Clinical observations of the therapeutic effect of CLAG or FLAG bridging BuCy conditioning regimen in the treatment of childhood acute leukemia / 中国输血杂志

【Objective】 To determine the therapeutic efficacy of cladribine combined with BuCy conditioning regimen for childhood acute leukemia, and compare it with fludarabine. 【Methods】 The clinical data of 70 children with acute leukemias who underwent all-HSCT from August 2018 to June 2020 were collected. The data of pretreatment-related toxicity, hematopoietic reconstitution, graft-versus-host disease, virus infection, relapsed and survival between CLAG and FLAG group were statistically analyzed. 【Results】 EBV infection in CLAG group was significantly more than that in FLAG group(P0.05). Multivariate analysis showed that there was no significant difference in the effect of conditioning regimen on relapsed and survival. Among other risk factors, types of diseases were significantly correlated with OS (P<0.05, HR: 0.088). Relapse was significantly correlated with bone marrow morphological remission before transplantation and the matching degree of donor and recipient HLA(P<0.05, HR: 34.678; P<0.05, HR: 0.024). 【Conclusion】 There was no significant difference in RRTs, hematopoietic reconstitution, GVHD occurrence, OS and relapsed between CLAG group and FLAG group. The overall efficacy of CLAG group was not inferior to FLAG group.

Better Failure-Free Survival and Graft-versus-Host Disease-Free/Failure Free Survival with Fludarabine-Based Conditioning in Stem Cell Transplantation for Aplastic Anemia in Children

BACKGROUND: This study aimed to assess the outcome of stem cell transplantation (SCT), including overall survival (OS), failure-free survival (FFS) and graft-versus-host disease (GvHD)-free/failure-free survival (GFFS), and to analyze prognostic factors in children with aplastic anemia (AA).METHODS: From 1991 to 2018, 43 allogeneic SCT recipients were enrolled in the study to investigate the demographic characteristics, survival outcomes and prognostic factors.RESULTS: With the median follow-up of 7.1 years, the estimated 10-year OS, FFS, GFFS were 86.0%, 60.5%, and 51.2%, respectively. Matched related donors (MRD, n = 28) showed better 10-year OS than unrelated donors (n = 15) (96.4% vs. 66.7%; P = 0.006). Engraftment failure was seen in 13 patients (30.2%). Donor-type aplasia was seen in 13.8% (4/29) after fludarabine (Flu)-based conditioning (Flu-group), while in 42.6% (6/14) after cyclophosphamide (Cy)-based regimen (Cy-group) (P = 0.035). Six patients died. The 10-year OS in Cy-group was 92.9% (n = 14, all MRD), while that of Flu-group was 82.1% (n = 29; P = 0.367). But Flu-group tended to have better FFS and GFFS than Cy-group, although Flu-group had less MRDs (41.4% vs. 100%; P = 0.019), and higher proportion of previous immunosuppressive treatment (IST; 62% vs. 21.4%, P = 0.012). In MRD transplants, OS was similar between Flu-group (100%, n = 14) and Cy-group (92.9%, n = 14), while FFS (100.0% vs. 42.9%; P = 0.001) and GFFS (85.7% vs. 35.7%; P = 0.006) were significantly better in Flu-group. Stem cell sources, irradiation in the conditioning, and method of GvHD prophylaxis did not significantly influence the outcome.CONCLUSION: This study reviewed SCT outcomes for pediatric AA with changes of transplant strategies over the last 25 years. The FFS and GFFS were higher in Flu-group than in Cy-group, especially in matched related transplantation. Graft failure including donor-type aplasia remains troublesome even with Flu-based conditioning. Further refinement of transplant strategies to ensure better quality-of-life should be pursued.

