BACKGROUND/AIMS: The relationship between patient survival and biopsy-proven acute rejection (BPAR) in liver transplant recipients with hepatitis C remains unclear. The aims of this study were to compare the characteristics of patients with and without BPAR and to identify risk factors for BPAR. METHODS: We retrospectively reviewed the records of 169 HCV-RNA-positive patients who underwent LT at three centers. RESULTS: BPAR occurred in 39 (23.1%) of the HCV-RNA-positive recipients after LT. The 1-, 3-, and 5-year survival rates were 92.1%, 90.3%, and 88.5%, respectively, in patients without BPAR, and 75.7%, 63.4%, and 58.9% in patients with BPAR (P<0.001). Multivariate analyses showed that BPAR was associated with the non-use of basiliximab and tacrolimus and the use of cyclosporin in LT recipients with HCV RNA-positive. CONCLUSION: The results of the present study suggest that the immunosuppression status of HCV-RNA-positive LT recipients should be carefully determined in order to prevent BPAR and to improve patient survival.
Antibodies, Monoclonal/therapeutic use ; Biopsy ; Cyclosporine/therapeutic use ; Drug Therapy, Combination ; Genotype ; Graft Rejection/mortality/*prevention & control ; Hepacivirus/genetics/isolation & purification ; Hepatitis C/drug therapy/*virology ; Humans ; Immunosuppressive Agents/*therapeutic use ; *Liver Transplantation/adverse effects ; Polymerase Chain Reaction ; RNA, Viral/blood ; Recombinant Fusion Proteins/therapeutic use ; Recurrence ; Retrospective Studies ; Survival Rate ; Tacrolimus/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

OBJECTIVETo compare the efficacy and safety of four different regimens for pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with or without combined human granulocyte colony-stimulating factor (G-CSF).

METHODThe authors retrospectively analyzed 105 children with SAA treated with IST with or without G-CSF in the hospital from February 2000 to September 2010. Regimen A, without G-CSF in the whole treatment, was used to treat Group A patients, n = 27; Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for Group D, n = 30, after the end of IST until hematologic recovery. The response rate, relapse rate, mortality, infection rate, infection-related death rate, risk of evolving into MDS/AML, survival rate, factors affecting the time of event-free survival and so on.

RESULT(1) The response (CR+PR) rates 4, 6, 12 and 24 months after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0% (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2-year survival rate was 90.5%; the follow-up of the patients for 13 years showed that the whole survival rate was 87.6%. (2) The differences of the response rates 4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05). (3) No significant differences were found in the mortalities 4, 6, 12 and 24 months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had relapsed disease in the period of time from 6 to 24 months after IST. All the four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not decrease the infection period before IST (day) (P = 0.273), and it had no impact on the infection rate after IST (P = 0.066). It did not reduce the rates of septicemia and infectious shock. And to the infection-related death rate no significant conclusion can be made. (6) Follow up of the patients for 13 years, showed that 2 had the evolution to MDS/AML in the 105 patients and the two children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did not show any differences in the survival rates of the four groups. (8) Cox regression analysis showed that the use of G-CSF had no benefit to the patients' long term survival. While the age of diagnosis and the infection history before IST were significantly related to the patients' long term survival.

CONCLUSIONThe use of G-CSF did not contribute to the early response and could not reduce the infection rate, infection-related death rate and the patients' long term survival. There were no significant differences in the survival rates of the four groups. Attention should be paid to the risk of the evolution to MDS/AML.

Adolescent ; Anemia, Aplastic ; drug therapy ; immunology ; mortality ; Antilymphocyte Serum ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Infant ; Male ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Treatment Outcome

