tacrolimus and Heart-Defects--Congenital

We contacted and analyzed the data of 18 lung transplant recipients who had had children. The complications we detected included: hypertension (50%), diabetes mellitus (21%), preeclampsia (13%), infection (21%), rejection (30%), loss of graft function (23%) and a lower percentage of live births than in transplant recipients of other organs. Other aspects to keep in mind are: the potential risk for fetal alterations (caused by drugs used as prophylaxis against rejection crossing the placental barrier); greater risk for infection and alterations in drug levels due to changes in metabolism typical of pregnancy and postpartum period. We describe the two cases in Spain of female lung transplant recipients who have had children after transplantation. Although pregnancy in these cases can have a similar evolution as in non-transplanted women, doctors should recommend their transplanted patients to avoid becoming pregnant, while explaining the high risk of both fetal and maternal morbidity and mortality after transplantation.

Topics: Adult; Cardiomyopathies; Female; Graft Rejection; Heart Defects, Congenital; Heart-Lung Transplantation; Humans; Hypertension; Hypertension, Pulmonary; Immunosuppressive Agents; Infant, Newborn; Infant, Premature, Diseases; Lung Diseases, Interstitial; Lung Transplantation; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Pregnancy in Diabetics; Pregnancy Outcome; Pregnancy, High-Risk; Spain; Survivors; Tacrolimus

Pediatric heart transplantation is a surgical therapy for dilated cardiomyopathy and for complex congenital heart defects with low pulmonary artery resistance. However, it is still discussed as controversial because of uncertain long-term results. We report our experience with pediatric heart transplantation in a heterogeneous population.. Since 1988, 50 heart transplants were performed in 47 patients (30 with dilated cardiomyopathy, 17 with congenital heart disease). Mean age was 9.4 +/- 6.9 years (range, 4 days to 17.9 years). Twenty-three patients had a total of 36 previous operations. Clinical outcome was evaluated retrospectively.. Perioperative mortality was 6% due to primary graft failure. Late mortality (12%) was caused by acute rejection (n = 2), pneumonia (n = 2), intracranial hemorrhage (n = 1), and suicide (n = 1). Mean follow-up was 5.24 +/- 3.6 years. Actuarial 1, 5, and 10 year survival was 86%, 86%, and 80% and improved significantly after 1995 (92% [1 year]; 92% [5 years]). There was no significant difference between patients with dilated or congenital heart disease (1 year: 86% vs 82%; 5 years: 83% vs 74%; 10 years 83% vs 74%; p = 0.62). Three patients with therapy resistant acute or chronic rejection and assisted circulation underwent retransplantation and are alive. Freedom from acute rejection after 5 years was 40% with primary cyclosporine immunosuppression regime and 56% with tacrolimus. Since the introduction of mycophenolate mofetil, freedom from acute rejection increased to 62%. All survivors are at home and in good cardiac condition.. Pediatric heart transplantation is the treatment of choice for end-stage dilated cardiomyopathy as for congenital heart disease with excellent clinical midterm results. It is a valid alternative to reconstructive surgery in borderline patients. However, further follow-up is necessary to evaluate the long-term side effects of immunosuppressants.

Topics: Adolescent; Antiviral Agents; Bacterial Infections; Cardiomyopathy, Dilated; Child; Child, Preschool; Cyclosporine; Cytomegalovirus Infections; Extracorporeal Membrane Oxygenation; Female; Follow-Up Studies; Ganciclovir; Germany; Graft Rejection; Heart Defects, Congenital; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Life Tables; Lymphoma, Non-Hodgkin; Male; Mycophenolic Acid; Pneumonia, Pneumocystis; Postoperative Complications; Reoperation; Retrospective Studies; Survival Analysis; Survival Rate; Tacrolimus; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Vascular Resistance; Virus Diseases