Clinical research progress of ibrutinib in the treatment of chronic lymphocytic leukemia / 中国基层医药

Chronic lymphocytic leukemia(CLL) is a heterogeneous mature B lymphocytic tumor.The apoptosis of mature lymphocyte is inhibited and clonal proliferation of mature lymphocyte aggregates in blood, bone marrow, spleen and lymph nodes, resulting in a class of inert hematological tumors.At present, the clinical pathogenesis is not completely clear, environmental and occupational factors do not occupy a major position.Studies have shown that long-term exposure to low-frequency electromagnetic fields may be associated with its incidence, but patients with primary and secondary relatives of lymphatic malignancies increased incidence.Many families still have patients whose age is earlier and the disease is more serious.In recent years, with the continuous improvement of medical level, a variety of treatment methods for chronic lymphoblastic leukemia have emerged, including a variety of new drugs.Ibutinib is the world's first marketed Bruton's tyrosine kinase(BTK) inhibitor, for more patients with chronic lymphoblastic leukemia has brought the gospel.This article reviews the clinical research progress of ibrutinib in treating CLL.

Efficacy of rituximab combined with cyclophosphamide and fludarabine in treatment of chronic lymphocytic leukemia: a Meta-analysis / 白血病·淋巴瘤

Objective@#To analyze the clinical efficacy and safety of fludarabine combined with cyclophosphamide (FC) and fludarabine and cyclophosphamide combined with rituximab (FCR) in the treatment of chronic lymphocytic leukemia (CLL).@*Methods@#FCR regimen was selected as the experimental group, and FC regimen was selected as the control group. The studies were retrieved from PubMed, Cochrane Library, Embase, CNKI, Wangfang and VIP databases by computer and the references listed in these studies were further searched. The randomized controlled trials (RCT) meeting inclusive criteria were extracted, and the quality was evaluated and cross-checked independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then the Meta-analysis was conducted by using StataMP 14.0 software.@*Results@#A total of 7 studies and 1 985 patients were included. The complete remission rate and overall response rate of FCR regimen were better than those of FC regimen, and the differences were statistically significant (RR = 1.89, 95% CI 1.64-2.18, P < 0.01; RR = 1.15, 95% CI 1.10-1.21, P < 0.01). In terms of grade Ⅲ-Ⅳ adverse reactions, the neutropenia of FCR regimen was more severe than that of FC regimen, and the difference was statistically significant (RR = 1.25, 95% CI 1.01-1.55, P = 0.004).@*Conclusion@#The FCR regimen has a better clinical outcome and prognosis than the FC regimen, and is accompanied by more severe grade Ⅲ-Ⅳ neutropenia.

Clinical research progress of ibrutinib in the treatment of chronic lymphocytic leukemia / 中国基层医药

Chronic lymphocytic leukemia(CLL) is a heterogeneous mature B lymphocytic tumor.The apoptosis of mature lymphocyte is inhibited and clonal proliferation of mature lymphocyte aggregates in blood,bone marrow,spleen and lymph nodes,resulting in a class of inert hematological tumors.At present,the clinical pathogenesis is not completely clear,environmental and occupational factors do not occupy a major position. Studies have shown that long -term exposure to low-frequency electromagnetic fields may be associated with its incidence,but patients with primary and secondary relatives of lymphatic malignancies increased incidence. Many families still have patients whose age is earlier and the disease is more serious.In recent years,with the continuous improvement of medical level,a variety of treatment methods for chronic lymphoblastic leukemia have emerged,including a variety of new drugs.Ibutinib is the world＇s first marketed Bruton＇s tyrosine kinase(BTK) inhibitor,for more patients with chronic lymphoblastic leukemia has brought the gospel.This article reviews the clinical research progress of ibrutinib in treating CLL.

