Sirolimus for rescue and primary immunosuppression in transplanted children receiving tacrolimus.
OBJECTIVE
The role of sirolimus (SRL) as a rescue agent (n=42) and as a component of primary immunosuppression (n=8) was evaluated in a mixed population of 50 transplanted children receiving tacrolimus (liver: 26, heart: 5, intestinal: 5, liver-intestine: 9, lung: 1, bone marrow: 1, liver-kidney: 1, multivisceral: 1). Rescue indications for tacrolimus (TAC) failure were recurrent acute rejection and acute rejection complicating withdrawal of immunosuppression in posttransplant lymphoproliferative disorder (PTLD). Rescue indications for TAC toxicity were nephrotoxicity, pancreatitis, seizures, hypertrophic cardiomyopathy, and graft-versus-host disease.


RESULTS
Mean age at rescue was 11.5 years and mean follow-up was 204 (range 18-800) days. As primary immunosuppression, SRL+TAC prevented early acute rejection in 7/8 children. The indication for rescue resolved in 33/42 children. In children with TAC toxicity, this was associated with decrease in TAC doses by 50%, significant improvements in renal function, and continuing decline in Epstein-Barr virus (EBV) viral load in PTLD patients. Serious adverse events led to discontinuation of SRL in 9/42 rescue patients, 3 of them also experienced acute rejection. Three additional children also experienced acute rejection on SRL therapy (overall incidence 6/50, 12%). Pharmacokinetic analysis in the first week of SRL administration suggested a short half-life (11.8+/-5.5 hr, n=21).


CONCLUSIONS
SRL and reduced-dose TAC may achieve adequate immunosuppression without compromising renal function or enhancing EBV viremia significantly.
Sindhi
R
R
Thomas E. Starzl Transplantation Institute, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA. sindhir@chplink.chp.edu
Webber
S
S
Venkataramanan
R
R
McGhee
W
W
Phillips
S
S
Smith
A
A
Baird
C
C
Iurlano
K
K
Mazariegos
G
G
Cooperstone
B
B
Holt
D W
DW
Zeevi
A
A
Fung
J J
JJ
Reyes
J
J
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000821:virology; D006084:Graft Rejection / Q000188:drug therapy* / Q000517:prevention & control*; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007223:Infant; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000821:virology; D012008:Recurrence; D020123:Sirolimus / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus