Months Of Cyclosporine Research Articles

Efficacy of Oral Cyclophosphamide for Treatment of Refractory T-cell Large Granular Lymphocytic Leukemia Accompanied with Pure Erythrocyte Aplastic Anemia

To explore the clinical effects of oral small dose of cyclophosphamide (CTX) in the treatment of T-cell large granular lymphocytic leukemia (T-LGLL) accompanied with pure red cell aplasia (PRCA). The clinical features, characteristics of laboratory examinations and the process of oral small dose of CTX treatment after the ineffective treatment of cyclosporine A combining with prednisone in 1 case of T-LGLL with PRCA were reported and discussed with related references. The elderly female patient had indolent process, mainly presenting with anemia and significant low hyperplasia of bone marrow erythrocyte cells. Peripheral blood smear showed mainly with characteristic large granular lymphocytic morphology. The results of immunophenotypic analyses and genetic reassortment were compatible with T-LGLL. No effects were shown after 5 months of cyclosporine A combining with prednisone treatment and the patient still needed recurrent blood transfusion. CTX was prescribed as a second-line medication and the dose was 100 mg/d. Hemoglobin could returned to normal level and the efficacy remained for 1 year even after the medication was stopped. T-LGLL accompanied with PRCA is a rare disease and oral small dose CTX can be an effective therapeutic regimen.

Cyclosporine for moderate-to-severe alopecia areata: A double-blind, randomized, placebo-controlled clinical trial of efficacy and safety

Despite widespread use of steroid-sparing agents, particularly cyclosporine, for treatment of alopecia areata (AA), there are no clinical trials investigating the efficacy of these agents. To evaluate the efficacy of cyclosporine compared with placebo at 3months in patients aged 18 to 65years with moderate-to-severe AA. A double-blind, randomized, placebo-controlled trial was conducted. Adults aged 18 to 65years of age with moderate-to-severe AA were randomized in a 1:1 ratio to receive 3months of cyclosporine (4mg/kg/d) or matching placebo. Blinded assessments included physical examination, blood biochemistry, photography, quality of life measurements, and efficacy evaluation using Severity of Alopecia Tool score and eyelash and eyebrow assessment scales. The results obtained for 32 participants (16 who received cyclosporine and 16 who received placebo) were analyzed. Compared with the placebo group, the cyclosporine group had a greater proportion of participants achieving at least a 50% reduction in Severity of Alopecia Tool score (31.3% vs 6.3% [P=.07]) and greater proportion of participants achieving a 1-grade improvement in eyelash (18.8% vs 0% [P=.07]) and eyebrow (31.3% vs 0% [P=.02]) scale score. Small sample size and single-institution trial may limit interpretation and generalizability of these results. Response approached but did not reach a statistically significant difference between cyclosporine and placebo.

Efficacy and Safety of a Tofacitinib-based Immunosuppressive Regimen After Kidney Transplantation: Results From a Long-term Extension Trial.

BackgroundTofacitinib is an oral Janus kinase inhibitor. This open-label, long-term extension (LTE) study (NCT00658359) evaluated long-term tofacitinib treatment in stable kidney transplant recipients (n = 178) posttransplant.MethodsPatients who completed 12 months of cyclosporine (CsA) or tofacitinib treatment in the phase IIb parent study (NCT00483756) were enrolled into this LTE study, evaluating long-term tofacitinib treatment over months 12 to 72 posttransplant. Patients were analyzed by tofacitinib less-intensive (LI) or more-intensive (MI) regimens received in the parent study. For both groups, tofacitinib dose was reduced from 10 to 5 mg twice daily by 6 months into the LTE. Patients were followed up through month 72 posttransplant, with a focus on month 36 results.ResultsTofacitinib demonstrated similar 36-month patient and graft survival rates to CsA. Biopsy-proven acute rejection rates at month 36 were 11.2% for CsA, versus 10.0% and 7.4% (both P > 0.05) for tofacitinib LI and MI, respectively. Least squares mean estimated glomerular filtration rates were 9 to 15 mL/min per 1.73 m2 higher for tofacitinib versus CsA at month 36. The proportions of patients with grade 2/3 interstitial fibrosis and tubular atrophy in month 36 protocol biopsies were 20.0% for LI and 18.2% for MI (both P > 0.05) versus 33.3% for CsA. Kaplan-Meier cumulative serious infection rates at month 36 were numerically higher for tofacitinib LI (43.9%; P = 0.45) and significantly higher for MI (55.9%; P < 0.05) versus CsA (37.1%).ConclusionsLong-term tofacitinib continued to be effective in preventing renal allograft acute rejection and preserving renal function. However, long-term tofacitinib and mycophenolic acid product combination was associated with persistent serious infection risk.

