OBJECTIVETo investigate the safety and effectiveness of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with related haploidentical bone marrow infusion for treatment of hematologic malignancies and to explore the mathod for reduction of aGVHD incidence and clinical significance.

METHODSA total of 30 patients with hematologic malignancies (8 cases of AML, 17 AML, 2 MDS and 3 Mix-AL) received related haploidentical and unrelated HLA-mismatched allo-HSCT combined with related haploidentical bone marrow infusion. Among them 20 cases received related haploidentical transplantation of the first donor, 10 cases received unrelated HLA-mismatched treaplantation. The new conditioning regimen for the patients underwent allo-HSCT consisted of fludarabine, busulfan, Me-CCNU and cyclophosphamide. The drugs for GVHD prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used.

RESULTSAll the patients achieved full engraftment. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (8-26 days), while the median time for platelets to reach over 20 × 10(9)/L was 11.5days (10-24 days). The incidence of I-II grade of aGVHD at 100 d was 22.28% (95% CI 9.9%-34.7%), the incidences of II-IV and III-IV grade of aGVHD were 22.7% (95% CI, 10%-35.4%) and 12.7% (95% CI 6.9%-15.5%) respectively. The incidences of I-II and III-IV cGVHD were 13.3% (95% CI, 1.4%- 26.8%) and 3.3 % (95% CI, 0%-12.2%), one case (3.3%) was in extensive cGVHD. DFS and OS of 2 years were 81.1% (95% CI, 66.0%-96.2%) and 68.2% (95% CI 51.0%-85.4%).

CONCLUSIONThese data suggest that the incidence of grade II-IV grade of aGVHD in recipients of 2 partially HLA-matched units was lower, co-infusion of haplo-BM and partially matched units in allogeneic transplantation is safe and effective for reducing the incidence of aGVHD and improving the survival in DFS.

Antilymphocyte Serum ; therapeutic use ; Busulfan ; therapeutic use ; Cyclosporine ; therapeutic use ; Graft vs Host Disease ; prevention & control ; HLA Antigens ; genetics ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Leukemia ; therapy ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Transplantation, Homologous ; Vidarabine ; analogs & derivatives ; therapeutic use

OBJECTIVETo explore the efficacy of unrelated umbilical cord blood transplantation (UCBT) in the treatment of Gaucher disease.

METHODThe clinical characteristics of three children with Gaucher disease underwent UCBT in our hospital between April 2013 and September 2014 were retrospectively analyzed. Literature on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of Gaucher disease was searched at Wanfang and Pubmed databases between 1983 and 2015 and was reviewed and summaried.

RESULTThree children with Gaucher disease, all were female, received UCBT. These patients' age at receiving transplantation was 3.8 years, 7.1 years and 2.6 years, respectively. The second case received the second transplantation. The first and third case received splenectomy before UCBT. The pretreatment regimen was busulfan (Bu)/fludarabine (Flu)/cyclophosphamide (CTX)/antithymocyte globulin (ATG), and for the patient received the second transplantation melphalan was added to the myeloablative conditioning regimen of Bu/Flu/CTX/ATG. Cyclosporine and mycophenolate mofetil (MMF) wee used for prophylaxis of acute graft versus host disease (aGVHD). The dose of cord blood stem cell nucleated cell counts was 9.7 × 10⁷ /kg,11.9 × 10⁷ /kg and 7.6 × 10⁷/kg respectively. The dose of cord blood stem cell CD34⁺ cell counts was 5.4 × 10⁵/kg , 3.5 × 10⁵/kg and 3.2 × 10⁵/kg respectively. The day of granulocytes exceeding 0.5 × 10⁹/L was day 11, 12 and 19 after transplantation, respectively. The day of platelets exceeding 20 × 10⁹/L was day 14, 33 and 74 after transplantation, respectively. At one month after transplantation the rate of chimerism was over 95% and all patients got donor complete chimerism. The level of β-glucocerebrosidase recovered to normal at one month after transplantation. During transplantation, all patients developed cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia. In case 1 immune thrombocytopenia occurred at five month after transplantation unresponding to steroids and mesenchymal stem cells infusion was administered and his platelet in routine blood test recovered to normal. But the patient died because she was infected with varicella-zoster virus out of hospital at nine month after transplantation and the level of β-glucocerebrosidase was normal before death and chronic GVHD (cGVHD) was not found. The case 2 is now in 19th month after transplantation and his level of β-glucocerebrosidase was normal. cGVHD was not found. The patient is currently free of disease. The case 3 was in 9th month after transplantation and his level of β-glucocerebrosidase was normal. cGVHD was found at 112 day after transplantation and was localized and could be controlled by hormonal therapy. The patient is currently free of disease. Three patients' size of liver was significantly reduced after their level of β-glucocerebrosidase ecovered. There were 50 cases with Gaucher disease who were treated with allo-HSCT in the literature and none of them were reported from China. Disease-free survival rate of patients treated with allo-HSCT for Gaucher disease was 85%. In all reports, there were 31 cases who had information of typing of Gaucher disease, of whom 22 cases had type 1 and 9 cases had type 3. Twenty-nine cases had information of survival, of whom 24 cases survived and 5 cases died of infection. Fifteen cases had data of engraftment, 2 of whom had graft failure and one had late graft failure.Glucocerebrosidase recovered to normal in 25 of 31 cases who had relevant data, in one of whom with late graft failure the enzyme recovered to normal 3 month after transplantation, but his enzyme decreased to the initial level 9 month after transplantation. Along with enzyme level's recovery to normal, in a part of cases bone pain and hepatomegaly were relieved and growth delay was improved.

