Minimal residual disease in childhood B-lineage lymphoblastic leukemia. Persistence of leukemic cells during the first 18 months of treatment.
BACKGROUND
Whether patients in clinical remission for acute lymphoblastic leukemia (ALL) continue to harbor leukemic cells is not known, because methods of detecting residual malignant cells have not been sufficiently sensitive. This information might be useful for predicting recurrence and determining the duration of therapy.


METHODS
Using a sensitive new method--identifying complementarity-determining region III sequences with the polymerase chain reaction--we estimated the number of residual leukemic cells in the bone marrow of eight children with B-lineage lymphoblastic leukemia before and after remission.


RESULTS
Induction chemotherapy produced a 3-to-4-log reduction in the number of leukemic cells. In all samples obtained up to 18 months after diagnosis, however, 0.004 to 2.6 percent of bone marrow nucleated cells were residual leukemic cells. Among the four patients studied more than 18 months after diagnosis, three had no detectable leukemic cells in marrow samples. Despite this, one of them, who was no longer receiving therapy, had a central nervous system relapse. In one patient receiving maintenance chemotherapy, there was a 60-fold increase in leukemic cells three months before bone marrow relapse.


CONCLUSIONS
The complete disappearance of leukemic cells (or their reduction below our method's threshold of detection, 1 in 100,000 cells) may be necessary to achieve a cure of ALL. The quantification of residual leukemic cells in serial marrow aspirates during therapy may allow the early detection of relapse.
Yamada
M
M
Wistar Institute, Philadelphia, PA 19104.
Wasserman
R
R
Lange
B
B
Reichard
B A
BA
Womer
R B
RB
Rovera
G
G
D000293:Adolescent; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology*; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013997:Time Factors
D004273:DNA, Neoplasm