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Paucity of Leukemic Progenitor Cells in the Bone Marrow of Pediatric B-Lineage Acute Lymphoblastic Leukemia Patients with an Isolated Extramedullary First Relapse¹

ALL Biology Reference Laboratory, Children’s Cancer Group, Parker Hughes Cancer Center, Hughes Institute, St. Paul, Minnesota 55113 [F. M. U., M. B. S.]; Department of Hematology-Oncology, Children’s Hospital, Los Angeles, California 90027 [P. S. G.]; Department of Preventive Medicine, University of Southern California, Los Angeles, California 90033 [D. O. S.]; Children’s Cancer Group, Arcadia, California 91066 [D. O. S., M. G. S.]; Department of Pediatric Hematology/Oncology, Methodist Children’s Hospital of South Texas, San Antonio, Texas 78229 [K. H. L.]; and Princess Margaret Hospital, Perth, Western Australia, Australia 6001 [M. W.]

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 0/10⁶ mononuclear cells (MNCs) to 356/10⁶ MNCs (mean ± SE, 27.8 ± 13.1/10⁶ 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 0/10⁶ to 175/10⁶ MNCs (mean ± SE, 15.9 ± 9.6/10⁶ 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.

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