Steroid-free Immunosuppressive Therapy Research Articles

Update in immunosuppressive therapy of myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Immunosuppressive treatments are part of the therapeutic armamentarium in MG. Long-term systemic steroid administration carry considerable risks and adverse events. Consequently, steroid-free immunosuppressive therapy is necessary to reduce the dose or discontinue steroids. First immunosuppressive drug trials in MG, were performed in the mid-60s, using standard and nonspecific immunosuppression. Since then, only few randomized controlled clinical trials were developed in MG, showing inconclusive results; and drug efficacy was assessed in terms of its steroid-sparing capacity and the ability to reduce myasthenic signs and symptoms. Treatment strategy in MG is quite challenging, mainly due to the disease heterogeneity in terms of clinical presentation, immunopathogenesis and drug response. To solve this dilemma, emerging treatment are based on biological drugs and use new targets of the immune pathway.

Clinical efficacy of steroid-free immunosuppressive regimen after liver transplantation for patients with primary liver cancer

Objective To study the clinical efficacy of steroid-free immunosuppressive therapy after liver transplantation in patients with primary liver cancer. Methods A retrospective study was conducted on the clinical data from January 2010 to October 2016 on 112 patients with primary liver cancer. There were 59 patients who had no steroid immunosuppressive regimen after operation, and 53 patients were in the steroid group. The immunosuppressive regimen used in the postoperative steroid-free group was tacrolimus + mycophenolate mofetil + basiliximab. For the steroid group it was: tacrolimus + mycophenolate moxibustion. The steroid was reduced daily in the first day after transplantation and was discontinued 3 months after transplantation. Follow-up observation of the differences between the two groups of patients on rejection, infection, tumor recurrence, hepatitis B virus recurrence and survival were compared. Results The infection rate was 18.6% in the postoperative steroid-free group, which was significantly lower than that in the steroid group (37.7%, P 0.05). Conclusions The use of the steroid-free immunosuppressive regimen in patients with hepatocellular carcinoma after transplantation was safe and did not increase the incidence of acute rejection. The regimen reduced the incidences of postoperative infection and hepatitis B virus recurrence, especially in patients who exceeded the Milan Criteria. It reduced the risk of tumor recurrence and improved patient survival. Key words: Primary liver cancer; Liver transplantation; Basiliximab; Glucocorticoid

Kidney transplantation in HIV-positive patients treated with a steroid-free immunosuppressive regimen.

One of the main concerns associated with renal transplantation in HIV-infected patients is the high risk of acute rejection, which makes physicians reluctant to use steroid-free immunosuppressive therapy in this subset of patients. However, steroid therapy increases cardiovascular morbidity and mortality. The aim of this study was to define the efficacy of a steroid-sparing regimen in HIV-infected renal transplant recipients. Thirteen HIV-infected patients were consecutively transplanted. The induction therapy consisted of basiliximab and methylprednisolone for 5days followed by a calcineurin inhibitor plus mycophenolate acid. The mean follow-up was 50±22months. Eight patients (61.5%) experienced acute rejection, and 75% of the first episodes occurred within 2months after transplantation. The probability of first acute rejection was 58% after 1year and 69% after 4years. Seven of eight patients recovered or maintained their kidney function after antirejection therapy and steroid resumption. At the last follow-up, seven of 13 patients (54%) had resumed steroid therapy. The 4-year patient and graft survivals were 100% and 88.9%, respectively. The benefits of this steroid-free regimen in HIV-infected renal recipients must be reconsidered because of the high rate of acute rejection. New immunosuppressive steroid-free strategies should be identi-fied in this set of patients.

P-75 Heart Transplantation in Patients with Diabetes Mellitus

Heart transplantation is the most effective therapy for endstage heart failure of diabetes mellitus. There are very few cases who underwent heart transplantation in Japan because DM remains a relative contraindication for heart transplantation. We enrolled 45 patients in Japan Organ Transpant Network, but there was only one patient with DM. Nevertheless, the increasing prevalence of both DM and congestive heart failure makes it necessary to perform heart transplantation in near future. We performed a retrospective analysis on long-term survival in 453 patients with DM who underwent heart transplantation at Heart and Diabetes Center NRW Bochum University in Germany. Survival rate and causes of death were compared with data of a group heart transplant recipients without DM. Mean follow-up time of all heart transplant recipients was 68.2 months (range: 0 204 months). Overall mortality during follow-up was 42.9%. Long-term survival did not differ significantly between study groups (P= 0.32). In addition, there was no significant differences in survival rates between groups with advanced DM and without DM. Steroid-free immunosuppressive therapy was associated with a higher percentage of long-term survivors compared with no steroid-free immunosuppression. Our data demonstrate that long-term survival is acceptable in heart transplant recipients with preoperatively diagnosed DM.

Heart transplantation in insulin?treated diabetic patients with diabetes?related complications

Heart transplantation is the most effective therapy for end-stage heart failure in patients with diabetes mellitus (DM). However, diabetes-related complications (DRCs) are a relative contraindication for heart transplantation. Nevertheless, the increasing prevalence of both DM and congestive heart failure makes it necessary to perform heart transplantation even in those patients with advanced DM. We performed a retrospective analysis on long-term survival in 47 patients with insulin-treated DM and DRCs (group 1). Survival rate and causes of death were compared with data of a group of heart transplant recipients without DM (n = 1061, group 2). Mean follow-up time of all heart transplant recipients was 68.2 months (range: 0-204 months). Overall mortality during follow-up was 42.9%. Long-term survival did not differ significantly between study groups, but tended to be shorter in group 1 than in group 2 (P = 0.07). In group 1, steroid-free immunosuppressive therapy was associated with a higher percentage of long-term survivors compared with no steroid-free immunosuppression. Our data demonstrate that long-term survival is acceptable in heart transplant recipients with preoperatively diagnosed DM and DRCs. Consequently, advanced DM should no longer be a relative contraindication for heart transplantation.

