Thorac Cardiovasc Surg 2019; 67(S 02): S101-S128
DOI: 10.1055/s-0039-1679045
Oral Presentations
Sunday, February 17, 2019
Terminale Herzinsuffizienz
Georg Thieme Verlag KG Stuttgart · New York

Improved Long-Term Survival with Adaptation of Immunosuppressive Therapy in Pediatric Heart Transplant Recipients

S. Schubert
1  Congenital Heart Disease, Pediatric Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany
,
K. Schmitt
2  Congenital Heart Disease, Pediatric Cardiology, German Heart Center Berlin, Berlin, Germany
,
O. Miera
2  Congenital Heart Disease, Pediatric Cardiology, German Heart Center Berlin, Berlin, Germany
,
F. Danne
2  Congenital Heart Disease, Pediatric Cardiology, German Heart Center Berlin, Berlin, Germany
,
Y. M. Cho
2  Congenital Heart Disease, Pediatric Cardiology, German Heart Center Berlin, Berlin, Germany
,
J. Photiadis
2  Congenital Heart Disease, Pediatric Cardiology, German Heart Center Berlin, Berlin, Germany
,
F. Berger
2  Congenital Heart Disease, Pediatric Cardiology, German Heart Center Berlin, Berlin, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
28 January 2019 (online)

 

    Objectives: Heart transplantation is well established for treatment of end-stage heart failure in pediatric patients. Nevertheless, lifelong immunosuppression (IS) and especially the use of calcineurin inhibitors (CNI) include a risk for side effects: renal insufficiency, lymphoproliferative disorder (PTLD), and acute or chronic infections or rejections. The question was, if patients might benefit from adaptive IS, which defines the optimal drug therapy according to their current acute or chronic problems.

    Methods: We compared retrospectively the use of standard (=CNI level > 100 ng/mL plus antimetabolite [MMF/AZA], group A) versus adapted IS in pediatric patients after heart transplantation: CNI reduced (CNI level 50–70 ng/mL + mTOR, group B) with a CNI-free regimen (mTOR + MMF, group C).

    Results: From 114 patients transplanted (2000–2017), 94 patients were analyzed. Overall survival in this group was 85% after 5 years, 80% after 10 years, and 74% after 15 years, which was superior, if compared with earlier decades. In 18/94 (19%) patients, PTLD was diagnosed, which results in reduced survival (p = 0.02) and a hazard ratio of 2.9. Group A included n = 42, group B n = 40, and group C n = 12 patients. Induction therapy and initial maintenance were similar in all groups. Age and posttransplant time were increased and mortality reduced in the CNI-free group C, if compared with both other groups. But this was not reaching statistical significance due to the different sized groups, see Table 1 and Fig. 1. Rejection episodes were similar in all groups (0.09–0.13) and ATG was used similar (0.19–0.24) per patient-years.

    Conclusion: Adaptive immunosuppressive (IS) and especially the use of CNI-free IS therapy show an improved survival and might be indicated in patients with side effects from their IS therapy. PTLD is a major risk factor for mortality and CNI-free IS should be considered in those patients. Although efficacy is not reduced in this regimen, it is still an “off-label” therapy.

    Table 1

    Group A

    Group B

    Group C

    Patients

    N

    42

    40

    12

    Posttransplant time

    Years

    7.8 (0.2–16.4)

    6.53 (0.12–16.7)

    13 (8.8–16.7)

    p = 0.08

    Age

    Years

    13.6 (2.6–28.5)

    10.2 (0.8–23)

    13.3 (10–28.4)

    p = ns

    Age at HTx

    Years

    11.6 (0.2–17.2)

    6.0 (0.3–17.8)

    2.2 (0.6–16.8)

    p = 0.03


    #

    No conflict of interest has been declared by the author(s).