| Objective To improve the conditioning regimen of anti-tumor effect, we explore the of efficacy and toxicity with once-daily intravenous busulfan (IV Bu)-based conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods Of 27 patients (25 cases with hematologic malignancies and 2 cases with adrenoleukodystrophy) were used once-dailyⅣBu with the improvement of busulfan/ cyclophosphamide (Bu/Cy), improvement of Bu/Cy + Pig anti-human thymocyte globulin (ATG) and fludarabine (Flu)/busulfan+ pig ATG conditioning regimens for allo-HSCT.The median age of patients was 31 years (3 years to 61 years). In which genetic human leukocyte antigen (HLA) full matched transplantation in 19 cases, relatives of HLA mismatched-transplantation in 4 cases, unrelated adult donor transplantation in 3 cases, unrelated cord blood transplantation in 1 case. Used in the pretreatment dose of IV Bu daily 3.2mg.kg-1.d-1, the daily dose was diluted to 10 times the original solution volume, the use of infusion pump completed the first injection, infusion time for 4 hours. Collected blood samples from using the IV Bu process started after the 2h,3.9h,6h,8h,12h,16h,22h in seven time points, the use of liquid chromatography to detect the intravenous busulfan at various time points blood concentration, and record related toxicity, the case of complications after transplantation,and survival and the primary disease condition.Results Median follow-up of 8 months (0.3 months to 18 months). The median concentration of busulfan clearance 0.067ml/min/kg, the average daily area under the curve is 13877.5ug/L*h. After transplantation 1 patient died of cerebral hemorrhage in 10 days, stem cells are not implanted, the more than 30 days after transplantation in patients with short tandem repeat lines (STR-PCR) test, only 1 case with adrenoleukodystrophy patients received cord blood transplantation is not implanted, the remaining patients showed complete donor for the genotypes.3 patients had mild mucositis,11 patients had mild gastrointestinal reactions,7 patients had abnormal liver function (including 6 cases of mild reversible abnormalities in 1 case severe jaundice),6 cases of hemorrhagic cystitis, but were delayed and no one case occured epilepsy and hepatic veno-occlusive disease (VOD). In the evaluable patients, incidence of acute graft-versus-host disease (aGVHD) was 64.0% (16/25), in which the degree of aGVHDⅢ～Ⅳonly in 28.0%(7/25), the incidence of chronic graft-versus-host Disease (cGVHD) 77.0%(17/22), the extensive type was 41.0% (9/22). Conclusions Once-daily IV Bu allo-HSCT conditioning regimen has good plasma stability, easy to use, safe and effective, and good clinical tolerance, toxicity did not increase to overcome the oral busulfan bioavailability is low and difficult to ensure accurate dosage. Objective To explore the method and effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with severe aplastic anemia (SAA). Methods 30 cases with SAA patients received allo-HSCT.18 males and 12 females, median age 25 years (3 years to 48 years). Including 2 cases reveived unrelated cord blood transplantation, unrelated adult donor transplantation in 4 cases, human leukocyte antigen (HLA) matched transplantation in 19 cases, HLA one locus incompatible transplants in 5 cases,3 patients were treated with cyclophosphamide (200mg/kg)+ pig anti-human thymocyte globulin (100mg/kg) of non-myeloablative conditioning, the other patients were treated with cyclophosphamide (100～120mg/kg)+Fludarabine (150mg/m2)+pig anti-human thymocyte globulin (100mg/kg). Among them,15 cases were reveived the granulocyte colony stimulating factor to mobilize bone marrow combined peripheral blood stem cell transplantation,10 patients reveived granulocyte colony stimulating factor mobilized peripheral blood stem cell transplantation,3 cases reveived bone marrow of granulocyte colony stimulating factor mobilization,2 cases received double unrelated umbilical cord blood infusion. Prevention of graft versus host disease (GVHD) in the matched relatives of HLA transplantation with cyclosporine A (CsA) combined short course methotrexate (MTX) program, the affinity for the HLA one locus mismatched transplants and unrelated donor transplantation received CsA combined transplantation program short course MTX based on the use of mycophenolate mofetil (MMF) program, for unrelated cord blood transplantation mycophenolate mofetil combined with CsA (MMF) program. Results In addition 3 patients died during the transplant outside (n=1 cord blood transplant patients died of infection 18 days after transplantation,1 patient died 9 days after transplantation died of septic shock,1 patient died 8 days after transplantation and severe hepatic veno-occlusive disease caused and multiple organ failure),1 patient without platelet engraftment, again obtained engraftment after the infusion of donor peripheral blood stem cells, the hematopoietic recovery after transplantation in patients over the smooth, the median day+12 (+6 To+21 days) WBC implantation,+15 days (+9 to+30 days) PLT implantation in patients with cord blood transplantation in 1 patient without graft implantation, self-recovery, the other patients were+30 days STR-PCR analysis showed that bone marrow is completely donor genotype, with a median follow-up of 25.6 months (0.3 months to 84 months), overall survival for all patients (OS) was 83.3%. In the evaluable patients, the incidence of acute graft-versus-host disease (aGVHD) was 11.1%(3 /27), in which only 1 occurredⅢgrade aGVHD, incidence of chronic graft versus host disease (cGVHD) was 21.7%(5/23), which extensive type was 8.7%(2/23).Conclusions Allogeneic hematopoietic stem cell transplantation is the effective treatment for severe aplastic anemia, but cord blood stem