Prediction of relapse by day 100 BCR-ABL quantification after allogeneic stem cell transplantation for chronic myeloid leukemia.
Chronic myeloid leukemia (CML) relapse after allogeneic stem cell transplantation (SCT) is a relatively frequent situation, which is correlated to disease status, time from diagnosis to transplant and T-cell depletion. We evaluated the potential for early minimal residual disease (MRD) BCR-ABL quantification to predict relapse of CML patients receiving allogeneic SCT. Minimal residual disease was analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) at day 100 (d100) in 38 patients with >1 year follow-up after conventional non-T-cell-depleted SCT. Normal ABL control values from 1724 follow-up blood samples were used to define an RQ-PCR amplifiability index and the limits of reliable use of BCR-ABL ratios. We then compared the 14 patients with a high-level d100 BCR-ABL/ABL ratio (> or = 10(-4)) to that of the 24 patients with a negative/low-level ratio (<10(-4)). Despite being comparable for all classical parameters, the incidence of relapse was significantly higher in the high MRD group (11/14 (79%)) compared to that of the low/negative MRD group (7/24 (29%)) (P = 0.009), with d100 MRD values representing an independent risk factor of relapse and disease-free survival, but not of overall survival, in multivariate analysis. These data should facilitate risk-adapted post-transplant immunosuppression and/or tyrosine kinase inhibitor therapy based on an early evaluation of MRD.
Laboratoire d'Hématologie, AP-HP Necker, Paris, France.
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V
Asnafi
M-T
MT
Rubio
E
E
Delabesse
E
E
Villar
F
F
Davi
G
G
Damaj
I
I
Hirsch
N
N
Dhédin
J P
JP
Vernant
B
B
Varet
A
A
Buzyn
E
E
Macintyre
D000293:Adolescent; D000328:Adult; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012313:RNA / Q000235:genetics; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012307:Risk Factors; D012680:Sensitivity and Specificity; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D018076:DNA, Complementary; D012313:RNA; D016044:Fusion Proteins, bcr-abl