CLINICAL-SIGNIFICANCE OF P53 MUTATIONS IN RELAPSED T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA

In T-cell acute lymphoblastic leukemia (T-ALL), p53 gene mutations wer e found in 12 of 51 patients in first relapse (24%). In a retrospectiv e study, bone marrow samples at diagnosis were obtained from 9 of the 12 relapsed patients with p53 mutation; only one patient was found to harbor a p53 mutation at diagnosis. No further p53 mutations were iden tified in 18 unpaired diagnosis T-ALL samples. This is the first repor t of a p53 mutation in T-ALL at diagnosis. p53 mutations in relapsed T -ALL were clinically relevant. Patients with p53 mutations experience a shorter duration of survival than those patients without p53 mutatio ns. Additionally, patients with p53 mutations were significantly less likely to have achieved a complete second remission from reinduction t herapy than those patients without p53 mutations and experience a shor ter duration of survival from relapse even when a second reinduction i s obtained. Though primarily identified only at relapse, p53 mutations were also associated with a decreased duration of first remission and overall decrease in survival from diagnosis. Patients with p53 mutati ons had a 3.8-fold increase in risk of death than those patients witho ut p53 mutations. These findings suggest that p53 mutation is associat ed with poor clinical outcome that is characterized by (1) a shortened duration of survival after first relapse; (2) a reduced response to r einduction therapy; (3) a shortened duration of first remission; and, hence, (4) an overall decreased duration of survival and increased ris k of death. (C) 1994 by The American Society of Hematology.