OBJECTIVE: To investigate the efficacy and safety of oral fludarabine in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). METHODS: The patients received oral fludarabine 40 mg/(m2.d) for 5 consecutive days, each treatment lasting 4 weeks. The efficacy was assessed with National Comprehensive Cancer Network (NCCN) criteria for response. RESULTS: Twenty-two patients received the treatment, a median of 4 cycles per patient. The rate of complete response (CR), partial response (PR), and overall response (OR) was 40.9% (9/22), 45.5% (10/22), and 86.4% (19/22), respectively. Among the 17 previously untreated patients, 7 (41.2%) achieved CR and 8 (47.0%) achieved PR. Two of the 5 pre-treated patients achieved CR and the other 2 achieved PR. During a median observation of 24 months, the overall survival rate was 81.8%. The main adverse reactions were myelosuppression and infection. Grade 1 to 3 granulocytopenia was found in 7 (31.8%) patients, and infection in 3 (13.6%) patients. Nonhematologic toxicity was mild. All the adverse reactions were reversible. CONCLUSION The oral fludarabine is effective, safe, and well-tolerated in the patients with CLL/ SLL.
Aged ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; Male ; Middle Aged ; Treatment Outcome ; Vidarabine ; adverse effects ; analogs & derivatives ; therapeutic use

OBJECTIVETo explore the feasibility and safety of conditioning regimen containing fludarabine (Flud) for haploidentical hematopoietic stem cell transplantation (HSCT).

METHODSPreparative regimen containing Flud 40 mgxm(-2)xd(-1) on day -7 to -3 in place of cyclophosphamide (CTX) for haploidentical HSCT was given to 35 patients with hematologic malignancies (4 standard risk, 16 high risk, 15 relapse with no remission). All donors received rhG-CSF followed by HSC harvest. One patient received peripheral blood HSCT (PBSCT), one bone marrow transplantation (BMT), and the others BM combination with PBSCT. The regimen-associated side effect, engraftment, incidence of graft-versus-host disease (GVHD) and disease-free survival (DFS) probabilities were observed.

RESULTSAll patients achieved sustained, full donor-type engraftment. Thirty-four patients obtained primary durable engraftment, and 1 who rejected graft from his mother obtained successful durable engraftment after the second graft from his father. The cumulative incidence of grade III-IV acute GVHD and chronic GVHD was 12.1% and 31.7%, respectively. With a follow-up duration of 8-25 months, 6 patients were dead, in which 3 died of relapse, 2 of acute GVHD, 1 of fungal infection, none died of regimen-associated side effect. The other 29 patients remained alive and DFS probability was 79.7%.

CONCLUSIONFlud based conditioning regimens for haploidentical HSCT is safe and feasible, which reduces regimen-associated side effect, with no increasing the rate of relapse and infection, and decreases the incidence of aGVHD.

Adolescent ; Adult ; Child ; Child, Preschool ; Cyclophosphamide ; Feasibility Studies ; Female ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Transplantation Conditioning ; adverse effects ; methods ; Transplantation, Homologous ; Vidarabine ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo explore the efficiency and toxicity of non-myeloablative stem cell transplantation (NAST) for hematological disease.

METHODSSeventeen patients, including 3 acute myeloid leukemia, 6 chronic myelogenous leukemia, 4 severe aplastic anemia, 2 non-Hodgkin's lymphoma, 1 multiple myeloma and 1 myelodysplastic syndromes received NAST from HLA-identical sibling donors. Peripheral blood stem cells were mobilized by G-CSF 300 microg/12 hours x 5 d. (2.15 -10.01) x 10(6) CD(34)(+) cells/kg were transplanted. A non-myeloablative conditioning regimen included fludarabine 30 mg.m(-2).d(-1) x 6 d;busulfan 4 mg.kg(-1).d(-1) x 2 d or cyclophosphamide 50 mg.kg(-1).d(-1) x 2 d and antilymphocytic globulin 12 approximately 15 mg.kg(-1).d(-1) x 4 d. Cyclosporin A was used to prevent graft versus host disease (GVHD) alone and no G-CSF was administered after NAST.

RESULTHematopoiesis reconstitution resumed on day 8 to day 19 (average of day 13). Severe mucositis was absent. Hepatic venoocclusive disease did not occur. Infectious complications were rare. Acute and chronic GVHD each occurred in 5 patients. Idiopathic pneumonia was developed in 5 patients. In the follow-up duration of 120 to 425 days, 16 of the 17 cases had a stable mixed or complete chimerical states. Fourteen of 17 patients are alive.