cells will need to be cautious, HLA matched patients and one locus mismatched patients of implantation of stem cell transplantation and overall survival was no difference, in the use of bone marrow transplant patients peripheral blood stem cell transplantation in the joint or single peripheral blood stem cell transplantation with stem cells both in terms of implantation has no difference. Unrelated donor transplantation in adults with advanced rejection rate increases, still need to optimize the conditioning regimen to prevent late implant failure. Objective To explore the efficacy of autologous peripheral blood stem cell transplantation (APBSCT) combined immunosuppressive for autoimmune diseases (AID).Methods AID patients in 17 cases received APBSCT also use the pig with or without antithymocyte globulin (ATG) or rituximab in vivo purging. Of these,16 patients were systemic lupus erythematosus,1 case with overlap syndrome (systemic sclerosis systemic and lupus erythematosus),1 case of autoimmune hemolytic anemia.17 patients were using cyclophosphamide (CTX) 4g/m2 chemotherapy and granulocyte colony stimulating factor (G-CSF) 5μg/kg/d mobilized peripheral blood stem cells in patients,14 patients received tCTX 50mg/kg/d×4d before reinfusion of peripheral blood stem cell preservation, and 1 patient received the BEAM conditioning. Before pretreatment transfusion of peripheral blood stem cells, we reinfuse the ATG (pig) 20mg/kg/d×2d, after transplantation we reinfused the ATG (pig) 20mg/kg/d×2d for in vivo purging.1 case occurred in the pretreatment of fungal sepsis, use only CTX 50mg/kg/d×4d, ATG is not used in vivo purging, and 1 case with autoimmune hemolytic anemia was not using ATG, but after transplantation +8d and+1 d we use the rituximab 600mg/d (375mg/m2) for in vivo purging. The median transfusion mononuclear cells (MNC) is greater than 5.0×108/kg, the median CD34 + cells greater than 2.0×106/kg, oral prednisone after transplantation 5～10 mg/d or mycophenolate mofetil (MMF) 0.5g/d for maintenance therapy. Results 17 patients of hematopoietic function recovered smoothly after transplantation, absolute neutrophil count (ANC) at a median time of +9 d (+8 d～+11 d) engraftment, the median time to platelets in the +12 d (+9 d～+15 d). Stem cell mobilization in the process of disease activity occurred in 5 patients, after prednisone was added they were controlled, 1 case with autoimmune hemolytic anemia after transplantation, reticulocytes returned to normal, bilirubin returned to normal, no recurrence of hemolytic performance. After transplantation in 5 months, Coomb's test was negative, all with connective tissue diseases caught in about 1 month after transplantation, skin rashes and joint pain gradually disappeared, SIEDAI decreased to 5 points or less, urine protein decreased or disappeared. Review 3 months after transplantation, autoantibodies titer decreased. Median follow-up of all patients to 42.6 months after transplantation,5 patients died, both in patients with systemic lupus erythematosus,3 cases of recurrence, were patients with systemic lupus erythematosus. Hematopoietic function in other patients with good recovery, the condition is sustained remission. Conclusions APBSCT is a effective treatment for autoimmune diseases,but we have strictly indications for AID. We should note the possibility of infection and disease activity during the transplantation process. After transplantation we should pay attention to the occurrence of fatal interstitial pneumonia. Objective To explore the allogeneic hematopoietic stem cell transplantation for patients with X linked adrenoleukodystrophy (X-ALD). Methods 2 cases with X-ALD have eurological symptoms received allogeneic stem cell transplantation. We used Fludarabine (150mg/m2)+intravenous busulfan (9.6mg/kg)+pig anti-human thymocyte globulin (100mg/kg) for non-myeloablative pretreatment,1 patient received transfusion of double unrelated umbilical cord blood, and the other 1 patient received transfusion of father's HLA 5/6 by the consistency of granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells. Unrelated cord blood transplantation to prevent graft versus host disease (GVHD) with cyclosporine A (CsA) combined mycophenolate mofetil (MMF) program, HLA 5/6 matched transplant to prevent GVHD with CsA combined short course MTX, was added on the basis of mycophenolate mofetil (MMF) program. Results Two patients of hematopoietic function recovered smoothly after transplantation, but the unrelated cord blood transplantation in patients with short tandem repeat (STR-PCR) analysis showed that the cord blood is not implanted, father's HLA 5/6 matched donor transplant get a complete chimera, cord blood transplant patients after resume their own autologous peripheral blood stem cell transfusion, white blood cells and platelet recovery. Cord blood transplantation in patients with no graft-versus-host disease (GVHD), performance of the migration process in the nervous system diseases have increased. The other patient received the father's HLA 5/6 matched transplant patients with gradeⅡacute GVHD,Ⅲgrade viral hemorrhagic cystitis, cytomegalovirus viremia were improved after treatment, but stay in bed longer, decreased activity. Early testing long chain fatty acids decreased compared with before transplantation. Conclusions Experience with review of the literature shows that allogeneic hematopoietic stem cell transplantation is a feasible and effective treatment method for X-ALD, but not obvious early symptoms in the nervous system in patients with good effect, patients in the transplant process may damage the nervous system, and the efficacy of transplantation still need long-term observation.
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