Clinical trial of focal segmental glomerulosclerosis in children and young adults

This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled, 138 were randomized to cyclosporine (72) or to mycophenolate/dexamethasone (66). The primary analysis compared the levels of an ordinal variable measuring remission during the first year. The odds ratio (0.59) for achieving at least a partial remission with mycophenolate/dexamethasone compared to cyclosporine was not significant. Partial or complete remission was achieved in 22 mycophenolate/dexamethasone- and 33 cyclosporine-treated patients at 12 months. The main secondary outcome, preservation of remission for 26 weeks following cessation of treatment, was not significantly different between these two therapies. During the entire 78 weeks of study, 8 patients treated with cyclosporine and 7 with mycophenolate/dexamethasone died or developed kidney failure. Thus, our study did not find a difference in rates of proteinuria remission following 12 months of cyclosporine compared to mycophenolate/dexamethasone in patients with steroid-resistant FSGS. However, the small sample size might have prevented detection of a moderate treatment effect.

Evaluation of the Effect of Topical Cyclosporine a with Impression Cytology in Dry Eye Patients

This study evaluated the efficacy of topical cyclosporine A 0.05% treatment with impression cytology in dry eye patients. Forty eyes of 40 patients with dry eye were included. Schirmer tear break-up time, and Ocular Surface Disease Index (OSDI) scores and goblet cell densities were noted before and after 6 months of topical cyclosporine A treatment. Patients were graded clinically and biomicroscopically as follows: grade 1, 12 patients; grade 2, 18; and grade 3, 10 patients. Mean age was 57.1 +/- 11.8 (23.0-80.0) years. A total of 36 (90%) of the patients were female and 4 (10%) were male. Mean Schirmer test value was 3.2 +/- 1.6 (0.0-8.0) mm in the beginning and was 8.4 +/- 4.3 (1.0-19.0) mm after 6 months of cyclosporine A topical treatment (p = 0.00). At the first visit, mean tear break-up time was 4.4 +/- 1.8 (2.0-8.0) seconds. It increased to 11.8 +/- 4.8 (2.0-20.0) seconds at the end of the sixth month (p = 0.00). Mean clinical grading was 1.9 +/- 0.8 (1.0-3.0) and this value regressed to 0.8 +/- 1.2 (0.0-3.0) after the treatment (p = 0.00). Mean OSDI score was 30.0 +/- 11.7 (9.0-50.0) before the treatment and 21.3 +/- 11.0 (4.0-47.0) after the treatment (p = 0.00). Mean goblet cell density of all cases was 12.3 +/- 8.7 before the treatment (2.0-28.0). It increased to 33.0 +/- 25.4 (6-70) after the treatment (p = 0.04). Topical cyclosporine A treatment is effective in grade 1 and grade 2 dry eye patients but results are poor in grade 3 patients.

Cyclosporine Alone for the Treatment of Early Recurrences of TTP.