CONCLUSIONNAST is an effective therapy in the treatment of hematological diseases with less complications, less blood transfusion and lower cost.

Adult ; Female ; Follow-Up Studies ; Hematologic Diseases ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Male ; Middle Aged ; Myeloablative Agonists ; administration & dosage ; Transplantation Conditioning ; adverse effects ; methods ; Transplantation, Homologous ; Treatment Outcome ; Vidarabine ; administration & dosage ; analogs & derivatives

OBJECTIVETo assess the efficacy and toxicity of the kangai injection combination of fludarabine (Flud), cytosine arabinoside (Ara-C), and granulocyte colony-stimulating factor (G-CSF) (FLAG) in refractory/relapsed acute leukemia (AL) patients.

METHODFrom 2004 to 2010 in our hospital, the 49 cases of refractory/relapsed acute luekemia were randomly divided into treatment group (28 cases) and control group (21 cases). The control group were treated by kangai injection plus FLAG regimen, and the control group were treated by FLAG regimen.

RESULTThe remission rate of treatment and total effective rate treatment group were 57.1% (16/28) and 71.4% (21/28), the control group were 52.3% (11/21) and 61.9% (13/21), there were no significant differences in the two groups. Duration of neutrophils less than 0.5 x 10(9)/L in treatment group was (14 +/- 6) day, control group was (23 +/- 3) day, Duration of platelet less than 25 x 10(9)/L in treatment group was (17 +/- 6) day, control group was (31 +/- 2) day, treatment group of III-IV degree of infection was 6.9% (1/28) and control group was 23.8% (5/21) between the two groups were significantly different (P < 0.05). treatment group of III- IV degree of gastrointestinal; toxicity was 10.7% (3/28) and control group was 28. 5% (6/ 21).

CONCLUSIONKangai injection plus FLAG regimen could increase the remission rate, shorten the period of bone marrow suppression, significantly reduced the incidence and degree of infection, play a important role in attenuated efficiency.

Acute Disease ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; Cytarabine ; administration & dosage ; adverse effects ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; adverse effects ; Humans ; Injections ; Leukemia ; drug therapy ; Male ; Middle Aged ; Vidarabine ; administration & dosage ; adverse effects ; analogs & derivatives

In order to evaluate the efficacy of FLAG protocol (fludarabine, cytosine arabinoside and granulocyte colony-stimulating factor) in treatment of the first time induced non-remission acute myeloid leukemia (AML), 19 patients with first time induced non-remission acute myeloid leukemia were treated with FLAG protocol. The results showed that out of the 19 patients 13 patients obtained complete remission (CR) and the CR rate was 68.4%, 2 patients obtained partial remission (PR) and the PR rate was 10.5%, the overall remission rate was 78.9%. Among the patients in CR 5 patients had been received allogeneic stem cell transplantation, 3 patients from them survived without disease, including 1 patient has survived 26 months and still remains in CR. Main toxicities of this protocol were gastrointestinal side effects, myelosuppression and neutropenia, slight abnormality of liver function and so on. It is concluded that the FLAG protocol should be employed for the the first time induced non-remission patients as early as possible, and provides conditions for the hematopoietic stem cell transplantation.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cytarabine ; adverse effects ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; adverse effects ; therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Remission Induction ; Vidarabine ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo evaluate the therapeutic efficiency and adverse effect of the fludarabine-containing regimens in the treatment of low grade non-Hodgkin's lymphoma.

METHODSThirty-two patients with low grade non-Hodgkin's lymphoma consisting of 19 primary one and 13 relapsed or refractory were treated with fludarabine-containing regimens, which included FMD (fludarabine, mitoxantrone and dexamethasone); FMC (fludarabine, cyclophosphamide and mitoxantrone) and FC ( fludarabine and cyclophosphamide).