While Tacrolimus (Tac) and Cyclosporine (Cya) immunosuppression are used after cardiac transplantation (tx), few studies have evaluated their use in pediatric patients.. We randomized 26 heart transplant recipients (pts) in a prospective, open-label trial to Tac (n = 14) or Cya (n = 12) to compare their efficacy and side-effects. Mean age at tx was 4.2 years for Tac and 5.8 years for Cya. Mean follow-up was 26 months (range: 11-39 months) for Tac and 24 months for Cya (range: 33-13 months).. Our data suggest that both regimens are efficacious in the pediatric population. Conversion from Cya to Tac was useful for dealing with persistent rejection, although this sample did not suggest lower incidence of acute cellular rejection in the Tac group.. Further studies are required to establish pharmacokinetic parameters to enhance therapeutic monitoring of these patients to minimize side effects and enhance outcomes.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Cardiomyopathy, Dilated; Cardiomyopathy, Restrictive; Child; Child, Preschool; Cross-Over Studies; Cyclosporine; Female; Follow-Up Studies; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Humans; Immunosuppressive Agents; Incidence; Infant; Infant, Newborn; Male; Prospective Studies; Survival Analysis; Tacrolimus; Transplantation, Homologous; Treatment Outcome

Black heart transplant recipients have higher risk of mortality than White recipients. Better understanding of this disparity, including subgroups most affected and timing of the highest risk, is necessary to improve care of Black recipients. We hypothesize that this disparity may be most pronounced among young recipients, as barriers to care like socioeconomic factors may be particularly salient in a younger population and lead to higher early risk of mortality.. We studied 22 997 adult heart transplant recipients using the Scientific Registry of Transplant Recipients data from January 2005 to 2017 using Cox regression models adjusted for recipient, donor, and transplant characteristics.. Young Black recipients have a high risk of mortality in the first year after heart transplant, which has been masked in decades of research looking at disparities in aggregate. To reduce overall racial disparities, clinical research moving forward should focus on targeted interventions for young Black recipients during this period.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; American Indian or Alaska Native; Antilymphocyte Serum; Black or African American; Cardiomyopathies; Cause of Death; Diabetes Mellitus; Educational Status; Female; Glucocorticoids; Graft Rejection; Healthcare Disparities; Heart Defects, Congenital; Heart Transplantation; Hispanic or Latino; Histocompatibility; Humans; Immunosuppressive Agents; Insurance, Health; Interleukin-2; Kaplan-Meier Estimate; Male; Middle Aged; Mortality; Mycophenolic Acid; Proportional Hazards Models; Registries; Sex Factors; Tacrolimus; White People; Young Adult

Heart transplantation has been an option for children in Sweden since 1989. As our unit faced an increased rate of post-transplant lymphoproliferative disorder, the objective of the study was to identify possible risk factors.. This is a retrospective study of all children aged 0-18 years who underwent heart transplantation in Gothenburg from 1989 to 2014.. A total of 71 children underwent heart transplantation. The overall incidence of post-transplant lymphoproliferative disorder was 14% (10/71); however, 17% (6/36) of those undergoing transplantation after 2007 developed lymphoma, compared with only 10% (4/35) of transplantation cases before 2007 (p=0.85). The mean age at transplantation was 9 years (0-17). The mean post-transplant follow-up time was 5.5 years (0.5-21.9) in the group that developed post-transplant lymphoproliferative disorder, compared with 10.2 years (0.02-25.2) in those who did not. In our study group, risk factors for post-transplant lymphoproliferative disorder were surgically palliated CHD (p=0.0005), sternotomy during infancy (p⩽0.0001), hypoplastic left ventricle (p=0.0001), number of surgical events (p=0.0022), mismatch concerning Epstein-Barr virus infection - that is, a positive donor-negative recipient (p⩽0.0001) - and immunosuppressive treatment with tacrolimus compared with ciclosporine (p=0.028). Discussion This study has three major findings. First, post-transplant lymphoproliferative disorder only developed in subjects born with CHD. Second, the vast majority (9/10) of the subjects developing the disorder had undergone sternotomy as infants. Third, the number of surgical events correlated with a higher risk for developing post-transplant lymphoproliferative disorder.

Topics: Adolescent; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Transplantation; Heart Ventricles; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Lymphoma; Lymphoproliferative Disorders; Male; Postoperative Complications; Proportional Hazards Models; Retrospective Studies; Risk Factors; Sternotomy; Sweden; Tacrolimus

