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Blood, Vol. 92 No. 7 (October 1), 1998:
pp. 2334-2337
Late Relapsing Childhood Lymphoblastic Leukemia
Ajay Vora,
Lindsay Frost,
Anne Goodeve,
Gill Wilson,
R.M. Ireland,
John Lilleyman,
Tim Eden,
Ian Peake, and
Sue Richards
From the Molecular Haematology Unit, Children's and Royal
Hallamshire Hospital, Sheffield; Greenwich District General Hospital,
London; and UK MRC Childhood Leukaemia Working Party, CTSU, Oxford, UK.
Childhood lymphoblastic leukemia (ALL) is usually assumed to have
been permanently eradicated in patients in long-term remission, but
occasionally can recur after many years. To learn more about the
problem, we studied a group of children whose leukemia had been in
remission for 10 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 followed up by the Clinical Trial Service Unit in Oxford. Detailed clinical and laboratory data was collected from the centers concerned on all who were reported to have had a
recurrence of their leukemia after 10 or more years from the time of
achieving first complete remission (CR1). To prove that the relapse was
a true recurrence rather than a second or secondary leukemia, DNA
extracted from archived marrow smears was subjected to polymerase chain
reaction (PCR) analysis for the presence 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 24 years) in CR1 and of those, 12 (approximately 1%) had subsequently relapsed. Relapse blast cells were
shown to express the common ALL antigen (CD 10) in all cases and an
identical clonal IgH or TCR gene rearrangement was found on PCR
analysis of DNA from diagnosis and relapse in all eight cases where DNA
extraction was successful. A further program 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 childhood ALL after 10 years
in remission appears to be small (around 1%), it persists. This raises
questions about how blasts can survive quiescent for so long and when
we can truly be confident of cure, if ever.
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