Impact of Conditioning Intensity on Clinical Outcomes of Second Allogeneic Hematopoietic Cell Transplantation for Relapse After First Transplantation

ABSTRACT Although second allogeneic hematopoietic cell transplantation HCT (HCT2) is a potentially curative treatment for patients relapsing after their first HCT (HCT1), it is associated with higher non‐relapse mortality (NRM) compared with HCT1. Furthermore, while reduced‐intensity conditioning (RIC) in HCT2 might decrease NRM, there is no consensus on which patients may benefit from RIC. We retrospectively analyzed 2478 patients who underwent HCT2 for relapse of hematologic malignancies after HCT1. In a multivariate analysis, older recipient age, short duration between HCT1 and HCT2, RIC in HCT1, HCT‐CI ≥ 2, and ECOG PS ≥ 2 were associated with an increased risk of NRM. RIC in HCT2 was associated with better NRM compared to myeloablative conditioning (MAC) (hazard ratio [HR] 0.83, 95% confidence interval [CI]: 0.72–0.97; p = 0.018), but was not significantly associated with overall survival (OS) (HR 0.91, 95% CI: 0.82–1.01; p = 0.075). We observed a significant interaction for NRM between extensive cGVHD in HCT1 and the conditioning intensity of HCT2 (interaction p < 0.001), meaning that the benefit of RIC in HCT2 was seen in patients with extensive cGVHD in HCT1, but not in those without cGVHD. RIC in HCT2 was also associated with superior OS in patients with extensive cGVHD in HCT1 (HR 0.68, 95% CI: 0.49–0.93; p = 0.02), with significant interaction between the conditioning intensity and the prior history of extensive cGVHD (interaction p = 0.01). This study suggests that RIC in HCT2 reduces NRM for HCT2 and improves OS, especially in patients with a history of extensive cGVHD.