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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2002-01-0006.
Submitted January 3, 2002
Accepted February 26, 2002
Prognostic significance of measuring early clearance of leukemiccells by flow cytometry in childhood acute lymphoblastic leukemia
Elaine Coustan-Smith, Jose Sancho, Frederick G Behm, Michael L Hancock, Bassem I Razzouk, Raul C Ribeiro, Gaston K Rivera, Jeffrey E Rubnitz, John T Sandlund, Ching-Hon Pui, and Dario Campana*
Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA
Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA
Biostatistics, St. Jude Children's Research Hospital, Memphis, TN, USA
Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA; Pediatrics, University of Tennessee College of Medicine, Memphis, TN, USA
Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA; Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA; Pediatrics, University of Tennessee College of Medicine, Memphis, TN, USA
* Corresponding author; email: dario.campana{at}stjude.org.
Early clearance of leukemic cells is a favorable prognostic indicator in childhood acute lymphoblastic leukemia (ALL). However, identification of residual leukemic cells by their morphology is subjective and lacks sensitivity. To improve estimates of leukemia clearance, we applied flow cytometric techniques capable of detecting 1 leukemic cell in 10,000 or more normal cells and prospectively measured residual leukemia in bone marrow samples collected at day 19 of remission induction chemotherapy from 248 children with newly diagnosed ALL. In 134 samples (54.0%) we identified  0.01% leukemic cells [0.01%-<0.1% in 51 samples (20.6%), 0.1%-<1% in 36 (14.5%) and 1% in 47 (19.0%)]. Among 110 children treated within a single chemotherapy program, 5-year cumulative incidence of relapse or failure to achieve remission was 32.2% ± 6.5% (SE) for the 59 patients with 0.01% residual leukemic cells at day 19 versus 6.0% ± 3.4% for the 51 patients with <0.01% leukemic cells (P <0.001). The prognostic strength of day 19 bone marrow status defined by flow cytometry was superior to that defined by morphology, and remained significant after adjusting for other clinical and biologic parameters. Lack of detectable leukemic cells at day 19 was more closely associated with relapse-free survival than lack of detectable residual disease at the end of remission induction (day 46). Thus, approximately half of children with ALL achieve profound clearance of leukemic cells after 2-3 weeks of remission induction chemotherapy; these patients have an excellent treatment outcome.
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