Efficacy of rituximab combined with cyclophosphamide and fludarabine in treatment of chronic lymphocytic leukemia: a Meta-analysis / 白血病·淋巴瘤

Objective To analyze the clinical efficacy and safety of fludarabine combined with cyclophosphamide (FC) and fludarabine and cyclophosphamide combined with rituximab (FCR) in the treatment of chronic lymphocytic leukemia (CLL). Methods FCR regimen was selected as the experimental group, and FC regimen was selected as the control group. The studies were retrieved from PubMed, Cochrane Library, Embase, CNKI, Wangfang and VIP databases by computer and the references listed in these studies were further searched. The randomized controlled trials (RCT) meeting inclusive criteria were extracted, and the quality was evaluated and cross-checked independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then the Meta-analysis was conducted by using StataMP 14.0 software. Results A total of 7 studies and 1 985 patients were included. The complete remission rate and overall response rate of FCR regimen were better than those of FC regimen, and the differences were statistically significant ( RR＝1.89, 95% CI 1.64-2.18, P<0.01; RR＝1.15, 95% CI 1.10-1.21, P<0.01). In terms of gradeⅢ-Ⅳadverse reactions, the neutropenia of FCR regimen was more severe than that of FC regimen, and the difference was statistically significant ( RR＝1.25, 95% CI 1.01-1.55, P＝0.004). Conclusion The FCR regimen has a better clinical outcome and prognosis than the FC regimen, and is accompanied by more severe grade Ⅲ-Ⅳneutropenia.

Fludarabine and Rituximab in Relapsed or Refractory Hairy Cell Leukmia Variant: A Case Report and Review of Literature / 고신대학교의과대학학술지

Hairy cell leukemia (HCL) is a rare chronic B cell leukemia morphologically characterized by cells with an abundant cytoplasm and hair-like projections that can be found in the peripheral blood and bone marrow. The treatment for HCL is splenectomy or chemotherapy with the purine analogs pentostatin and cladribine. However, patients continue to relapse. Retreatment with the same or alternate purine analogs produces lower response rates and a shorter duration of response. Fludarabine is another purine analog widely used in treating indolent lymphoid cancers, often in combination with rituximab. Here, we report a case of HCL variant in a 60-year-old man who experienced multiple relapses after splenectomy and retreatment with cladribine. The patient was then treated with fludarabine and rituximab combination chemotherapy. After the treatment, he achieved complete remission that continued for 35 months.

Effect of fludarabine combined with cytarabine on acute myeloid leukemia / 新乡医学院学报

Objective To investigate the effect of fludarabine combined with medium dose cytarabine on acute myeloid leukemia(AML).Methods A total of 55 AML patients were selected from January 2011 to January 2016 in the First People's Hospital of Xinxiang City.Among the patients,there were 16 cases of poor response after initial induction of chemotherapy (double induction group),15 cases of first induction failure(first induction failure group) and 24 cases of relapsed and refractory AML(relapsed-refractory group).All the patients were treated with fludarabine combined with medium dose cytarabine,four weeks was a course,and after treated for two courses the therapeutic effect and survival status of the patients in the three groups were compared.Results The total effective rate in the double induction group,the first induction failure group and the relapsed-refractory group was 81.3％ (13/16),66.7％ (10/15) and 33.3％ (8/24),respectively;the total effective rate in the double induction group and the first induction failure group was significantly higher than that in the relapsed-refractory group (x2 =8.839,4.127;P ＜ 0.05),but there was no significant difference in the total effective rate between the double induction group and the first induction failure group(x2 =0.860,P ＜ 0.05).The median of disease-free survival time in the double induction group,the first induction failure group and the relapsed-refractory group was 29,21 and 10 months,respectively.The disease-free survival time in the double induction group was significantly longer than that in the first induction failure group and the relapsed-refractory grouP(x2 =9.536,33.256;P ＜ 0.05),and the disease-free survival time in the first induction failure group was significantly longer than that in the relapsed-refractory group (x2 =21.077,P ＜ 0.05).The median overall survival time in the double induction group,the first induction failure group and the relapsed-refractory group was 40,29 and 12 months,respectively.The median overall survival time in the double induction group and the first induction failure group was significantly longer than that in the relapsed-refractory group (x2 =33.686,28.649;P ＜ 0.05),but there was no significant difference in the median overall survival time between the double induction group and the first induction failure group (x2 =2.417,P ＜0.05).Conclusion Fludarabine combined with medium dose cytarabine in the treatment of AML can obtain significant curative effect,and the effect in the patients with poor response after initial induction and the first induction failure is better than that in the patients with relapsed and refractory AML.

