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Novel Prognostic Indices Validated for Cytogenetically Normal Acute Myeloid Leukemia

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Key Points

  • A novel prognostic index distinguished low-, intermediate-, and high-risk groups for overall survival and relapse-free survival in cytogenetically normal acute myeloid leukemia.
  • The prognostic index distinguishes risk in both patients aged < 60 years and those aged ≥ 60 years.

Cytogenetically normal acute myeloid leukemia (AML) is the largest and most heterogeneous cytogenetic AML subgroup. As reported in the Journal of Clinical Oncology, Pastore et al have developed a widely applicable prognostic model for cytogenetically normal AML that combines established patient and disease characteristics.

In the study, prognostic indices for overall survival (PINA-OS) and relapse-free survival (PINA-RFS) were derived from data from 572 patients with cytogenetically normal AML treated in the German AML Cooperative Group 99 Study.

Overall Survival and Relapse-Free Survival Index Performance

On the basis of age, Eastern Cooperative Oncology Group performance status, white blood cell count, and mutation status of NPM1, CEBPA, and FLT3-internal tandem duplication, patients were categorized into low-risk (29%), intermediate-risk (56%), and high-risk (15%) groups with 5-year overall survival of 74%, 28%, and 3%, respectively (P < .001 overall). Hazard ratios (HRs) were 4.1 (95% confidence interval [CI] = 2.7–5.6) for intermediate vs low risk and 2.3 (95% CI = 1.8–2.9) for high vs intermediate risk. 

Similarly, PINA-RFS categorized patients with complete response (n = 381) into low- (32%), intermediate- (39%), and high-risk (29%) groups, with respective 5-year relapse-free survival rates of 55%, 27%, and 5% (P < .001 overall). Hazard ratios were 2.4 (95% CI = 1.5–3.4) for intermediate vs low risk and 1.8 (95% CI = 1.3–2.4) for high vs intermediate risk.

By Age

Among patients aged < 60 years, 5-year overall survival was 82% in the PINA-OS low-risk group (52% of patients) and 36% in the intermediate-risk group (46% of patients, P < .001; only four patients were in high-risk group); among those aged ≥ 60 years, 5-year overall survival was 57%, 25%, and 3% (P < .001 overall) in the low- (9%), intermediate- (64%), and high-risk (27%) groups.

Among the patients with complete response, 5-year relapse-free survival was 75%, 31%, and 7% (P < .001 overall) among those aged < 60 years and 32%, 28%, and 5% (P < .001 overall) among those aged ≥ 60 years in the respective PINA-RFS risk groups.

Validation Cohort

In a validation cohort (n = 529) from Cancer and Leukemia Group B/Alliance trials, PINA-OS classified 38%, 50%, and 12% of patients as low, intermediate, and high risk, with 5-year overall survival of 51%, 18%, and 3% (P < .001 overall) and hazard ratios of 2.6 (95% CI = 2.1–3.3) for intermediate vs low risk and 1.8 (95% CI = 1.4–2.4) for high vs intermediate risk.

Among 402 patients with complete response, PINA-RFS categorized 41%, 40%, and 19% of patients as low, intermediate, and high risk, with 5-year relapse-free survival of 47%, 22%, and 4% (P < .001 overall) and hazard ratios of 2.3 (95% CI = 1.8–3.0) for intermediate vs low risk and 1.7 (95% CI =1.3–2.3) for high vs intermediate risk.

The investigators concluded:We have developed and validated, to our knowledge, the first prognostic indices specifically designed for adult patients of all ages with [cytogenetically normal]-AML that combine well-established molecular and clinical variables and that are easily applicable in routine clinical care. The integration of both clinical and molecular markers could provide a basis for individualized patient care through risk-adapted therapy of [cytogenetically normal]-AML.”

Friederike Pastore, MD, of University Hospital Munich, is the corresponding author for the Journal of Clinical Oncology article.

The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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