CONCLUSIONThe unrelated UCBT may be a form of treatment that offers the potential of permanent cure and a procedure with possible long-term benefits in patients with Gaucher disease.

Antilymphocyte Serum ; therapeutic use ; Busulfan ; therapeutic use ; Child ; Child, Preschool ; China ; Cyclophosphamide ; therapeutic use ; Cyclosporine ; therapeutic use ; Disease-Free Survival ; Female ; Gaucher Disease ; therapy ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Retrospective Studies ; Transplantation Conditioning ; Vidarabine ; analogs & derivatives ; therapeutic use

OBJECTIVETo retrospectively study the impacts of ABO incompatibility on early outcome after single unit unrelated cord blood transplantation（UCBT）, such as cumulative incidence of engraftment, incidence of acute graft- versus- host disease （aGVHD） and 180- day transplant- related mortality（TRM）.

METHODS208 patients underwent single unit UCBT from April 2008 to October 2014 were analyzed, included 99 ABO- identical, 60 minor, 38 major and 11 bidirectional ABO- incompatible recipients. All the patients received intensified myeloablative conditioning, and a combination of cyclosporine A and mycophenolate mofetil was given for GVHD prophylaxis.

RESULTSCumulative incidences of neutrophil engraftment, platelet recovery, erythroid lineage reconstitution, Ⅱ-Ⅳ aGVHD, Ⅲ-Ⅳ aGVHD and 180- day TRM showed no significant difference among the patients receiving ABOidentical, minor, major, and bidirectional UCBT（all P>0.05, respectively）. What's more, none of the patients developed pure red- cell aplasia（PRCA）after UCBT. Group A donor and a group O recipient patients didn't appeared to influence the clinical results when compared with others（all P>0.05, respectively）.

CONCLUSIONPatients receive ABO- incompatible UCBT may not develop PRCA. The presence of ABO- incompatibility did not influence the hematopoietic reconstitution, the incidence of aGVHD and 180-day TRM in this cohort. There is not support for the need to regard ABO-compatibility as an UCB-graft selection criterion.

ABO Blood-Group System ; Blood Group Incompatibility ; Cord Blood Stem Cell Transplantation ; adverse effects ; Cyclosporine ; therapeutic use ; Graft vs Host Disease ; complications ; Humans ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Red-Cell Aplasia, Pure ; complications ; Retrospective Studies ; Tissue Donors ; Transplantation, Homologous

BACKGROUND/AIMS: The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT). METHODS: Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT. RESULTS: In the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively. CONCLUSIONS: A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.
Adult ; Aged ; Area Under Curve ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Gastrointestinal Diseases/etiology ; Graft Rejection/prevention & control ; Humans ; Immunosuppressive Agents/blood/*pharmacokinetics ; Leukopenia/etiology ; Liver/pathology ; Liver Failure/*therapy ; *Liver Transplantation ; Male ; Middle Aged ; Mycophenolic Acid/adverse effects/*analogs & derivatives/blood/pharmacokinetics ; ROC Curve ; Retrospective Studies ; Tacrolimus/therapeutic use ; Tissue Donors

OBJECTIVETo investigate the clinical characteristics, renal pathology, treatment and prognosis of children with atypical hemolytic uremic syndrome associated with H factor antibody.

