Immunosuppression Monotherapy Outcomes After Pediatric Heart Transplant

Following pediatric heart transplantation, immunosuppression monotherapy is noninferior to immunosuppression with multiple medications.

Among pediatric heart transplant (HT) recipients initially placed on monotherapy, after the first year posttransplant immunosuppression with a single immunosuppressive drug is noninferior to standard therapy with at least 2 immunosuppressive drugs in the medium-term, according to findings published in The Journal of Heart and Lung Transplantation.

Investigators evaluated graft failure (a composite of retransplantation and death) in pediatric patients with a first heart transplant placed on a single immunosuppressive drug vs those taking 2 or more immunosuppressive drugs. Graft failure was the primary endpoint. Secondary endpoints included cardiac allograft vasculopathy (CAV), malignancy, infection, rejection, and dialysis. The investigators hypothesized that pediatric HT patients on monotherapy have noninferior graft survival compared with those on at least 2 immunosuppressive drugs.

The investigators conducted an international, multicenter, retrospective, observational cohort study using data from 3493 patients from the Pediatric Heart Transplant Society. Patients (44.9% girls) that were aged less than 18 years and received a first-time heart transplant between 1999 and 2020 with at least 1 year of follow-up were included.

Posttransplant median follow-up time was 6.7 years (IQR, 4.5-10 years). During that time 893 patients were switched to monotherapy at least once. The remaining 2600 patients were always on at least 2 immunosuppressive drugs. Median time on monotherapy was 2.8 years (IQR, 1.1-5.9 years) after the first-year posttransplant. Patients on monotherapy vs those taking 2 or more immunosuppressive drugs were younger at transplantation (median 1.3 years vs 6.2 years) and transplantation was more likely as a neonate (5.4% vs 1.4%).

. . . monotherapy was not associated with change in the incidence of rejection, infection and malignancy, and even the development of CAV.

Cardiomyopathy (53.2%) and congenital heart disease (43.8%) were the most common underlying diagnoses leading to heart transplantation with no clear difference in diagnosis between those never on monotherapy and those always on monotherapy. At the start of follow-up, 7.5% of patients were on monotherapy. This proportion peaked at 23.9% at 12.4 years post-HT.

The adjusted hazard ratio (HR) favored monotherapy (HR, 0.65; 95% CI, 0.47-0.88; P =.002). Tacrolimus (69.7%) and cyclosporine (26.5%) were the most commonly used agents during monotherapy. Sirolimus, mycophenolate mofetil, steroids, azathioprine, and everolimus were each used less than 2% for monotherapy.

Patients with a previous post-transplant lymphoproliferative disease diagnosis had an overall higher graft failure in adjusted models (HR, 2.24; 95% CI, 1.64-3.08) but without a statistically significant modification of the effect of monotherapy on graft failure (Pinteraction =.44).

Other than a lower rate of CAV in patients on monotherapy (HR, 0.58; 95% CI, 0.45-0.74), investigators found no meaningful differences in between-group incidence of secondary endpoints.

Study limitations include lack of data on rationale for clinical decisions and potential survivorship bias.

“We concluded that for pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD [immunosuppressive drug] after the first year posttransplant was noninferior to standard therapy with ≥2 ISDs in the medium term,” the investigators wrote. “…monotherapy was not associated with change in the incidence of rejection, infection and malignancy, and even the development of CAV.”


Watelle L, Toure M, Lamour JM, et al. Single-drug immunosuppression is associated with non-inferior medium-term survival in pediatric heart transplant recipients. J Heart Lung Transplant. Published online March 3, 2023. doi:10.1016/j.healun.2023.02.1705