Minimal Residual Disease(MRD) in Childhood Acute Lymphoblastic Leukemia(ALL) in Relapse. A Children’s Oncology Group (COG) Study.

In spite of the excellent outcome of children with ALL, those who relapse fare poorly. To date, time to relapse is the most powerful predictor of outcome. Most studies indicate that children with early marrow relapse (ER), occurring within 36 months of diagnosis, have a long-term event-free survival (EFS) of 10–20%, while those with a late marrow relapse (LR) have an EFS of 40–45%. MRD, detected either by flow cytometry or polymerase chain reaction is an important prognostic factor in patients with newly diagnosed ALL, and recent studies indicate that it is prognostic of outcome following relapse. However studies in relapse are more limited and generally only one time point at end induction has been tested. COG AALL01P2 is a pilot study designed to administer three sequential blocks of intensive therapy to children and adolescents with first marrow relapse of ALL with the goal of improving remission rates and achieving a lower level of disease burden prior to post induction therapy such as bone marrow transplantation. We measured MRD in 52 patients on COG AALL01P2 by flow cytometry using the 4-color combinations CD20-FITC/CD10-PE-CD45-PerCP/CD19-APC; CD34/9/45/19; and CD38/58/45/19. We detected MRD in 35 patients (67%) after the first block, a much higher figure than the 28% seen at end induction in more than 2000 patients with newly diagnosed ALL, consistent with the poor prognosis of relapse patients. Of 32 ER patients, 26(81%) were MRD+ compared to only 45% (9/20) of LR patients (p 1% MRD at all time points tested, while 4 patients with a level