Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We treated 115 patients in a phase I/II dose-escalation study of ifosfamide/carboplatin/etoposide (ICE) followed by autologous stem cell rescue. Patients treated had a variety of diagnoses, including breast cancer (high-risk stage II disease with eight or more positive nodes, stage III disease, and responsive metastatic disease), non-Hodgkin's lymphoma, Hodgkin's disease, acute leukemia in first remission, and various solid tumors that were responsive to induction therapy. Patients received autologous bone marrow stem cells or peripheral blood stem cells primed by one of several methods. The maximum tolerated dose of ICE was determined to be ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2 when administered as a 6-day regimen. The dose-limiting toxicities included acute renal failure, severe central nervous system toxicity, and "leaky capillary syndrome" with hypoalbuminemia, profound fluid overload, and pulmonary insufficiency. Analysis of hematologic recovery based on stem cell source and influence of hematopoietic growth factor administration was undertaken. Hematopoietic growth factor use significantly reduced neutrophil engraftment time for patients receiving bone marrow stem cells, with evidence of earlier recovery times for patients receiving granulocyte colony-stimulating factor compared with granulocyte-macrophage colony-stimulating factor. Neutrophil recovery times varied based on the source of stem cells used, with the earliest engraftment times seen for patients receiving peripheral blood stem cells primed with cyclophosphamide and granulocyte colony-stimulating factor. Platelet recovery times were not statistically different for any of the subsets. In conclusion, the maximum tolerated dose of ICE has been defined, and the source of stem cells and the use of hematopoietic growth factors influence hematopoietic recovery.
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PMID:High-dose ifosfamide/carboplatin/etoposide: maximum tolerable doses, toxicities, and hematopoietic recovery after autologous stem cell reinfusion. 752 92

Interleukin-1 alpha (IL-1 alpha) can act as both a hematopoietic growth factor and a stimulant of cellular and humoral immune responses. To promote acceleration of hematologic recovery and induce immune antitumor activity, we initiated a phase I/II dose escalation trial of 6-hour daily infusions of recombinant human IL-1 alpha after autologous transplantation. Forty patients with Hodgkin's disease (n = 9) and non-Hodgkin's lymphoma (n = 31) transplanted with unmobilized autologous peripheral blood stem cells or bone marrow stem cells received daily 6-hour infusions of IL-1 alpha (day 0 to day +13) at daily doses between 0.1 to 10 micrograms/m2/d; 7 patients received only 7 planned days of IL-1 alpha (day 0 through 6). Most patients received all 14 days of therapy, although 5 patients discontinued treatment early (after 1 to 6 doses) because of fever and severe chills. Toxicity included IL-1 alpha-related fever (occurring on a median of 9 of 14 treatment days), fatigue, and severe chills. Hypotension was dose-limiting and led to discontinuation of IL-1 alpha in both patients receiving 10 micrograms/m2/d. IL-1 alpha-treated patients receiving 3.0 micrograms/m2/d (the maximum tolerated dose) achieved neutrophil recovery (absolute neutrophil count greater than 500/microL) significantly earlier (median, 12 days; range, 11 to 27) than untreated control patients or those receiving IL-1 alpha at 0.1 to 1.0 micrograms/m2/d (median, 27; range, 9 to 63; P < .0001). In addition, the IL-1 alpha patients' bone marrows at day +14 were significantly enriched with committed myeloid progenitor cells. Strong trends to earlier freedom from red blood cell (P = .06) and platelet (P = .09) transfusions were also noted after IL-1 alpha treatment. This earlier hematopoietic engraftment after 3.0 micrograms/m2/d IL-1 alpha allowed earlier hospital discharge (median, 25 v 37 days for control or low-dose IL-1 alpha patients [P < .0001]) and a concomitant reduction (by $38,000) in median hospital charges (P = .01). The clinical toxicities of IL-1 alpha infusion are substantial, though not life-threatening. The accelerated hematopoiesis and immune response activation observed in this trial suggest the value of its further investigation in controlled trials and perhaps in combination with other hemopoietins after transplantation.
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PMID:Interleukin-1 alpha administered after autologous transplantation: a phase I/II clinical trial. 791 16