Anti-CD3 Antibody Ameliorates Transfusion-Associated Graft-Versus-Host Disease in a Chemotherapy-Based Mouse Model With Busulfan and Fludarabine

ABSTRACT To establish a transfusion-associated graft-versus-host disease (TA-GVHD) mouse model with busulfan and fludarabine for effective treatment evaluation. BALB/c (H-2d) mice were injected with busulfan (15 mg/kg) and fludarabine (30 mg/kg) twice a day for 4 days. The mice were transfused with 106 T cell-depleted bone marrow (TCD-BM )and cells in different groups 3 days after chemotherapy: syngeneic BALB/c, MHC minor mismatch DBA/2 (H-2d), or MHC major mismatch C57BL/6(H2-b). Recipient BALB/c mice were injected with either blood only or blood+splenocyte. TA-GVHD was monitored in terms of body weight loss, clinical scores, and survival. Dexamethasone (50 mg/kg), cyclophosphamide (50 mg/kg), cyclosporine A (30 mg/kg), and anti-CD3 (1 mg/kg) were injected to each group to examine the treatments. Blood transfusion alone is insufficient to induce TA-GVHD in a chemotherapy-based mouse model. A MHC-mismatched TA-GVHD model can be induced by splenocyte and blood transfusion. This MHC-mismatched TA-GVHD model was resistant to dexamethasone treatment. Treatment based on anti-CD3 monoclonal antibody slightly ameliorated TA-GVHD. Treatment effectiveness was associated with T-cell depletion following activation by anti-CD3. Busulfan and fludarabine chemotherapy regimen can be used to establish a TA-GVHD mouse model. Anti-CD3 monoclonal antibody is a potential alternative to treat TA-GVHD.

The effect of chemotherapeutic drugs on CD19-CAR-T cells in vitro / 实用医学杂志

Objective The research about the effect of different chemotherapeutic drugs on CD19?CAR?T cells with CCK8 test to provide the theoretical support about the development of chemotherapy for clinical support. Methods Extract T cells from a normal adult peripheral blood and synthesize CD19?CAR?T cell. CD19?CAR?T cells were treated with different doses of chemotherapeutic drugs for 24,48,72 h and(or)96 h,and inhibition rate was calculated. Results First,we observed that the inhibition rates of fludarabine and Mafosfamide for CD19?CAR?T cells were increasing with the time and concentration (P 0.05). Finally ,Cyclophosphamide had no effect in CD19?CAR?T cells in vitro (P > 0.05). Conclusion Mafosfamide and Fludarabine can inhibit the CD19?CAR?T cells. Cyclophosphamide have no activity in vitro.

Cellular response to fludarabine treatment in combination with different ionizing radiation in renal carcinoma 786-O cells / 中华放射肿瘤学杂志

Objective To investigate DNA double-strand breaks and radiosensitization in renal carcinoma 786-O cells induced by fludarabine (FA) combined with different ionizing radiations.Methods The 786-O cells were exposed to FA combined with X-ray or heavy ion beam irradiation.Flow cytometry was used to evaluate the percentage of γH2AX-positive cells and cell cycle.The neutral comet assay was used to detect DNA double-strand breaks.The colony-forming assay was used to evaluate the effects of different treatments on cell survival.Comparison between groups was made by one-way analysis of variance or Dunnet' s t test.Results Compared with FA alone or irradiation alone,FA combined with different ionizing radiations increased DNA double-strand breaks as shown by significantly increased levels of γH2AX (P=0.007,0.001);FA combined with heavy ion beam irradiation lead to a cell cycle block at the radiosensitive G2/M phase and significantly increased the expression of γH2AX in the G2/M phase (P=0.000,0.000);the neutral comet assay revealed that FA combined with irradiation significantly increased DNA sublethal damage (P=0.020,0.060);FA significantly reduced the colony-forming rate after irradiation (P=0.000,0.030;0.001,0.040).Conclusions FA enhances the effects induced by X-ray and heavy ion beam irradiation with different properties.Particularly,FA substantially enhances the cell death induced by heavy ion beam irradiation.