RESULTSThe average course completed in these 32 patients was 4.1 with a complete response rate (CR), partial response rate (PR) and overall response rate (OR) of 65.6%, 18.8% and 84.4% , respectively. There were no significant difference in CR, PR and OR between primary and relapsed or refractory group (71.4%, 21.0%, 92.4% vs. 46.2%, 13.1%, 59.3%, respectively). Myelotoxicity and immunotoxicity was the dominating adverse effects. Ill to IV grade granulocytopenia and thrombocytopenia were observed in 31.3% (10/32) and 9.4% (3/32) of these patients respectively. Infection developed in 7 patients, and two of them died of pulmonary infection. The median follow-up period was 16 months (1-30 months) with 2-year overall-survival rate (OS) and progression-free survival rate (PFS) of 93.8% and 84.4%, respectively. No significant difference was observed between primary and relapsed or refractory group in OS (100% vs. 76.9%) and PFS (94.7% vs. 69.2%).

CONCLUSIONFludarabine-containing regimens is well tolerated and effective in the treatment of low grade non-Hodgkin's lymphoma.

Adult ; Aged ; Agranulocytosis ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cyclophosphamide ; administration & dosage ; adverse effects ; Dexamethasone ; administration & dosage ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; pathology ; Lymphoma, B-Cell, Marginal Zone ; drug therapy ; pathology ; Lymphoma, Follicular ; drug therapy ; pathology ; Lymphoma, Non-Hodgkin ; drug therapy ; pathology ; Male ; Middle Aged ; Mitoxantrone ; administration & dosage ; adverse effects ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Remission Induction ; Survival Rate ; Thrombocytopenia ; chemically induced ; Vidarabine ; administration & dosage ; adverse effects ; analogs & derivatives

In order to evaluate the effects of FLAG regimen in treatment of refractory and relapsed acute myeloid leukemia (AML), 27 patients with refractory or relapsed acute myeloid leukemia (10 refractory AML patients, 17 relapsed AML patients) were treated with FLAG regimen. The results show that the rate of complete remission was 48.2% (13/27), the rate of partial remission was 14.8% (4/27), and the overall response rate was 63.0%. Main toxicities were gastrointestinal side effectes, myelosupression and neutropenia. It is concluded that FLAG regimen can be employed in treatment of the refractory or relapsed patients who were not respond to other regimen, and the regiment was safe.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cytarabine ; administration & dosage ; adverse effects ; Diarrhea ; chemically induced ; Drug Resistance, Neoplasm ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; adverse effects ; Humans ; Leukemia, Monocytic, Acute ; drug therapy ; pathology ; Leukemia, Myeloid, Acute ; drug therapy ; pathology ; Leukemia, Myelomonocytic, Acute ; drug therapy ; pathology ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Recurrence, Local ; Respiratory Tract Infections ; chemically induced ; Treatment Outcome ; Vidarabine ; administration & dosage ; adverse effects ; analogs & derivatives

OBJECTIVETo observe the signal transducers and activator of transcriptions (STATs) protein expression changes and investigate the functional role of STATs pathway in case of high glucose-induced cardiac fibroblasts (CFs) proliferation and collagen deposition in vitro.

METHODSRat cardiac fibroblasts were isolated from 1- to 3-day-old SD rats, cells from the second to fourth passages were used for the experiment. CFs were cultured in Dulbecco's modified Eagle's medium, supplemented with 5.5 mmol/L glucose (NG), 5.5 mmol/L glucose plus 19.4 mmol/L mannose (OC) or 25 mmol/L glucose (HG) in the presence of absence of STAT1 inhibitor (fludarabine, FLU) and STAT3 inhibitor (S3I-201). After 24 h and 48 h culture in vitro, the proliferation of CFs was measured by 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After 12 h and 24 h culture in vitro, the production of type I and III collagen was evaluated using real-time quantitative PCR and ELISA. After 0, 30, 60 and 120 min culture in vitro, the phosphorylated expression of STAT1 and STAT3 was analyzed by Western blot.

RESULTSCFs proliferation was significantly enhanced post 24 h and 48 h HG stimulation, and procollagen I and III mRNA expression was significantly upregulated post 12 h and 24 h HG stimulation. Deposition of collagen I and III was also significantly increased post 24 h and 72 h HG stimulation. STAT1 phosphorylation in CFs was increased after 120 min HG stimulation and STAT3 phosphorylation in CFs was increased post 60 min and 120 min HG stimulation. FLU and S3I-201 could inhibit HG-induced CFs proliferation and suppress of which was stimulated by FLU and S3I-201 could both suppress upregulated procollagen I and III mRNA expression and the deposition of collagen types I and III post HG stimulation. STAT1 phosphorylation inhibition resulted in less mRNA downregulation of procollagen type III than that of procollagen type I post 12 h HG stimulation. The STAT3 phosphorylation inhibition resulted in more significantly upregulated procollagen type III mRNA expression than procollagen type I mRNA expression at 12 h post HG stimulation.

