Beta-blocker use and outcome after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for patients with acute myeloid leukemia (AML) through an immune-mediated graft-versus-leukemia effect, but relapse is common. Studies in solid tumors have shown that adrenergic stress impairs anti-tumor immunity, and that beta-blockade can prolong survival in mice and patients receiving immunotherapy. To this end, we investigated whether beta-blocker use impacts outcomes in AML patients undergoing HSCT. We analyzed the cumulative incidences of relapse (CIR), non-relapse mortality (NRM) and overall survival (OS) in 413 patients with AML who underwent first allogeneic HSCT. A total of 112 patients (27%) received beta-blockers after HSCT. The use of beta-blockers was associated with a lower CIR (P = 0.024), but with a higher NRM (P = 0.002); OS did not differ. In multivariable analyses, beta-blocker use emerged as an independent factor associated with CIR (P = 0.024) and NRM (P = 0.012), but not OS (P = 0.353). The occurrence of acute or chronic graft-versus-host disease (GvHD) was not significantly associated with beta-blocker use, but chronic GvHD or organ toxicity was more often the primary cause of death in the beta-blocker group (P = 0.041). The use of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) or calcium channel blockers was not significantly associated with outcome. Our study is the first to demonstrate an association between beta-blocker use and post-transplant outcome in AML and supports further investigation of carefully titrated beta-adrenergic blockade as a potential means to influence donor cell immune responses in the transplant setting.