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Randomized Controlled Trial
. 2008 Mar 1;111(5):2563-72.
doi: 10.1182/blood-2007-10-116186. Epub 2007 Dec 21.

Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study

Vinod Pullarkat  1 , Marilyn L Slovak, Kenneth J Kopecky, Stephen J Forman, Frederick R Appelbaum
Affiliations
Randomized Controlled Trial

Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study

Vinod Pullarkat et al. Blood. .

Abstract

We examined the prognostic impact of cytogenetics on the outcome of 200 acute lymphoblastic leukemia (ALL) patients 15 to 65 years of age enrolled in Southwest Oncology Group (SWOG)-9400 study. Evaluable cytogenetics or fluorescence in situ hybridization 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%]) and the biologically and clinically relevant ALL ploidy subgroups were prospectively defined. Overall survival (OS) decreased significantly with increasing age (P = .009) and varied with karyotype category (P < .001). OS was worst for 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 with 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 = .30) but was heterogeneous among karyotype categories (P < .001) primarily because of poor RFS in t(9;22)/BCR/ABL1 (HR = 3.49; 95% CI, 1.80-6.75) compared with the normal diploid group. After accounting for the variation among karyotype groups, age was not a significant prognostic factor for OS or RFS, highlighting cytogenetics as the most important prognostic factor in adult ALL. This trial was registered at www.ClinicalTrials.gov as #NCT00002665.

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Figures

Figure 1
Figure 1
Estimated overall survival of 200 adult patients with non-L3 ALL, by karyotype category.
Figure 2
Figure 2
Estimated overall survival by MRC UKALLXII/ECOG E2993 karyotypic categories.
Figure 3
Figure 3
Proposed cytogenetic and molecular genetic prognostic risk grouping for adult acute lymphoblastic leukemia.
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