Fludarabine (Flu), a purine nucleoside analogue, is the firstline drug for patients with chronic lymphocytic leukemia (CLL), and can induce apoptosis of malignant cells in CLL patients. However, CLL remains an incurable disease. Fludarabine-resistance is one of the predominant reasons for treatment failure. In this paper, the metabolism, action and drug-resistance mechanisms of Fludarabine in CLL as well as possible reversible strategies are reviewed, with particular emphasis on recent advances in the characterization of nucleoside transporters and p53-mediated apoptosis and on the potential role of activating or inactivating enzymes in the induction of clinical resistance to Flu.
Drug Resistance, Neoplasm ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Vidarabine ; analogs & derivatives ; pharmacology ; therapeutic use

The study was aimed to investigate the clinical characteristics, diagnosis and therapy of patients with lymphoma associated hemophagocytic syndrome (LAHS) so as to provide the clinical basis for improving its recognition and giving effective therapy. The clinical data of 14 patients with LAHS in Beijing Friendship Hospital, Capital Medical University during the period from June 2005 to May 2008 were collected, the informations including primary diseases, clinical manifestations, laboratory findings, therapy and outcome were analyzed retrospectively, the coincidence of each diagnostic index was compared before and after diagnosis. All 14 patients were given therapeutic regimens containing fludarabine, methylprednisolone and gammaglobulin (FDIg) after final diagnosis. The results indicated that 100% patients had abnormal changes on NK cell activity and sCD25 level in serum, but hemophagocytosis in less than 40% patients at early stage was found in bone marrow. Even after confirmed diagnosis of the disease, the percentage of patients with hemophagocytosis was not up to 50%. 9 out of the 14 patients had a good prognosis after treatment, and the other 5 patients died. It is concluded that the detection of NK cell activity and sCD25 level in serum may be valuable for the early diagnosis of LAHS, the hemophagocytosis is not necessary for the diagnosis of LAHS. Fludarabine combined with methylprednisolone and gamma globulin may provide a new strategy for LAHS therapy.
Humans ; Lymphohistiocytosis, Hemophagocytic ; complications ; diagnosis ; drug therapy ; Lymphoma ; complications ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Vidarabine ; analogs & derivatives ; therapeutic use

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; Vidarabine ; analogs & derivatives ; therapeutic use

Animals ; Bone Marrow Transplantation ; Busulfan ; Disease Models, Animal ; Drug Combinations ; Graft vs Host Disease ; Mice ; Transplantation Conditioning ; Vidarabine ; analogs & derivatives

OBJECTIVE: To investigate effect and mechanism of miR-214 in fludarabine resistance of chronic lympho-cytic leukemia (CLL). METHODS: A total of 10 patients with CLL resistante to fludarabine (Flu) and 10 healthy persons admitted to Hematology Department of our hospital in August 2014 - July 2018 were selected. Expression level of miR-214 in mononuclear cells in patients with CLL and healthy persons were determined by RT-PCR. Primary CLL cells from patients with CLL were divided into normal control group (control group), negative control group (miR-214-NC group) and viral transinfection group (miR-214-ASO group). After 24 h-transfection, CLL cells were cultured with different con-centration of Flu for 48 h, then the cell proliferation and apoptosis were detected, and the levels of down-stream genes and proteins releted with PTEN and PI3K/AKT signialing pathway were determined. RESULTS: The expression level of miR-214 in mononuclear cells of CLL patients significantly increased in comparison with healthy persons(P<0.05); the expression level of miR-214 in miR-214-ASO group significantly decreased (P<0.05); Absorbance in control group at Flu concentration of 3, 10 and 30 μmol/L was significantly decreased (P<0.05). Apoptosis rate in miR-214-ASO group at Flu concentration of 10 mmol/L significantly increased (P<0.05). At Flu concentration of 10 mmol/L, mRNA levels PTEN and BAD in miR-214-ASO group significantly increased (P<0.05), but mRNA levels of MDM2 and NF-κB significantly decreased (P<0.05). At Flu concentration of 10 mmol/L, protein levels of PTEN and p-BAD in miR-214-ASO group significantly increased (P<0.05), but protein levels of MDM2 and NF-κB significantly decreased (P<0.05). CONCLUSION Inhibition of miR-214 can enhance the sensitivity of drug-resistant CLL cells to fludarabine, which may be raleted with the promotion of cell apotosis and regulation of down-stream molecules expression of PTEN/AKT signaling pathway.
Apoptosis ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; MicroRNAs ; Phosphatidylinositol 3-Kinases ; Vidarabine ; analogs & derivatives ; genetics ; therapeutic use