Pediatric heart transplantation is entering its third decade, allowing for the first time an analysis of a large group of true long-term survivors, specifically children who have survived > or =10 years post-transplantation.. Fifty-two patients < or =18 years, who had undergone heart transplantation at Stanford between August 1974 and June 1993 and survived > or =10 years, were retrospectively reviewed.. Forty (77%) patients are currently alive. Thirteen survived >15 years and 5 >20 years (the longest being 26 years). Actuarial survival was 79.4% at 14 years and 53.1% at 20 years. Cardiomyopathy was the reason for transplantation in 71% and congenital heart disease (CHD) in 29%. At last evaluation, 71% were on a cyclosporine-based regimen and 23% a tacrolimus-based regimen; 33% were steroid-free. Twenty-seven percent were totally free from treatable rejection, 44% developed serious infections, 69% were receiving anti-hypertensives, and 8% required renal transplantation. Neoplasms occurred in 23%, graft coronary artery disease (CAD) in 31%, and 15% required re-transplantation. Of the 12 deaths, CAD was the most common cause (n = 4), followed by non-specific late graft failure (n = 3), infection (n = 2), rejection (n = 1), non-lymphoid cancer (n = 1) and lymphoid cancer (n = 1). Physical rehabilitation and return to normal lifestyle has been nearly 100%.. Heart transplantation in pediatric patients is compatible with true long-term survival with a growing cohort of children approaching their second and third decades. The gradual constant-phase decrease in survival noted in earlier studies appears to be continuing. Rejection and infection are low but persistent risks after the first years. Graft CAD and non-specific late graft dysfunction are the leading causes of death after 10 years. Rehabilitation is excellent.

Topics: Actuarial Analysis; Adolescent; Bacterial Infections; Cardiomyopathies; Child; Child, Preschool; Coronary Artery Disease; Cyclosporine; Female; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Lymphoproliferative Disorders; Male; Reoperation; Retrospective Studies; Survival Analysis; Survivors; Tacrolimus

Early experience with intravenous tacrolimus at high doses (0.1-0.15 mg/kg/day) was associated with frequent clinical toxicity. The optimal dosing regimen after pediatric heart transplantation is unknown.. We retrospectively reviewed data on the last 45 pediatric heart transplant recipients to document the time required to achieve therapeutic blood levels and the safety of 2 differing intravenous dosing regimens (tacrolimus 0.03 & 0.05 mg/kg/day as continuous i.v. infusion). Target plasma levels were (1.2-1.7 ng/ml) with levels >2.0 ng/ ml considered toxic, and target whole blood levels were 15-20 ng/ml with levels >25 ng/ml considered toxic.. Mean age at transplantation was 7.5 +/- 5.6 years (0.1-18), and 14 were infants. Intravenous tacrolimus was commenced at a mean of 7 +/- 3 hours (range 2-16) after arrival in the ICU. Eight patients were excluded from analysis because of protocol modifications. Of the remaining 37 pts, 9 received initial infusion at 0.03 mg/kg/day; 3 (33%) achieved 'therapeutic' levels within 48 hours and 1 patient had a toxic level (27 ng/ml) at 36 hours. Twenty-eight patients received 0.05 mg/kg/day; 18 (64%) achieved therapeutic levels within 48 hours and 9 (32%) developed toxic levels. Patients with toxic whole blood levels had higher tacrolimus levels on first blood assay compared to those who did not develop toxicity (16.4 +/- 3.4 vs 9.3 +/- 3.9, p < .0001; level >10 ng/ml on first assay in 7/7 toxic patients vs 7/19 without toxicity, p = .004). Patients receiving the higher dose regimen had fewer episodes of moderate or severe rejection (> or =Grade 3A) at first biopsy than those receiving the lower dose infusion (32% vs 75%; p = .046). No patient required renal dialysis.. Dosing below 0.05 mg/kg/day may result in clinically important delay in achieving therapeutic levels. Toxicity may be reduced by frequent monitoring of levels for the first 48 hours after transplantation especially when the initial level is >10 ng/ml.

Topics: Adolescent; Biopsy; Cardiomyopathy, Dilated; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Injections, Intravenous; Intensive Care Units, Pediatric; Kidney; Male; Postoperative Care; Retrospective Studies; Tacrolimus

Topics: Actuarial Analysis; Adolescent; Age Factors; Cardiomyopathies; Cause of Death; Child; Child, Preschool; Cyclosporine; Europe; Forecasting; Glucocorticoids; Heart Defects, Congenital; Heart Transplantation; Heart-Lung Transplantation; Hospitalization; Humans; Immunosuppressive Agents; Infant; Logistic Models; Lung Transplantation; Multivariate Analysis; Odds Ratio; Patient Readmission; Prednisone; Registries; Risk Factors; Societies, Medical; Survival Analysis; Tacrolimus; United States