Patients: The 3 patients detailed in this report presented to Ohio State University Hospitals and were enrolled on our prospective study of plasma exchange as initial therapy of TTP. Given the close outpatient follow-up during the first month after the tapering of plasma exchange, 2 patients were found to have an early recurrence of their TTP. The third patient had a recurrence 8 weeks after completing 6 months of CSA after being treated with concurrent CSA and PE for a previous acute episode of TTP. She completed the planned 6 months of cyclosporine therapy but relapsed 8 weeks after discontinuing the drug. Her recurrence was characterized by numbness and tingling in her right hand in addition to laboratory findings consistent with TTP. Complete demographic and clinical details of these 3 patients are shown in Table 1.Methods: All 3 patients received oral cyclosporine (2–3 mg/kg) daily for six months in a divided dose. None of the patients underwent plasma exchange, infusion, or transfusion of blood products of any kind. Patients were seen daily to monitor for any clinical or laboratory findings that would warrant the re-initiation of plasma exchange therapy. Remissions were defined as a normal platelet count, normalization of LDH for at least 2 consecutive days, and improvement or stabilization of any renal and neurologic abnormalities. Serial measurements of ADAMTS13 activity and inhibitors were performed at regular intervals throughout therapy and follow-up.Results: All three patients showed clear laboratory and clinical signs of improvement within the first 7 days of therapy and met criteria for clinical remission 14, 24, and 34 days respectively from the time they began treatment with cyclosporine. The third patient that presented with numbness and tingling in her right hand also had complete resolution of her neurologic symptoms within one week of restarting cyclosporine. Pretreatment ADAMTS13 activity was determined to be 33%, 25%, and 10% in all 3 patients respectively with all 3 patients having documented inhibitors of ADAMTS13.Conclusions: Treatment with cyclosporine alone resulted in the suppression of ADAMTS13 inhibitors and normalization of ADAMTS13 activity. [Display omitted] All three patients have completed the planned 6 months of cyclosporine and have maintained their remission 4, 3, and 1 month respectively after discontinuing cyclosporine.Patient Demographic and Clinical DataLaboratory Studies at the TIme CSA InitiatedAgeSexRaceTherapy Preceeding RecurrenceTime to Relapse After Most Recent TherapyPlatelet Count (150-450 K/uL)LDH (100-190 U/L)Patient 148FCPE + S17d113212Patient 239FCPE6d135400Patient 356FAACSA56d51418PE=Plasma Exchange, CSA=Cyclosporine, S=Corticosteroids

Impact of Immunosuppressive Treatment on Liver Fibrosis in Autoimmune Hepatitis

The impact of treatment on progression of fibrosis in autoimmune hepatitis (AIH) is unknown. We assessed the changes in liver fibrosis before and after treatment among these patients. Nineteen AIH patients who had paired liver biopsies were studied. Of these, seven had been treated with 6 months of cyclosporine A and the rest with 6 months of prednisolone for induction of remission. Thereafter all had been maintained on azathioprine. Biopsy specimens before and after treatment were reviewed by one pathologist and scored by the Ishak method. Mean fibrosis stages before and after treatment were compared. Also, factors predicting significant fibrosis (stage > or =3) and cirrhosis (stage > or =5) at presentation were assessed. Mean interval between biopsies was 3.38 years. Mean fibrosis stage decreased from 4.53 to 2.16 following treatment (P < 0.001). Mean decrement in inflammatory grade was 8 scores (range, 4-10) in patients in whom fibrosis improved, and 2 scores (range, 0-4) in patients in whom fibrosis did not decrease after treatment (P < 0.001). ALT-to-platelet ratio was the best predictor of significant fibrosis and also cirrhosis. Fibrosis commonly improves after immunosuppressive treatment in AIH. ALT-to-platelet ratio can predict accurately the presence of significant fibrosis and cirrhosis in AIH.

