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Blood, Vol. 92 No. 11 (December 1), 1998:
pp. 4072-4079
Minimal Residual Disease Status Before Allogeneic Bone Marrow
Transplantation Is an Important Determinant of Successful Outcome for
Children and Adolescents With Acute Lymphoblastic Leukemia
Christopher J.C. Knechtli,
Nicholas J. Goulden,
Jeremy P. Hancock,
Victoria L.G. Grandage,
Emma L. Harris,
Russell J. Garland,
Claire G. Jones,
Anthony W. Rowbottom,
Linda P. Hunt,
Ann F. Green,
Emer Clarke,
Alan W. Lankester,
Jacqueline M. Cornish,
Derwood H. Pamphilon,
Colin G. Steward, and
Anthony Oakhill
From the Department of Pathology and Microbiology, School of Medical
Sciences, University of Bristol; the Department of Paediatric
Haematology, Royal Hospital for Sick Children, Bristol; Institute for
Transplantation Sciences, National Blood Service, Bristol; and the
Division of Child Health, University of Bristol, Royal Hospital for
Sick Children, Bristol, UK.
The efficacy of allografting in acute lymphoblastic leukemia (ALL)
is heavily influenced by remission status at the time of transplant.
Using polymerase chain reaction (PCR)-based minimal residual disease
(MRD) analysis, we have investigated retrospectively the impact of
submicroscopic leukemia on outcome in 64 patients receiving allogeneic
bone marrow transplantation (BMT) for childhood ALL. Remission BM
specimens were taken 6 to 81 days (median, 23) before transplant. All
patients received similar conditioning therapy; 50 received grafts from
unrelated donors and 14 from related donors. Nineteen patients were
transplanted in first complete remission (CR1) and 45 in second or
subsequent CR. MRD was analyzed by PCR of Ig or T-cell receptor  or
 rearrangements, electrophoresis, and allele-specific oligoprobing.
Samples were rated high-level positive (clonal band evident after
electrophoresis; sensitivity 10 2 to 103),
low-level positive (MRD detected only after oligoprobing; sensitivity 103 to 105), or negative. Excluding 8 patients transplanted in CR2 for isolated extramedullary relapse (all
MRD), MRD was detected at high level in 12 patients, low
level in 11, and was undetectable in 33. Two-year event-free survival
for these groups was 0%, 36%, and 73%, respectively (P < .001). Follow-up in patients remaining in continuing remission is 20 to
96 months (median, 35). These results suggest that MRD analysis could
be used routinely in this setting. This would allow identification of
patients with resistant leukemia (who may benefit from innovative BMT
protocols) and of those with more responsive disease (who may be
candidates for randomized trials of BMT versus modern intensive relapse
chemotherapy).
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