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.
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Data di pubblicazione: | 2005 | |
Titolo: | 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. | |
Autori: | Pane, F.; Cimino, G.; Izzo, B.; Camera, A.; Vitale, A.; Quintarelli, C.; Picardi, M. ; Specchia, G. ; Mancini, M. ; Cuneo, A. ; Mecucci, C. ; Martinelli, G. ; Saglio, G. ; Rotoli, B. ; Mandelli, F.; Salvatore, F. ; Foà, R. ; Levis, A. ; Leoni, P. ; Volpe, E. ; Tirelli, U. ; Liso, V. ; Baccarani, M. ; Quarta, G. ; Giustolisi, R. ; Peta, A. ; Gallamini, A. ; Castoldi, G. ; Bosi, A. ; Mozzana, R. ; Santini, G. ; Patrone, F. ; De Blasio, A. ; Nalli, G. ; Bregni, M.; Torelli, G.aa, ; Montanaro, M. ; Miraglia, E. ; Ferrara, F. ; Rotoli, B. ; Mettiver, V. ; Morra, E. ; Avanzi, G.; Gabbas, A. ; Saglio, G. ; Mirto, S. ; Mariani, G. ; Citarella, P. ; Ascari, E. ; Martelli, M. ; Visani, G. ; Fioritoni, G. ; Ricciuti, F. ; Nobile, F. ; Gugliotta, L. ; Mandelli, F. ; Leono, G.; Amadori, S.; Carella, A.M.; Longinotti, M.; Lauria, F. ; Mazza, P.; Boccadaro, M.; Gallo, E.; Pizzolo, G. | |
Rivista: | LEUKEMIA | |
Abstract: | 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. | |
Handle: | http://hdl.handle.net/11392/1199379 | |
Appare nelle tipologie: | 03.1 Articolo su rivista |