Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For phase II studies in patients with solid tumors, the National Cancer Institute recommended that the starting dose of fludarabine phosphate be 20 mg/m2/day as a short intravenous infusion for 5 days every 21 days. Twenty-one patients with untreated, advanced, measurable colorectal carcinoma received fludarabine phosphate as a 30-minute infusion at a median dose of 25 mg/m2/day (range 15-35 mg/m2/day) for 5 consecutive days repeated every three weeks. Antitumor response was evaluated following two courses of therapy. No patient achieved complete or partial response. Minor regression of lung metastases occurred for less than 12 weeks in one patient. Therapy was generally well tolerated. Frequent toxicities included lymphopenia, mild nausea and vomiting, mucositis, and anorexia. One patient died of sepsis, bleeding, and progressive disease while she was severely myelosuppressed. Neurotoxicity was not observed in any patient. Fludarabine phosphate at this schedule and dose range is inactive against colorectal carcinoma.
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PMID:Phase II study of fludarabine phosphate in patients with advanced colorectal carcinoma. 245 66

Fludarabine phosphate selectively eliminates normal and malignant mononuclear cells in large animals and man through the inhibition of DNA synthesis. The drug depletes mononuclear cells from culture within 24 hours of initial exposure, CD4 and CD8 T cells being more sensitive than either CD20 B cells or CD34 bone marrow precursors. Mitogenic activation of lymphocytes enhances cellular elimination from culture. Fludarabine inhibits PHA-induced T-cell proliferation by >90 per cent and mixed lymphocyte reactions (allogeneic and xenogeneic) by >95 per cent. Fludarabine exerts its cytolytic effects through the induction of endonuclease-independent apoptosis. A 5-day course of fludarabine (50 mg/m2 intravenously once daily) induces both T- and B-cell lymphopenia in Cynomolgus monkeys and Papio baboons. Transient neutropenia was the only side-effect seen in experimental animals. Pretreatment of Cynomolgus monkeys with this regimen of fludarabine causes a prolongation of ABO-compatible skin allograft survival from 8 days (control) to 16 days (drug treated group). Secondary allotransplantation into presensitized recipients showed a similar prolongation of graft survival with fludarabine pretreatment (8 days vs 5 days control). Fludarabine promises to be a potent immunosuppressive agent with low clinical toxicity.
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PMID:Fludarabine phosphate: A DNA synthesis inhibitor with potent immunosuppressive activity and minimal clinical toxicity. 865 23

Fludarabine phosphate, a purine analogue currently used in the therapy of hematological malignancies, is known to cause immunosuppression and long-lasting T cell lymphopenia. In this study, the effect of fludarabine on murine graft-versus-host disease occurring after marrow transplantation across major and minor histocompatibility barriers was evaluated. Survival of (BALB/c x C57BL/6)F1 mice irradiated and transplanted across the major histocompatibility barrier with C57BL/6 spleen cells, and subsequently treated with fludarabine was significantly longer than that of the control animals (P < 0.0001). On the other hand, fludarabine had no effect on the graft-versus-host disease and survival of CBA mice transplanted by B10.BR and of BALB/c mice transplanted by B10.D2 spleen cells across the minor histocompatability barrier. The results indicate that in certain murine models, particularly a major mismatch, fludarabine has the potential to induce bilateral tolerance and stable chimerism after marrow transplantation. Bone Marrow Transplantation (2000) 25, 263-266.
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PMID:The prophylactic potential of fludarabine monophosphate in graft-versus-host disease after bone marrow transplantation in murine models. 1067 97

The increasing number of allogeneic stem cell transplantations has made the management of graft-versus-host disease (GVHD) a continuing problem for transplantation professionals. GVHD is a complicated disease the treatment of which requires an equally multifaceted approach. Despite therapeutic efforts to decrease its distressing and potentially lethal clinical manifestations, treatment is still not optimal. Fludarabine phosphate is a purine analogue, which is known to cause immunosuppression and long-lasting T-cell lymphopenia it is commonly employed in the therapy of hematological malignancies and non-myeloablative stem cell transplantation conditioning regimens. Myelosuppression, especially leuko- and lymphopenia is the major dose-limiting toxicity of fludarabine. However, a prolonged reduction in CD4+ T-cell count may be a desired effect for the treatment of GVHD. Clinical observations, preclinical data on the management of GVHD and well-known immunosuppressive properties suggest that fludarabine should be tested in clinical grounds for GVHD prophylaxis and treatment.
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PMID:Fludarabine phosphate may be useful in the treatment of graft-versus-host disease. 1582 5