Randomized trial of blood eosinophil count monitoring as a guide to corticosteroid dosage adjustment after heart transplantation.
BACKGROUND
Increases in blood eosinophil counts (EOS) beyond 0.06 x 10(9)/liter precede treated heart allograft rejection. An oral prednisolone dose of 0.35 mg/kg/day usually suppresses EOS below this threshold.


METHODS
We designed a randomized trial to compare our empirical protocol for steroid dose adjustment with a novel protocol guided by EOS monitoring during the first 3 months after heart transplantation. Eighty patients were randomized to either have their EOS reported and used for steroid dose adjustment (RG; n=40), or not reported (NG; n=40). RG patients had their steroid dosage increased if EOS exceeded 0.06 x 10(9)/liter.


RESULTS
RG patients had an 83% lower risk of treated rejection (P=0.035) and lower median intravenous dose of methyl-prednisolone (P=0.017) than NG during the first 6 postoperative weeks. The proportion of diagnostic increases in EOS that were followed within 2 weeks by treated rejection was 42% greater in NG than RG (P=0.0001), compatible with a direct impact of EOS-guided prednisolone dose adjustment on the risk of subsequent rejection. Overall, RG had less than half the risk of rejection of any grade (P<0.001) and significantly more rejection-free biopsies than NG (P=0.001). The mean oral prednisolone dosage was significantly greater in RG than NG during the first (P=0.014) and second (P=0.001) 6 weeks of follow-up. This did not increase the incidence of serious steroid-related side effects.


CONCLUSIONS
EOS monitoring is a simple, cheap, and effective means of optimizing steroid immunosuppression. Restriction of the EOS-guided steroid dosing protocol to periods of prolonged hospitalisation during the first 3 postoperative months should limit the requirement for higher prednisolone dosage without affecting immunosuppressive efficacy.
Trull
A K
AK
Pharmacology Clinical Research, Research and Development, Department of Pathology, Papworth Hospital, Cambridge, UK.
Steel
L A
LA
Sharples
L D
LD
Akhlaghi
F
F
Parameshwar
J
J
Cary
N
N
Wallwork
J
J
Large
S
S
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D011239:Prednisolone / Q000008:administration & dosage
D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D007166:Immunosuppressive Agents; D011239:Prednisolone