Fludarabine的临床应用

Fludarabine(FDB)是近年来发展的新型抗肿瘤药物,在血液系统恶性肿瘤,尤其是淋巴系统恶性疾病,如慢性淋巴细胞性白血病(CLL)、淋巴瘤(lymphoma)治疗中有广泛应用。FDB不仅可以作为单药化疗,而且可以联合其它化疗药物治疗低度恶性NHL(LGL),提高疗效;并且还可应用于AML/MDS等髓系恶性疾病的治疗。

RETREATMENT WITH FLUDARABINE AND CYCLOSPORINE FOR ONE CASE OF REFRACTORY PURE RED CELL APLASIA

MANY cases of pure red cell aplasia （PRCA） were mediated by over-function of immune cells, and responded well to immunosuppressive therapy. Sometimes refractory cases also arose. Fludarabine is an analogue of adenosine resistant to deamination which is widely used for B-chronic lymphocytic leukemia （CLL） and other hematological malignancies.^2 As a strong immunosuppressive agent, fludarabine has generally been used in nonmyeloblative conditioning regimens for hematopoietic stem cells transplantation for hematological malignancies and severe aplastic anemia recently.^3 In this study,

Clinical Observation of FMD Regimen:Fludarabine,Mitoxantrone,Dexamethasone,in Treatment of Non-Hodgkin's Lymphoma

OBJECTIVE To evaluate the clinical effectivity and toxicity of the regimen FMD （fludarabine, mitoxantrone, dexamethasone） in patients with non-Hodgkin＇s lymphoma. METHODS Thirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell lymphoma, received FMD. Treatment comprised： fludarabine 25-30 mg/m^2 days 1-3, mitoxantrone 8-10 mg/m^2 day 1, and dexamethasone 20-30 mg/m^2 days 1-5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole, fluconazole, acyclovir and immunoglobulin. RESULTS Of the thirty-two patients treated, the complete response （CR） rate, partial response （PR） rate and overall response （OR） rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7% and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3-4 neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3-4 thrombocytopenia. At a median follow-up of 24 （5-54） months, the 2-year overall-survival rate and progression-free survival rate were （87.5 ± 1.4）% and （83.3 ± 1.6）% respectively. The 2-year OS and PFS rates of the indolent group were （93.75 ± 6.25）% and （87.5 ± 8.54）%. CONCLUSION FMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin＇s lymphoma, especially in indolent B-cell lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.

Remission of Relapsing Immunotactoid Glomerulonephritis with Fludarabine

Immunotactoid gloemrulonephritis is a glomerular disease characterized by organized microtubular deposits of monoclonal immunoglobulin. These deposits are Congo red-negative, have hollow centers, measure > 30 nm, and are arranged in stacked or parallel arrays. Treatment of immunotactoid glomerulonephritis is not well-defined, with poor outcomes seen in native kidneys. In fewer than 10% of the cases, trials with steroids alone or cytotoxic agents with steroids or plasmapheresis with steroids has been associated with clinical remission of proteinuria. 50% of patients with renal impairment progress to end stage renal disease (ESRD) in two to four years. There are three case reports of recurrent ITG in renal allograft;one was treated with pulse steroids plus cyclophosphamide, pulse steroids in second case and use of rituximab in the third case. Recurrence of ITG has been described in the renal allograft but there is no literature on relapse of ITG in the native kidneys. Here, we have a case of ITG that relapsed in the native kidneys eight years after being in remission. Renal function improved with fludarabine both times and the patient had stable renal function at last follow-up.