Recombinant human Interleukin-3 (RhIL-3) is a haemopoietic growth factor with effect both on early and differentiated cells, such as eosinophils and basophils, and it also acts as a histamine-releasing agent. The purpose of the present study was to examine whether in vivo rhIL-3 administration after chemotherapy affected basophil histamine levels and whether a concordance between rhIL-3 induced histamine release and side effects during the treatment could be demonstrated. Thirty patients with non-Hodgkin's lymphoma entered the study. All patients received 6 courses of chemotherapy, rhIL-3 was administered subcutaneously once daily after the second and the fourth course of chemotherapy from cycle day 2-15 at the dose levels 0.5, 1.0, 5.0, 7.5 and 10 micrograms/kg with 6 patients at each dose level. In cycle 6 recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (rhGM-CSF) (3.0 micrograms/kg) was administered sequential/concurrent day 9-15 to rhIL-3 (day 2-15) at all dose levels except 7.5 micrograms/kg, where rhIL-3 was given day 2-8 and rhGM-CSF sequential day 9-15. Cycles 1, 3 and 5 served as control cycles with no cytokine therapy. During rhIL-3 treatment, and after CHOP chemotherapy, the basophil counts increased moderately especially during the recovery period day 15-22, and mainly at the two highest dose levels 7.5 and 10 micrograms/kg, but never exceeded the normal upper limit. Histamine levels in basophils were the same in patients before chemotherapy and healthy volunteers, and except from a trend to increased histamine level at 10 micrograms/kg on day 15, no difference was noted between rhIL-3 cycles and control cycles. Within 3-4 hr after rhIL-3 administration, a drop in histamine level in basophils was noted, which could be due to histamine-releasing properties of rhIL-3 as previously demonstrated by in vitro studies. No serious side effects were noted during the cytokine treatment, and despite that most patients had mild flushing of the face, neck and upper chest, no patients experienced sensitization throughout the study. Although a significant increase in rhIL-3-induced histamine release from basophils was noted in some of the patients, no correlation to the dose of rhL-3 was found, and no correlation was noted between side effects and histamine release or histamine levels in basophils.
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PMID:The in vivo effects of interleukin-3 on histamine levels in non-Hodgkin's lymphoma patients. 922 66

Fusion tyrosine kinases (FTKs) such as BCR/ABL, TEL/ABL, TEL/JAK2, TEL/PDGF beta R and NPM/ALK arise from reciprocal chromosomal translocations and cause acute and chronic myelogenous leukemias and non-Hodgkin's lymphoma. Murine hematopoietic growth factor dependent BaF3 cells and cells transformed by FTK (BaF3-FTK) were used to investigate the role of FTKs in response to DNA damage. FTK-transformed cells displayed resistance to genotoxic treatment including gamma-radiation and cytostatic agents such as idarubicin and MNNG. More FTK-transformed cells survived genotoxic treatment and were able to proliferate in comparison to parental non-transformed cells. Similar or higher levels of DNA damage was detected in gamma-irradiated in BaF3-FTK cells in comparison to BaF3 parental cells. Idarubicin induced different amounts of DNA damage in various BaF3-FTK cells. All BaF3-FTK cells treated with MNNG displayed significantly more DNA damage in comparison to BaF3 cells. Despite the extent of genotoxic effect BaF3-FTK cells were often able to repair damaged DNA more efficiently that the non-transformed counterparts. Inhibition of BCR/ABL kinase activity by STI571 (Gleevec, inatinib mesylate) abrogated the resistance to genotoxic treatment and inhibited DNA repair mechanisms. We hypothesize that facilitation of the DNA repair in FTK-positive cells may contribute to their resistance to genotoxic treatment.
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PMID:Fusion oncogenic tyrosine kinases alter DNA damage and repair after genotoxic treatment: role in drug resistance? 1253 80

Interleukin-8 (LL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are cytokines/hematopoietic growth factor and are important mediators of inflammation and immune resoponse producing pathophysiological changes in human disease. Levels of IL-8 and GM-CSF in circulation of various hematologic diseases are unknown. To demonstrate their importance in lymphoproliferative disorders, we have measured the circulating levels of these two cytokines from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). IL-8 and GM-CSF levels were determined by highly specific enzyme-linked immunosorbent assays. IL-8 levels were elevated in most patients with B-cell malignancies, B-cell CLL (B-CLL) and B-cell NHL (B-NHL) as well as in patients with HD. However, GM-CSF levels were higher in most patients with NHL (T-NHL and B-NHL) and HD. IL-8 was undetectable in T-cell malignancies (T-CLL and T-NHL), whereas GMCSF was undetectable from CLL (T-CLL and B-CLL). Of interest, IL-8 levels were correlated with white blood cell counts (WBC) in B-cell malignancies (B-CLL and B-NHL) but not in HD. These results suggest that both IL-8 and GMCSF may play an important role in pathophysiological changes in B-NHL and HD. IL-8 may be related with recruitment and activation of neutrophils, whereas, GM-CSF in proliferation and differentiation of hematopoietic progenitor cells and immune response in these malignancies. The clinical status of B-CLL patients in regards to WBC counts appeared to be associated with the serum levels of IL-8.
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PMID:Interleukin-8 and granulocyte-macrophage colony-stimulating factor secretion in hematologic malignancies. 2155 12