Disease relevance of fludara

• Fludarabine for chronic lymphocytic leukemia [1].
• RESULTS: Assignment of patients to the fludarabine-plus-chlorambucil group was stopped when a planned interim analysis revealed excessive toxicity and a response rate that was not better than the rate with fludarabine alone [2].
• Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil (P=0.08), although, overall, toxic effects were tolerable with the two single-drug regimens [2].
• One patient with Coombs-positive hemolytic anemia who had no response to three courses of fludarabine had a partial remission, with resolution of hypogammaglobulinemia, when treated with 2-chlorodeoxyadenosine [3].
• METHODS: Nineteen consecutive patients with refractory metastatic renal-cell carcinoma who had suitable donors received a preparative regimen of cyclophosphamide and fludarabine, followed by an infusion of a peripheral-blood stem-cell allograft from an HLA-identical sibling or a sibling with a mismatch of a single HLA antigen [4].

Psychiatry related information on fludara

• A series of 30 patients who were not eligible for standard conditioning therapy received transplants from HLA-matched related (n = 14) or unrelated (n = 16) donors after administration of treosulfan 10 g/m2 intravenously daily for 3 days and fludarabine 30 mg/m2 intravenously daily for 5 days [5].

High impact information on fludara

• Fludarabine and psoriasis [6].
• 2-Chlorodeoxyadenosine for patients with B-cell chronic lymphocytic leukemia resistant to fludarabine [7].
• 2-Chlorodeoxyadenosine for patients with B-cell chronic lymphocytic leukemia resistant to fludarabine [8].
• Fludarabine caused a specific depletion of STAT1 protein (and mRNA) but not of other STATs [9].
• Fludarabine is a nucleoside analog used in the treatment of hematologic malignancies that can induce severe and prolonged immunosuppression [9].

Chemical compound and disease context of fludara

• Lack of effect of 2-chlorodeoxyadenosine therapy in patients with chronic lymphocytic leukemia refractory to fludarabine therapy [10].
• BACKGROUND: Fludarabine, a purine analogue with activity in chronic lymphocytic leukemia, is usually well tolerated [11].
• OBJECTIVE: To determine whether therapy with fludarabine plus prednisone in patients with chronic lymphocytic leukemia increases the risk for developing listeriosis [12].
• We report results in 41 consecutive patients with chronic lymphocytic leukemia (CLL) who underwent allogeneic hematopoietic cell transplantation (HCT) after fludarabine, melphalan, and alemtuzumab conditioning [13].
• Postulating favorable antileukemic effect with improved safety, we used intravenous busulfan and fludarabine as conditioning therapy for allogeneic hematopoietic stem cell transplantation (HSCT) for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) [14].

Biological context of fludara

• A Fas-blocking antibody (ZB4) did not inhibit spontaneous, chlorambucil-, fludarabine-, or radiation-induced apoptosis [15].
• Our findings support a role of fludarabine-mediated DNA repair inhibition as a mechanism critical for the cytotoxic synergy of the 2 drugs [16].
• For example, fludarabine sensitized host stem cells to the toxicity of TBI, because animals conditioned with both agents had higher chimerism than animals conditioned with TBI alone (P <.05) [17].
• Inhibiting STAT1alpha by STAT1beta increased the growth rate of transfected cells and their resistance to fludarabine-induced apoptosis and cell cycle arrest [18].
• When adaphostin was combined with fludarabine (F-ARA-AMP), a synergistic effect on cell death was observed in all 10 CLL samples [19].

Anatomical context of fludara

• Patients with untreated B-cell chronic lymphocytic leukemia have a high rate of complete remission when given the halogenated nucleoside analogue fludarabine [3].
• CONCLUSIONS: Fludarabine used in previously treated patients with chronic lymphocytic leukemia may be associated with infections involving T-cell dysfunction, such as listeriosis, pneumocystosis, mycobacterial infections, and opportunistic fungal and viral infections [11].
• Univariate analysis identified previous chemotherapy, advanced disease, failure to respond to fludarabine, elevated serum beta2-microglobulin level (P < 0.001), low serum albumin level (P = 0.024), elevated serum creatinine concentration (P = 0.008), and low granulocyte count (P = 0.003) as risk factors for infection [11].
• These results indicate that stable engraftment of MHC-incompatible cells can be induced after fludarabine-based, nonmyeloablative conditioning and that it serves as a platform for adoptive immunotherapy with donor lymphocyte infusions [17].
• Fludarabine also makes autologous bone marrow transplant feasible as a consolidation therapy [20].

Associations of fludara with other chemical compounds

• A dramatic reduction in CD4 counts occurred in patients after fludarabine and prednisone treatment and coincided with the development of listeriosis [12].
• We analyzed the impact of multiple factors on donor myeloid and T-cell engraftment in 36 patients with metastatic tumors undergoing cyclophosphamide/fludarabine-based conditioning [21].
• Rapid induction of complete donor chimerism by the use of a reduced-intensity conditioning regimen composed of fludarabine and melphalan in allogeneic stem cell transplantation for metastatic solid tumors [22].
• Chemotherapy consisted of fludarabine (4 x 30 mg/m(2)), cytarabine (4 x 2 g/m(2)), and amsacrine (4 x 100 mg/m(2)), followed 4 days later by RIC, comprising 4 Gy total body irradiation (TBI), cyclophosphamide, and antithymocyte globulin [23].
• Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS [14].

Gene context of fludara

• Nuclear translocation of p53 after fludarabine treatment was decreased when STAT1beta was overexpressed, and it was increased when STAT1alpha was induced [18].
• Overexpressing STAT1beta reversed the negative regulation of Mdm2 expression observed after treatment with interferon-gamma (IFN-gamma), which activates STAT1, or with fludarabine [18].
• Treatment with CXCR4 antagonists resensitized CLL cells cultured with stromal cells to fludarabine-induced apoptosis [24].
• Electrophoretic mobility shift assay revealed that OSM stimulated AP-1-DNA binding, which was also abolished by PD 98059, fludarabine, and piceatannol [25].
• Likewise, apoptosis induction by cladribine or fludarabine was not hampered upon inhibition of caspase-8 in MOLT-3 and MOLT-4 cells or overexpression of a dominant-negative FADD mutant in BJAB cells [26].
• Further studies found that fludarabine accumulated NF-kappaB and inhibitory subunit of NF-kappaB in cytosole in conjunction with downregulation of NF-kappaB in nucleus, suggesting that fludarabine blocked nuclear translocation of NF-kappaB [27].

Analytical, diagnostic and therapeutic context of fludara

• RESULTS: Seven of 408 patients in the fludarabine group developed listeriosis (1.7%; 95% Cl, 0.2% to 6%) compared with 0 of 387 patients who received conventional chemotherapy alone (0% to 0.9%; P = 0.015) [12].
• Fludarabine is a nonmyeloablative immunosuppressant increasingly used as a component of alternative conditioning regimens before allogeneic bone marrow transplantation [28].
• One received fludarabine and 2-Gy total body irradiation (TBI) [29].
• The clinical response and survival of 113 patients with at least 3-year follow-up after treatment with fludarabine as a single agent for chronic lymphocytic leukemia has been evaluated [30].
• FC combination chemotherapy resulted in significantly higher complete remission rate (24%) and overall response rate (94%) compared with fludarabine alone (7% and 83%; P < .001 and P = .001) [31].

References