Feasibility of Non-TBI Conditioning with Busulfan and Fludarabine for Allogeneic Stem Cell Transplantation in Lymphoid Malignancy

BACKGROUND/AIMS: This retrospective study evaluated the transplantation outcomes of patients with adult lymphoid malignancies who received chemotherapy-based conditioning with busulfan and fludarabine (BuFlu) and busulfan and cyclophosphamide (BuCy2). METHODS: Thirty-eight patients (34 with acute lymphoblastic leukemia and 4 with lymphoblastic lymphoma) were included in the current study. The conditioning regimen was BuCy2 for 14 patients and BuFlu for the remaining 24 patients. Eight and 13 patients were high risk disease in the BuCy2 and BuFlu groups, respectively. RESULTS: The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 56.5% and 55.2% and that of extensive chronic GVHD 17.0% and 55.6% (p = 0.018) for the BuFlu and BuCy2 groups, respectively. The 3-year relapse rate was 27.8% and 31.4% and 3-year overall survival 34.3% and 46.8% for the BuFlu and BuCy2 groups, respectively. Treatment-related mortality (TRM) was significantly lower in the BuFlu group (16.9%) than in the BuCy2 group (57.1%, p = 0.010). In multivariate analyses, the BuFlu regimen was identified as an independent favorable risk factor for TRM (hazard ratio [HR], 0.036; p = 0.017) and extensive chronic GVHD (HR, 0.168; p = 0.034). CONCLUSIONS: Our BuFlu regimen would appear to be an acceptable conditioning option for lymphoid malignancies, including high-risk diseases. It was safely administered with a lower TRM rate than BuCy2 conditioning.

Fludarabine in lymphoproliferative malignancies: a single-centre experience.

BACKGROUND: Fludarabine has been reported to be an effective drug for the treatment of chronic lymphocytic leukaemia (CLL) and indolent lymphomas. However, its safety and efficacy in Indian patients has not been studied. We retrospectively analysed our experience with fludarabine in low grade lymphomas and CLL. METHODS: The records of all patients with low grade lymphoma or CLL who received fludarabine between April 1999 and November 2006 were analysed. Response evaluation was done as per the National Cancer Institute-Working Group guidelines for CLL and International Workshop criteria for non-Hodgkin lymphomas, respectively, in those patients who received at least 3 cycles of fludarabine. Toxicity was graded as per the common terminology criteria for adverse events, version 3.0. Median event-free survival was obtained using Kaplan-Meier survival analysis. RESULTS: Forty-seven patients were included in the study and 189 cycles were administered (median: 4 cycles per patient). Sixteen patients had a treatment delay, 14 due to myelosuppression. Twenty-five patients had low grade lymphoma and 22 had CLL. The response was evaluable in 22 patients with low grade lymphoma and 20 with CLL. The overall response rate for CLL was 100% in those treated upfront (n=9) and 55% in those with relapsed disease (n=11). The overall response rate for low grade lymphoma was 88% (63% complete remission) in untreated patients and 79% (43% complete remission) in those with relapsed disease. Common adverse events were myelosuppression and infection. Two patients died of sepsis and 4 due to disease progression on treatment. Median event-free survival for patients treated upfront with fludarabine was 31.4 months. CONCLUSION: In our patient population, response to fludarabine is similar to that in the published literature. Our patients had a higher frequency of haematological toxicity.

Chronic lymphocytic leukemia in the recent 10 years and treatment effects of Fludarabin.

OBJECTIVE: CLL (Chronic Lymphocytic Leukemia) is the most common form of leukemia in the western world and because of prolonged survival of patients, the prevalence is high. Chemotherapy is usually not indicated in early and stable disease and using Chlorambucil with or without steroids has been the drug of choice in the treatment of CLL for many years .Clinical studies have shown that using Fludarabin can cause a complete response in significant number of untreated and/or previously treated CLL patients. The aim of this study is evaluating of CLL patients and determining the effects of treatment with Fludarabin. METHODS: A retrospective (descriptive/cross sectional) study of CLL patients who admitted to Hematology and Oncology Research Center of Tabriz university of Medical Sciences, between 1995-2005 was made and 126 patients enrolled. Collection of data was carried out according to special questionnaire and response to Fludarabin was analyzed by SPSS 11 software. RESULTS: The patients mean age of diagnosis was 63.7 years (SD=8.9), 69.8% were males. Illness and fatigue were the commonest presenting symptoms in 54% and lymphadenopathy was the most common clinical sign in 88.9%.Most of the patients were in stage C in Binet system (52.4%) and/or stage IV in Rai system (44.4%).Chemotherapy with chlorambucil and Prednisolone was the most common regimen used (60.3%) and 49.2% of patients were in partial remission with this treatment. Forty two patients treated with Fludarabin and 50% were in partial remission, 35% in static disease, 10% in progressive disease and 5% in complete remission (P=0.053). CONCLUSION: The median survival with Fludarabin was 43.9 months (SD=27.2) and in the case of Chlorambucil+Prednisolone and CVP or Chop it was 45 months (SD=26.5) and 50 months (SD=32.2), respectively (P>0.05). P value in the relationship with survival and response to Fludarabin was more than 0.05.Above all, Fludarabin is the choice treatment as first and second line therapy, as well as for patients who have failed therapy with standard regimens.