Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed a phase I/II study of recombinant human interleukin-3 (rhIL-3) in 21 patients with aplastic anemia (AA) or myelodysplasia (MDS). Patients received 21-day cycles of IL-3 (0.5, 1.25, 2.5, 5.0, or 10 micrograms/kg/d) by subcutaneous injection followed by a 10- to 14-day washout period. Nineteen patients completed at least one 21-day cycle of IL-3. Frequent toxicities of IL-3 included headache, low-grade fever, and erythema at the injection site; at higher doses, weight gain and peripheral edema was seen. Eleven patients developed eosinophilia. Of the 20 evaluable patients, eight had increases in absolute neutrophil counts (seven with MDS, one with AA) including six of the nine patients receiving > or = 5.0 micrograms/kg/d. One AA patient became transfusion-independent for 8 months, while another AA patient had decreased transfusion requirements. Three patients with MDS had at least a doubling of their platelet count, and another patient experienced a 1.9-fold increase. One patient with RAEB progressed to aleukemic AML by the end of one treatment cycle. IL-3 was well-tolerated, but multilineage effects were seen in only 25% of patients with primary bone marrow failure states (five of 20 evaluable) and more commonly in patients with myelodysplastic syndromes. Its optimal use may be as part of combination hematopoietic growth factor therapy.
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PMID:A phase I/II study of interleukin-3 in patients with aplastic anemia and myelodysplasia. 806 86

Interleukin 3 (IL-3) is a multipotent hematopoietic growth factor which became available as a recombinant (rh) growth factor for use in the clinic a few years ago. In dose-finding studies, this hematopoietic growth factor has been evaluated without and after standard chemotherapy. Stimulatory effects on leukocytes, neutrophils, eosinophils, monocytes, reticulocytes and platelets were observed in some studies. Chemotherapy postponement due to insufficient bone marrow recovery was less frequent when IL-3 was administered. There are some clinical studies available in which rhIL-3 is combined with rh granulocyte-macrophage colony-stimulating factor (GM-CSF). The results do not clearly suggest superiority of these combinations over rhGM-CSF alone, but this may be partly due to the time scheduling of the growth factors. Administration s.c. is not inferior to i.v. Side effects mainly consist of flu-like symptoms and headache. The role of rhIL-3 after high-dose chemotherapy and autologous bone marrow reinfusion is still questionable. The addition of rhIL-3 to rhGM-CSF both administered after chemotherapy may allow a very high yield of peripheral stem cells suitable for bone marrow reconstitution after high-dose chemotherapy. rhIL-3 can stimulate leukemia tumor cell proliferation in vitro as well as proliferation of solid tumor cell lines. It is not yet clear in which way rhIL-3 combined with chemotherapy will effect tumor response and patient survival. It is too early to define the exact place of rhIL-3 in oncology. Additional studies with rhIL-3 alone and in combination with other growth factors are needed.
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PMID:Recombinant human interleukin 3 in clinical oncology. 845 87

Recombinant human interleukin 3 (rhIL-3, expressed in Escherichia coli) is a hematopoietic growth factor with protean biological effects on bone marrow in animal models, including enhanced granulocyte and platelet production and the capacity to ameliorate chemotherapy-induced bone marrow toxicity. We, therefore, undertook a Phase I trial in patients with advanced solid tumors and normal bone marrow function. Cohorts of four to six patients each received daily s.c. doses of rhIL-3 (SDZ-ILE-964; Sandoz) at dose levels of 1. 0, 2.5, 5.0, and 10.0 microgram/kg according to the following schedule: cycle 1, rhIL-3 days 1-14; cycle 2, carboplatin (350 mg/m2) on day 1 and etoposide (100 mg/m2) on days 1-3; and cycle 3, carboplatin (350 mg/m2) on day 1, etoposide (100 mg/m2) on days 1-3, and rhIL-3 on days 4-17. Each cycle was a total of 28 days. An analysis of 20 patients entered into all four escalating dose levels revealed that, during cycle 1, absolute neutrophil count (ANC) increased from a median baseline of 6,643/mm3 to a median of 12,692/mm3, and platelets increased from a median baseline of 314,000/mm3 to a median of 465,000/mm3. When cycle 2 was compared with cycle 3, the median ANC nadir increased from 192/mm3 to 988/mm3, and the mean ANC nadir increased from 458/mm3 to 1,297/mm3. Median platelet count nadirs increased from 29,000/mm3 to 84,000/mm3, and the mean nadir platelet counts increased from 72,000/mm3 to 129,000/mm3. Total days on which platelets were <50,000/mm3 was 52 for cycle 2 and 19 for cycle 3. The maximum tolerated dose of rhIL-3 was 5.0 microgram/kg/day; dose-limiting toxicities included fatigue, chills, fever, and headache. These data suggest a clear but variable biological activity observed with IL-3, as measured by the reduction in the depth and duration of thrombocytopenia and/or neutropenia when cycle 2 was compared with cycle 3. rhIL-3 is a promising cytokine that may help to ameliorate the bone marrow toxicity observed with the use of chemotherapeutic agents.
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PMID:Phase I trial of recombinant interleukin 3 before and after carboplatin/etoposide chemotherapy in patients with solid tumors: a southwest oncology group study. 981 5

Granulocyte-colony stimulating factor (G-CSF), a hematopoietic growth factor, is widely used to accelerate recovery from neutropenia after severe chemotherapy, both decreasing the risk of infection and mobilizing peripheral blood stem cells. Adverse effects occur with G-CSF use in approximately 30% of cases, comprised predominantly of bone pain, headache, and general fatigue. Pulmonary toxicity is very rare. Here, we describe a healthy donor for allogeneic hematopoietic stem cell transplantation who developed acute lung injury (ALI) after 4 days of G-CSF administration. Among the serum cytokines examined, only Interleukin (IL)-1beta level was elevated in this case. As a high level of IL-1beta was detected at the onset of ALI, on day 4 after G-CSF administration, and decreased to below the level of detection on day 11, it is possible in a certain part that IL-1beta was involved in the onset of G-CSF-related ALI in the present case. Granulocyte-colony stimulating factor (G-CSF) is commonly administered to healthy donors to mobilize peripheral blood stem cells (PBSC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Adverse events from G-CSF use in healthy donors have been described in approximately 30% of cases, and are comprised predominantly of bone pain, headache, and general fatigue. Pulmonary complications caused by G-CSF include cough, dyspnea, and interstitial or alveolar pulmonary edema with mild-to-severe deterioration of blood oxygen level. Few cases of acute respiratory distress syndrome (ARDS) following G-CSF administration have been reported. The present report describes a healthy donor for allo-HSCT with acute lung injury (ALI) after 4 days of G-CSF administration. The cytokine-related mechanisms of G-CSF administration that contribute to ALI are discussed.
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PMID:Acute lung Injury in a healthy donor during mobilization of peripheral blood stem cells using granulocyte-colony stimulating factor alone. 1575 51


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