title: Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML).
abstract: In the face of competing first-line treatment options for CML, early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation tyrosine kinase inhibitor (TKI). A total of 1303 newly diagnosed imatinib-treated patients (pts) were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). The persistence of BCR-ABL transcript levels >10% according to the international scale (BCR-ABL(IS)) at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with >1-10% BCR-ABL(IS) (41% of pts; 5-year OS: 94%; P=0.012) and from a group with ≤1% BCR-ABL(IS) (31% of pts; 5-year OS: 97%; P=0.004). Cytogenetics identified high-risk pts by >35% Philadelphia chromosome-positive metaphases (Ph+, 27% of pts; 5-year OS: 87%) compared with ≤35% Ph+ (73% of pts; 5-year OS: 95%; P=0.036). At 6 months, >1% BCR-ABL(IS) (37% of pts; 5-year OS: 89%) was associated with inferior survival compared with ≤1% (63% of pts; 5-year OS: 97%; P<0.001) and correspondingly >0% Ph+ (34% of pts; 5-year OS: 91%) compared with 0% Ph+ (66% of pts; 5-year OS: 97%; P=0.015). Treatment optimization is recommended for pts missing these landmarks.
authors.affiliation: III Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Hanfstein
authors.forename: M C
authors.initials: MC
authors.lastname: Müller
authors.forename: R
authors.initials: R
authors.lastname: Hehlmann
authors.forename: P
authors.initials: P
authors.lastname: Erben
authors.forename: M
authors.initials: M
authors.lastname: Lauseker
authors.forename: A
authors.initials: A
authors.lastname: Fabarius
authors.forename: S
authors.initials: S
authors.lastname: Schnittger
authors.forename: C
authors.initials: C
authors.lastname: Haferlach
authors.forename: G
authors.initials: G
authors.lastname: Göhring
authors.forename: U
authors.initials: U
authors.lastname: Proetel
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kolb
authors.forename: S W
authors.initials: SW
authors.lastname: Krause
authors.forename: W-K
authors.initials: WK
authors.lastname: Hofmann
authors.forename: J
authors.initials: J
authors.lastname: Schubert
authors.forename: H
authors.initials: H
authors.lastname: Einsele
authors.forename: J
authors.initials: J
authors.lastname: Dengler
authors.forename: M
authors.initials: M
authors.lastname: Hänel
authors.forename: C
authors.initials: C
authors.lastname: Falge
authors.forename: L
authors.initials: L
authors.lastname: Kanz
authors.forename: A
authors.initials: A
authors.lastname: Neubauer
authors.forename: M
authors.initials: M
authors.lastname: Kneba
authors.forename: F
authors.initials: F
authors.lastname: Stegelmann
authors.forename: M
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: C F
authors.initials: CF
authors.lastname: Waller
authors.forename: S
authors.initials: S
authors.lastname: Branford
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
authors.forename: K
authors.initials: K
authors.lastname: Spiekermann
authors.forename: G M
authors.initials: GM
authors.lastname: Baerlocher
authors.forename: M
authors.initials: M
authors.lastname: Pfirrmann
authors.forename: J
authors.initials: J
authors.lastname: Hasford
authors.forename: S
authors.initials: S
authors.lastname: Saußele
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D003561:Cytarabine / Q000008:administration & dosage; D020732:Cytogenetic Analysis; D018450:Disease Progression; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D007372:Interferons / Q000008:administration & dosage; 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; D012074:Remission Induction; D015996:Survival Rate; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D007372:Interferons; D016044:Fusion Proteins, bcr-abl