Early outcomes comparing induction with antithymocyte globulin vs alemtuzumab in two steroid-avoidance protocols in pediatric renal transplantation.
Adolescent
Alemtuzumab
/ therapeutic use
Antilymphocyte Serum
/ therapeutic use
Child
Child, Preschool
Drug Therapy, Combination
Female
Graft Rejection
/ prevention & control
Humans
Immunosuppressive Agents
/ therapeutic use
Induction Chemotherapy
/ methods
Infant
Infant, Newborn
Kidney Transplantation
Male
Steroids
Treatment Outcome
ATG
alemtuzumab
graft outcome
neutropenia
Journal
Pediatric transplantation
ISSN: 1399-3046
Titre abrégé: Pediatr Transplant
Pays: Denmark
ID NLM: 9802574
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
15
11
2019
revised:
24
01
2020
accepted:
05
02
2020
pubmed:
1
3
2020
medline:
10
4
2021
entrez:
1
3
2020
Statut:
ppublish
Résumé
Steroid avoidance in pediatric kidney transplants was found effective with extended daclizumab induction. Upon discontinuation of daclizumab, lymphocyte-depleting agents became used, with little comparative data. We assessed outcomes in children undergoing low immunologic-risk deceased donor (DD) kidney transplants using induction with antithymocyte globulin (ATG) compared to alemtuzumab. We reviewed consecutive DD kidney transplants from January 2015 to September 2017 at two pediatric centers that used different lymphocyte-depleting agents in steroid-avoidance protocols: ATG (Center A) and alemtuzumab (Center B), with tacrolimus and MMF as maintenance immunosuppression. Anti-infective prophylaxis was based on center protocol. Over the first year post-tx, there were similar rates of infections. EBV and BK viremia were comparable though Center A manifested more low-grade CMV viremia (A 46% vs B 0%; P = .0009) at median onset 1.8 months, followed by early seroconversion. Reduction of immunosuppression did not differ between groups. DSA at 1 year was similar (A 8% vs 13%) with low rates of BPAR. Need for steroid-based conversion was low. There were no graft losses and no differences in median eGFR at 30, 90, 180, and 365 days. (a) 1-year graft outcomes are excellent in steroid-avoidance regimens using ATG or alemtuzumab induction; (b) conversion to steroid-based therapy is low; (c) alemtuzumab/high-dose MMF is associated with lower WBC and more GCSF use; (d) alemtuzumab/higher dose MMF results in more diarrhea and azathioprine conversion than ATG/lower dose MMF; (e) CMV viremia is seen more often with ATG use with infection prophylaxis reduction; however, seroconversion occurs promptly.
Substances chimiques
Antilymphocyte Serum
0
Immunosuppressive Agents
0
Steroids
0
Alemtuzumab
3A189DH42V
Types de publication
Clinical Trial
Comparative Study
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13685Informations de copyright
© 2020 Wiley Periodicals, Inc.
Références
Birkeland SA, Larsen KE, Rohr N. Pediatric renal transplantation without steroids. Pediatr Nephrol. 1998;12(2):87-92.
Sarwal MM, Ettenger RB, Dharnidharka V, et al. Complete steroid avoidance is effective and safe in children with renal transplants: a multicenter randomized trial with three-year follow-up. Am J Transplant. 2012;12(10):2719-2729.
Sarwal MM, Vidhun JR, Alexander SR, Satterwhite T, Millan M, Salvatierra Jr O. Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation. Transplantation. 2003;76(9):1331-1339.
Sarwal MM, Yorgin PD, Alexander S, et al. Promising early outcomes with a novel, complete steroid avoidance immunosuppression protocol in pediatric renal transplantation. Transplantation. 2001;72(1):13-21.
Bhakta N, Marik J, Malekzadeh M, Gjertson D, Ettenger R. Can pediatric steroid-free renal transplantation improve growth and metabolic complications? Pediatr Transplant. 2008;12(8):854-861.
Delucchi A, Valenzuela M, Ferrario M, et al. Early steroid withdrawal in pediatric renal transplant on newer immunosuppressive drugs. Pediatr Transplant. 2007;11(7):743-748.
