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Patterns of hematopoietic chimerism following bone marrow transplantation
for childhood acute lymphoblastic leukemia from volunteer unrelated donors
K Molloy, N Goulden, M Lawler, J Cornish, A Oakhill, D Pamphilon, M Potter, C Steward, K Langlands, P Humphries and SR McCann
Department of Haematology and Oncology, St James's Hospital, Dublin,
Ireland.
Hematopoietic chimerism was analyzed in serial bone marrow samples taken
from 28 children following T-cell depleted unrelated donor bone marrow
transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric
status was determined by polymerase chain reaction (PCR) of simple tandem
repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial
samples were examined in 23 patients. Of these, two had evidence of
complete donor engraftment at all times and eight showed stable low level
mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these
patients remain in remission with a minimum follow-up of 24 months. By
contrast, 13 patients demonstrated a progressive return of recipient
hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of
cytomegalovirus pneumonitis and seven remain in remission with a minimum
follow-up of 24 months. Five children were excluded from serial analysis as
two serial samples were not collected before either relapse (3) or graft
rejection (2). We conclude that as with sibling transplants, ex vivo T
depleted UD BMT in children with ALL is associated with a high incidence of
MC. Stable donor engraftment and low level MC always correlated with
continued remission. However, detection of a progressive return of
recipient cells did not universally correlate with relapse, but highlighted
those patients at greatest risk. Serial chimerism analysis by PCR of STRs
provides a rapid and simple screening technique for the detection of
relapse and the identification of patients with progressive MC who might
benefit from detailed molecular analysis for minimal residual disease
following matched volunteer UD BMT for childhood ALL.
Volume 87,
Issue 7,
pp. 3027-3031,
04/01/1996
Copyright © 1996 by The American Society of Hematology

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