Residual leukemia and immunomagnetic bead purging in patients with BCR-ABL-positive acute lymphoblastic leukemia.
Residual leukemia was evaluated in autologous bone marrow grafts harvested in first (n = 11) or second (n = 3) complete remission from 14 patients with BCR-ABL-positive acute lymphoblastic leukemia after treatment according to the German multicenter ALL protocols. The intervals from diagnosis to BM harvest were median 159 (range 78-463) and from preceding chemotherapy to BM harvest median 39 (range 26-69) days, respectively. A limiting log(10)-dilution RT-PCR was used to semiquantify BCR-ABL-positive cells. All autografts appeared to be significantly contaminated with residual leukemic cells. The BCR-ABL-specific titers ranged from 1:10(3) to 1:10(6) (median 1:10(4)) above the limit of detection. This was the rationale to purge the grafts using two cycles of IgM anti-CD10, CD19, and AB4 MoAbs-coated immunomagnetic beads (IMB). Purging depleted median 3 (range 2-4) logs of residual leukemia, resulting in a median 1:10(1) (range 1:10(0) to 1:10(3)) postpurge BCR-ABL-specific titer. The second purging cycle accounted for 1 log of depletion. The mean +/- s.e.m. post-purge recoveries of MNC and CFU-GM were 59 +/- 4%, and 61 +/- 9%, respectively. We conclude that all BCR-ABL-positive ALL patients achieving CR by cytological criteria have critically high levels of residual leukemia in their bone marrow, which can be reduced by median 3 log using immunomagnetic bead purging.
Atta
J
J
Department of Hematology, Johann Wolfgang Goethe-University, Frankfurt/Main, Germany.
Martin
H
H
Bruecher
J
J
Elsner
S
S
Wassmann
B
B
Rode
C
C
Russ
A
A
Kvalheim
G
G
Hoelzer
D
D
D000293:Adolescent; D000328:Adult; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002648:Child; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis*; D006801:Humans; D018189:Immunomagnetic Separation; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*
D016044:Fusion Proteins, bcr-abl