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Significant reduction of the hybrid BCR/ABL transcripts after induction and consolidation therapy is a powerful predictor of treatment response in adult Philadelphia-positive acute lymphoblastic leukemia

2005; Springer Nature; Volume: 19; Issue: 4 Linguagem: Inglês

10.1038/sj.leu.2403683

1476-5551

Fabrizio Pane, Giuseppe Cimino, Barbara Izzo, Andrea Camera, Alessandro Vitale, Concetta Quintarelli, Marco Picardi, Giorgina Specchia, Marco Mancini, Antonio Cuneo, Cristina Mecucci, Giovanni Martinelli, Giuseppe Saglio, Bruno Rotoli, Franco Mandelli, Francesco Salvatore, Robin Foà,

Lymphoma Diagnosis and Treatment

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has a dismal prognosis. We prospectively evaluated minimal residual disease (MRD) by measuring BCR/ABL levels with a quantitative real-time PCR procedure after induction and after consolidation in 45 adults with Ph+ ALL who obtained complete hematological remission after a high-dose daunorubicin induction schedule. At diagnosis, the mean BCR-ABL/GUS ratio was 1.55±1.78. A total of 42 patients evaluable for outcome analysis were operationally divided into two MRD groups: good molecular responders (GMRs; n=28) with >2 log reduction of residual disease after induction and >3 log reduction after consolidation therapy, and poor molecular responders (PMRs; n=14) who, despite complete hematological remission, had a higher MRD at both time points. In GMR, the actuarial probability of relapse-free, disease-free and overall survival at two years was 38, 27 and 48%, respectively, as compared to 0, 0 and 0% in PMR (P=0.0035, 0.0076 and 0.0026, respectively). Salvage therapy induced a second sustained complete hematological remission in three GMR patients, but in no PMR patient. Our data indicate that, as already shown in children, adult Ph+ ALL patients have a heterogeneous sensitivity to treatment, and that early quantification of residual disease is a prognostic parameter in this disease.