PURPOSE: We undertook an observational study to investigate the effects of immunosuppressive treatment on proteinuria and renal function in 179 Korean idiopathic membranous nephropathy patients with nephrotic syndrome. MATERIALS AND METHODS: The primary outcome was regarded as the first appearance of remission and the secondary outcomes as a decline in estimated glomerular filtration rate (eGFR) >50% or initiation of dialysis, and all-cause mortality. Seventy-two (40.2%) and 50 (27.9%) patients were treated with corticosteroids alone (C) and corticosteroids plus cyclosporine (C+C), respectively, whereas 57 (31.8%) did not receive immunosuppressants (NTx). Cyclosporine was added if there was no reduction in proteinuria of >50% from baseline by corticosteroids alone within 3 months. RESULTS: There were no differences in baseline renal function and the amount of proteinuria among the three groups. Overall, complete remission (CR) was achieved in 88 (72.1%) patients by immunosuppressants. In a multivariate analysis adjusted for covariates associated with adverse renal outcome, the probability of reaching CR was significantly higher in the C [hazard ratio (HR), 4.09; p<0.001] and C+C groups (HR, 2.57; p=0.003) than in the NTx group. Kaplan-Meier analysis revealed that 5-year CR rates of C, C+C, and NTx groups were 88.5%, 86.2%, and 56.7% (p<0.001). Ten-year event-free rates for the secondary endpoints in these three groups were 91.7%, 79.9%, and 57.2% (p=0.01). CONCLUSION: Immunosuppressive treatment was effective in inducing remission and preserving renal function in these patients. Therefore, stepwise treatment using corticosteroids alone and in combination with cyclosporine is warranted in these patients.
Adrenal Cortex Hormones/adverse effects/*therapeutic use ; Adult ; Aged ; Cyclosporine/adverse effects/*therapeutic use ; Drug Administration Schedule ; Female ; Glomerular Filtration Rate/drug effects ; Glomerulonephritis, Membranous/*drug therapy/mortality ; Humans ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Kaplan-Meier Estimate ; Kidney/drug effects/physiology ; Male ; Middle Aged ; Proteinuria/chemically induced ; Treatment Outcome

BACKGROUNDThe management of patients with refractory immune thrombocytopenia (ITP) is challenging, as there is no standard treatment option. The aim of this study was to investigate the efficacy of recombinant human thrombopoietin (rhTPO) in combination with cyclosporin A (CsA) for the management of patients with corticosteroid-resistant primary ITP.

METHODSThirty-six patients with corticosteroid-resistant ITP were randomly divided into an observation group and control group. In the observation group, 19 patients received subcutaneous injection of rhTPO at a dose of 1 µg/kg (300 U/kg) once daily up to day 14. Simultaneously they also received oral CsA at a dose of 1.5-2.0 mg/kg twice daily for three months. In the control group, rhTPO alone was administered subcutaneously at 1 µg/kg once daily in the other 17 ITP patients for 14 consecutive days and then the treatment was withdrawn.

RESULTSThere was no significant difference in the response rate at the end of the first week after treatment initiation between the observation group and the control group (63.2% vs. 58.8%, P > 0.05), neither was there at the end of the second week (89.5% vs. 94.1%, P > 0.05). However, the relapse rate in the observation group was significantly lower than that in control group at the end of the first (17.7% vs. 50.0%, P < 0.05), second (29.4% vs. 68.8%, P < 0.05) and the third month (29.4% vs. 87.5%, P < 0.01). In addition, rhTPO plus CsA were well tolerated and adverse events recorded were mild.

CONCLUSIONSCombination therapy with rhTPO and CsA was effective in the management of patients with corticosteroidresistant ITP, with a relatively short time to response and low recurrence rate. It might be considered as a potential secondline treatment regimen for ITP.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Adult ; Aged ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Resistance ; Female ; Humans ; Male ; Middle Aged ; Recombinant Proteins ; therapeutic use ; Thrombocytopenia ; drug therapy ; Thrombopoietin ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult

PURPOSE: This study was performed in order to evaluate the incidence and characteristics of cytomegalovirus (CMV) infection in children with acute leukemia according to donor source and graft type. MATERIALS AND METHODS: We retrospectively identified children with acute leukemia who had received allogeneic hematopoietic cell transplantation at Samsung Medical Center in Korea from October 1998 to December 2009. RESULTS: In total, 134 recipients were identified. The patients were classified into the following three groups: unrelated cord blood (CB, n=36), related bone marrow or peripheral blood stem cells (RD, n=41), and unrelated bone marrow or peripheral blood stem cells (UD, n=57). The 365-day cumulative incidence of CMV antigenemia was not significantly different among the three groups (CB 67% vs. RD 49% vs. UD 65%, p=0.17). However, CB recipients had the highest median value of peak antigenemia (CB 160/2x10(5) leukocytes vs. RD 7/2x10(5) leukocytes vs. UD 19/2x10(5) leukocytes, p<0.01) and the longest duration of CMV antigenemia than the other stem cell source recipients (CB 87 days vs. RD 17 days vs. UD 28 days, p<0.01). In addition, the 730-day cumulative incidence of CMV disease was the highest in the CB recipients (CB 36% vs. RD 2% vs. UD 5%, p<0.01). Thirteen CB recipients developed CMV disease, in which five of them had more than one organ involvement. Two patients, who were CB recipients, died of CMV pneumonia. CONCLUSION: This study suggests that CB recipients had both longer and higher cumulative incidences of CMV infection. Therefore, a more aggressive and effective strategy of CMV management should be considered in CB recipients.
Acyclovir/therapeutic use ; Adolescent ; Antiviral Agents/therapeutic use ; Child ; Child, Preschool ; Cyclosporine/therapeutic use ; Cytomegalovirus Infections/*diagnosis/drug therapy/etiology ; Female ; Graft vs Host Disease/diagnosis/drug therapy/etiology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunosuppressive Agents/therapeutic use ; Infant ; Leukemia/therapy ; Male ; Retrospective Studies ; Young Adult

BACKGROUNDCyclosporin A (CsA) is a substrate of both cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), some of the single nucleotide polymorphisms (SNPs) in these genes are associated with interindividual variations in CsA pharmacokinetics. We studied the influence of these SNPs on the incidence of rejection and CsA nephrotoxicity, as well as pneumonia within one year after renal transplant and post-transplantation diabetes mellitus (PTDM), in order to find whether genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.

METHODSA total of 208 renal transplant recipients receiving CsA were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T), CYP3A4 1G, and CYP3A5 3 by direct sequencing method. Retrospective case control study was utilized to identify the association between CYP3A4 1G, CYP3A5 3, ABCB1 genetic polymorphisms and CsA-related outcomes.

RESULTSThe patients with a CYP3A4 1G/ 1G genotype were found to have a higher incidence of acute rejection compared with those with CYP3A4 1/1.

CONCLUSIONCYP3A4 1G/1G genotype predict increased risk of acute rejection, so genetic evaluation may partly help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.

ATP Binding Cassette Transporter, Sub-Family B ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Asian Continental Ancestry Group ; genetics ; Case-Control Studies ; Cyclosporine ; adverse effects ; therapeutic use ; Cytochrome P-450 CYP3A ; genetics ; Genotype ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Kidney Transplantation ; Polymorphism, Genetic ; genetics ; Retrospective Studies

OBJECTIVETo observe the effects of Chailing Decoction (CD) on transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), renal cell apoptosis and proliferation in rats with chronic cyclosporine A nephropathy (CCN), and to explore its possible mechanism for inhibiting renal fibrosis.

METHODSThe CCN rat model was prepared using oral administration of cyclosporine A (CsA, 30 mg x kg(-1) x d(-1)). Meanwhile, they were treated with CD (3 g x kg(-1) x d(-1)) by gastrogavage. The serum blood urea nitrogen (BUN), serum creatinine (SCr), and creatinine clearance rate (CCr) were measured by the end of the fourth week of the experiment. The kidneys were taken out on the next day. The degree of renal fibrosis was detected using Masson staining. The protein and gene expressions of TGF-beta1, and CTGF were observed using immunohistochemical assay and RT-PCR. The renal cell apoptosis rate and the proliferation index were detected by flow cytometry.

