Clonal stability in children with acute lymphoblastic leukemia (ALL) who relapsed five or more years after diagnosis

Although most relapses of childhood acute lymphoblastic leukemia (ALL) occu r 24-36 months after first CR has been achieved, few patients relapse 5 or more years after On achievement. The assessment of clonality has proved to be useful in determining whether even those very late events represent the reoccurrence of the original clone or alternatively a secondary leukemia. T o gain further information on clonal stability in such late relapse, we per formed detailed comparative Southern blotting and PCR analyses of TcR delta and TcR gamma gene rearrangements in five ALL at presentation and subseque nt relapse which occurred more than 5 years after diagnosis. At least one s table rearranged allele of the TcR delta and TcR gamma loci was traced in a ll cases at presentation and clinical relapse despite a wide heterogeneity of the pattern of rearrangements. Our study extends to a larger series of p atients previous findings which have sought to analyze the phenomenon of cl onal evolution in children relapsed after more than 5 years of CCR. With re spect to the potential pitfalls in monitoring minimal residual disease in c hildhood ALL for the presence of clonal evolution, our results highlight th e combination of two target genes (such as TcR gamma and TcR delta) as a to ol to reduce false negative MRD results.