Does anti-thymocyte globulin have a place in busulfan/fludarabine conditioning for matched related donor hematopoietic stem cell transplantation?

BACKGROUND/AIMS: There is controversy about the prophylactic effect of anti-thymocyte globulin (ATG) on graft versus host disease (GVHD) in the setting of matched related-donor hematopoietic stem cell transplantation (HSCT). This study assessed the inf luences of ATG on the incidences of acute and chronic GVHD and other clinical outcomes in matched related-donor HSCT. METHODS: Sixty-one patients received allogeneic HSCT from human leukocyte antigen-matched, related donors. Patients received busulfan/fludarabine conditioning regimens and standard GVHD prophylaxis with or without additional ATG. RESULTS: There was no significant difference in the cumulative incidences of overall acute GVHD, grade II to IV acute GVHD at day 100, and chronic GVHD during the follow-up period between the ATG and non-ATG groups. Three-year overall survival rates were very similar, but three year disease-free survival of the non-ATG group was higher than that of the ATG group (56.2% for ATG vs. 63.1% for non-ATG, p = 0.597). Relapse rate at 3 years in the ATG group was slightly higher than that of the non-ATG group (37.5% vs. 20%, p = 0.29). Non-relapse mortality rate at 3 years was lower in the ATG group (6.25% vs. 15.6%, p = 0.668). CONCLUSIONS: Although the addition of ATG doesn't guarantee a reduction in the incidences of acute and chronic GVHD, pre-transplantation ATG may result in lower non-relapse mortality in the context of matched related-donor HSCT with a busulfan/fludarabine conditioning regimen. However, caution is needed when using ATG because of a possibility to increase relapse rate.

Targeted busulfan and fludarabine-based conditioning for bone marrow transplantation in chronic granulomatous disease / 소아과

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days –8 to –5), and the target area under the curve was 75,000 µg·hr/L. Fludarabine (40 mg/m2) was administered once daily for 6 consecutive days from days –8 to –3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days –4 to –2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.

Adverse reactions of fludarabine in the treatment of chronic lymphoproliferative disorders / 白血病·淋巴瘤

Fludarabine (Flu) is a synthetic purine analog,which has been widely used in the treatment of B-cell chronic lymphoproliferative disorders (B-CLPD) such as chronic lymphocytic leukemia (CLL),nonHodgkin lymphoma (NHL) as an anti-metabolic cytotoxic chemotherapeutic drug and achieved good effect.Main adverse reactions in clinical application of Flu are dose-dependent bone marrow suppression and secondary infection.Non-hematologic adverse reactions are so rare and mild that most patients can tolerate.

Control study of fludarabine instead of cyclophosphamide in modified busulfan-cyclophosphamide as a myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation for treatment of acute leukemia / 白血病·淋巴瘤

