Additional Cytogenetic Abnormalities in Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukaemia: A Study of the Cancer and Leukaemia Group B

Br J Haematol. 2004 Feb;124(3):275-88. doi: 10.1046/j.1365-2141.2003.04736.x.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Benzamides
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 2
  • Chromosomes, Human, Pair 22*
  • Chromosomes, Human, Pair 7
  • Chromosomes, Human, Pair 9*
  • Female
  • Humans
  • Imatinib Mesylate
  • Karyotyping
  • Male
  • Middle Aged
  • Piperazines / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Prognosis
  • Prospective Studies
  • Pyrimidines / therapeutic use
  • Recurrence
  • Remission Induction
  • Translocation, Genetic

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate