Funding
National Institutes of Health (NIH)
Howard Hughes Medical Institute (HHMI)
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...U.S. Department of Defense (DOD)
ARTICLE ABSTRACT
Peripheral nerves promote mouse bone marrow regeneration by activating β2- and β3-adrenergic receptor signaling, raising the possibility that nonselective β-blockers could inhibit engraftment after hematopoietic cell transplants (HCT). We observed no effect of β-blockers on steady-state mouse hematopoiesis. However, mice treated with a nonselective β-blocker (carvedilol), but not a β1-selective inhibitor (metoprolol), exhibited impaired hematopoietic regeneration after syngeneic or allogeneic HCTs. At two institutions, patients who received nonselective, but not β1-selective, β-blockers after allogeneic HCT exhibited delayed platelet engraftment and reduced survival. This was particularly observed in patients who received posttransplant chemotherapy for graft-versus-host disease prophylaxis, which also accentuated the inhibitory effect of carvedilol on engraftment in mice. In patients who received autologous HCTs, nonselective β-blockers were associated with little or no delay in engraftment. The inhibitory effect of nonselective β-blockers after allogeneic HCT was overcome by transplanting larger doses of hematopoietic cells.Significance: Patients who receive allogeneic HCTs followed by posttransplant chemotherapy for graft-versus-host disease prophylaxis may be at risk of delayed engraftment and increased mortality if administered nonselective β-blockers after transplantation. Transient discontinuation of nonselective β-blockers or transitioning to β1-selective inhibitors after HCT may accelerate engraftment and improve clinical outcomes.See related commentary by Bhatia, p. 666
