Early prediction of molecular remission by monitoring BCR-ABL transcript levels in patients achieving a complete cytogenetic response after imatinib therapy for posttransplantation chronic myelogenous leukemia relapse.
Imatinib induces a high complete cytogenetic response (CCR) rate in relapsed chronic myelogenous leukemia. By analyzing minimal residual disease (MRD) under the levels of CCR, we tried to assess the molecular response after imatinib therapy. By using real-time quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR), MRD was evaluated in 23 patients (3 in cytogenetic relapse, 6 in chronic phase, 9 in accelerated phase, and 5 in blast crisis) who were treated with standard-dose imatinib for relapsed chronic myelogenous leukemia after allogeneic stem cell transplantation. With a median therapy time of 399 days (range, 35-817 days), 19 (83%) patients achieved a CCR. Meanwhile, 11 (58%) of them achieved a molecular remission (MR), which was associated with improved survival. The Q-RT-PCR data were compared according to the best response (MR, n = 11; CCR, n = 8) in the patients achieving a CCR. The BCR-ABL/ABL ratios were similar in 2 groups at 3 months but were significantly different at 6 months (median, 0.0000012 for MR and 0.00022 for CCR; P =.003). The probability of a subsequent MR was significantly higher in patients with a lower BCR-ABL/ABL ratio at 6 months (100% for <0.0001 versus 33% for >/=0.0001; P =.006) or a greater reduction in the level between 3 and 6 months (log-reduction >/=1.0;, 100%; <1.0, 17%; P =.003). Q-RT-PCR is a reliable method for monitoring MRD: the early trends in the BCR-ABL/ABL ratio may be clinically useful in discriminating patients who will achieve an MR from those who will remain in CCR.
Kim
Yoo-Jin
YJ
Catholic Hematopoietic Stem Cell Transplantation Center, Catholic University of Korea, Seoul, Korea.
Kim
Dong-Wook
DW
Lee
Seok
S
Min
Chang-Ki
CK
Goh
Hyun-Gyung
HG
Kim
Su-Hyun
SH
Lee
Ji-Young
JY
Kim
Yoo-Li
YL
Kim
Hee-Je
HJ
Kim
Hyeoung-Jun
HJ
Lee
Jong-Wook
JW
Kim
Tai-Gyu
TG
Min
Woo-Sung
WS
Kim
Chun-Choo
CC
D000328:Adult; D001549:Benzamides; D020732:Cytogenetic Analysis; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012334:RNA, Neoplasm / Q000032:analysis*; D012008:Recurrence; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016879:Salvage Therapy / Q000379:methods*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012334:RNA, Neoplasm; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl