Minimal residual disease in childhood acute lymphoblastic leukemia: analysis of patients in continuous complete remission or with consecutive relapse.

Differences in tumor cell burden among acute lymphoblastic leukemia (ALL) patients are largely unexplored, because methods of detecting residual malignant cells have not been sufficiently sensitive. Using the polymerase chain reaction (PCR) amplification of rearranged T-cell receptor delta(TCR delta)-chain junctional sequences for the preparation of clonospecific probes, we performed a retrospective PCR study of remission bone marrow (BM) samples in seven pediatric patients with ALL who subsequently relapsed (the largest series studied so far) and in 10 patients who were in longterm (greater than 39 to greater than 72 months) remission. Following two rounds of PCR primed by nested amplimers, 1 x 10(-4) to 1 x 10(-6) cells could be identified in 16 out of 17 cases. PCR analysis of 39 BM and peripheral blood samples obtained from ALL patients considered to be in complete remission according to morphological criteria revealed the following results. In BM remission specimens of all 10 patients in continuous complete remission for a long time (median 55 months), no residual leukemic cells could be identified in the latest remission sample available for PCR analysis. In three patients the persistence of residual leukemic cells, or the continuous increase of residual blasts to the point of clinical manifestation, were indicative of impending relapse. In three patients PCR analysis failed to identify residual leukemic cells in BM samples obtained 2, 6 and 16 months respectively before clinical relapse. Differences in the duration of minimal residual disease were not associated with distinct clinical-hematological features. In one patient a different pattern of V delta 2 recombination occurred in leukemic cells from diagnosis to relapse, thus preventing the further monitoring of the patient by the initial clonospecific probe.