title: Factors predictive of relapse of acute leukemia in children after allogeneic hematopoietic cell transplantation.
abstract: The presence of minimal residual disease (MRD) before transplantation is the most important prognostic risk factor predictive of post-transplantation relapse in hematologic malignancies. However, MRD alone does not adequately predict relapse in all patients. To improve upon the ability to identify patients likely to relapse, we evaluated risk factors, in addition to MRD, that may be associated with development of post-transplantation relapse. In this single institution, retrospective cohort study of children with acute leukemia or myelodysplastic syndrome who had undergone a first allogeneic transplantation and had pretransplantation MRD evaluation, 40 of 93 patients (43%) experienced relapse. Univariate analysis demonstrated that African American race, high initial white blood cell count, central nervous system (CNS) disease at diagnosis, short first complete remission, nonmyeloablative (NMA) conditioning, lack of remission, and MRD before transplantation were associated with worse relapse-free survival (RFS). In a Cox multivariable analysis, CNS disease (P = .009), lack of remission (P = .01), and NMA conditioning (P = .04) were independently associated with inferior RFS. Among those in a morphologic complete remission who underwent a myeloablative transplantation, having both CNS disease at diagnosis (specifically in acute lymphoblastic leukemia) and MRD positivity was an independent risk factor predictive of relapse, which has not been previously reported. Results from our study support the existence of risk factors complimentary to pretransplantation MRD. Validation in a larger independent homogenous cohort is needed to develop a prognostic tool for clinical use to predict post-transplantation relapse.
authors.affiliation: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Pediatric Oncology, Johns Hopkins University, Baltimore, Maryland. Electronic address: shahnn@mail.nih.gov.
authors.forename: Nirali N
authors.initials: NN
authors.lastname: Shah
authors.affiliation: Department of Pathology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borowitz
authors.affiliation: Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Pediatric Oncology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Robey
authors.affiliation: Pediatric Oncology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Gamper
authors.affiliation: Pediatric Oncology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Symons
authors.affiliation: Pediatric Oncology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: David M
authors.initials: DM
authors.lastname: Loeb
authors.affiliation: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Wayne
authors.affiliation: Pediatric Oncology, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Allen R
authors.initials: AR
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000473:pathology / Q000628:therapy*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000473:pathology / Q000628:therapy*; D018365:Neoplasm, Residual; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
keywords: Leukemia; Minimal residual disease; Post-transplantation relapse; Risk factors