Bone marrow leukemic progenitor cell content in pediatric T-lineage acute lymphoblastic leukemia patients with an isolated extramedullary first relapse

Isolated extramedullary relapse in childhood acute lymphoblastic leukemia ( ALL) is associated frequently with the T-lineage immunophenotype and may be accompanied by occult bone marrow disease. We employed highly sensitive mu ltiparameter flow cytometry and blast colony assays to quantify the leukemi c progenitor cell (LPC) burden in the pretreatment bone marrows of 15 pedia tric T-lineage ALL patients with an isolated extramedullary first relapse. Sites of extramedullary relapse were CNS (11 patients), testes (3 patients) . and both CNS and testes (1 patient). Bone marrow LPC were detectable in 8 patients (53%) and undetectable in 7 patients (47%) at day 0 of post-relap se induction therapy. with LPC counts ranging from 0/10(6) mononuclear cell s (MNC) to 518/10(6) MNC (mean +/- SEM. 50 +/- 34 /10(6) MNC). Five of 9 pa tients with an early relapse (< 18 months after achieving a first complete remission (CR1)) and 3 of 6 patients with a late relapse (greater than or e qual to 18 months from CRI) had detectable bone marrow LPC at day 0. Five o f 8 patients with NCI-defined poor risk ALL and 3 of 7 patients with NCI-de fined standard risk ALL had detectable LPC at day 0. Following post-relapse induction chemotherapy. LPC counts were detectable in bone marrows of 4 of 6 evaluated patients. Thus. approximately half of the extramedullary relap se T-lineage ALL patients studied had substantial occult involvement of the bone marrow. These findings may partly explain the previously observed poo r prognosis of T-lineage patients following a CNS relapse.