title: Detectable minimal residual disease before hematopoietic cell transplantation is prognostic but does not preclude cure for children with very-high-risk leukemia.
abstract: In patients with acute leukemia, detection of minimal residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) correlates with risk of relapse. However, the level of MRD that is most likely to preclude cure by HCT is unclear, and the benefit of further chemotherapy to reduce MRD before HCT is unknown. In 122 children with very-high-risk acute lymphoblastic leukemia (ALL; n = 64) or acute myeloid leukemia (AML, n = 58), higher MRD levels at the time of HCT predicted a poorer survival after HCT (P = .0019); MRD was an independent prognostic factor in a multivariate analysis (P = .0035). However, the increase in risk of death associated with a similar increment of MRD was greater in ALL than in AML, suggesting that a pretransplantation reduction of leukemia burden would have a higher impact in ALL. At any given MRD level, survival rates were higher for patients treated in recent protocols: the 5-year overall survival for patients with ALL was 49% if MRD was detectable and 88% if it was not and the corresponding rates for patients with AML were 67% and 80%, respectively. Although MRD before HCT is a strong prognostic factor, its impact has diminished and should not be regarded as a contraindication for HCT.
authors.affiliation: Department of Bone Marrow Transplantation and Cellular Therapy, St Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105-2794, USA. wing.leung@stjude.org
authors.forename: Wing
authors.initials: W
authors.lastname: Leung
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Elaine
authors.initials: E
authors.lastname: Coustan-Smith
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Deqing
authors.initials: D
authors.lastname: Pei
authors.forename: Kwan
authors.initials: K
authors.lastname: Gan
authors.forename: Ashok
authors.initials: A
authors.lastname: Srinivasan
authors.forename: Christine
authors.initials: C
authors.lastname: Hartford
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Triplett
authors.forename: Mari
authors.initials: M
authors.lastname: Dallas
authors.forename: Asha
authors.initials: A
authors.lastname: Pillai
authors.forename: David
authors.initials: D
authors.lastname: Shook
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: John T
authors.initials: JT
authors.lastname: Sandlund
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.forename: Hiroto
authors.initials: H
authors.lastname: Inaba
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Laver
authors.forename: Dario
authors.initials: D
authors.lastname: Campana
mesh_terms: D002648:Child; D015331:Cohort Studies; D000075202:Contraindications; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000473:pathology* / Q000628:therapy*; D008297:Male; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology* / Q000628:therapy*; D011379:Prognosis; D012307:Risk Factors; D014184:Transplantation, Homologous