Waldenstrom's macroglobulinemia is an uncommon low-grade B-cell lymphoproliferative disorder in which monoclonal immunoglobulin M is produced. Neurological symptoms due to hyperviscosity are frequent manifestations of Waldenstrom's macroglobulinemia. However, central nervous system infiltration by plasmacytoid lymphocytes (Bing-Neel syndrome) has only rarely been reported. We report a case of a 51-yr-old woman suffering from Waldenstrom's macroglobulinemia who complained of persistant headache. Brain magnetic resonance imaging revealed an extra-axial soft tissue mass along the left cavernous sinus, left tentorium, right tentorium, and falx cerebri. A stereotactic biopsy of dural tissue from the falx was performed and showed plasmacytoid lymphocyte infiltration. The patient became symptom- free with irradiation of the whole brain followed by chemotherapy with fludarabine.
Antibodies, Monoclonal/therapeutic use ; Brain/pathology ; Central Nervous System Diseases/etiology/*therapy ; Cranial Irradiation ; Female ; Humans ; Middle Aged ; Syndrome ; Vidarabine/analogs & derivatives/therapeutic use ; Waldenstrom Macroglobulinemia/*complications

Adult ; Cyclosporine ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Red-Cell Aplasia, Pure ; drug therapy ; Vidarabine ; analogs & derivatives ; therapeutic use

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cytarabine ; therapeutic use ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; pathology ; therapy ; Vidarabine ; analogs & derivatives ; therapeutic use

One case of hairy cell leukemia with survival for 10 years was reported. The patient received Interferon-alpha(2b) treatment continuously for more than 9 years and intravenous administration of fludarabine for 2 courses of treatment in the later period, and died due to complication of severer infection in thd end. The manifestation, diagnosis and treatment of hairy cell leukemia were discussed.
Aged ; Humans ; Immunophenotyping ; Interferon-alpha ; therapeutic use ; Leukemia, Hairy Cell ; diagnosis ; drug therapy ; mortality ; Male ; Recombinant Proteins ; Vidarabine ; analogs & derivatives ; therapeutic use

The aim of this study was to explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) by myeloablative conditioning regimen with fludarabine for high risk leukemia patients. 25 refractory and relapsed leukemia patients underwent allo-HSCT with new conditioning regimen consisted of fludarabine, busulfan and cyclophosphamide. Donors for 15 patients were sibling, but donors for the rest 10 patients were all unrelated. HLA matched and mismatched donors were for 15 and 10 patients respectively. The graft versus host disease (GVHD) prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used in case of unrelated and HLA mismatched HSCT. The results showed that unrelated donor HSCT in 10 cases was successful (100%), 14 out of 15 patients with donors of sibling or parent also reconstructed their haematopoietic system. One mismatched patient (4/6) died of graft failure. The time from transplantation to ANC > 0.5 × 10(9)/L and Plt > 20 × 10(9)/L were 13 (11 - 19) days and 13 (12-20) days after transplantation respectively. The cumulative incidence of grade II-IV acute GVHD and chronic GVHD was 12.5% (3/24) and 47.4% (9/19), respectively. In a follow-up duration of 6-84 months, 12 patients were dead, out of which 8 died of relapse; 1 cases died of regimen-associated side effect. 3 cases died of serious infection. The other 13 patients remained alive and disease-free survival probability was 48.7%. It is concluded that allo-HSCT by myeloablative conditioning regimen with fludarabine is a safe and effective option for high risk leukemia patients, which reduces aGVHD incidence and regimen-associated side effect, but it should be modified for higher rate of relapse.
Adolescent ; Adult ; Child ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia ; surgery ; Male ; Middle Aged ; Transplantation Conditioning ; methods ; Treatment Outcome ; Vidarabine ; analogs & derivatives ; therapeutic use ; Young Adult