METHODFour children less than 18 yr of age admitted from Nov. 2010 to May 2011 in Peking University First Hospital were included. They all met the criteria for atypical hemolytic uremic syndrome and with positive serum anti factor H antibody. They aged from 5 to 11 yr. Data on clinical manifestations, renal pathology, treatment and prognosis were analyzed.

RESULTAll of the 4 cases had gastrointestinal symptoms such as vomiting, abdominal pain, or abdominal distension. None of them had diarrhea. Two children had hypertension. One child had episodes of convulsion. One child had history of atypical hemolytic uremic syndrome. All of them had low serum complement C3. Three of them had low serum factor H (38.0, 88.4, 209.4 mg/L). All of them had serum antibody to factor H (1: 7 068, 1: 1 110, 1: 174, and 1: 869). Three of them received renal biopsy, all of them showed thrombotic microangiopathy. All of them were treated with steroid combined with mycophenolate mofetil. Two children received plasma exchange. They were followed up for 8 to 29 months. The renal function became normal and proteinuria relieved in all of them. The serum factor H concentration increased to 405.8, 155.8 and 438.4 mg/L, respectively. The titer of anti factor H antibody decreased to 1: 119, 1: 170, 1: 123, and 1: 674, respectively.

CONCLUSIONGastrointestinal symptom is common in children with atypical hemolytic uremic syndrome associated with H factor antibody. Hypocomplementemia was observed in all of them. Steroid combined with mycophenolate mofetil seemed to be effective for them. The monitoring of serum factor H and antibody to factor H may help diagnosis and treatment.

Atypical Hemolytic Uremic Syndrome ; Autoantibodies ; blood ; immunology ; Child ; Child, Preschool ; Complement Factor H ; immunology ; Creatinine ; blood ; Female ; Hemolytic-Uremic Syndrome ; drug therapy ; immunology ; pathology ; Humans ; Kidney ; pathology ; physiopathology ; Kidney Function Tests ; Male ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Plasma Exchange ; Prednisolone ; administration & dosage ; therapeutic use ; Prognosis ; Retrospective Studies

OBJECTIVETo determine the optimal dose range (therapeutic window) of mycophenolate mofetil (MMF) for preventing acute graft rejection following renal transplantation.

METHODSThe trough concentration of MMF (MPA-C0) at 12 h after oral administration of the drug (two doses daily given at an interval of 12 h) was monitored in 110 renal transplant recipients within a month, in 2-3 months, and over 4 months after the transplantation using EMIT method. The occurrence of acute graft rejection and drug toxicity were observed in all the patients during the one-year follow-up.

RESULTSs The incidence of acute graft rejection after transplantation was 13.64% (15/110) in these patients. Drug toxicity and complications occurred in 32.73% (36/110) of the patients, including 12 cases with reduced white blood cell counts, 10 with MMF cid-associated diarrhea, 10 with infection, 4 with liver function damage. Acute rejection was successfully reversed after methylprednisolone treatment and drug toxicity was managed by corresponding treatment and adjustment of MMF dose. No deaths or graft removal occurred in these patients. The ROC curve showed that a MPA-C0 of 1.40-2.80 mg/L was optimal in preventing acute rejection after the transplantation and reducing adverse drug effects.

CONCLUSIONMonitoring MPA-C0 and individualized MMF dosing help to prevent acute graft rejection, reducing drug toxicity and complications, and improving graft survival rate after renal transplantation.

Graft Rejection ; drug therapy ; prevention & control ; Graft Survival ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Kidney Transplantation ; Methylprednisolone ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; therapeutic use ; Survival Rate ; Time Factors

BACKGROUNDMycophenolate mofetil (MMF) and cyclophosphamide (CTX) are widely used in treating various kidney diseases. However, whether they are effective and which one is better for treating IgA nephropathy patients with proliferative pathological phenotype in renal diseases, such as endocapillary proliferation, cellular crescents, and/or capillary loops fibrinoid necrosis is still unknown. We, therefore, initiated a study to compare the effects of MMF and CTX in treating IgA nephropathy with the above pathological lesions.

METHODSOne hundred and nineteen patients with IgA nephropathy who had at least one of the three aforementioned lesions were enrolled. All patients were treated with prednisone; 48 patients received prednisone only (Pred group), 40 received MMF and prednisone (MMF + Pred group), and 31 were treated with CTX and prednisone (CTX + Pred group). The median time of follow-up was 30 months (maximum: 96 months). The primary endpoint was defined as renal survival. The incidence of remission of proteinuria was the secondary endpoint.