Objective To evaluate the fludarabine instead of cyclophosphamide in modified busulfancyclophosphamide (mBuCy) regimen as a new myeloablative conditioning regimen for the treatment of acute leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT).Methods The clinic data of 45 acute leukemia patients undergoing allogeneic HSCT were analyzed.Among them,23 patients received mBuCy as conditioning regimen and 22 patients received BuFlu regimen (fludarabine 40 mg·m-2·d-1 for 5 days,instead of cyclophosphamide in mBuCy).Hematopietic engraftment,regimen-related toxicity (RRT),graft-versus-host disease (GVHD),infection condition,non relapse mortality,and overall survival were compared between the two groups.Results All patients achieved hematopoietic reconstitution and complete donor chimerism except for one patient of mBuCy group died of cerebral hemorrhage during conditioning.The incidence of RRT was no significant differences (P ＞ 0.05).In BuFlu group,the incidence of virus infection was higher (P =0.009),and the incidence of Ⅲll-Ⅳ aGVHD were 26.l ％ (6/23) and 4.5 ％ (1/22) (P =0.046) in mBuCy and in BuFlu group respectively.With a median follow up of 41 months,the incidence of non relapse mortality in mBuCy group was 17.4 ％ (4/23) and in BuFlu group was 9.1％ (2/22) (P =0.665).In mBuCy group and in BuFlu group,the relapse rates were 30.3 ％ (7/23) and 40.9 ％ (9/22) (P =0.474),the 5-year overall survival rates were (55.1±11.9) ％ and (61.4±10.8) ％ (P =0.659),and disease-free survival rates were (44.5±12.1) ％ and (22.1±12.3) ％ (P =0.747),respectively.Conclusions Fludarabine instead of cyclophosphamide in mBuCy regimen as a new myeloablative conditioning regimen has well tolerance,lower incidence of sever GVHD,satisfied overall survival,but the risk of infection and replase should be considered.

Retrospective clinical analysis of fludarabine and cyclophosphamide with or without rituximab for the treatment of patients with chronic lymphocytic leukemia / 中国肿瘤临床

Objective:This study aimed to compare the clinical efficacy and prognosis between rituximab plus fludarabine and cyclophosphamide (FCR) and fludarabine and cyclophosphamide (FC) regimens for patients with chronic lymphocytic leukemia (CLL). Methods:The clinical data of 58 patients with CLL treated with FCR or FC regimens from December 2002 to January 2012 were analyzed retrospectively. Therapy efficacy and prognosis were compared between the two groups. Results:Among the 58 pa-tients, 27 (44.4%) experienced complete remission (CR) in the FCR group and 31 patients (19.4%) experienced CR in the FC group (P=0.039). The overall response rate (ORR) of the FCR group was higher than that of the FC group (81.5%and 51.6%, respectively, P=0.017). Fourteen patients achieved MRD-negative rating after therapy. PFS and OS in MRD-negative patients were superior compared with the MRD-positive group (P=0.000, 0.003). The proportion of MRD-negative patients in the FCR group was higher than that in the FC group (37.0%and 12.9%, respectively, P=0.032). PFS in high-risk genetic patients was lower than that in low-risk genetic patients (P=0.011, 0.027). The OS time between the two groups did not exhibit any difference. Conclusion:FCR produced a high CR and ORR in patients with CLL. Many patients in the FCR group were responsive to the treatment. Thus, FCR could be a more effective regimen than FC for patients with CLL.

T-cell large granular lymphocytic leukemia: treatment experience with fludarabine

OBJECTIVES: The aim of this retrospective study was to investigate the results of T-cell large granular lymphocytic leukemia treatment with fludarabine by assessing the complete hematologic response, the complete molecular response, progression-free survival, and overall survival. METHODS: We evaluated the records of six patients with T-cell large granular lymphocytic leukemia who were treated with fludarabine as a first-, second-, or third-line therapy, at a dose of 40 mg/m², for three to five days per month and 6 to 8 cycles. RESULTS: Of the six patients investigated with T-cell large granular lymphocytic leukemia who were treated with fludarabine, five (83.3%) were female, and their median age was 36.5 years (range 18 to 73). The median lymphocyte level was 3.4x10(9)/L (0.5 to 8.9). All patients exhibited a monoclonal T-cell receptor gamma gene rearrangement at diagnosis. Two (33.3%) patients received fludarabine as first-line treatment, two (33.3%) for refractory disease, one (16.6%) for relapsed disease after the suspension of methotrexate treatment dueto liver toxicity, and one (16.6%) due to dyspesia. A complete hematologic response was achieved in all cases, and a complete molecular response was achieved in five out six cases (83.3%). During a mean follow-up period of 12 months, both the progression-free survival and overall survival rates were 100%. CONCLUSION: T-cell large granular lymphocytic leukemia demonstrated a high rate of complete hematologic and molecular response to fludarabine, with excellent compliance and tolerability rates. To confirm our results in this rare disease, we believe that fludarabine should be tested in clinical trials as a first-line treatment for T-cell large granular lymphocytic leukemia.

