OBJECTIVETo compare the therapeutic effects of prednisone combined with mycophenolate mofetil (MMF) versus cyclosporin A (CsA) in children with steroid-resistant nephrotic syndrome (SRNS).

METHODSThe clinical data of 164 SRNS children who were treated with prednisone combined with MMF or CsA between January 2004 and December 2013 were collected, and the clinical effect of prednisone combined with MMF (MMF group, 112 children) or CsA (CsA group, 52 children) was analyzed retrospectively.

RESULTSAt 1 month after treatment, the CsA group had a significantly higher remission rate than the MMF group (67.3% vs 42.9%; P<0.05). At 3 months after treatment, the CsA group also had a significantly higher remission rate than the MMF group (78.8% vs 63.3%; P<0.05). The 24-hour urinary protein excretion in both groups changed significantly with time (P<0.05) and differed significantly between the two groups (P<0.05). There were no serious adverse events in the two groups.

CONCLUSIONSPrednisone combined with MMF or CsA is effective and safe for the treatment of SRNS in children, and within 3 months of treatment, CsA has a better effect than MMF.

Adolescent ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; Infant ; Male ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; Nephrotic Syndrome ; drug therapy ; Prednisone ; administration & dosage ; Retrospective Studies ; Treatment Outcome

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 evaluate the outcomes of allogeneic hematopoietic stem cell transplantation（allo-HSCT）for paroxysmal nocturnal haemoglobinuria（PNH）and aplastic anemia（AA）- PNH syndrome.

METHODSThe clinical data of 18 PNH or AA-PNH patients, including 4 classic PNH and 14 AA-PNH, received allo-HSCT from Dec 2007 to Feb 2015 were analyzed retrospectively. Nine patients received HLA-haploidentical donor HSCT（1 patient received salvage HLA-haploidentical donor HSCT after the graft failure of double cord blood transplantation）, 7 patients received HLA-identical sibling donor HSCT, and 2 HLA-identical unrelated donor HSCT. The conditioning regimens were as follow: 13 patients received modified BU/CY- based regimens, 5 non- myeloablative regimens ［fludarabine （Flu） + antithymocyte globulin（ATG）+ cyclophosphamide（CY）or busulfan（BU）］. Prophylaxis for graft- versushost disease（GVHD）: the patients with HLA-identical sibling donor received cyclosporine（CsA）plus short-term methotrexate（MTX）, the patients with HLA -haploidentical donor or HLA-identical unrelated donor received CsA or tacrolimus（FK506）+ mycophenolate mofetil（MMF）+ short- term methotrexate （MTX）.

RESULTSAll patients were engrafted successfully（1 patient engrafted by haploidentical donor after the graft failure of double cord blood transplantation）. The median days of neutrophils（ANC）above 0.5 × 109/L and platelets （PLT） more than 20 × 10⁹/L were 11（10- 26）days and 15（11- 120）days, respectively. Three patients（17.6%）developed acute GVHD（aGVHD）, 2 for grade Ⅱ aGVHD, 1 for grade Ⅳ aGVHD. Of 16 patients, 2 occurred limited chronic GVHD（cGVHD）. After a median follow-up of 14.6（2.0-86.7）months, 3 patients（17.6%）died, out of which one died of severe aGVHD, one died of severe pulmonary infection, one pulmonary infection with transplant- associated thrombotic microangiopathy. The 5- year estimated disease free survival was（80.5 ± 10.2）%. No patient relapsed.

CONCLUSIONAllo-HSCT is an effective and curable therapy for PNH or AA-PNH with improved prognosis, and offers a valid therapeutic option for these patients before humanized monoclonal antibody against C5 are widely used clinically.

Anemia, Aplastic ; therapy ; Antilymphocyte Serum ; Busulfan ; Cyclophosphamide ; Cyclosporine ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hemoglobinuria, Paroxysmal ; therapy ; Humans ; Methotrexate ; Mycophenolic Acid ; analogs & derivatives ; Retrospective Studies ; Siblings ; Tacrolimus ; Transplantation Conditioning ; Treatment Outcome ; Unrelated Donors ; Vidarabine ; analogs & derivatives

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

OBJECTIVETo evaluate the therapeutic efficacy and related risk factors of acute myelogenous leukemia （AML） patients treated with unrelated cord blood transplantation （UCBT）.

METHODSA retrospective analysis was performed on the clinical data of 58 AML patients that consisted of 1 case of M0, 1 case M1, 35 cases M2, 3 cases M4, 14 cases M5, 3 cases M6, and 1 case acute mixed leukemia, respectively. Of them, 1 case AML secondary to myelodysplastic syndrome, and 36 in first complete remission （CR1）, 14 in second complele remission （CR2）, 8 in non- remission （NR）, 43 cases were refractory or high-risk patients（70.1%）. The median age was 14.5 years with the median weight of 45 kg, 49 patients received sUCBT and 9 dUCBT. All the patients conditioned with intensified myeloablative regimen and received a combination of Cyclosporine A（CsA）and mycophenolate mofetil（MMF）to prevent graft- versus- host disease（GVHD）.

RESULTS56 out of 58 patients achieved engraftment with implantation rate 96.6%. The median time of ANC≥0.5×10⁹/L was 17（12-37）days, and that of PLT≥20× 109/L 33（17-140）days respectively. 24 cases developed acute GVHD（aGVHD）, the incidence rate of grade Ⅱ to Ⅳ aGVHD was 30.4%. The chronic GVHD（cGVHD）was occured in 7 patients of the 49 evaluable patients, all were limited. The estimated 3-year overall survival（OS）and disease-free survival （DFS）were（60.3±6.4）% and（60.1±6.5）% respectively. And the cumulative incidences of 3-year nonrelapse mortality（NRM）and relapse were 33.3% and 9.1% respectively. The 3- year OS rates of AML patients were（66.0 ± 6.7）% for CR and（25.0 ± 15.3）% for NR, differences were statistical significance.

CONCLUSIONFor AML patients, UCBT was conducive to improve outcome with lower incidences of cGVHD and relapse, the patients after transplantation could obtain high quality of life.

Acute Disease ; Adolescent ; Cyclosporine ; Disease-Free Survival ; Fetal Blood ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Leukemia, Myeloid, Acute ; Mycophenolic Acid ; analogs & derivatives ; Quality of Life ; Recurrence ; Remission Induction ; Retrospective Studies

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 investigate the therapeutic efficacy of nonmyeloablative allogeneic hematopoietic stem cells transplantation for severe acquired aplastic anemia (SAA).

METHODSFourteen patients with severe acquired aplastic anemia received nonmyeloablative allogeneic hematopoietic stem cells transplantation from HLA matched sibling donors, among them 8 cases were dagnosed as SAA-I, 6 cases were diagnosed as SAA-II. The conditioning regimen consisted of fludarabine (FIUD), cyclophosphamide (CTX) and anti-thymocyte globulin (ATG/ALG). The prophylaxis for graft-versus-host disease (GVHD) was performed with cyclosporine (CsA) combined with mycophenolate mofetil (MMF) or tacrolimus (FK506).

RESULTSAll the patients gained a quick successfully engraftment of donor hametopoietic cells. The mean recovery time for neutrophil and platelet was 9 d and 13 d respectively. All the patients have acquired a full donor chimerism before 14 d. There were only 2 cases of GVHD: one out of them was acute skin GVHD (grade I) at day 70 after transplantation and the other was chronic liver GVHD (grade I) in 1 years after transplantation, the GVHD more than degree II did not coccur in all patients, 9 patients with bacterial and fungal mixed infection and (or) virus infection were observed, and improved after anti-infection therapy. The median follow-up time were 54.5 months (ranged between 5-144 months), and 12 patients remain disease-free survival currently, only 2 patients died of fungal infectin.

CONCLUSIONTransplantation of nonmyeloablative allogeneic hematopoietic stem cell is safe and effective for the treatment of severe acquired aplastic, but the prevention, treatment and monitoring of infection need to be enhance.

Allografts ; Anemia, Aplastic ; Antilymphocyte Serum ; Cyclophosphamide ; Cyclosporine ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Mycophenolic Acid ; analogs & derivatives ; Neutrophils ; Siblings ; Tissue Donors ; Transplantation Conditioning ; Vidarabine ; analogs & derivatives

This study was purposed to evaluate the curative efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) after failure of the first allo-HSCT in aplastic anemia patients, the cause of implant failure after allo-HSCT and clinical data of 10 severe aplastic anemia (SAA) patients in the second allo-HSCT were retrospectively analyszed. The second HSCT conditioning programs include: cyclophosphamide (CTX) + fludarabine (FLU)+ anti-thymocyte globulin (ATG) combination chemotherapy for 3 cases; CTX + FLU + white busulfan (Bu) + ATG combination chemotherapy for 7 cases. The prevention regimen of graft-versus-host disease (GVHD) include cyclosporine (CsA), mycophenolate mofetil (MMF) and methotrexate (MTX). The median count of mononuclear cell infusion was 12.17 (5.99-18.12)×10(8)/kg. The CD34(+) cell count was 5.2 (3.8-10.9)×10(6)/kg. The results showed that 10 evaluable patients achieved hematopoietic reconstitution with absolute neutrophil >0.5×10(9)/L, platelets >20×10(9)/L at 15d (8-21d) and 17d (11-27d) after transplantation. The grade I aGVHD occurred in 2 case, grade II in 1 case, chronic GVHD in 3 cases. Transplant-related deaths occurred in 4 cases. The disease-free survival rate, transplant-related mortality, GVHD after transplantation were 60%, 40% and 50% respectively. It is concluded that the second allo-HSCT is an effective therapy for aplastic anemia after allo-HSCT implant failure.
Allografts ; Anemia, Aplastic ; therapy ; Antilymphocyte Serum ; Cyclosporine ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Methotrexate ; Mycophenolic Acid ; analogs & derivatives ; Retrospective Studies

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