title: Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia.
abstract: We determined the prognostic importance of morphologically identifiable persistent disease at day 15 and days 22 to 25 of remission induction in childhood acute lymphoblastic leukemia (ALL). Among 546 patients entered on 2 consecutive protocols, 397 patients had evaluable bone marrow (BM) examinations on day 15 (+/- 1 day) and 218 on days 22 to 25 (+/- 1 day). Fifty-seven patients (14%) had persistent lymphoblasts (> or = 1%) in the BM on day 15 and 27 patients (5.5%) had persistent lymphoblasts on days 22 to 25. The 5-year event-free survival (EFS) was significantly worse for patients with lymphoblasts on day 15 (40% +/- 6%) or on days 22 to 25 (4% +/- 3%) as compared to those without lymphoblasts on these dates (78% +/- 2% and 76% +/- 2%, respectively, P <.001 for both comparisons). A worse prognosis was observed even for patients with a low percentage of lymphoblasts (ie, 1%-4%) at either day 15 (5-year EFS = 56% +/- 8%) or days 22 to 25 (5-year EFS = 0%) compared to those without morphologically identifiable persistent lymphoblasts at these times (P <.001 for both comparisons). The prognostic impact of persistent lymphoblasts on both dates remained significant after adjusting for other known risk factors, including treatment protocol, age, white blood cell count, DNA index, cell lineage, and central nervous system status, and National Cancer Institute/Rome criteria simultaneously. Hence, persistence of lymphoblasts (even 1%-4%) on day 15 of remission induction was associated with a poor prognosis and on days 22 to 25 signified a particularly dismal outcome; these very high-risk patients require novel or more intensive therapy to improve outcome.
authors.affiliation: Department of Hematology-Oncology, St Jude Children's Research Hospital, and the University of Tennessee, College of Medicine, Memphis, TN 38105, USA. john.sandlund@stjude.org
authors.forename: John T
authors.initials: JT
authors.lastname: Sandlund
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Harrison
authors.forename: Gaston
authors.initials: G
authors.lastname: Rivera
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Behm
authors.forename: David
authors.initials: D
authors.lastname: Head
authors.forename: James
authors.initials: J
authors.lastname: Boyett
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Susana
authors.initials: S
authors.lastname: Raimondi
authors.forename: Raul
authors.initials: R
authors.lastname: Ribeiro
authors.forename: Melissa
authors.initials: M
authors.lastname: Hudson
authors.forename: Mary
authors.initials: M
authors.lastname: Relling
authors.forename: William
authors.initials: W
authors.lastname: Evans
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
mesh_terms: D001752:Blast Crisis / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006801:Humans; D007223:Infant; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000401:mortality / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012074:Remission Induction; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors