Prospective Karyotype Analysis in Adult Acute Lymphoblastic Leukemia: The Cancer and Leukemia Group B Experience

The Cancer and Leukemia Group B (CALGB) has been conducting a prospective cytogenetic companion study (CALGB 8461) to all CALGB treatment protocols for newly diagnosed adults with acute lymphoblastic leukemia (ALL). These protocols underwent a significant change in 1988 when a new intensive chemothe...

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Bibliographic Details
Published in:Blood 1999-06, Vol.93 (11), p.3983-3993
Main Authors: Wetzler, Meir, Dodge, Richard K., Mrózek, Krzysztof, Carroll, Andrew J., Tantravahi, Ramana, Block, AnneMarie W., Pettenati, Mark J., Beau, Michelle M. Le, Frankel, Stanley R., Stewart, Carleton C., Szatrowski, Ted P., Schiffer, Charles A., Larson, Richard A., Bloomfield, Clara D.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Chromosome Aberrations
Chromosome Disorders
Disease-Free Survival
Genetic Markers
Hematologic and hematopoietic diseases
Humans
Karyotyping
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Multivariate Analysis
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - physiopathology
Prognosis
Prospective Studies
Risk Factors
Survival Analysis
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Summary:The Cancer and Leukemia Group B (CALGB) has been conducting a prospective cytogenetic companion study (CALGB 8461) to all CALGB treatment protocols for newly diagnosed adults with acute lymphoblastic leukemia (ALL). These protocols underwent a significant change in 1988 when a new intensive chemotherapy program was introduced (CALGB 8811). We asked whether karyotype continued to represent a significant prognostic factor in adult ALL patients after the change. A total of 256 patients had adequate pretreatment cytogenetic analyses: 67 before 1988 and 189 subsequently. The complete remission (CR) rate for the whole group was 80%. Patients with t(9;22), t(4;11), −7, or +8 had significantly lower probabilities of continuous CR and survival at 5 years (.11 and .12) than patients with a normal karyotype (.38 and .37) and patients with miscellaneous cytogenetic abnormalities (.52 and .49;P < .001 for each comparison). When analyzed by treatment period, the CR rate before CALGB 8811 was 63%; subsequently, it was 86% (P < .001). Patients with cytogenetic abnormalities other than t(9;22), t(4;11), −7, or +8 had better CR rates, disease-free survival (DFS), and survivals (P = .001,P = .04, and P = .004, respectively) after the change to the more intensive chemotherapy regimens. Patients with normal cytogenetics had improved CR rate but no improved DFS or survival, whereas no significant benefit for patients with t(9;22), t(4;11), −7, or +8 was seen. In a multivariate analysis, karyotype retained its prognostic significance for DFS but not for survival; it remained the most important factor for DFS. We conclude that cytogenetic analysis at diagnosis should be used to guide treatment decisions in adults with ALL.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V93.11.3983