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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2563-2572.
Prepublished online as a Blood First Edition Paper on December 21, 2007; DOI 10.1182/blood-2007-10-116186.
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Submitted October 2, 2007
Accepted December 9, 2007
Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group study SWOG-9400
Vinod A Pullarkat*, Marilyn L. Slovak, Kenneth J Kopecky, Stephen J. Forman, and Frederick R. Appelbaum
Division of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA, United States
Department of Cytogenetics, City of Hope Comprehensive Cancer Center, Duarte, CA, United States
Southwest Oncology Group, Statistical Center, Seattle, WA, United States
Medical Oncology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, United States
* Corresponding author; email: vpullarkat{at}coh.org.
We examined the prognostic impact of cytogenetics on the outcome of 200 ALL patients aged 15-65 years who were enrolled in study SWOG-9400. Evaluable cytogenetics or FISH studies were available in 140 (70%) patients. Four karyotype categories (normal [n=31, 22%], t(9;22)/BCR/ABL1 [n=36, 26%], other unfavorable [-7, +8, or 11q23 rearrangement, n=19, 13%] and miscellaneous [n=54, 39%]) as well as the biologically and clinically relevant ALL ploidy subgroups were prospectively defined. Overall survival (OS) decreased significantly with increasing age (p=0.0089) and varied with karyotype category (p < 0.0001). OS was worst for the t(9;22)/BCR/ABL1 followed by other unfavorable karyotypes, with hazard ratios (HR) of 3.45 (95% confidence interval [CI] 1.88-6.31) and 2.14 (95% CI 1.04-4.04) respectively, compared to normal diploid group. OS of the miscellaneous group was similar to that of the normal diploid group (HR = 0.82, 95% CI 0.44-1.53). Relapse-free survival (RFS) was not significantly associated with age (p=0.30), but was heterogeneous among karyotype categories (p < 0.0001) due primarily to poor RFS in the t(9;22)/BCR/ABL1 group (HR = 3.49, 95% CI 1.80-6.75) compared to normal diploid group. After accounting for the variation among karyotype groups, age was not a significant prognostic factor for OS or RFS, highlighting the importance of cytogenetics as the single most important prognostic factor in adult ALL. This trial was registered at www.ClinicalTrials.gov as #NCT00002665.
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