Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation.
Thirty-six patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) were studied for the presence of the bcr-abl fusion mRNA transcript after an allogeneic matched related (N = 12), partially matched related (N = 4), matched unrelated (N = 14), autologous (N = 5), or syngeneic (N = 1) bone marrow transplant (BMT). Seventeen were transplanted in relapse, and 19 were transplanted in remission. Twenty-three patients had at least one positive bcr-abl polymerase chain reaction (PCR) assay after BMT either before a relapse or without subsequent relapse. Ten of these 23 relapsed after a positive assay at a median time from first positive PCR assay of 94 days (range, 28 to 416 days). By comparison, only 2 relapses occurred in the 13 patients with no prior positive PCR assays; both patients had missed at least one scheduled follow-up assay and were not tested 2 months and 26 months before their relapse. The unadjusted relative risk (RR) of relapse associated with a positive PCR assay compared with a negative assay was 5.7 (95% confidence interval 1.2 to 26.0, P = .025). In addition, the data suggest that the type of bcr-abl chimeric mRNA detected posttransplant was associated with the risk of relapse: 7 of 10 patients expressing the p190 bcr-abl relapsed, compared with 1 of 8 who expressed only the p210 bcr-abl mRNA (P = .02, log-rank test). The RR of p190 bcr-abl positivity compared to PCR-negative patients was 11.2 (confidence interval 2.3-54.8, P = 0.003), whereas a positive test for p210 bcr-abl was apparently not associated with an increased relative risk. In separate multivariable models, PCR positivity remained a statistically significant risk factor for relapse after separately adjusting for donor (unrelated and partially matched v matched, autologous, and syngeneic), remission status at the time of transplant, the presence of acute graft-versus-host disease (GVHD), and type of conditioning regimen (total body irradiation dose of < or = 1,200 cGy v > 1,200 cGy). The PCR assay appears to be a useful test for predicting patients at high risk of relapse after BMT and may identify patients who might benefit from therapeutic interventions. The finding that the expression of p190 bcr-abl may portend an especially high risk of relapse suggests a different clinical and biologic behavior between p190 and p210 bcr-abl.
Radich
J
J
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Gehly
G
G
Lee
A
A
Avery
R
R
Bryant
E
E
Edmands
S
S
Gooley
T
T
Kessler
P
P
Kirk
J
J
Ladne
P
P
Thomas
E D
ED
Appelbaum
F R
FR
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis* / Q000235:genetics; D006086:Graft vs Host Disease / Q000453:epidemiology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D012008:Recurrence; D012306:Risk; D017211:Treatment Failure
D014408:Biomarkers, Tumor; D016044:Fusion Proteins, bcr-abl