Molecular residual disease status at the end of chemotherapy fails to predict subsequent relapse in children with B-lineage acute lymphoblastic leukemia.
OBJECTIVE
We have investigated whether the extent of residual leukemia in the marrows obtained at the completion of chemotherapy can predict subsequent relapse in children with B-lineage acute lymphoblastic leukemia (ALL).


METHODS
Marrow samples of 24 patients were examined for residual disease at the end of treatment using a quantitative method based on the polymerase chain reaction (PCR) amplification of the complementarity determining region-3 of the immunoglobulin heavy chain.


RESULTS
Of the 15 patients who remain in continuous bone marrow remission (range, 41 to 98 months), 14 had no detectable leukemic cells; one patient had a very low level (one in approximately 335,000 marrow cells) of residual leukemic cells that underwent clonal evolution. Among the nine patients who had a marrow relapse after the completion of treatment, eight patients whose relapses occurred 4 to 54 months from the end of therapy had no detectable leukemic cells, whereas only the one patient who relapsed 2 months after the completion of therapy had detectable residual disease.


CONCLUSIONS
These observations indicate that the absence of detectable residual leukemia by PCR at the end of chemotherapy is not sufficient to assure that the patient is cured and suggest that frequent serial monitoring is required for the early prediction of relapse off therapy.
Ito
Y
Y
Wistar Institute, Philadelphia, PA 19104.
Wasserman
R
R
Galili
N
N
Reichard
B A
BA
Shane
S
S
Lange
B
B
Rovera
G
G
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D011237:Predictive Value of Tests; D012008:Recurrence
D004273:DNA, Neoplasm