title: Failure to achieve a complete hematologic response at the time of a major cytogenetic response with second-generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase.
abstract: Second-generation tyrosine kinase inhibitors are effective in Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML). Occasionally, patients with Ph(+) ALL, or accelerated phase (AP) or blast phase (BP) CML achieve a major cytogenetic response (MCyR) but not a complete hematologic response (CHR). We analyzed 126 patients with CML in AP or BP, or with Ph(+) ALL treated with dasatinib or nilotinib after imatinib failure. Twenty patients received sequential treatment with both dasatinib and nilotinib for a total of 146 instances. CHR and MCyR rates were 54% and 37%, respectively in AP, 17% and 39% in BP, and 33% and 50% in Ph+ ALL. Failure to achieve a CHR at the time of achievement of a MCyR was associated with an inferior outcome, similar to that of patients without a MCyR (2-year survival rate, 37% and 35%, respectively). In contrast, patients with MCyR and concomitant CHR had a 77% 2-year survival rate. Twelve of 29 patients with MCyR without concomitant CHR later achieved a CHR; the 2-year survival rate for these patients was 55% compared with 22% for those who never achieved a CHR. These results suggest that achievement of a MCyR without concomitant CHR is associated with poor outcome.
authors.affiliation: Department of Leukemia, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fava
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Nitin
authors.initials: N
authors.lastname: Jain
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides; D001752:Blast Crisis; D020732:Cytogenetic Analysis; D000069439:Dasatinib; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D015465:Leukemia, Myeloid, Accelerated Phase; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage; D012074:Remission Induction / Q000379:methods; D016019:Survival Analysis; D013844:Thiazoles / Q000008:administration & dosage; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib