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

Abstract

Summary 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 ≥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 ≥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.

Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial

“…This effect was independent of age and WCC, both of which are significantly higher among Ph ϩ patients. In contrast to the CALGB study 31 we did not find heterogeneity of outcome among Ph ϩ patients according to the presence of Ϫ7 or an extra Ph. There are differences between the 2 cohorts and in the methods of analysis.…”

High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols

“…As far as concerns t-HeH patients with t(9;22), it has been suggested that they either have a more favorable survival and/or treatment response compared with t(9;22)-positive near-diploid ALL 20,21 or the same dismal outcome as all other patients with this translocation. 22,23 The fact that all six t-HeH with t(9;22) in our Nordic cohort achieved complete remission and all but one remain alive would rather agree with the former view ( Table 2; Online Supplementary Table S1). Obviously, larger series are needed to address this clinically important issue, and this is something that will require international collaboration due to the rarity of t-HeH in pediatric patients.…”

The frequency and prognostic impact of dic(9;20)(p13.2;q11.2) in childhood B-cell precursor acute lymphoblastic leukemia: results from the NOPHO ALL-2000 trial

“…[5][6][7] Apart from the t(9;22)-positive case in this report, the t(9;22) has been reported in association with dic (9;20) in five previous casesFthree adult 1,10,20 and two pediatric BCP ALLs. 6,13 Furthermore, in the only dic(9;20)-positive T-cell ALL reported to date, a t(8;14)(q24;q11) was also present.…”