LATE RELAPSING CHILDHOOD LYMPHOBLASTIC-LEUKEMIA

Childhood lymphoblastic leukemia (ALL) is usually assumed to have been permanently eradicated in patients in longterm remission, but occasio nally can recur after many years. To learn more about the problem, we studied a group of children whose leukemia had been in remission for 1 0 or more years before relapse and tried to determine whether they had true recurrences or second malignancies. We studied children treated on Medical Research Council ALL protocols between 1970 and 1984 and fo llowed up by the Clinical Trial Service Unit in Oxford. Detailed clini cal and laboratory data was collected from the centers concerned on al l who were reported to have had a recurrence of their leukemia after 1 0 or more years from the time of achieving first complete remission (C R1). To prove that the relapse was a true recurrence rather than a sec ond or secondary leukemia, DNA extracted from archived marrow smears w as subjected to polymerase chain reaction (PCR) analysis for the prese nce of an identical Ig heavy chain (IgH) or T-cell receptor (TCR) gene rearrangement at initial diagnosis and subsequent relapse. A total of 1,134 of 2,746 children had survived 10 years or more (range, 10 to 2 4 years) in CR1 and of those, 12 (approximately 1%) had subsequently r elapsed. Relapse blast cells were shown to express the common ALL anti gen (CD 10) in all cases and an identical clonal IgH or TCR gene rearr angement was found on PCR analysis of DNA from diagnosis and relapse i n all eight cases where DNA extraction was successful. A further progr am of therapy was successful in inducing a second CR in all patients, four of whom have succumbed to a second relapse after 12 to 27 months. The remaining eight are in continuing CR2 at a follow-up of 12 to 108 months (median, 52) from relapse. Although the risk of relapse of chi ldhood ALL after 10 years in remission appears to be small (around 1%) , it persists. This raises questions about how blasts can survive quie scent for so long and when we can truly be confident of cure, if ever. (C) 1998 by The American Society of Hematology.