Successful autologous stem cell collection in patients with chronic myeloid leukemia in complete cytogenetic response, with quantitative measurement of BCR-ABL expression in blood, marrow, and apheresis products.
Imatinib mesylate is the initial therapy of choice for chronic myeloid leukemia in chronic phase (CML-CP), but in some patients, the disease becomes resistant to imatinib. Autologous stem cell transplantation using cells collected while in complete cytogenetic response (CCyR) may represent a therapeutic option for these patients. We mobilized and collected autologous CD34(+) stem cells from 20 CML-CP patients in CCyR, 19 of whom were taking imatinib, and measured BCR-ABL expression in the apheresis products, blood and bone marrow using real-time quantitative PCR (RQ-PCR). Stem cells were mobilized with G-CSF 10 microg/kg daily for 5 days. In patients whose initial collection was <2x10(6) CD34(+) cells/kg, G-CSF dose was increased to 10 microg/kg twice daily on the second attempt, and imatinib was held for 14 days if a third attempt was necessary. All 20 patients successfully mobilized the target yield of 2 to 5x10(6) CD34(+) cells/kg; 16 reached target yield with the first mobilization. The median number of CD34(+) cells collected was 4.4 (range, 2.0 - 8.4)x10(6)/kg in a median of 3 (range, 2 - 6) apheresis days. Of 17 patients whose stem cell products were evaluable by RQ-PCR, 11 (65%) had >or=1 daily product with undetectable BCR-ABL; 4 of these (24%) had no detectable BCR-ABL in any apheresis products. BCR-ABL expression in apheresis products was correlated with levels of expression in the blood and marrow prior to mobilization. No patient has yet required transplantation. With median follow-up of 18 months, all patients remain in CCyR and 9 of 16 (54%) have undetectable BCR-ABL in the most recent blood and marrow sample.
Gordon
Melinda K
MK
Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
Sher
Dorie
D
Karrison
Theodore
T
Kebriaei
Partow
P
Chuang
Karen
K
Zhang
Yanming
Y
McDonnell
Diane
D
Artz
Andrew
A
Godley
Lucy
L
Odenike
Olatoyosi
O
Rich
Elizabeth
E
Michaelis
Laura
L
Thirman
Michael J
MJ
Wickrema
Amittha
A
van Besien
Koen
K
Larson
Richard A
RA
Stock
Wendy
W
D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis*; D001549:Benzamides; D001781:Blood Component Removal / Q000379:methods*; D001853:Bone Marrow / Q000737:chemistry; D020732:Cytogenetic Analysis; D005260:Female; D000069585:Filgrastim; D016044:Fusion Proteins, bcr-abl / Q000032:analysis* / Q000097:blood; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D011994:Recombinant Proteins; D012074:Remission Induction; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D018952:Antigens, CD34; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000069585:Filgrastim