RESULTSSerum creatinine in all groups declined significantly at different follow-up times (P = 0.002), and the differences among the three groups were significant (P < 0.001). At 24 months of follow-up, the decline rates were 12.35%, 32.95%, and 24.14% in the Pred, MMF + Pred, and CTX + Pred groups respectively. For urine protein excretion, the decline rates were 49.12% (Pred), 73.67% (MMF + Pred), and 63.53% (CTX + Pred) respectively at 24 months of follow-up. The differences among the three groups were not significant (P = 0.714). Renal survival (the primary endpoint) was significantly different (P = 0.027); however, the sencondary endpoint was similar for all the three groups (P = 0.100).

CONCLUSIONSFor IgA nephropathy patients with endocapillary proliferation, cellular crescents, and/or fibrinoid necrosis of capillary loops, prednisone combined with MMF was more effective in lowering the serum creatinine than with CTX. Combined MMF and prednisone treatment led to a better renal survival compared to that of prednisone with CTX.

Adult ; Female ; Glomerulonephritis, IGA ; drug therapy ; pathology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Retrospective Studies ; Young Adult

Aged ; Aortic Valve ; surgery ; Cyclosporine ; therapeutic use ; Female ; Heart Defects, Congenital ; drug therapy ; surgery ; Heart Valve Diseases ; drug therapy ; surgery ; Heart Valve Prosthesis ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Transplant Recipients

AIM: To investigate the chemical constituents of the cultures of Laetiporus sulphureus (Bull.) Murrill. METHOD: Compounds were isolated and purified by various chromatographic techniques. The structure of the new compound was determined by interpretation of MS and 1D-, 2D-NMR spectroscopic data, while the known compounds were identified by comparison of their data with those reported. RESULTS: Three mycophenolic acid derivatives, 6-((2E, 6E)-3, 7-dimethyldeca-2, 6-dienyl)-7-hydroxy-5-methoxy-4-methylphtanlan-1-one (1), 6-((2E, 6E)-3, 7, 11-trimethyldedoca-2, 6, 10-trienyl)-5, 7-dihydroxy-4-methylphtanlan-1-one (2), and 6-((2E, 6E)-3, 7, 11-trimethyldedoca-2, 6, 10-trienyl)-7-hydroxy-5-methoxy-4-methylphtanlan-1-one (3) were isolated. CONCLUSION Among them, compound 1 was new, and compound 2 exhibited moderate cytotoxicity against HL-60, SMMC-7721, A-549, and MCF-7 cells, with IC50 values of 39.1, 31.1, 27.4, and 35.7 μmol·L(-1), respectively.
Agaricales ; Biological Products ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; HL-60 Cells ; Humans ; MCF-7 Cells ; Molecular Structure ; Mycophenolic Acid ; analogs & derivatives ; chemistry ; isolation & purification ; Neoplasms ; drug therapy ; Phenols ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Polyporales ; chemistry

Treatment of thrombocytopenia in systemic lupus erythematosus (SLE) is considered in cases of current bleeding, severe bruising, or a platelet count below 50,000/microliter. Corticosteroid is the first choice of medication for inducing remission, and immunosuppressive agents can be added when thrombocytopenia is refractory to corticosteroid or recurs despite it. We presented two SLE patients with thrombocytopenia who successfully induced remission after intravenous administration of low-dose cyclophosphamide (CYC) (500 mg fixed dose, biweekly for 3 months), followed by azathioprine (AZA) or mycophenolate mofetil (MMF). Both patients developed severe thrombocytopenia in SLE that did not respond to pulsed methylprednisolone therapy, and started the intravenous low-dose CYC therapy. In case 1, the platelet count increased to 50,000/microliter after the first CYC infusion, and remission was maintained with low dose prednisolone and AZA. The case 2 achieved remission after three cycles of CYC, and the remission continued with low dose prednisolone and MMF.
Azathioprine/therapeutic use ; Bone Marrow/pathology ; Cyclophosphamide/*therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Immunosuppressive Agents/*therapeutic use ; Infusions, Intravenous ; Lupus Erythematosus, Systemic/complications/*diagnosis ; Middle Aged ; Mycophenolic Acid/analogs & derivatives/therapeutic use ; Platelet Count ; Thrombocytopenia/*diagnosis/*drug therapy/etiology ; Young Adult