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: Gunnar Cario, Peter Rhein, Rita Mitlöhner, Martin Zimmermann, Obul R Bandapalli, Renja Romey, Anja Moericke, Wolf-Dieter Ludwig, Richard Ratei, Martina U Muckenthaler, Andreas E Kulozik, Martin Schrappe, Martin Stanulla, Leonid Karawajew
• Journal: Haematologica (Haematologica) Vol. 99 Issue 1 Pg. 103-10 (Jan 2014) ISSN: 1592-8721 [Electronic] Italy
• PMID: 23911702 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CRLF2 protein, human
• P2RY8 protein, human
• Receptors, Cytokine
• Receptors, Interleukin-7
• Receptors, Purinergic P2Y
• Leukocyte Common Antigens

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Child
• Child, Preschool
• Chromosome Aberrations
• Female
• Humans
• Immunophenotyping
• Induction Chemotherapy
• Infant
• Leukocyte Common Antigens (genetics, metabolism)
• Male
• Mutation
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, metabolism, mortality)
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, metabolism, mortality)
• Prognosis
• Receptors, Cytokine (genetics, metabolism)
• Receptors, Interleukin-7 (genetics, metabolism)
• Receptors, Purinergic P2Y (genetics, metabolism)
• Recurrence
• Treatment Outcome