Bone Marrow Leukemic Progenitor Cell Content in Pediatric T-Lineage Acute Lymphoblastic Leukemia Patients with an Isolated Extramedullar First Relapse

Abstract

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 multiparameter flow cytometry and blast colony assays to quantify the leukemic progenitor cell (LPC) burden in the pretreatment bone marrows of 15 pediatric 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-relapse induction therapy, with LPC counts ranging from 0/10⁶ mononuclear cells (MNC) to 518/10⁶ MNC (mean × SEM, 50 × 34 /10⁶ MNC). Five of 9 patients with an early relapse (< 18 months after achieving a first complete remission (CR1)) and 3 of 6 patients with a late relapse (× 18 months from CR1) had detectable bone marrow LPC at day 0. Five of 8 patients with NCI-defined poor risk ALL and 3 of 7 patients with NCI-defined 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 relapse T-lineage ALL patients studied had substantial occult involvement of the bone marrow. These findings may partly explain the previously observed poor prognosis of T-lineage patients following a CNS relapse.

Key Words:

• children
• MRD
• CNS relapse
• testicular relapse
• T — acute lymphoblastic leukemia Supported in part by CA-13539 from the National Cancer Institute
• National Institutes of Health