Allogeneic peripheral blood stem cell transplantation using a low toxicity conditioning regimen with fludarabine and busulfan for 13 patients with hematological malignancies / 白血病·淋巴瘤

[Objective]To discuss the clinical effect of fludarabine and busulfan (Bu+Flu) as a low toxicity myeloablative conditioning regimen for allogeneic peripheral blood stem cell transplantation (allo-HSCT)in leukemia patients.[Methods]Clinical data of 13 patients with hematological malignancies receiving conditioning regimen with Bu+Flu for allo-HSCT were analyzed retrospectively.Conditioning regimen was Bu+Flu,compalriot mismatched and unrelated transplantation combined with rabbit anti-human thymocytes immune globulin (ATG).CsA+short course of methotrexate or CsA + mycophenolate mofetil were used to prevent graft-versus-host disease (GVHD).DNA sequencing of short tandem repeat (STR)polymorphism analysis method was performed for identification of donor stem cells implantation.[Results]13 patients all tolerated with this conditioning regimen well,no serious complications occurred.Neutrophil engraftment was at 9-15 days (median 11 days),platelet engraftment at 8-25 days (median 13 days).10 patients achieved hematopoiesis reconstitution with their full donor chimerisms confirmed by STR-DNA analysis.Acute GVHD occurred in 5 cases,accounting for 38.5％.Chronic GVHD occurred in 4 cases of 10 patients could be assessed,accounting for 40.0％.Severe GVHD more than Ⅱ degree did not happen.1-39 months (median time 11 months)of follow-up revealed the overall survival rate of 76.9％(10/13),disease-free survival of 61.5％ (8/13).The causes for death were relapse in all.[Conclusion]The conditioning regimen with Bu+Flu has low toxicity,well tolerance and better effect.

A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia / 中华内科杂志

Objective To compare the transplant-related toxicity and the efficacy of busulfan/fludarabine (Bu/Flu) and busulfan/cyclophosphamide (Bu/Cy) as conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia(AML) in the first complete remission (CR1).Methods Totally 32 AML-CR1 patients underwent allo-HSCT were divided into Bu/Cy (Bu 3.2 mg· kg-1 · d-1,7-4 days before transplantation; Cy 60 mg · kg-1 · d-1,3-2 days before transplantation) and Bu/Flu (Bu 3.2 mg · kg-1 · d-1,5-2 days before transplantation; Flu 30 mg · m-2·d-1,6-2 days before transplantation) groups.The regimen-related toxicity (RRT),incidence and severity of graft-versus-host disease (GVHD),3-year cumulative relapse rate,non-relapse mortality (NRM),3-year event-free survival (EFS) rate and overall survival (OS) rate were compared between the two groups.Results The median follow-up duration was 617.5 (6-1261) days.All patients achieved successful engraftment on 30 day after transplantation.There were no significant differences in the median time to neutrophil engraftment (P =0.121) and platelet engraftment (P =0.171) between the two groups.The median duration of neutrophil count under 0.1 × 109/L and platelet count under 20 × 109/L in the Bu/Cy group were significantly longer than those in the Bu/Flu group (P =0.000 and P =0.047).The incidence of grades Ⅱ-Ⅳ RRT were 68.8％ and 25.0％ (P =0.032) in the Bu/Cy and the Bu/Flu groups,respectively.There were no significant differences in the incidence of acute GVHD (P =0.149),chronic GVHD (P =0.149),incidence of NRM (P =0.333),3-year cumulative relapse rates (P =0.834),3-year EFS rate (P =0.362) and OS rate (P =0.111) between the two groups.Conclusion Compared with Bu/Cy,Bu/Flu is a myeloablative condition regimen with milder bone marrow suppression and lower RRT incidence rate in allogeneic HSCT for AML-CR1 patients without compromising the efficacy.

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.