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Blood, 1 July 2002, Vol. 100, No. 1, pp. 43-47
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
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
John T. Sandlund,
Patricia
L. Harrison,
Gaston Rivera,
Frederick G. Behm,
David Head,
James Boyett,
Jeffrey E. Rubnitz,
Amar Gajjar,
Susana Raimondi,
Raul Ribeiro,
Melissa Hudson,
Mary Relling,
William Evans, and
Ching-Hon Pui
From the Departments of Hematology-Oncology, Pathology
and Laboratory Medicine, Biostatistics and Epidemiology, and
Pharmaceutical Sciences, St Jude Children's Research Hospital, and the
University of Tennessee, College of Medicine, Memphis, TN.
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 ( 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.
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