Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia: need for new response definitions?
BACKGROUND
Response rates in chronic myeloid leukemia (CML) are now reported based on the cumulative incidence of a single-time best response. The study aim was to examine the significance of different response criteria for CML on imatinib therapy.


METHODS
In all, 276 patients with chronic phase CML on imatinib therapy were analyzed. Cytogenetic and molecular responses were coded as to single best response and response at specific intervals of treatment.


RESULTS
The cumulative incidence of complete cytogenetic response (CGCR) with imatinib was 91%; however, the incidence of CGCR at 48 months into therapy was only 78%. Similarly, the incidence of major molecular responses (best cumulative vs landmark at 48 months) were 74% versus 62%, and of undetectable BCR-ABL transcripts 38% versus 24%. There was a strong association between achievement of major cytogenetic response (Philadelphia chromosome [Ph]-positivity <or=35%) at 6 months to 12 months and survival as well as progression-free survival (PFS). Achievement of major molecular response (vs lesser molecular response) in patients in complete cytogenetic response was not associated with significant differences in survival, but showed some association with PFS. Durable CGCR and major molecular responses (documented continuously for >or=12 months) were associated with longer PFS duration but not with survival duration differences. Of interest, major molecular responses documented at least twice were noted in 71% of patients on imatinib therapy; undetectable BCR-ABL transcripts documented at least twice were noted in 34%.


CONCLUSIONS
Achievement and durability of CGCR and of major and complete molecular responses at landmark times predict outcome in CML, and may help in comparing the efficacy of different treatments.
Kantarjian
Hagop
H
Department of Leukemia, The University of Texas MD Anderson Cancer, Houston, Texas 77030, USA. hkantarj@mdanderson.org
O'Brien
Susan
S
Shan
Jianqin
J
Huang
Xuelin
X
Garcia-Manero
Guillermo
G
Faderl
Stefan
S
Ravandi-Kashani
Farhad
F
Verstovsek
Srdan
S
Beth Rios
Mary
M
Cortes
Jorge
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D020732:Cytogenetic Analysis; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014178:Translocation, Genetic / Q000187:drug effects; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl