More precisely defining risk peri-HCT in pediatric ALL: Pre- vs post-MRD measures, serial positivity, and risk modeling
Detection of minimal residual disease (MRD) pre– and post–hematopoietic cell transplantation (HCT) for pediatric acute lymphoblastic leukemia (ALL) has been associated with relapse and poor survival. Published studies have had insufficient numbers to: (1) compare the prognostic value of pre-HCT and post-HCT MRD; (2) determine clinical factors post-HCT associated with better outcomes in MRD1 patients; and (3) use MRD and other clinical factors to develop and validate a prognostic model for relapse in pediatric patients with ALL who undergo allogeneic HCT. To address these issues, we assembled an international database including sibling (n 5 191), unrelated (n 5 259), mismatched (n 5 56), and cord blood (n 5 110) grafts given after myeloablative conditioning. Although high and very high MRD pre-HCT were significant predictors in univariate analysis, with bivariate analysis using MRD pre-HCT and post-HCT, MRD pre-HCT at any level was less predictive than even low-level MRD post-HCT. Patients with MRD pre-HCT must become MRD low/negative at 1 to 2 months and negative within 3 to 6 months after HCT for successful therapy. Factors associated with improved outcome of patients with detectable MRD post-HCT included acute graft-versus-host disease. We derived a risk score with an MRD cohort from Europe, North America, and Australia using negative predictive characteristics (late disease status, non–total body irradiation regimen, and MRD [high, very high]) defining good, intermediate, and poor risk groups with 2-year cumulative incidences of relapse of 21%, 38%, and 47%, respectively. We validated the score in a second, more contemporaneous cohort and noted 2-year cumulative incidences of relapse of 13%, 26%, and 47% (P, .001) for the defined risk groups.
|Persistent URL||dx.doi.org/10.1182/bloodadvances.2019000449, hdl.handle.net/1765/121570|
Bader, P.I, Salzmann-Manrique, E. (Emilia), Balduzzi, A. (Adriana), Dalle, J.-H. (Jean-Hugues), Woolfrey, A.E. (Ann E.), Bar, M. (Merav), … Pulsipher, M.A. (Michael A.). (2019). More precisely defining risk peri-HCT in pediatric ALL: Pre- vs post-MRD measures, serial positivity, and risk modeling. Blood Advances, 3(21), 3393–3405. doi:10.1182/bloodadvances.2019000449