title: Paucity of leukemic progenitor cells in the bone marrow of pediatric B-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse.
abstract: Isolated extramedullary relapse in childhood acute lymphoblastic leukemia (ALL) may be accompanied by occult bone marrow disease. We used a highly sensitive assay to quantify leukemic progenitor cells (LPCs) in the bone marrow of such patients. Multiparameter flow cytometry and blast colony assays were used to detect LPCs in the bone marrow of 31 pediatric B-lineage ALL patients with an isolated extramedullary first relapse. Sites of relapse were central nervous system (22 patients), testes (7 patients), and eye (2 patients). Bone marrow (BM) LPC counts ranged from 0/10(6) mononuclear cells (MNCs) to 356/10(6) MNCs (mean +/- SE, 27.8+/-13.1/10(6) MNCs). LPCs were undetectable in 19 patients (61%). The BM LPC burden at the time of extramedullary relapse was similar, regardless of site (Wilcoxon P = 0.77) or time of relapse (Wilcoxon P = 0.80). Compared with higher risk, standard risk at initial diagnosis showed a trend for increased BM LPC burden (mean +/- SE, 44.6+/-17.1 versus 7.5+/-3.3; Wilcoxon P = 0.22). After successful postrelapse induction chemotherapy, LPC counts in 21 evaluated patients ranged from 0/10(6) to 175/10(6) MNCs (mean +/- SE, 15.9+/-9.6/10(6) MNCs). By comparison, LPC burden was higher after successful induction chemotherapy among children with an early BM relapse (range, 0 to 3262/ 106 MNC; mean +/- SE, 166+/-107; Wilcoxon P = 0.11). Thus, not all patients with an extramedullary relapse have occult systemic failure with substantial involvement of the bone marrow, and after reinduction therapy, LPC counts were lower in these patients than in patients treated for an overt BM first relapse.
authors.affiliation: ALL Biology Reference Laboratory, Parker Hughes Cancer Center, Hughes Institute, St. Paul, Minnesota 55113, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
authors.forename: P S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: D O
authors.initials: DO
authors.lastname: Stram
authors.forename: M G
authors.initials: MG
authors.lastname: Sensel
authors.forename: M B
authors.initials: MB
authors.lastname: Sarquis
authors.forename: K H
authors.initials: KH
authors.lastname: Lazarus
authors.forename: M
authors.initials: M
authors.lastname: Willoughby
mesh_terms: D000293:Adolescent; D001853:Bone Marrow / Q000473:pathology*; D002051:Burkitt Lymphoma / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000473:pathology / Q000556:secondary; D002648:Child; D002675:Child, Preschool; D005134:Eye Neoplasms / Q000473:pathology / Q000556:secondary; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000473:pathology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D013736:Testicular Neoplasms / Q000473:pathology / Q000556:secondary; D014410:Tumor Stem Cell Assay