Rituximab treatment in refractory idiopathic thrombocytopenic purpura in children

Sir: Children with refractory idiopathic thrombocytopenic purpura (ITP) present a therapeutic challenge. Due to the lack of controlled clinical trials, management of these patients is based on patient- and disease-related factors including platelet count, risk of bleeding and adverse effects of treatment. Pusiol et al. [1] reported two children successfully treated with rituximab. Based on reported findings, in 14-year-old girl presenting with repeated episodes of severe menorrhagia, most haematologists would consider laparoscopic splenectomy. In life-threatening intracranial haemorrhage of the same patient, assuming that conventional critical care measurements are already underway, appropriate management should include intravenous immunoglobulins (IVIg, 1 g/kg/day for 2 days), high-dose parenteral glucocorticoid (methylprednisolone 1 g/day for 3 days) and platelet transfusions [3]. In this report IVIg, documented previously to have prompt response, was not administered. Recombinant Factor VIIa, reported to be a very attractive alternative to control severe thrombocytopenic bleeding, was not considered. In addition, aminocaproic acid could be effective in such an emergency treatment. I report on 16-year-old girl suffering from chronic ITP refractory to corticosteroids, IVIg, and splenectomy. After two episodes of life-threatening bleeding (intracranial, and intraperitoneal from a ruptured corpus luteum), combined therapy consisting of rituximab and cyclosporine A was administered. The patient had no response to rituximab, despite a rapid and dramatic decrease in CD20+ cells. She is resistant to 6 months of cyclosporine A therapy. At present, chemotherapeutic drugs are being considered in this particularly serious situation.

Renal changes associated with cyclosporine in recent type I diabetes mellitus.

The effects of cyclosporine A treatment on arterial pressure and renal function were assessed in 11 young patients with type I diabetes of short duration. Cyclosporine was started at 7.5 mg/kg/day, progressively decreased to 6.3 mg/kg/day at 6 months, and then continued at a lower dose (4.1 mg/kg/day) for an additional 3 months in patients in whom remission of insulin dependency was obtained (n = 6). After 3 months of cyclosporine, a slight but significant increase in arterial pressure (+5.2 +/- 1.5 mm Hg), a rise in renal vascular resistance (approximately 20%), a decrease in glomerular filtration rate (approximately 25%), and a fall in filtration fraction were observed. Such changes were sustained after 6 and eventually 9 months of therapy. The decrease in glomerular filtration rate observed during cyclosporine treatment contrasted with the lack of change in simultaneously estimated creatinine clearance; in fact, the creatinine clearance/glomerular filtration ratio increased from 1.07 +/- 0.05% to 1.33 +/- 0.09% within 3 months of cyclosporine therapy, thus suggesting an enhanced tubular secretion of creatinine. Plasma renin activity and urinary excretion of kallikrein decreased significantly (approximately 50%), whereas plasma aldosterone concentration remained unaltered and plasma concentration of potassium increased during cyclosporine therapy. These changes were observed in the presence of a constant urinary excretion of sodium and potassium and a constant body weight. All parameters returned to pretreatment values within 3 months after cessation of cyclosporine. These results indicate that cyclosporine given for 6-9 months at a moderate dose causes a deleterious but reversible effect on arterial pressure and renal function in young diabetic patients.

Effect of cyclosporine on blood pressure and renal function of recent type 1 diabetes mellitus.

The effect of cyclosporine A therapy on blood pressure and renal function was assessed in 11 young adults with type 1 diabetes of recent onset (7 +/- 1 weeks). Metabolic control and renal haemodynamics and function were evaluated at 3-month intervals before, during and after cessation of a 6-month course of cyclosporine A (initial dose 7.5 mg/kg per day, then adapted on whole-blood trough levels of 401 +/- 45 and 308 +/- 49 ng/ml at 3 and 6 months, respectively). A significant increase in blood pressure (from 117 +/- 2/65 +/- 2 to 122 +/- 2/72 +/- 3 mmHg; P less than 0.01) and a decrease in 99Tc-DTPA (diethylene triaminepentaacetic acid) clearance (124 +/- 6 to 98 +/- 5 ml/min per m2; P less than 0.01) were observed after 3 months of cyclosporine A; both alterations remained unchanged after 6 months. No variation in body weight, 24-h urinary sodium or urinary albumin excretion was observed. Blood pressure and the glomerular filtration rate returned to basal levels 3 months after the cyclosporine A therapy ceased. These results suggest that even moderate doses of cyclosporine A have a reversible deleterious effect on blood pressure and renal function in young diabetic patients.