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.
Werk et al. (Tue,) studied this question.