Masahiro Teramoto, Yoshimitsu Shimomura, Masamitsu Yanada, Shohei Mizuno, Koji Nagafuji, Hirohisa Nakamae, Masao Ogata, Noboru Asada, Tetsuya Eto, Toshihiko Ando, Atsushi Wake, Masatsugu Tanaka, Masashi Sawa, Naoyuki Uchida, Yuta Hasegawa, Masahito Tokunaga, Hideki Nakasone, Fumihiko Ishimaru, Junya Kanda, Yoshiko Atsuta, Takaaki Konuma
Post-transplant cyclophosphamide-based haploidentical transplantation (PTCy-haplo) and umbilical cord blood transplantation (uCBT) have the potential to mitigate the adverse impact of pretransplant measurable residual disease (MRD) on post-transplant survival of patients with acute myeloid leukemia (AML). To compare outcomes between PTCy-haplo and uCBT in patients with MRD-positive AML, we retrospectively analyzed MRD-positive AML patients aged ≥16 years enrolled in the Japanese nationwide registry from 2015 to 2023 who underwent PTCy-haplo (n = 94) or single uCBT (n = 275) as first transplantation. MRD was evaluated by polymerase chain reaction for chimeric genes (n = 139) or Wilms' tumor 1 expression (n = 230). In multivariable analyses, the PTCy-haplo and uCBT groups showed comparable relapse-free survival (RFS) (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.67‒1.67; P = 0.809), overall survival (HR, 0.92; 95% CI, 0.57‒1.49; P = 0.735), graft-versus-host disease (GVHD)-free RFS (HR, 0.89; 95% CI, 0.61‒1.31; P = 0.560), chronic GVHD (cGVHD)-free RFS (HR, 1.20; 95% CI, 0.81‒1.78; P = 0.368), relapse (HR, 0.78; 95% CI, 0.39-1.57; P = 0.490) and nonrelapse mortality (HR, 1.48; 95% CI, 0.79-2.79; P = 0.230). Compared to the uCBT group, the PTCy-haplo group showed lower incidences of grade II‒IV (HR, 0.60; 95% CI, 0.39-0.92; P = 0.020) and III‒IV acute GVHD (aGVHD) (HR, 0.28; 95% CI, 0.10-0.79; P = 0.016), but a higher incidence of extensive cGVHD (HR, 2.23; 95% CI, 1.16-4.29; P = 0.017). Furthermore, higher likelihoods of neutrophil (HR, 2.12; 95% CI, 1.61-2.80; P < 0.001) and platelet engraftment (HR, 1.96; 95% CI, 1.39-2.76; P < 0.001) were observed in the PTCy-haplo group. In subgroup analysis, uCBT was associated with improved RFS in AML with poor cytogenetic risk (HR for PTCy-haplo versus uCBT, 2.49; 95% CI, 1.04-5.97; P for interaction = 0.032). In conclusion, survival outcomes were comparable between PTCy-haplo and uCBT in patients with MRD-positive AML. PTCy-haplo was associated with a lower risk of aGVHD, a higher risk of cGVHD and superior hematopoietic engraftment. In the subgroup of patients with poor cytogenetic risk, uCBT was associated with improved RFS.