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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2002-01-0006.
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Blood, 1 July 2002, Vol. 100, No. 1, pp. 52-58
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Prognostic importance of measuring early clearance of
leukemic cells 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
From the Departments of Hematology-Oncology, Pathology,
Biostatistics, St Jude Children's Research Hospital; and the
University of Tennessee, Memphis, TN.
Early clearance of leukemic cells is a favorable prognostic
indicator in childhood acute lymphoblastic leukemia (ALL). However, identification of residual leukemic cells by their morphologic features
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 on day 19 of remission-induction chemotherapy from 248 children with newly
diagnosed ALL. In 134 samples (54.0%), we identified at least 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, the 5-year mean ± SE cumulative incidence of relapse or failure to achieve remission was
32.2% ± 6.5% for the 59 patients with 0.01% residual leukemic cells
or greater on day 19 and 6.0% ± 3.4% for the 51 patients with less
than 0.01% leukemic cells (P < .001). The prognostic
value of day-19 bone marrow status defined by flow cytometry was
superior to that defined by morphologic studies and remained
significant after adjustment for other clinical and biologic variables.
Lack of detectable leukemic cells on day 19 was more closely associated
with relapse-free survival than was lack of detectable residual disease
at the end of remission induction (day 46). Thus, approximately half of
the children with ALL achieve profound clearance of leukemic cells
after 2 to 3 weeks of remission-induction chemotherapy, and these
patients have an excellent treatment outcome.
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