title: Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested?
abstract: We previously showed that minimal residual disease (MRD) detection pre-hematopoietic cell transplant (HCT) and acute GvHD (aGvHD) independently predicted risk of relapse in pediatric ALL. In this study we further define risk by assessing timing of relapse and the effects of leukemia risk category and post-HCT MRD. By multivariate analysis, pre-HCT MRD <0.1% and aGvHD by day +55 were associated with decreased relapse and improved event-free survival (EFS). Intermediate leukemia risk status predicted decreased relapse, and improved EFS and overall survival (OS). Patients with pre-HCT MRD ⩾0.1% who did not develop aGvHD compared with those with MRD <0.1% who did develop aGvHD had much worse survival (2 years EFS 18% vs 71%; P=0.001, 2 years OS 46 vs 74%; P=0.04). Patients with pre-HCT MRD <0.1% who did not experience aGvHD had higher rates of relapse than those who did develop aGvHD (40% vs 13%; P= 0.008). Post-HCT MRD led to a substantial increase in relapse risk (HR=4.5, P<0.01). Patients at high risk of relapse can be defined after transplant using leukemia risk category, presence of MRD pre or post HCT, and occurrence of aGvHD. An optimal window to initiate intervention to prevent relapse occurs between day +55 and +200 after HCT.
authors.affiliation: Division of Hematology and Hematological Malignancies, Huntsman Cancer Institute/University of Utah School of Medicine, Primary Children's Hospital, Salt Lake City, UT, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Pulsipher
authors.affiliation: Department of Preventive Medicine, USC Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Langholz
authors.affiliation: Manitoba Blood and Marrow Transplant Program, Winnepeg, Manitoba, Canada.
authors.forename: D A
authors.initials: DA
authors.lastname: Wall
authors.affiliation: Department of Pediatrics University of BC, BC Children's Hospital, Vancouver, British Columbia, Canada.
authors.forename: K R
authors.initials: KR
authors.lastname: Schultz
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bunin
authors.affiliation: NYU Department of Pediatrics and Cancer Institute, NYU Langone Medical Center, New York, NY, USA.
authors.forename: W
authors.initials: W
authors.lastname: Carroll
authors.affiliation: Division of Hematology and Hematological Malignancies, Huntsman Cancer Institute/University of Utah School of Medicine, Primary Children's Hospital, Salt Lake City, UT, USA.
authors.forename: E
authors.initials: E
authors.lastname: Raetz
authors.affiliation: NYU Department of Pediatrics and Cancer Institute, NYU Langone Medical Center, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gardner
authors.affiliation: Division of Blood and Marrow Transplantation and Cellular Therapies, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Goyal
authors.affiliation: Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA.|Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gastier-Foster
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Borowitz
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Teachey
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Department of Pathology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Grupp
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000517:prevention & control; D012008:Recurrence; D015996:Survival Rate; D013997:Time Factors