Early landmark analysis of imatinib treatment in CML chronic phase: less than 10% BCR-ABL by FISH at 3 months associated with improved long-term clinical outcome.
Imatinib has dramatically improved the clinical outcome in chronic myeloid leukemia, chronic phase (CMLcp), but a risk of resistance and serious disease progression still prevails. We have studied 45 newly diagnosed CMLcp patients initiated on imatinib, assessing treatment responses by interphase extral signal (ES)-fluorescence in situ hybridization (FISH), quantitative real-time (q-RT) polymerase chain reaction (PCR), and chromosome banding analysis. In a landmark analysis, an early favorable response, defined as less than 10% BCR-ABL-positive cells by FISH after 3 months of treatment, was identified as a predictive marker of an improved long-term clinical outcome. Of evaluable patients, 51% achieved this response. A large majority, 95% of such responders reached complete cytogenetic responses (CCyR) within 12 months and 100% event-free survival (EFS) at 48 months, when compared with 67 and 65%, respectively, of patients with higher breakpoint cluster region - Abelson (BCR-ABL) positivity at 3 months (P = 0.04; P = 0.006). No similar, significant correlations were noted between early disease assessments with PCR of BCR-ABL mRNA transcripts or of cytogenetics versus a 12-month CCyR or long-term EFS. Our data, based on a limited patient cohort, indicate that (i) FISH can effectively be used in the early assessment of remaining Ph-positive cells to identify patients at risk for a long-term nonoptimal response to imatinib and that (ii) FISH may be more useful than PCR for this purpose.
Divisions of Hematology and Clinical Genetics, Karolinska University Hospital, Karolinska Insitutet, Stockholm, Sweden. lotta.ohm@swipnet.se
Lotta
L
Ohm
Ingrid
I
Arvidsson
Gisela
G
Barbany
Robert
R
Hast
Leif
L
Stenke
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl