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Volume 336:317-323 January 30, 1997 Number 5 Next

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ABSTRACT

Background Complete remission of B-precursor acute lymphoblastic leukemia (ALL) has traditionally been defined as the near absence of lymphoblasts in a light-microscopical examination of stained bone marrow smears, but a patient in remission may still harbor up to 10¹⁰ leukemia cells. We investigated whether there is a relation between the outcome of treatment and submicroscopic evidence of residual disease.

Methods We conducted a prospective study of patients during a first clinical remission using a quantitative polymerase-chain-reaction (PCR) assay capable of detecting 1 viable leukemia cell among 200,000 normal marrow mononuclear cells and a clonogenic blast-colony assay. Bone marrow specimens from 24 children were sequentially evaluated during a five-year period, and the results were compared with the clinical outcome.

Results Seven patients relapsed and 17 remained in remission 2 to 35 months after the completion of treatment. The levels of residual leukemia-cell DNA in the two groups were significantly different (P<0.001; 95 percent confidence interval for the difference in the mean log-transformed ratio of leukemia-cell DNA to normal bone marrow–cell DNA, 0.38 to 1.28). Autoregression analyses identified trends for individual patients that were associated with relapse. Despite continued remission in 17 patients, evidence of residual leukemia was detected by PCR in 15 and by both PCR and blast-colony assays in 7.

Conclusions Molecular signs of residual leukemia can persist up to 35 months after the cessation of chemotherapy in children with ALL in remission. This suggests that eradication of all leukemia cells may not be a prerequisite for cure.

Source Information

From the Division of Pediatrics (W.M.R., M.V.O., T.F.Z.), the Department of Bioimmunotherapy, Division of Medicine (Z.E.), and the Department of Biomathematics (D.A.J.), University of Texas M.D. Anderson Cancer Center, Houston; and Texas Children's Cancer Center and Hematology Service, Baylor College of Medicine, Houston (K.L.M.).

Address reprint requests to Dr. Zipf at the Division of Pediatrics, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 087, Houston, TX 77030.

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Residual Clones in Childhood Leukemia
Dibenedetto S. P., Schilirò G., Loscalzo C. P., Rabkin C. S., Muller J., Goedert J. J., Roberts W. M., McClain K. L., Zipf T. F.
Extract | Full Text  
N Engl J Med 1997; 337:50-51, Jul 3, 1997. Correspondence

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