Integrated genetic and clinical prognostic factors for aggressive adult T-cell leukemia/lymphoma

Haematologica. 2023 Aug 1;108(8):2178-2191. doi: 10.3324/haematol.2022.281510.

Abstract

The prognosis of aggressive adult T-cell leukemia/lymphoma (ATL) is poor, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment. In order to identify favorable prognostic patients after intensive chemotherapy, and who therefore might not require upfront allo-HSCT, we aimed to improve risk stratification of aggressive ATL patients aged <70 years. The clinical risk factors and genetic mutations were incorporated into risk modeling for overall survival (OS). We generated the m7-ATLPI, a clinicogenetic risk model for OS, that included the ATL prognostic index (PI) (ATL-PI) risk category, and non-silent mutations in seven genes, namely TP53, IRF4, RHOA, PRKCB, CARD11, CCR7, and GATA3. In the training cohort of 99 patients, the m7-ATLPI identified a low-, intermediate-, and highrisk group with 2-year OS of 100%, 43%, and 19%, respectively (hazard ratio [HR] =5.46; P<0.0001). The m7-ATLPI achieved superior risk stratification compared to the current ATL-PI (C-index 0.92 vs. 0.85, respectively). In the validation cohort of 84 patients, the m7-ATLPI defined low-, intermediate-, and high-risk groups with a 2-year OS of 81%, 30%, and 0%, respectively (HR=2.33; P=0.0094), and the model again outperformed the ATL-PI (C-index 0.72 vs. 0.70, respectively). The simplified m7-ATLPI, which is easier to use in clinical practice, achieved superior risk stratification compared to the ATLPI, as did the original m7-ATLPI; the simplified version was calculated by summing the following: high-risk ATL-PI category (+10), low-risk ATL-PI category (-4), and non-silent mutations in TP53 (+4), IRF4 (+3), RHOA (+1), PRKCB (+1), CARD11 (+0.5), CCR7 (-2), and GATA3 (-3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell* / genetics
  • Leukemia-Lymphoma, Adult T-Cell* / therapy
  • Lymphoma*
  • Prognosis
  • Receptors, CCR7
  • Retrospective Studies

Substances

  • Receptors, CCR7

Grants and funding

Funding: This research was supported by grants JP19ck0106254, 20ck0106538h0001, and 21ck0106538h0002 to KS from the Japan Agency for Medical Research and Development.