Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.

http://www.jsht.jp/uploads/ISHLT_GL_TaskForce2_110810.pdf

The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

/pdf/anti-inflammatory-and-immunosuppressive-drugs-and-3enlo6fxtc.pdf

Anti-inflammatory and immunosuppressive drugs and reproduction.

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/lt.23566

Long‐term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

Background. Cyclosporine (CsA) therapy must often be continued during pregnancy to maintain maternal health in such conditions as organ transplantation and autoimmune disease. This meta-analysis was performed to determine whether CsA exposure during pregnancy is associated with an increased risk of congenital malformations, preterm delivery, or low birthweight. Methods. Various health science databases were searched to identify relevant articles. Articles selected for inclusion in the study were required to be free of any apparent selection bias and report outcomes in at least 10 newborns exposed to CsA in utero, specifically commenting on the presence or absence of congenital malformations. Article selection and data extraction were performed by two independent reviewers, with adjudication in cases of disagreement. To assess risks of CsA exposure, a summary odds ratio was calculated. Prevalence of malformations was calculated as a rate for all cyclosporine-exposed live births and for the subgroups identified. Ninety-five percent confidence intervals were constructed for both the odds ratio and prevalence rates. Results. Fifteen studies (6 with control groups of transplant without use of cyclosporine; total patients: 410) met the inclusion criteria for major malformations, 10 for preterm delivery (4 with control groups; total patients: 379) and 5 for low birth weight (1 with control groups; total number of patients: 314). The calculated odds ratio of 3.83 for malformations did not achieve statistical significance (CI 0.75‐19.6). The overall prevalence of major malformations in the study population (4.1%) also did not vary substantially from that reported in the general population. OR for prematurity [1.52 (CI 1.00 ‐2.32)] did not reach statistical significance although the overall prevalence rate was 56.3%. The OR for low birth weight [1.5 (CI 0.95‐ 2.44 based on 1 study)]. Conclusions. CsA does not appear to be a major human teratogen. It may be associated with increased rates of prematurity. More research is needed to evaluate whether cyclosporine increases teratogenic risk.

Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-6143.2005.00969.x

Reproduction and Transplantation: Report on the AST Consensus Conference on Reproductive Issues and Transplantation

The NTPR continues to maintain an ongoing active database as a resource for health professionals counseling recipients regarding pregnancy and for recipients themselves to contact the registry and request information. This includes female transplant recipients as well as male recipients who father pregnancies. Recipients who consent are entered into a database; analyses are ongoing, including long-term follow-up of the recipient, the graft and the offspring. The safety of pregnancy for parent and child remains the goal of the registry. Guidelines for counseling recipients proposed in 1976 remain applicable. Recipients should be in general good health and graft function should be stable and ideally rejection free. Comorbid conditions should be well controlled, especially hypertension and diabetes. While these counseling guidelines were formulated for kidney recipients, they may be extrapolated for other organ recipients. Analyses this year included pregnancy outcomes of recipients on newer agents, MMF and sirolimus. It remains unclear whether these adjunctive therapies should be altered for pregnancy. The balance of immunosuppression and the prevention of rejection need to be weighed against the potential for teratogenicity when counseling these recipients inquiring about pregnancy. Although there are periodic reports of recipients with graft dysfunction, rejection or graft loss possibly related to pregnancy events throughout all the organ groups, whether transplanted as adults or as pediatric patients, the majority of pregnancy outcomes reported to the NTPR appear favorable for parent and newborn. Whether recipients should breastfeed remains controversial. Recent reports in the literature as well as NTPR data appear favorable. This represents the last report from our initial established location at Thomas Jefferson University. In January of this year, the registry moved to Temple University School of Medicine, Department of Surgery, Philadelphia, PA. The NTPR remains committed to investigating outcomes of pregnancies reported by centers or self-referrals nationwide. Some of the active issues for the upcoming year include the potential for teratogenicity with combinations of newer agents, incidence of viral hepatitis, risk assessment for pregnancy in female lung recipients, and long-term maternal and pediatric follow-up.

Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation.

Basiliximab is a chimeric monoclonal antibody that selectively binds to the alpha-subunit (CD25) of IL-2 receptors on the surface of activated T lymphocytes, and is a highly effective prophylaxis agent against rejection in organ transplant recipients. Its pharmacokinetic profile is characterized by a biphasic and slow clearance with long terminal half-life and a volume of distribution within the central compartment and outside the circulatory system. Basiliximab induction demonstrated an excellent safety profile, with no increase in the incidence of malignancy, infections or death. It has also been used effectively in high-risk recipients, steroid-sparing and steroid-minimization protocols, and in post-transplant patients with renal dysfunction who would benefit from delayed introduction of calcineurin inhibitors. Basiliximab induction therapy given at days 0 and 4 after transplantation appears to be safe and cost-effective for immunoprophylaxis in solid organ transplant recipients, specifically in kidney and liver transplantation, when given in conjunction with dual or triple immunosuppressive therapy.

The role of basiliximab induction therapy in organ transplantation

https://www.kidney-international.org/article/S0085-2538(15)55761-X/pdf

The adipose tissue production of adiponectin is increased in end-stage renal disease.

Anti-IL2 induction in liver transplantation with 93% rejection-free patient and graft survival at 18 months.

Introduction

Corticosteroids (CS) have been standard immunosuppression to prevent and treat rejection. However, CS are associated with increased risk of infection, obesity, hypertension, hyperlipidemia, diabetes, and accelerated hepatitis C virus (HCV) recurrence post-orthotopic liver transplantation (OLT). This study assesses the safety and efficacy of CS-free immunosuppressive regimen in adult OLT.



Methods

A two-yr, prospective, randomized study of CS with delayed withdrawal (CS) or CS-free regimen with basiliximab, tacrolimus, and enteric-coated mycophenolate sodium (EC-MPS) was performed in 39 patients (CS=20; CS-free=19). CS group received intra-operative methylprednisolone weaned by six months. HCV patients had HCV PCR pre-OLT and 0.5, one, three, and six months post-OLT. Protocol liver biopsies were performed at OLT, 2 and 24 wk post-OLT or when indicated.



Results

Rejection occurred in two patients. Patient survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (80% vs. 63%) post-OLT were similar between CS and CS-free group, respectively. Death-censored graft survival at one yr (100% vs. 95%), three yr (85% vs. 63%), and five yr (75% vs. 63%) were also similar. The risk of new-onset DM, hypertension, hypercholesterolemia, and weight gain was similar between groups.



Conclusion

CS avoidance with basiliximab, calcineurin inhibitor, and EC-MPS is safe and effective as CS- containing immunosuppression in adult OLT.

/pdf/completely-steroid-free-immunosuppression-in-liver-4nlotrgixn.pdf

Carlo B. Ramirez

Papers

Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation.

The role of basiliximab induction therapy in organ transplantation

The adipose tissue production of adiponectin is increased in end-stage renal disease.

Anti-IL2 induction in liver transplantation with 93% rejection-free patient and graft survival at 18 months.

Completely steroid-free immunosuppression in liver transplantation: a randomized study.