Hypereosinophilia in an Islet Transplant Recipient

A 38-year-old male subject, with a 36-year history of type 1 diabetes mellitus, received two allogeneic islet infusions with a steroid-free immunosuppressive therapy (1) resulting in insulin independence for 15 months and partial graft function for the following 7 months. Ten months posttransplant, progressive elevation of eosinophil count occurred reaching a peak value of 6,350 cells/mm3. Clinically he complained of scalp and upper torso itching exacerbated by exercise and hot water (treated with antihistamines) associated with intermittent rash. A skin biopsy demonstrated eosinophilic infiltrate, IgE antibody tests (for allergies) were negative, and thyroid function was normal. There was no weigh loss, upper and lower respiratory tract symtomatology, abdominal pain, or dyspepsia. After commencing immunosuppression, the patient suffered intermittent diarrhea, severe at times. Stool samples were consistently negative for infectious organism except on one occasion when giardia and iodamoeba were detected, successfully treated with metronidazole. A GI biopsy was normal. The diarrhea was presumed secondary to sirolimus. Causes for reactive eosinophilia were sought; infections, parasitic (angiostrongyliasis, capillariasis, fascioliasis, trichinosis), viral (HIV, HTLV, CMV, Parvovirus), and fungal (aspergillosis, candidiasis) were excluded. Malignancy was sought, chest and abdomen CT showed no masses or splenomegaly. Connective tissue diseases were excluded. An echocardiogram was normal. Drug reaction was evaluated by transiently removing all medications other than immunosuppression, no effect on eosinophilia was noted. A bone marrow biopsy demonstrated normocellularity with mild eosinophilia, without immunophenotypic abnormalities or clonality in any cell population. Interleukin-5 levels (an eosinophil growth factor) and serum tryptase (sign of mast cell degranulation) were slightly elevated. In our patient the most likely diagnosis was idiopathic hypereosinophilic syndrome (HES) associated with mast cell activation. Immunosuppressive drugs were discontinued, without alteration in eosinophil levels excluding sensitivity to the medications. The graft was at this point rejected (Fig. 1). Progression of eosinophilia argued against hypereosinophilia secondary to graft rejection.FIGURE 1. White blood cell and eosinophil counts during the clinical follow-up of the patient after transplantation. Important events in the clinical history of the patient is highlighted in the with arrows and relative legends.Eosinophilias can be classified into reactive forms, e.g., secondary to atopy or parasitic infestation, malignancies including lymphomas, connective tissue diseases, GVHD, bone marrow transplantation (2), and graft rejection, and nonreactive forms, e.g., chronic eosinophilic leukemia (CEL), systemic mastocytosis (SM) with eosinophilia, T-cell clonal and non-clonal disease-associated eosinophilia, and HES (3,4). HES is a collective term for those that cannot otherwise be classified, and, while the risk of malignancy is unclear, there is a risk of end-organ damage from the serum eosinophil granule proteins. The recent discovery of cytogenetic abnormality (fusion of the FIP1L1 gene with the platelet-derived growth factor receptor alpha gene) and therapeutic sensitivity to the tyrosine kinase inhibitor Imatinib in some forms of HES is leading to novel therapeutic approaches (5). Treatment with Imatinib mesylate (Gleevec 100 mg increased to 200 mg/day) was initiated and led to rapid remission of clinical signs and near normalization of laboratory abnormalities. Treatment will be continued indefinitely. Chronic (>6 months) hypereosinophilia, skin involvement, and therapeutic response to Imatinib are compatible with a diagnosis of primary HES. Since it developed during immunosuppressive therapy with tacrolimus, sirolimus, and daclizumab, a causal relationship cannot be excluded. Raffaella Poggioli Tatiana Froud David A. Baidal Jacqueline V. Ferreira Muhammad M. Hafiz Camillo Ricordi Diabetes Research Institute and Department of Surgery, University of Miami School of Medicine, Miami, Florida Gerald J. Gleich Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, Utah Rodolfo Alejandro Diabetes Research Institute and Department of Medicine, University of Miami School of Medicine, Miami, Florida

Weight changes after renal transplantation: a comparison between patients on 5-mg maintenance steroid therapy and those on steroid-free immunosuppressive therapy

Abstract After renal transplantation (RTx), an increase in body weight (BW) is usually observed, in which corticosteroids may play an important role. However, the effects of a low maintenance dosage of corticosteroids on BW have not been studied longitudinally in RTx patients. The aim of this study was to compare changes in BW after RTx in patients on steroid- or steroid-free immunosuppressive therapy and to assess the relationship between posttransplant weight changes and other potentially important factors. The charts of 123 RTx patients (72 male, 51 female) were retrospectively examined for BW changes in the first 5 years after RTx. Sixty-six patients were on 5-mg maintenance steroid dose and 57 patients underwent steroid-free immunosuppression. Mean post-transplant BW gain was 3.0±5.3 kg after 6 months, 3.9±6.2 kg after 1 year and 6.2±8.6 kg after 5 years. Weight gain in the first year after RTx was related neither to maintenance- nor to cumulative steroid dose, age, gender, occurrence of rejection, or renal function. Weight gain was, however, significantly related to pretransplant BMI and dialysis modality. After the first year, weight gain was significantly and positively related only to the cumulative steroid dose. The course of weight gain in the first year after RTx turned out to be independent from factors such as maintenance- or cumulative steroid dose, age, gender, occurrence of rejection, and renal function; weight gain was, however, dependent on pre-transplant BMI and dialysis modality. After the first year, the weight course was significantly affected by cumulative steroid dose.