Fludarabine and cytarabine combined chemotherapy followed by transfusion of donor blood stem cells for treating relapse of acute leukaemia after allogeneic haematopoietic stem cell transplantation

Background Relapse remains an obstacle to successful allogeneic haematopoietic stem cell transplantation （allo-HSCT） for patients with acute leukaemia and no standard treatment is available. We assessed fludarabine and cytarabine with transfusion of donor haematopoietic stem cell in treating the relapse of acute leukaemia after allo-HSCT. Methods Seven patients, median age 34 years, with relapse of acute leukaemia after allo-HSCT received combination chemotherapy of fludarabine with cytarabine for 5 days. Five patients suffered from acute myeloid leukaemia （2 refractory） and 2 refractory acute lymphoblastic leukaemia. After the transplantation, the median relapse time was 110 days （range, 38-185 days）. Two days after chemotherapy, 5 patients received infusion of donor＇s peripheral blood stem cells, mobilized by granulocyte colony stimulating factor. No prophylactic agents of graft versus host diseases were administered, Results Six patients achieved haematopoietic reconstitution. DNA sequence analysis at day 30 after treatment identified all as full donor chimera type. The median observation time was 189 days. After the treatment, the median time for neutrophilic granulocyte value 〉0.5×10^9/L and for platelet value 〉20×10^9/L were 13 days （range, 10-18 days） and 15 days （range, 11-24 days）, respectively. Graft versus host disease occurred in 2 patients （acute） and 3 （chronic）. Five patients suffered from pulmonary fungal infection （2 died）, 3 haemorrhagic cystitis and 2 cytomegalovirus viraemia. The other patients died of leukaemia related deaths. Three patients with chronic graft versus host disease who had received donor peripheral blood stem cells reinfusion have survived for 375 days, 232 days and 195 days, respectively. Conclusions Fludarabine with cytarabine plus the donor haematopoietic stem cell should be considered as an effective therapeutic regimen for relapse of acute leukaemia after alIo-HSCT. The disease free state of patients may increase, though with high risk of secondary fungal infection.

应用Fludarabine治疗毛细胞白血病

毛细胞白血病(HCL)是一种以浸润骨髓、肝、脾为主引起全血细胞减少、脾大及各种免疫低下为特征的慢性B淋巴细胞增生性疾病。脾切除是治疗本病的主要手段,临床有效率为75％。α-干扰素、2-去氧助间型霉素(DCF)和-2氯脱氧腺苷也可治疗HCL,DCFα-干扰素治疗耐药的HCL仍然有效,变异型的HCL(HCL-V)对一般治疗效果较差。 fludarabine是一种腺嘌呤核苷的类似物,其结构与DCF和2-氯脱氧腺苷相似,能抑制腺苷脱氨酶的活性。

Analyses of therapeutic effects using rludarabine and cytarabine on acute myeloid leukemia at different stages during treatment

Objective: To evaluate the therapeutic effect of the fludarabine and cytarabine (FA) regimen on acute myeloid leukemia (AML) at different phases during treatment. Methods: A total of 185 patients with AML were divided into 4 groups based on the outcome of previous treatments. Patients in Group 1 had no remission after the first course of induction chemotherapy (n = 55). Patients in Group 2 had no remission after no less than two courses of induction chemotherapy (n = 41). Patients in Group 3 had early relapse (n = 40). Patients in Group 4 had late relapse (n = 49). Patients in groups 2, 3 and 4 had refractory AML or AML with relapse. We assessed the efficacy and toxicity of FA combination chemotherapy in each of these 4 groups. Results: The complete remission (CR) rates of Groups 1, 2, 3 and 4 were 74.5% (41/55), 45.9% (19/41), 17.5% (7/40) and 38.8% (19/49), respectively. The CR rate was higher in Group 1 than in the other 3 groups (34.6%, 45/130) (P = 0.000). A significant correlation was found between CR rate and the number of chemotherapeutic courses (P = 0.023). The main adverse reactions included bone marrow suppression and secondary infection. Conclusion: FA regimen is a good choice for patients with AML, especially those who have failed to achieve CR after the first course of induction chemotherapy.

慢性移植物抗宿主反应是迷你异体造血干细胞移植后改善生存期的最强因素

降低强度处理（RIC）迷你异体干细胞移植（allo—SCT）可减少非复发性病死率（NRM），这使得对不适合接受高剂量清髓allo-SCT的患者能从移植物抗白血病反应中获益。在对AML患者和高风险骨髓异常增生综合征（MDS）患者进行的多中心前瞻性研究中，巴塞罗那自治大学的Valcárcel D等研究了接受fludarabine和busulfan治疗并进行人白细胞抗原特异同属RIC allo-SCT的有效性。