title: Implications of delayed bone marrow aspirations at the end of treatment induction for risk stratification and outcome in children with acute lymphoblastic leukaemia.
abstract: Minimal residual disease (MRD) at the end of induction therapy is important for risk stratification of acute lymphoblastic leukaemia (ALL), but bone marrow (BM) aspiration is often postponed or must be repeated to fulfil qualitative and quantitative criteria for morphological assessment of haematological remission and/or MRD analysis. The impact of BM aspiration delay on measured MRD levels and resulting risk stratification is currently unknown. We analysed paired MRD data of 289 paediatric ALL patients requiring a repeat BM aspiration. MRD levels differed in 108 patients (37%) with a decrease in the majority (85/108). This would have resulted in different risk group allocation in 64 of 289 patients (23%) when applying the ALL-Berlin-Frankfurt-Münster 2000 criteria. MRD change was associated with the duration of delay; 40% of patients with delay ≥7 days had a shift to lower MRD levels compared to only 18% after a shorter delay. Patients MRD-positive at the original but MRD-negative at the repeat BM aspiration (n = 50) had a worse 5-year event-free survival than those already negative at first aspiration (n = 115) (86 ± 5% vs. 94 ± 2%; P = 0·024). We conclude that BM aspirations should be pursued as scheduled in the protocol because delayed MRD sampling at end of induction may result in false-low MRD load and distort MRD-based risk assessment.
authors.affiliation: CLIP, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Zuna
authors.affiliation: Department of Paediatrics, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Moericke
authors.affiliation: Department of Paediatrics, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Mari
authors.initials: M
authors.lastname: Arens
authors.affiliation: Institute of Human Genetics, Ruprecht-Karls University, Heidelberg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Koehler
authors.affiliation: Children's Cancer Research Institute and St. Anna Kinderspital, Department of Paediatrics, Medical University, Vienna, Austria.
authors.forename: Renate
authors.initials: R
authors.lastname: Panzer-Grümayer
authors.affiliation: Institute of Human Genetics, Ruprecht-Karls University, Heidelberg, Germany.
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.affiliation: Children's Cancer Research Institute and St. Anna Kinderspital, Department of Paediatrics, Medical University, Vienna, Austria.
authors.forename: Susanna
authors.initials: S
authors.lastname: Fischer
authors.affiliation: CLIP, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Fronkova
authors.affiliation: CLIP, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Zaliova
authors.affiliation: Department of Paediatrics, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Schrauder
authors.affiliation: Department of Paediatric Haematology and Oncology, Medical School Hannover, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.affiliation: Department of Paediatric Haematology and Oncology, Medical School Hannover, Hannover, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: CLIP, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Trka
authors.affiliation: CLIP, Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University Prague and University Hospital Motol, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.affiliation: Children's Cancer Research Institute and St. Anna Kinderspital, Department of Paediatrics, Medical University, Vienna, Austria.
authors.forename: Andishe
authors.initials: A
authors.lastname: Attarbaschi
authors.affiliation: Children's Cancer Research Institute and St. Anna Kinderspital, Department of Paediatrics, Medical University, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.affiliation: Department of Paediatrics, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.affiliation: Department of Paediatrics, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Cario
mesh_terms: D000293:Adolescent; D044963:Biopsy, Fine-Needle; D001856:Bone Marrow Examination / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D057210:Delayed Diagnosis; D003951:Diagnostic Errors / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000473:pathology*; D012074:Remission Induction; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
keywords: Paediatric acute lymphoblastic leukaemia; bone marrow aspiration delay; minimal residual disease; risk stratification; treatment outcome