Imatinib improves but may not fully reverse the poor prognosis of patients with CML with derivative chromosome 9 deletions.
Deletions of the derivative chromosome 9 occur in a subset of patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) and are associated with a poor prognosis on standard drug therapy. However, it is currently unknown if the presence of deletions influences the response to imatinib, an Abl-specific tyrosine kinase inhibitor, that has recently shown excellent hematologic and cytogenetic responses in patients with CML. We, therefore, compared hematologic and cytogenetic responses with imatinib in 397 patients with CML, and survival and progression in 354 of these patients, according to deletion status and disease phase. We found no difference in survival between patients with and without deletions, contrasting with previous reports in cohorts with a lower proportion of patients treated with imatinib. However, the time to disease progression on imatinib treatment was significantly shorter for patients with deletions, both in chronic phase (P =.02) and advanced phases (P =.02). Moreover, both in chronic phase and more advanced phases of CML, hematologic and cytogenetic responses were uniformly lower in patients with deletions, with significant differences seen for hematologic response (P =.04), for major cytogenetic response (P =.008) in chronic phase, and for hematologic response in advanced phases (P =.007) of CML. This finding suggests that differences in survival may become apparent with longer follow-up.
Huntly
Brian J P
BJ
Bone Marrow Transplantation/Leukemia, Oregon Health and Science University, Portland, OR.
Guilhot
Francois
F
Reid
Alistair G
AG
Vassiliou
George
G
Hennig
Evelin
E
Franke
Christina
C
Byrne
Jennie
J
Brizard
Andre
A
Niederwieser
Dietger
D
Freeman-Edward
Julie
J
Cuthbert
Gavin
G
Bown
Nick
N
Clark
Richard E
RE
Nacheva
Elizabeth P
EP
Green
Anthony R
AR
Deininger
Michael W N
MW
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D002872:Chromosome Deletion; D002899:Chromosomes, Human, Pair 9; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage*; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate