood cell number and/or modulation of blood cell function.
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PMID:Hematopoietic growth factors in AIDS. 138 Jul 30

Transforming growth factor-beta 1 (TGF-beta 1) induces cell death in myeloid leukemia by apoptosis. In the M1 myeloid leukemia, this induction of apoptosis was inhibited by granulocyte colony-stimulating factor (G-CSF) or interleukin-6 (IL-6) and to a lesser extent by IL-1 alpha. IL-3 and stem cell factor/mast cell growth factor (SCF) showed only a marginal effect, and granulocyte-macrophage and macrophage CSFs (GM-CSF and M-CSF, respectively) were inactive. The induction of apoptosis by TGF-beta 1 in a different myeloid leukemia (7-M12) was inhibited by GM-CSF and IL-3 but not by the other cytokines. In the absence of TGF-beta 1, both M1 and 7-M12 leukemic cells were independent of hematopoietic cytokines for cell viability and growth. The cytotoxic compounds vincristine, vinblastine, adriamycin, cytosine arabinoside, cycloheximide, and sodium azide, some of which are used in cancer chemotherapy, induced cell death by apoptosis in both leukemias. As with TGF-beta 1, apoptosis induced by these cytotoxic compounds was inhibited by GM-CSF (7-M12 leukemia) and by G-CSF or IL-6 (M1 leukemia). Cyclosporine A decreased cell multiplication in M1 cells without inducing apoptosis, and G-CSF and IL-6 inhibited the cytostatic effect of cyclosporine A. It is suggested that the clinical use of cytokines to correct therapy-associated myelosuppression should be carefully timed to avoid protection of malignant cells from the cytotoxic action of the therapeutic compounds.
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PMID:Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor beta 1 and cancer chemotherapy compounds in myeloid leukemic cells. 138 3

These ECOG trials have demonstrated that progressive increments in the intensity of post-remission therapy result in improving long-term, disease-free survival in adults with AML. The median duration of disease-free survival and long-term outcome from different post-remission therapies are summarized in Table 4. [table: see text] Despite the suggestive evidence of the ordered increment in value of intensive consolidation therapy, allogeneic and autologous bone marrow transplantation, it remains to be proved that the differences observed in our preceding studies are statistically significant and clinically meaningful. These remaining questions led to the current ECOG study, EST 3489, a randomized intergroup study conducted with members of the Southwest Oncology Group. The study includes all patients with de novo AML up to age 55; the schema is shown in Figure 3. Induction therapy consists of idarubicin plus cytarabine instead of DAT. A modified short course of this induction therapy is repeated after CR. Patients who have a histocompatible sibling are offered allogeneic bone marrow transplantation. The remaining patients are randomized to receive either autologous bone marrow transplantation or a single course of high-dose cytarabine. Autologous bone marrow transplantation utilizes the previously described high-dose busulfan and cyclophosphamide regimen plus 4-HC purging of the bone marrow. The dosage of cytarabine in the intensive consolidation arm is 3 gm/M2/day IV on days 1-6. The results of this study should determine the relative merits of these different approaches to post-remission therapy. [table: see text] As mentioned earlier, demonstration of improved CR rates is limited by the morbidity and mortality from the myelosuppression that results from induction therapy. This is especially marked for older patients with AML. In patients, ages 55-70 years old, the ECOG is conducting a randomized trial (EST 1490) of conventional induction therapy +/- GM-CSF to determine if accelerated neutrophil recovery can reduce the mortality of induction therapy and thereby increase the remission rate. It may be that the application of GM-CSF and other colony-stimulating factors can increase the CR rate for all patients, increasing the number of patients potentially eligible for cure by post-remission therapy.
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PMID:Escalating the intensity of post-remission therapy improves the outcome in acute myeloid leukemia: the ECOG experience. The Eastern Cooperative Oncology Group. 157 10

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

The network of interactions between human myelopoietic growth factors can lead to signal amplification that all regulate normal myelopoiesis. The present study identified synergistic interactions between recombinant human interleukin-3, GM-CSF and G-CSF on normal human marrow day 14 CFU-GM suggesting that the interactions between these human myelopoietic growth factors are mainly confined to the early stages of normal human myelopoiesis. The synergistic combinations of recombinant human interleukin-3 plus G-CSF and GM-CSF plus G-CSF warrant clinical trial for the recovery from cancer chemotherapy or radiotherapy-induced myelosuppression and for augmenting human defence against infections.
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PMID:Synergistic interactions between recombinant human interleukin-3, GM-CSF and G-CSF in normal human marrow granulocyte-macrophage colony formation. 170 93

The use of intravenous melphalan at higher doses is limited by severe myelosuppression. It was postulated that GM-CSF would permit the use of higher dose melphalan with only moderate myelosuppression easily manageable in an outpatient setting. Therefore, a phase I study of intravenous melphalan utilizing GM-CSF (recombinant granulocyte-macrophage colony-stimulating factor) support was initiated. Intravenous melphalan at doses of 15-45 mg/m2 was administered every 28 days. GM-CSF was utilized at doses of 10-20 micrograms/kg/day subcutaneously Days 2-21 on a 28-day cycle. Twenty-five patients received 53 courses of therapy. The dose-limiting toxicities were severe or life-threatening granulocytopenia and thrombocytopenia. Utilizing 20 micrograms/kg/day GM-CSF, the maximum tolerated dose (MTD) of melphalan is 30 mg/m2 and, with 10 mg/kg/day GM-CSF, the maximum tolerated melphalan dose is only 20 mg/m2. One patient with ovarian cancer achieved a partial response. Because the reported MTD of intravenous melphalan without GM-CSF is 30 mg/m2, GM-CSF has not allowed sufficient escalation of the intravenous melphalan dose for routine outpatient use.
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PMID:SWOG 8825: melphalan GM-CSF: a phase I study. 173 Apr 28


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