CONCLUSIONHG could enhance the protein expression of phosphorylated STAT1 and STAT3 in CFs, which are responsible for HG-induced increased CFs proliferation and collagen deposition in vitro.

Aminosalicylic Acids ; pharmacology ; Animals ; Benzenesulfonates ; pharmacology ; Cell Proliferation ; Cells, Cultured ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Fibroblasts ; cytology ; drug effects ; Glucose ; adverse effects ; Myocardium ; cytology ; Phosphorylation ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; STAT1 Transcription Factor ; metabolism ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Up-Regulation ; Vidarabine ; analogs & derivatives ; pharmacology

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.
Adolescent ; Adult ; Busulfan/adverse effects/*therapeutic use ; Chi-Square Distribution ; Disease-Free Survival ; Drug Therapy, Combination ; Feasibility Studies ; Female ; Graft vs Host Disease/etiology ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multivariate Analysis ; Myeloablative Agonists/adverse effects/*therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/mortality/surgery/*therapy ; Proportional Hazards Models ; Republic of Korea ; Retrospective Studies ; Risk Assessment ; Risk Factors ; *Stem Cell Transplantation/adverse effects/mortality ; Time Factors ; Transplantation Conditioning/adverse effects/*methods/mortality ; Transplantation, Homologous ; Treatment Outcome ; Vidarabine/adverse effects/*analogs & derivatives/therapeutic use ; Young Adult

BACKGROUND: The long-term survival of patients with non-Hodgkin's lymphoma after conventional chemotherapy is about 35%, with the remaining 65% of patients tending to be refractory or experience relapse. As such, primary refractory patients responding to salvage chemotherapy, and sensitive relapsed patients and primary high- risk patients are recommended to receive high-dose chemotherapy (HDC) and autologous peripheral blood stem cell transplantation (PBSCT). We evaluated the role of HDC and autologous PBSCT in patients with primary refractory, primary high risk, and sensitive relapsed non-Hodgkin's lymphoma. METHODS: We performed a retrospective analysis of the data from 50 patients with non-Hodgkin's lymphoma who were treated with HDC and autologous PBSCT in the Catholic Hematopoietic Stem Cell Transplantation Center between 1997 and 2002. RESULTS: Of the 50 patients, the conditioning regimen was BEAM in 20, CMT (cyclophosphamide, melphalan and thiotepa) in 19, fludarabine- and total body irradiation (TBI) -based regimen in 8, and cyclophosphamide and TBI in 2. There were 3 (6%) deaths due to treatment-related toxicity within the first 50 days after transplantation. Twenty-five patients remain alive at a median follow-up duration of 40.5 months (range 9~61). Among the patients with partial response before transplantation, 76% showed further response after transplantation. In half of these responders, the disease state was changed into complete response (CR) after transplantation. 2-year overall survival was 52% and 2-year progression free survival was 36.8%. Median overall survival was 34 months (range 8~60), and median progression-free survival was 8 months (range 1~14). Median overall survival was 14 months (range 9~19) in the primary high-risk group (n=13), 7 months (range 4~10) in the resistance relapse group (n=5), and 6 months (range 0~14) in the primary refractory group (n=10). Overall survival in the sensitive relapse group (n=22) did not reach the median; the mean overall survival in this group was 33 months. The disease status before transplantation was the only significant prognostic factor in determining overall survival (p=0.032) and progression- free survival (p=0.001). CONCLUSION: HDC and autologous PBSCT appears to produce high response rate. Primary high-risk group and sensitive relapse group had good prognosis, while refractory and resistance relapse group had poor prognosis. And the pre-transplantation disease status was the only significant prognostic factor in multivariate analysis.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/adverse effects/*therapeutic use ; Chemotherapy, Adjuvant ; Cyclophosphamide/administration & dosage ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Non-Hodgkin/drug therapy/radiotherapy/surgery/*therapy ; Male ; Melphalan/administration & dosage ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy/radiotherapy/surgery/*therapy ; Retrospective Studies ; *Stem Cell Transplantation ; Survival Analysis ; Thiotepa/administration & dosage ; Transplantation Conditioning/methods ; Transplantation, Autologous ; Treatment Outcome ; Vidarabine/administration & dosage/analogs & derivatives ; *Whole-Body Irradiation