title: Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia Group B.
abstract: We analysed the nature and prognostic significance of secondary cytogenetic changes in 111 newly diagnosed adults with acute lymphoblastic leukaemia (ALL) and t(9;22)(q34;q11.2) or its variants. Secondary aberrations were seen in 75 (68%) patients. They included, in order of descending frequency: +der(22)t(9;22), +21, abnormalities of 9p, high hyperdiploidy (>50 chromosomes), +8, -7, +X and abnormalities resulting in loss of material from 8p, gain of 8q, gain of 1q and loss of 7p. Eighty patients (72%) had > or =1 normal metaphase in their karyotype. There were four balanced and 12 unbalanced translocations previously unreported in ALL with t(9;22). The t(2;7)(p11;p13) and der(18)t(8;18)(q11.2;p11.2) were seen in two cases each, and have never before been reported in haematological malignancy. All but four patients were treated on front-line Cancer and Leukaemia Group B clinical protocols. The presence of -7 as a sole secondary abnormality was associated with a lower complete remission (CR) rate (P = 0.004), while the presence of > or =3 aberrations was associated with a higher CR rate (P = 0.009) and +der(22)t(9;22) with a higher cumulative incidence of relapse (P = 0.02). It will be of interest to see if newly diagnosed t(9;22)-positive adult ALL patients with these and other secondary aberrations respond differently to treatment regimens that include imatinib mesylate.
authors.affiliation: Department of Medicine, Leukemia Section, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. meir.wetzler@roswellpark.org
authors.forename: Meir
authors.initials: M
authors.lastname: Wetzler
authors.forename: Richard K
authors.initials: RK
authors.lastname: Dodge
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Mrózek
authors.forename: Carleton C
authors.initials: CC
authors.lastname: Stewart
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Carroll
authors.forename: Ramana
authors.initials: R
authors.lastname: Tantravahi
authors.forename: James W
authors.initials: JW
authors.lastname: Vardiman
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D002869:Chromosome Aberrations; D002889:Chromosomes, Human, Pair 2; D002892:Chromosomes, Human, Pair 22; D002897:Chromosomes, Human, Pair 7; D002899:Chromosomes, Human, Pair 9; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D014178:Translocation, Genetic
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate