Adjuvants, Immunologic ; adverse effects ; therapeutic use ; Azathioprine ; adverse effects ; therapeutic use ; Cyclosporine ; adverse effects ; therapeutic use ; Glucocorticoids ; adverse effects ; therapeutic use ; Humans ; Mycophenolic Acid ; adverse effects ; analogs & derivatives ; therapeutic use ; Tacrolimus ; adverse effects ; therapeutic use

Treatment of myelodysplastic syndrome (MDS) remains unsatisfactory. It is possible that immunosuppressive therapy might be effective for a certain subset of patients with MDS. In this review 105 patients with MDS who were treated with cyclosporin A (CsA) including 90 RA, 5 RARS, 10 RAEB, were analyzed. The dose of CsA was 2 - 12 mg/(kg x d) for at least three months. Hematological improvement was observed in 64 patients (61%), and complete remission was observed in 14 patients (13.3%). These results indicated that CsA immunosuppressive therapy may be useful for IPSS low, intermediate-1 and intermediate-2 MDS patients.
Cyclosporine ; adverse effects ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Myelodysplastic Syndromes ; drug therapy ; immunology

OBJECTIVETo evaluate the efficacy and safety of cyclosporine A(CsA) in the treatment of refractory nephrotic syndrome (RNS) in children.

METHODSThe Cochrane library, PubMed, EMBASE, CBMdisk, CNKI and VIP were searched from the time when the databases were established to December 31, 2008. Reports on RCTs on treating RNS in children with CsA were collected. Data were extracted and assessed independently by three reviewers. The methodological quality of included RCTs was assessed by the revised Jadad-scale (including randomization, allocation concealment, blinding method and withdrawal). Meta-analysis of homogenous RCTs was managed by using RevMan4.2.3.

RESULTNine RCTs involving 293 participants were included. Six RCTs were assessed as high-quality studies with scores from 4 to 7 and 3 RCTs were assessed as low-quality studies with scores from 1 to 3. Sub-category meta-analysis was based on different clinical types and interventions of RNS in children. Meta-analysis based on included RCTs showed the following results. (1) In children with steroid-dependent or frequent relapse nephrotic syndrome: the short-term efficacy of CsA plus prednisone was better than that of prednisone alone [OR 0.14, 95% CI (0.03, 0.71)]; the short-term efficacy of CsA, cyclophosphamide (CTX) and mycophenolate mofetil had no significant differences, but compared with chlorambucil, CsA had a worse short-term efficacy [OR 6.93, 95% CI (1.53, 31.38)] and a higher relapse rate [OR 0.06, 95% CI (0.01, 0.58)]; maintaining a blood level of CsA between 60 and 80 microg/L during remission period could reduce the long term relapse rate [OR 6.43, 95% CI (1.21, 34.19)]; the incidence of end-stage renal disease (ESRD) or mortality was zero in both groups. (2) In children with steroid-resistant nephrotic syndrome, the short-term efficacy of CsA was better than that of placebo or supportive treatment and CTX, OR and 95% CI were 0.15 (0.02, 0.96) and 0.41 (0.03, 5.00), respectively, but no significant differences were found in the relapse rate and the incidence of ESRD or mortality. (3) Side effects of CsA: the incidence of nephrotoxicity, hypertrichosis and gum hypertrophy was higher in the CsA group than in that of control group, OR and 95% CI were 0.19 (0.05, 0.79), 0.06 (0.02, 0.19), 0.05 (0.02, 0.18), respectively, but no significant differences were found in the incidence of hypertension and liver toxicity.

CONCLUSIONSAvailable evidence showed that CsA could improve short term efficacy in RNS in children, but could not improve long term and endpoint efficacy, therefore CsA could be one of the ideal second-line drugs for RNS in children. There was a trend that the effect of CsA on steroid-dependent or frequent relapse nephrotic syndrome was superior to that on steroid-resistant nephrotic syndrome.

Child ; Cyclosporine ; adverse effects ; therapeutic use ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Nephrotic Syndrome ; drug therapy ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome

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 sum up the clinical characteristics of patients with central pontine myelinolysis (CPM) after orthotopic liver transplantation (OLT) and to document the possible causes on CPM.

METHODS142 patients' data with OLT between January 1999 to May 2003 were analyzed retrospectively. The following risk factors during preoperation were analyzed between patients with and without CPM: primary liver disease, preoperative serum sodium level, magnesium level and plasma osmolality, fluctuation degree of serum sodium concentration, and immunosuppressive drugs level etc.

RESULTSA total of 13 (9.2%) neurologic symptoms appeared in 142 patients post operation, including 5 cases (3.5%) with CPM and 8 cases (5.6%) with cerebral hemorrhage or infarct. 2 patients who developed CPM after OLT had hyponatremia history before operation (serum sodium <130 mmol/L), and the mean serum sodium level was (130.6 +/- 5.54) mmol/L. The serum sodium level was significantly lower in CPM than that of patients without neurologic complication or with cerebral hemorrhage/infarct (P <0.05). The rises of serum sodium perioperative 48 h after OLT in patients with CPM was significantly greater than that in patients with cerebral hemorrhage/infarct or no neurologic complication (19.5 +/- 6.54) mmol/L, (10.1 +/- 6.43) mmol/L, (4.5 +/- 4.34) mmol/L, respectively, (P < 0.05). Plasma osmolality increased greatly postoperatively in patients with CPM. Hypomagnesemia was noted in all patients perioperatively, but there was not significant difference among groups. The duration of operation in CPM was longer than in others (492 +/- 190.05) min (P <0.05). Cyclosporin A (CsA) levels were normal in all patients, but there was significant difference between patients with and without neurologic complication (P <0.05).

