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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1253-1258
IMMUNOBIOLOGY
Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and
an excellent outcome
Charlotte Nyvold,
Hans O. Madsen,
Lars P. Ryder,
Jeanette Seyfarth,
Arne Svejgaard,
Niels Clausen,
Finn Wesenberg,
Olafur G. Jonsson,
Erik Forestier, and
Kjeld Schmiegelow on behalf of the Nordic
Society for Pediatric Hematology and Oncology
From the Department of Clinical Immunology and
Department of Pediatrics, National University Hospital, Rigshospitalet,
Copenhagen, Denmark; Skejby University Hospital, Aarhus, Denmark;
University Hospital, Rikshospitalet, Oslo, Norway; Reykjavik Hospital,
Reykjavik, Iceland; and University Hospital, Umeå, Sweden.
The postinduction level of minimal residual disease (MRD) was
quantified with a competitive polymerase chain reaction (PCR) technique
in 104 children with acute lymphoblastic leukemia (ALL) diagnosed
between June 1993 and January 1998 and followed for a median of 4.2 years. A significant correlation was found between the MRD level on day
15 (D15) and day 29 (D29) after the start of induction therapy
(rs = 0.70, P < .0001). The 15 patients
with T-cell disease had higher D29 MRD than those with B-lineage ALL (P = .01). Age was positively related to D29 MRD
(rs = 0.32, P = .001). The 16 patients who
had a relapse had higher D15 and D29 MRD levels than the patients who
stayed in remission (median levels D15, 1% versus 0.1%,
P = .03; D29, 0.4% versus 0.01%,
P = .0001). No patients with a MRD level less than 0.01%
on D29 have so far had a relapse, whereas the 7-year probability of
event-free survival for patients with higher MRD levels was 0.52 (P = .0007). The group of patients with a D29 MRD less
than 0.01% included patients with T-cell disease, white blood cell
count more than 50 × 109/L at diagnosis, or age 10 years
or older, and could not be identified by up-front criteria. The
best-fit Cox model to predict the risk of relapse included D29 MRD
(P = .004) and age (P = .009). These findings indicate that with the present treatment protocol MRD quantification at an early stage of therapy identifies patients with a
very low risk of relapse. Further trials are needed to reveal whether
such patients with D29 MRD less than 0.01% can be cured with less
intensive chemotherapy, which would reduce the risk of serious late
effects as well as the costs of therapy.

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