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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3983-3993
Prospective Karyotype Analysis in Adult Acute Lymphoblastic
Leukemia: The Cancer and Leukemia Group B Experience
Meir Wetzler,
Richard K. Dodge,
Krzysztof Mrózek,
Andrew J. Carroll,
Ramana Tantravahi,
AnneMarie W. Block,
Mark J. Pettenati,
Michelle M. Le Beau,
Stanley R. Frankel,
Carleton C. Stewart,
Ted
P. Szatrowski,
Charles A. Schiffer,
Richard A. Larson, and
Clara D. Bloomfield
From the Roswell Park Cancer Institute, Buffalo, NY; the Duke
University Medical Center, Durham, NC; the Comprehensive Cancer Center
of The Ohio State University, Columbus, OH; the University of Alabama
at Birmingham, Birmingham, AL; the Dana Farber Cancer Institute,
Boston, MA; the Wake Forest University School of Medicine,
Winston-Salem, NC; the University of Chicago, Chicago, IL; the
Georgetown University Medical Center, Washington, DC; the New York
Hospital-Cornell Medical Center, New York, NY; and the Karmanos Cancer
Institute, Wayne State University School of Medicine, Detroit, MI.
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.
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