Grenda R, Watson A, Trompeter R, et al. A randomized trial to assess the impact of early steroid withdrawal on growth in pediatric renal transplantation: the TWIST study. Am J Transplant. 2010;10(4):828-836.
Nehus E, Liu C, Hooper DK, Macaluso M, Kim MO. Clinical practice of steroid avoidance in pediatric kidney transplantation. Am J Transplant. 2015;15(8):2203-2210.
Mohty M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia. 2007;21(7):1387-1394.
Warejko JK, Hmiel SP. Single-center experience in pediatric renal transplantation using thymoglobulin induction and steroid minimization. Pediatr Transplant. 2014;18(8):816-821.
Li L, Chaudhuri A, Chen A, et al. Efficacy and safety of thymoglobulin induction as an alternative approach for steroid-free maintenance immunosuppression in pediatric renal transplantation. Transplantation. 2010;90(12):1516-1520.
Kim IK, Choi J, Vo AA, et al. Safety and efficacy of alemtuzumab induction in highly sensitized pediatric renal transplant recipients. Transplantation. 2017;101(4):883-889.
Bartosh SM, Knechtle SJ, Sollinger HW. Campath-1H use in pediatric renal transplantation. Am J Transplant. 2005;5(6):1569-1573.
Kaabak MM, Babenko NN, Shapiro R, et al. Eight-year follow-up in pediatric living donor kidney recipients receiving alemtuzumab induction. Pediatr Transplant. 2017;21(5):e12941.
Supe-Markovina K, Melquist JJ, Connolly D, et al. Alemtuzumab with corticosteroid minimization for pediatric deceased donor renal transplantation: a seven-yr experience. Pediatr Transplant. 2014;18(4):363-368.
Saull HE, Enderby CY, Gonwa TA. Wadei HM. Comparison of alemtuzumab vs. antithymocyte globulin induction therapy in primary non-sensitized renal transplant patients treated with rapid steroid withdrawal. Clin Transplant. 2015;29(7):573-580.
Farney AC, Doares W, Rogers J, et al. A randomized trial of alemtuzumab versus antithymocyte globulin induction in renal and pancreas transplantation. Transplantation. 2009;88(6):810-819.
LaMattina JC, Mezrich JD, Hofmann RM, et al. Alemtuzumab as compared to alternative contemporary induction regimens. Transpl Int. 2012;25(5):518-526.
Schwartz GJ, Munoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629-637.
Ettenger R, Chin H, Kesler K, et al. Relationship among viremia/viral infection, alloimmunity, and nutritional parameters in the first year after pediatric kidney transplantation. Am J Transplant. 2017;17(6):1549-1562.
Moudgil A, Dharnidharka VR, Feig DI, et al. Phase I study of single-dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients. Am J Transplant. 2019;19(4):1218-1223.
De Serres SA, Mfarrej BG, Magee CN, et al. Immune profile of pediatric renal transplant recipients following alemtuzumab induction. J Am Soc Nephrol. 2012;23(1):174-182.
Casciello N, Hulbert A, Snyder L, Byrns J. Incidence of acute cellular rejection following granulocyte colony-stimulating factor administration in lung transplantation: A retrospective case-cohort analysis. Clin Transplant. 2017;31(5):e12965.
Becker-Cohen R, Ben-Shalom E, Rinat C, Feinstein S, Geylis M, Frishberg Y. Severe neutropenia in children after renal transplantation: incidence, course, and treatment with granulocyte colony-stimulating factor. Pediatr Nephrol. 2015;30(11):2029-2036.
Jacqz-Aigrain E, Khan Shaghaghi E, Baudouin V, et al. Pharmacokinetics and tolerance of mycophenolate mofetil in renal transplant children. Pediatr Nephrol. 2000;14(2):95-99.
Weber LT, Hocker B, Mehls O, Tonshoff B. Mycophenolate mofetil in pediatric renal transplantation. Minerva Urol Nefrol. 2003;55(1):91-99.