autologous blood and marrow transplantation - Blog Science ...

Autologous BMT/PBSCT in BCR-ABL-positive ALL:
Rationale for Purging
Hans Martin, Johannes Atta, Dieter Hoelzer
Department of Internal Medicine 111, Johann Wolfgang Goethe-University,
Frankfurt, Germany
ABSTRACT
The BCR-ABL rearrangement is a useful disease-specific clonal marker to detect
leukemic cells at a sensitivity of about 1 malignant cell in 10 6
cells. To quantify the burden
of residual leukemia in autologous grafts, we prospectively analyzed 20 bone marrow and
30 peripheral blood autografts using a semiquantitative limited log-dilution reverse
transcription polymerase chain reaction (RT-PCR) from a total of 41 patients with BCR-
ABL' 1
' acute lymphoblastic leukemia (ALL) who all were in complete morphologic
remission. Leukemic contamination was found in 19 of 20 unpurged bone marrow (BM)
autografts at a level of median 4 (range 0-6) log above the limit of detection, while
median 3 log lower BCR-ABL titers were detected in unpurged peripheral blood stem cell
(PBSC) autografts. Thus all grafts were purged with CD10 and CD19 immunomagnetic
beads resulting in a median 2.5 (range log BCR-ABL signal depletion in BM and
median 1 (range 0-2) log depletion in PBSC autografts. After purging, BCR-ABLnegative
grafts were achieved in 10 of 21 PBSC patients but only in one of 20 BM
patients. A total of 34 patients received either single (ra=25) or double autologous
transplants (n=9) in first («=26) or in/beyond second (n=6) CR. The posttransplant relapse
rate was 65% at 2 years for single transplants in CR1 («=19). After double autologous
PBSC transplantation in first CR, two of seven patients relapsed with a median follow-up
of 213 (range 40-400) days. All patients transplanted beyond CR 1 relapsed. Four patients
remaining in complete CR for >2 years after single autologous bone marrow transplant
(autoBMT) had a median 1:10 titer of residual BCR-ABL signals in the purged grafts.
Overall, relapse rate after transplantation did not correlate with the BCR-ABL titer in the
reinfused purged cells. In conclusion, the rationale for purging in BCR-ABL +
ALL is
based on the evidence of leukemia in unpurged grafts, and low titer residual BCR-ABL
signals after purging are not necessarily associated with relapse.
INTRODUCTION
The Philadelphia chromosome (Ph)-positive/BCR-ABL +
ALL is the most
unfavorable subgroup of adult acute lymphoblastic leukemia. 12
About 20-25% of
84