title: Minimal residual disease levels in bone marrow and peripheral blood are comparable in children with T cell acute lymphoblastic leukemia (ALL), but not in precursor-B-ALL.
abstract: Sensitive and quantitative detection of minimal residual disease (MRD) in bone marrow (BM) samples of children with acute lymphoblastic leukemia (ALL) is essential for evaluation of early treatment response. In this study, we evaluated whether the traumatic BM samplings can be replaced by peripheral blood (PB) samplings. MRD levels were analyzed in follow-up samples of 62 children with precursor-B-ALL (532 paired BM-PB samples) and 22 children with T-ALL (149 paired BM-PB samples) using real-time quantitative PCR (RQ-PCR) analysis of immunoglobulin and T cell receptor gene rearrangements with sensitivities of 10(-3) to 10(-5) (one ALL cell in 10(3) to 10(5) normal cells). In 14 of the 22 T-ALL patients, detectable MRD levels were found in 67 paired BM-PB samples: in 47 pairs MRD was detected both in BM and PB, whereas in the remaining pairs very low MRD levels were detected in BM (n = 11) or PB (n = 9) only. The MRD levels in the paired BM-PB samples were very comparable and strongly correlated (r(s) = 0.849). Comparable results were obtained earlier by immunophenotyping in 26 T-ALL patients (321 paired BM-PB samples), which also showed a strong correlation between MRD levels in paired BM and PB samples (r(s) = 0.822). In 39 of the 62 precursor-B-ALL patients, MRD was detected in 107 BM-PB pairs: in 48 pairs MRD was detected in both BM and PB, in 47 pairs MRD was solely detected in BM (at variable levels), and in 12 pairs only the PB sample was MRD-positive at very low levels (</=10(-4)). Furthermore, in the 48 double-positive pairs, MRD levels in BM and PB varied enormously with MRD levels in BM being up to 1000 times higher than in the corresponding PB samples. Consequently, BM samples cannot easily be replaced by PB sampling for MRD analysis in childhood precursor-B-ALL, in line with their BM origin. In T-ALL, which are of thymic origin, BM sampling might be replaced by PB sampling, because the dissemination of T-ALL cells to BM and PB appears to be comparable.
authors.affiliation: Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: V H J
authors.initials: VH
authors.lastname: van der Velden
authors.forename: D C H
authors.initials: DC
authors.lastname: Jacobs
authors.forename: A J M
authors.initials: AJ
authors.lastname: Wijkhuijs
authors.forename: W M
authors.initials: WM
authors.lastname: Comans-Bitter
authors.forename: M J
authors.initials: MJ
authors.lastname: Willemse
authors.forename: K
authors.initials: K
authors.lastname: Hählen
authors.forename: W A
authors.initials: WA
authors.lastname: Kamps
authors.forename: E R
authors.initials: ER
authors.lastname: van Wering
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor / Q000032:analysis*; D001773:Blood Cells / Q000737:chemistry / Q000473:pathology*; D001854:Bone Marrow Cells / Q000737:chemistry / Q000473:pathology*; D001856:Bone Marrow Examination; D002648:Child; D003199:Computer Systems; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D015329:Gene Rearrangement, T-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D016130:Immunophenotyping; D009363:Neoplasm Proteins / Q000235:genetics; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction / Q000379:methods*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics / Q000473:pathology*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics / Q000473:pathology*; D011518:Proto-Oncogene Proteins; D012680:Sensitivity and Specificity; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human