70855
document
Prolonged sirolimus administration after allogeneic hematopoietic cell transplantation is associated with decreased risk for moderate-severe chronic graft-versus-host disease . Effective pharmacological strategies employed in allogeneic hematopoietic cell transplantation should prevent serious chronic graft-versus-host disease and facilitate donor-recipient immune tolerance . Based on demonstrated pro-tolerogenic activity , sirolimus ( rapamycin ) is an agent with promise to achieve these goals . In a long-term follow-up analysis of a randomized phase II trial comparing sirolimus/tacrolimus versus methotrexate/tacrolimus for graft-versus-host disease prevention in matched sibling or unrelated donor transplant , we examined the impact of prolonged sirolimus administration ( ≥ 1 year post-transplant ) . Median follow-up time for surviving patients at time of this analysis was 41 months ( range 27-60 ) for sirolimus/tacrolimus and 49 months ( range 29-63 ) for methotrexate/tacrolimus . Sirolimus/tacrolimus patients had significantly lower National Institutes of Health Consensus moderate-severe chronic graft-versus-host disease ( 34 % vs. 65 % ; P=0.004 ) and late acute graft-versus-host disease ( 20 % vs. 43 % ; P=0.04 ) . While sirolimus/tacrolimus patients had lower prednisone exposure and earlier discontinuation of tacrolimus ( median time to tacrolimus discontinuation 368 days vs. 821 days ; P=0.002 ) , there was no significant difference in complete immune suppression discontinuation ( 60-month estimate : 43 % vs. 31 % ; P=0.78 ) . Prolonged sirolimus administration represents a viable approach to mitigate risk for moderate-severe chronic and late acute graft-versus-host disease . Further study of determinants of successful immune suppression discontinuation is needed .
70856
Intervention_Pharmacological
sirolimus
70857
Intervention_Pharmacological
sirolimus ( rapamycin )
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Intervention_Pharmacological
sirolimus/tacrolimus
70859
Intervention_Pharmacological
methotrexate/tacrolimus
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Intervention_Pharmacological
sirolimus
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Outcome_Physical
chronic graft-versus-host disease .
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Outcome_Physical
post-transplant ) .
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Outcome_Other
Median follow-up time for surviving patients
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Outcome_Physical
lower National Institutes of Health Consensus moderate-severe chronic graft-versus-host disease
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Outcome_Physical
and late acute graft-versus-host disease
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Outcome_Physical
lower prednisone exposure
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Outcome_Physical
earlier discontinuation of tacrolimus
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Outcome_Physical
in complete immune suppression discontinuation
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Participant_Condition
allogeneic hematopoietic cell transplantation
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Participant_Condition
allogeneic hematopoietic cell transplantation