RESULTSCompared with the control group (BUN: 6.123 +/- 0.588 mmol/L; SCr: 75.654 +/- 8.196 micromol/L; CCr: 0.539 +/- 0.169 mL/min), the renal function of the model group (BUN: 11.600 +/- 1.437 mmol/L; SCr: 101.985 +/- 10.809 micromol/L; CCr: 0.272 +/- 0.060 mL/min) obviously declined (P < 0.01). The collagen deposition in the renal interstitial area significantly increased. The protein and mRNA expressions of TGF-beta1, and CTGF in the tubular epithelial cells and the mesenchymal cells were significantly enhanced (P < 0.01). The cell proliferation index and the apoptosis rate both increased, but the ratio of apoptosis to proliferation (0.317 +/- 0.059) decreased more than that in the control group (0.680 +/- 0.150, P < 0.01). After treatment by CD, the renal function (BUN: 7.340 +/- 0.857; SCr: 84.923 +/- 10.627; CCr: 0.405 +/- 0.081) was significantly enhanced (P < 0.05, P < 0.01), the collagen deposition decreased, the high protein and mRNA expressions of TGF-beta1 and CTGF were down-regulated (P < 0.01), the ratio of apoptosis to proliferation increased (0.650 +/- 0.092, P<0. 01).

CONCLUSIONCD could improve the renal function of CCN model rats, inhibit the expressions of TGF-beta1 and CTGF, and recover the balance between the renal cell apoptosis and proliferation by inducing cell apoptosis and inhibiting cell proliferation, thus delaying the renal fibrosis process.

Animals ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Connective Tissue Growth Factor ; metabolism ; Cyclosporine ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Fibrosis ; Kidney ; drug effects ; metabolism ; pathology ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

BACKGROUNDWith the increase of survival in liver transplantation recipients, more patients are at a high risk of developing osteonecrosis, especially in the femoral head, due to immunosuppressive treatment. The purpose of this study was to report the incidence, possible risk factors, and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China.

METHODSA retrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008. The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months. The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported.

RESULTSThe incidence of ONFH was 1.33% in patients after OLT. ONFH occurred at a mean of (14 ± 6) months (range, 10 - 21 months) after transplantation. Male patients more often presented with osteonecrosis as a complication than female patients. The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH. Patients were treated either pharmacologically or surgically. All patients showed a nice curative effect without major complications during the 18 - 63 months post-treatment follow up.

CONCLUSIONSThe symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.

Adult ; Aged ; Cyclosporine ; adverse effects ; therapeutic use ; Female ; Femur Head Necrosis ; epidemiology ; etiology ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Liver Transplantation ; adverse effects ; Male ; Methylprednisolone ; adverse effects ; therapeutic use ; Middle Aged ; Osteonecrosis ; epidemiology ; etiology ; Retrospective Studies ; Risk Factors ; Sirolimus ; adverse effects ; therapeutic use ; Tacrolimus ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVETo study the effectiveness and safety of immunosuppressive therapy (IST) in the treatment of childhood aplastic anemia (AA) and to study the main factors influencing the effectiveness.

METHODSThe clinical data of 55 children with severe aplastic anemia (SAA) and 51 children with chronic aplastic anemia (CAA) were retrospectively analyzed. All patients received IST from January 2007 to December 2010.

RESULTSIn children with CAA, the effective rate of antithymocyte globulin (ATG) plus cyclosporine A(CsA) combination therapy was significantly higher than that of CsA alone (80% vs 44%; P<0.05); in children with SAA, the effective rate of ATG plus CsA combination therapy was also significantly higher than that of CsA alone (75% vs 40%; P<0.05). No patients developed clonal disease such as myelodysplastic syndrome, paroxysmal nocturn hemoglobinuria or acute myelocytic leukemia. In patients treated with the ATG plus CsA combination therapy, the response rate was relatively high for children whose disease course was less than six months, bone marrow hematopoietic area was more than 40%, had no severe infections, and experienced granulocyte colony stimulating factor (G-CSF) reaction during the early treatment; however, it was not related to AA subtypes and age.

CONCLUSIONSATG plus CsA combination therapy is effective and safe in the treatment of childhood AA. The disease course, bone marrow hematopoietic area, severe infections and G-CSF reaction to early treatment are the main factors influencing the therapeutic effects.

Adolescent ; Anemia, Aplastic ; drug therapy ; Antilymphocyte Serum ; administration & dosage ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; Drug Therapy, Combination ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Male ; Retrospective Studies