title: Persistent MRD before and after allogeneic BMT predicts relapse in children with acute lymphoblastic leukaemia.
abstract: Minimal residual disease (MRD) during early chemotherapy is a powerful predictor of relapse in acute lymphoblastic leukaemia (ALL) and is used in children to determine eligibility for allogeneic haematopoietic stem cell transplantation (HSCT) in first (CR1) or later complete remission (CR2/CR3). Variables affecting HSCT outcome were analysed in 81 children from the ANZCHOG ALL8 trial. The major cause of treatment failure was relapse, with a cumulative incidence of relapse at 5 years (CIR) of 32% and treatment-related mortality of 8%. Leukaemia-free survival (LFS) and overall survival (OS) were similar for HSCT in CR1 (LFS 62%, OS 83%, n = 41) or CR2/CR3 (LFS 60%, OS 72%, n = 40). Patients achieving bone marrow MRD negativity pre-HSCT had better outcomes (LFS 83%, OS 92%) than those with persistent MRD pre-HSCT (LFS 41%, OS 64%, P < 0·0001) or post-HSCT (LFS 35%, OS 55%, P < 0·0001). Patients with B-other ALL had more relapses (CIR 50%, LFS 41%) than T-ALL and the main precursor-B subtypes including BCR-ABL1, KMT2A (MLL), ETV6-RUNX1 (TEL-AML1) and hyperdiploidy >50. A Cox multivariate regression model for LFS retained both B-other ALL subtype (hazard ratio 4·1, P = 0·0062) and MRD persistence post-HSCT (hazard ratio 3·9, P = 0·0070) as independent adverse prognostic variables. Persistent MRD could be used to direct post-HSCT therapy.
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Sutton
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Venn
authors.forename: Tamara
authors.initials: T
authors.lastname: Law
authors.forename: Anuruddhika
authors.initials: A
authors.lastname: Dissanayake
authors.forename: Tatjana
authors.initials: T
authors.lastname: Kilo
authors.forename: Michelle
authors.initials: M
authors.lastname: Haber
authors.forename: Murray D
authors.initials: MD
authors.lastname: Norris
authors.forename: Chris
authors.initials: C
authors.lastname: Fraser
authors.forename: Frank
authors.initials: F
authors.lastname: Alvaro
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: Toby N
authors.initials: TN
authors.lastname: Trahair
authors.forename: Luciano
authors.initials: L
authors.lastname: Dalla-Pozza
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Marshall
authors.forename: Tracey A
authors.initials: TA
authors.lastname: O'Brien
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D003131:Combined Modality Therapy; D005260:Female; D017353:Gene Deletion; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D012008:Recurrence; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome
chemical_list: C497239:IKZF1 protein, human; D009363:Neoplasm Proteins; D051740:Ikaros Transcription Factor
keywords: IKZF1; acute lymphoblastic leukaemia; bone marrow transplantation; childhood leukaemia; minimal residual disease