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Blood, Vol. 112, Issue 5, 1993-2003, September 1, 2008
Genomic complexity identifies patients with aggressive chronic lymphocytic leukemia
Blood Kujawski et al.
112: 1993
Supplemental materials for: Kujawski et al
Files in this Data Supplement:
- Table S1. Univariate analysis of TTFT or TTST in relation to established risk factors (XLS, 20 KB)
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TTFT and TTST were the clinical endpoints used. For univariate analysis, we considered each prognostic factor (Rai-stage, IgVH mutation status, p53 mutation status for exon 5-9, ZAP-70 expression status, individual or combined FISH categories as indicated, CD38 expression status) separately. TTFT data are based on 139 patients, TTST data are based on 48 patients. The Kaplan-Meier method was used to estimate the survivor function to first treatment for each subgroup, and the log-rank test was used to calculate two-sided p-values testing significant differences in the survivor function between subgroups.
- Table S2. The relationship of total genomic complexity ≥2.5 and other prognostic variables for previously untreated CLL patients (XLS, 22.5 KB)
- Table S3. The relationship of total genomic complexity ≥2.5 and other prognostic variables for previously treated CLL patients (XLS, 22.0 KB)
- Figure S1. Internal Validation of the clinical CLL cohort using established biomarkers and TTFT estimates (Kaplan-Meier plots) (JPG, 121 KB)
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(A) ZAP-70 expression (positive = greater than 20% of CD19+ cells, negative = less than 20% CD19+ cells) and effect on time to first therapy. (B) Mutations in p53 exons 5-9 and effect on time to first therapy. (C–D) Mutation status of variable heavy chain gene segments (using either 98% or 97% homology to germ-line as the cut-off) and effect on time to first therapy. (E–F) CD38 expression (using either 7% or 30% positivity as the cut-off) and effect on time to first therapy. (G) Prioritized FISH findings and effect on time to first therapy. (H) Grouped prioritized FISH25 findings and effect on time to first therapy. (I) Rai stages and effect on time to first therapy.
- Figure S2. Internal Validation of the clinical CLL cohort using established biomarkers and TTST estimates (Kaplan-Meier plots) (JPG, 143 KB)
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(A) ZAP-70 expression (positive = greater than 20% of CD19+ cells, negative = less than 20% CD19+ cells) and effect on time to subsequent therapy. (B) Mutations in p53 exons 5–9 and effect on time to subsequent therapy. (C–D) Mutation status of variable heavy chain gene segments (using either 98% or 97% homology to germ-line as the cut-off) and effect on time to subsequent therapy. (E–F) CD38 expression (using either 7% or 30% positivity as the cut-off) and effect on time to subsequent therapy. (G) Prioritized FISH findings and effect on time to subsequent therapy. (H) Grouped prioritized FISH findings and effect on time to subsequent therapy.
- Figure S3. The total visual complexity score predicts for a short time to first therapy in univariate analysis in a cohort of previously untreated CLL patients (Kaplan-Meier plots) (JPG, 117 KB)
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The numbers of sub-chromosomal losses, gains and uniparental disomie (UPD) were determined using 50kXbaI SNP array technology for each patient as described in Methods and combined to derive the total visual complexity score. The mean score as determined by two independent observers was subsequently correlated against the clinical endpoint time-to-first therapy (TTFT). Depicted are Kaplan-Meier estimates (A–F) for increasing complexity score cut-offs (e.g.
- Figure S4. The total visual complexity score predicts for a short time to subsequent therapy in univariate analysis in a cohort of previously treated CLL patients (Kaplan-Meier plots) (JPG, 105 KB)
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The numbers of sub-chromosomal losses, gains and uniparental disomie (UPD) were determined using 50kXbaI SNP array technology for each patient as described in Methods and combined to derive the total visual complexity score. The mean score as determined by two independent observers was subsequently correlated against the clinical endpoint time-to-subsequent therapy (TTST). Depicted are Kaplan-Meier estimates (panel A-F) for increasing complexity score cut-offs (e.g.
- Figure S5. The algorithmic complexity score predicts for a short TTFT or TTST in univariate analysis in a cohort of previously untreated or pretreated CLL patients (Kaplan-Meier plots) (JPG, 117 KB)
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The sum of sub-chromosomal losses was determined using 50kXbaI SNP array technology for each patient and a sliding window algorithm (the 8/7/1.45 rule) that was applied to dChip-based copy number estimates as described in Methods (the algorithmic complexity score) and correlated against the clinical endpoints time-to-first therapy (TTFT) and time-to-subsequent therapy (TTST). Depicted are Kaplan-Meier estimates for various complexity scores and TTFT (A-D) or TTST (E-H).
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