Additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a study of the Cancer and Leukaemia Group B.

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.