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

• Published in: British journal of haematology Vol. 124; no. 3; pp. 275 - 288
• Main Authors: Wetzler, Meir, Dodge, Richard K., Mrózek, Krzysztof, Stewart, Carleton C., Carroll, Andrew J., Tantravahi, Ramana, Vardiman, James W., Larson, Richard A., Bloomfield, Clara D.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.02.2004; Blackwell; Blackwell Publishing Ltd
• Subjects: acute lymphoblastic leukaemia; additional aberrations; Adult; Aged; Antineoplastic Agents - therapeutic use; BCR/ABL; Benzamides; Biological and medical sciences; Chromosome Aberrations; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 7; Chromosomes, Human, Pair 9; Female; Hematologic and hematopoietic diseases; Hematology; Humans; imatinib; Imatinib Mesylate; karyotype; Karyotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Philadelphia chromosome; 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; Chromosomal aberration; Human; Hematology; BCR/ABL; Acute; imatinib; Malignant hemopathy; B-Lymphocyte; Malignant tumor; additional aberrations; Philadelphia chromosome; Abnormal chromosome C9; karyotype; Lymphoproliferative syndrome; acute lymphoblastic leukaemia; Abnormal chromosome G22; Cytogenetics; Abnormal chromosome; Adult; Acute lymphocytic leukemia
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2003.04736.x

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.