BEST trial halted due to high rate of severe bleeding following low-dose platelet transfusion

A noninferiority trial conducted to compare low-dose and standard-dose strategies for platelet transfusion was stopped early after reaching a preset limit for grade-4 bleeding.

Researchers with the BEST Collaborative, who conducted the randomized, controlled trial, said more research was required to determine whether the bleeding associated with low-dose platelet transfusion was clinically significant or merely the result of chance.

The researchers hoped to show that a low-dose platelet component for prophylactic transfusion (1.5 to 3.0 × 10¹¹ platelets per transfusion) was as safe as a standard dose (3.0 to 6.0 × 10¹¹ platelets per transfusion) at preventing chemotherapy-induced thrombocytopenia. They randomly assigned 58 patients to the low-dose strategy and 61 patients to the standard-dose strategy.

The study was to be stopped “if the difference in the proportion of patients with grade-4 bleeding between the two treatment arms exceeded 5% at any time after 50 patients had been enrolled per arm.”

An independent data safety monitoring board stopped the study after three patients (5.2%) in the low-dose arm developed grade-4 bleeding compared with none in the standard-dose arm. Two patients had retinal bleeding with visual impairment and the third had a cerebral bleed. – by Jason Harris

Heddle NM. Blood. 2009;113:1564-1573.

It was very unfortunate that the BEST study was stopped. They had an arbitrarily-established stopping rule, and I think it was clearly by chance that the stopping rule was met. Our trial, the PLADO trial, had many more patients and showed no difference in bleeding grade between any of the arms. I would encourage people to wait until results from PLADO become available, but the abstract is available and there was no difference in bleeding in the arms.

– Sherrill Slichter, MD

Director of Platelet Transfusion Research,

Puget Sound Blood Center, Seattle