Experience with lung transplantation in infants and young children is limited. Small size, vulnerability to infection, and limited modalities for rehabilitation and surveillance of the transplanted lung make this group particularly challenging.. We reviewed the course of all children up to the age of 25 months who underwent lung transplantation at two centers between July 1990 and February 1995.. Lung transplantation was performed in 17 patients under the age of 25 months, with concurrent cardiac repair in 14. Prior thoracic surgery had been performed in 12; six patients had mechanical ventilation, and three were supported with extracorporeal membrane oxygenation while waiting for lungs. The mean waiting time was 37 days (range 1 to 197 days). Hospital survival was 12 of 17 (71%); there was one late death. Early deaths were due to hemorrhage (two patients), cytomegalovirus and lymphoproliferative disease (one patients), and viral pneumonitis (two patients). The one late death was due to overwhelming gastroenteritis of unknown origin. One additional patient had graft failure caused by viral pneumonitis and underwent successful retransplantation. Bronchial stenosis occurred at 3 of 33 anastomoses. At a mean follow-up of 22 months, surviving patients were well, without supplemental oxygen, and, although small in stature, had normal linear growth.. Lung transplantation is a reasonable therapy for very young patients with limited life expectancy and no other therapeutic alternative, with outcomes comparable with those achieved in older patients. Early recognition of lung transplant candidates and advances in the prevention, diagnosis, and treatment of viral illness may improve survival in these patients.

Topics: Actuarial Analysis; Azathioprine; Cause of Death; Cyclosporine; Graft Rejection; Heart Defects, Congenital; Humans; Immunosuppressive Agents; Infant; Lung Diseases; Lung Transplantation; Prednisone; Retrospective Studies; Survival Analysis; Tacrolimus; Treatment Outcome; Virus Diseases

The decade from 1982 through 1992 witnessed tremendous growth in pediatric cardiac transplantation. At Children's Hospital of Pittsburgh 66 cardiac transplants were performed during this period (age range 7 hours to 18 years). The cause of cardiomyopathy was congenital (n = 30), cardiomyopathy (n = 29), myocarditis (n = 2), doxorubicin toxicity (n = 2), ischemic (n = 1), valvular (n = 1), and cardiac angiosarcoma (n = 1). Nine children (14%) required mechanical circulatory support before transplantation: extracorporeal membrane oxygenation (n = 8) and Novacor left ventricular assist system (n = 1) (Baxter Healthcare Corp., Novacor Div., Oakland, Calif.). The mean follow-up time was 2 years (range 4 months to 8 years). The overall survival in the group was 67%. In children with congenital heart disease (> 6 months of age) the perioperative (30 day) mortality was 66% before mid-1988 (n = 10) and 0% since mid-1988 (n = 11). The late mortality (> 30 days) in children with cardiomyopathy transplanted prior to mid-1988 was 66% (n = 14) and 7% since mid-1988 (n = 15). Since mid-1988 1- and 3-year survival was 82% in children with congenital heart disease and 90% in children with cardiomyopathy. Twenty-six children have had FK 506 as their primary immunosuppressive therapy since November 1989. Survival in this group was 82% at 1 and 3 years. The actuarial freedom from grade 3A rejection in the FK group was 60% at 3 and 6 months after transplantation versus 20% and 12%, respectively, in the 15 children operated on before the advent of FK 506, who were treated with cyclosporine-based triple-drug therapy (p < 0.001, Mantel-Cox and Breslow). Twenty of 24 children (83%) in the FK 506 group are receiving no steroids. The prevalence of posttransplantation hypertension was 4% in the FK 506 group versus 70% in the cyclosporine group (p < 0.001, Fisher). Renal toxicity in children treated with FK 506 has been mild. Additionally, eight children have been switched to FK 506 because of refractory rejection and drug toxicity. FK 506 has not produced hirsutism, gingival hyperplasia, or abnormal facial bone growth. The absence of these debilitating side effects, together with the observed immune advantage and steroid-sparing effects of FK 506, hold tremendous promise for the young patient facing cardiac transplantation and a future wedded to immunosuppression.

Topics: Adolescent; Cardiomyopathies; Child; Child, Preschool; Cyclosporine; Extracorporeal Membrane Oxygenation; Female; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Infant, Newborn; Infections; Kidney; Lymphoproliferative Disorders; Male; Postoperative Complications; Tacrolimus