CONCLUSIONSCPM may be more prevalent following liver transplantation. Although the diagnosis of CPM after OLT can be made by complete neurologic evaluation including magnetic resonance imaging (MRI) of the head, the mortality is still very high. The occurrence of CPM may be associated with hyponatremia, rapid rise of serum sodium concentration, postoperative increase of plasma osmolality, the duration of operation and high CsA levels.

Adult ; Aged ; Cyclosporine ; adverse effects ; therapeutic use ; Female ; Humans ; Hyponatremia ; complications ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Monitoring, Intraoperative ; Myelinolysis, Central Pontine ; etiology ; Retrospective Studies ; Sodium ; blood ; Transplantation, Homologous

Anemia, Aplastic ; drug therapy ; epidemiology ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Cyclosporine ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Sarcoma, Kaposi ; epidemiology ; Skin Neoplasms ; epidemiology ; Vincristine ; therapeutic use

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

OBJECTIVE: To observe the effect of cyclosporine and simulect mono or combination therapy on cardiac allo-transplantation in rats. METHODS: Recipients with allografts were treated with different doses of cyclosporine and/or simulect after cardiac allo-transplantation. Graft survival time was observed; the histopathological examination of graft tissues was performed; and levels of serum IL-2 and IL-4 were determined. RESULTS: Mono or combination therapy with cyclosporine and/or simulect increased the survival of cardiac allografts. With the prolongation of survival time of the grafts, the rejection of grafts was moderated. The serum IL-2 level increased in acute rejected grafts; the serum IL-4 level increased evidently in long survival grafts. CONCLUSION Cyclosporine and simulect have an effect in the prolongation of cardiac allograft survival in rats, and the combination therapy shows an evident synergistic effect.
Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Basiliximab ; Combined Modality Therapy ; Cyclosporine ; pharmacology ; therapeutic use ; Female ; Graft Rejection ; immunology ; Heart Transplantation ; adverse effects ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Recombinant Fusion Proteins ; pharmacology ; therapeutic use

BACKGROUNDCyclosporine is effective in treating nephrotic syndrome (NS) with idiopathic membranous nephropathy (IMN) in adults. But high relapse rate remains a major concern. The way to manipulate cyclosporine is inconclusive. The aim of this study was to introduce the way how to titrate the cyclosporine to maintain complete remission without relapse.

METHODSPatients with biopsy-proven IMN with NS treated with cyclosporine for at least 1 month from 1996 to 2011 at Peking Union Medical College Hospital were reviewed.

RESULTSMean age of the 51 eligible patients was 52 years, with 39 men. Mean proteinuria was (7.47 ± 3.14) g/d, serum albumin (24.50 ± 6.29) g/L, and serum creatinine (82.62 ± 21.18) mmol/L. Cyclosporine was commenced at a mean dose of (3.46 ± 0.63) mg×kg(-1)×d(-1). Oral prednisone (0.40 ± 0.29) mg×kg(-1)×d(-1) was given concomitantly in 38 patients. Cyclosporine was administered for a median of 16 months (range 1 - 93 months) and stopped in non-responders by month six. By month 3 (n = 47), the number in complete remission (CR) and partial remission (PR) was 3 and 24, which shifted to 12 and 17 by month 6 (n = 41). Male gender, heavy proteinuria, low serum albumin level, and high serum creatinine level were significant determinants in poor response by month six (P < 0.05 in all variables compared with responders). There was a significant reversible serum creatinine increase within 25% during month 3 to 12 (P < 0.05 in all variables compared with baseline value). Eleven patients maintained cyclosporine for more than 24 months with a cyclosporine dose of (1.04 ± 1.06) mg×kg(-1)×d(-1). Nine patients were in CR. Renal function, systolic and diastolic blood pressure remained stable. Renal impairment (> 30% rise of serum creatinine), secondary infection, hypertension, gingival hyperplasia and liver impairment occurred in 6, 4, 10, 4, and 1 patients, respectively.

CONCLUSIONSThe observation time for cyclosporine to effectively induce CR of NS in IMN adults should be at least six months. Long-term and low-dose of cyclosporine therapy is safe and effective to maintain CR in those responders.

Adult ; Aged ; Cyclosporine ; adverse effects ; therapeutic use ; Female ; Glomerulonephritis, Membranous ; drug therapy ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Nephrotic Syndrome ; drug therapy ; Retrospective Studies ; Treatment Outcome

Aged ; Animals ; Cyclosporine ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Graft Rejection ; drug therapy ; prevention & control ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Diseases ; chemically induced ; prevention & control ; Kidney Transplantation ; Phytotherapy