title: High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol.
abstract: Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from intensified treatment. We earlier identified PTPRC (CD45) gene expression as a potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 was measured by flow cytometry in 1065 patients treated according to the ALL-BFM-2000 protocol. The 75(th) percentile was used as cut-off to distinguish a CD45-high from a CD45-low group. As mean CD45 expression was significantly higher in T-cell acute lymphoblastic leukemia than in B-cell-precursor acute lymphoblastic leukemia (P<0.0001), the analysis was performed separately in both groups. In B-cell-precursor acute lymphoblastic leukemia we observed a significant association of a high CD45 expression with older age, high initial white blood cell count, ETV6/RUNX1 negativity, absence of high hyperdiploidy (P<0.0001), MLL/AF4 positivity (P=0.002), BCR/ABL1 positivity (P=0.007), prednisone poor response (P=0.002) and minimal residual disease (P<0.0001). In T-cell acute lymphoblastic leukemia we observed a significant association with initial white blood cell count (P=0.0003), prednisone poor response (P=0.01), and minimal residual disease (P=0.02). Compared to CD45-low patients, CD45-high patients had a lower event-free survival rate (B-cell-precursor acute lymphoblastic leukemia: 72 ± 3% versus 86 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 60 ± 8% versus 78 ± 4%, P=0.02), which was mainly attributable to a higher cumulative relapse incidence (B-cell-precursor acute lymphoblastic leukemia: 22 ± 3% versus 11 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 31 ± 8% versus 11 ± 3%, P=0.003) and kept its significance in multivariate analysis considering sex, age, initial white blood cell count, and minimal residual disease in B-cell-precursor- and T-cell acute lymphoblastic leukemia, and additionally presence of ETV6/RUNX1, MLL/AF4 and BCR/ABL1 rearrangements in B-cell-precursor acute lymphoblastic leukemia (P=0.002 and P=0.025, respectively). Consideration of CD45 expression may serve as an additional stratification tool in BFM-based protocols. (ClinicalTrials.gov identifier: NCT00430118).
authors.affiliation: g.cario@pediatrics.uni-kiel.de.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Cario
authors.forename: Peter
authors.initials: P
authors.lastname: Rhein
authors.forename: Rita
authors.initials: R
authors.lastname: Mitlöhner
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Obul R
authors.initials: OR
authors.lastname: Bandapalli
authors.forename: Renja
authors.initials: R
authors.lastname: Romey
authors.forename: Anja
authors.initials: A
authors.lastname: Moericke
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: Richard
authors.initials: R
authors.lastname: Ratei
authors.forename: Martina U
authors.initials: MU
authors.lastname: Muckenthaler
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Kulozik
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.forename: Leonid
authors.initials: L
authors.lastname: Karawajew
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D060828:Induction Chemotherapy; D007223:Infant; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009154:Mutation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000235:genetics / Q000378:metabolism; D058470:Receptors, Purinergic P2Y / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: C498762:CRLF2 protein, human; C578279:P2RY8 protein, human; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7; D058470:Receptors, Purinergic P2Y; D017493:Leukocyte Common Antigens
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