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

Fab Pane, G. Cimino, B. Izzo, A. Camera, A. Vitale, C. Quintarelli, M. Picardi, G. Specchia, M. Mancini, A. Cuneo, C. Mecucci, G. Martinelli, G. Saglio, B. Rotoli, F. Mandelli, F. Salvatore, R. Foà, Alessandro Levis, Pietro Leoni, Ettore VolpeUmberto Tirelli, Vicencio Liso, Michele Baccarani, Giovanni Quarta, Rosario Giustolisi, Antonio Peta, Andrea Gallamini, Gianluigi Castoldi, Alberto Bosi, Ruggero Mozzana, Gino Santini, Franco Patrone, Angelo De Blasio, Guilio Nalli, Marco Bregni, Guiseppe Torelli, Marco Montanaro, Eustachio Miraglia, Felicito Ferrara, Bruno Rotoli, Vicenzo Mettiver, Enrica Morra, Giancarlo Avanzi, Attilo Gabbas, Guiseppe Saglio, Salvatore Mirto, Guglielmo Mariani, Pietro Citarella, Edoardo Ascari, Massimo Martelli, Giuseppe Visani, Giuseppe Fioritoni, Francesco Ricciuti, Francesco Nobile, Luigi Gugliotta, Franco Mandelli, Giuseppe Leono, Sergio Amadori, A. Michele Carella, Maurizio Longinotti, Francesco Lauria, Patricio Mazza, Mario Boccadaro, Eugenio Gallo, Giovanni Pizzolo

Research output: Contribution to journalArticle

66 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)628-635
Number of pages8
JournalLeukemia
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 2005

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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Residual Neoplasm
Salvage Therapy
Philadelphia Chromosome
Daunorubicin
Therapeutics
Disease-Free Survival
Real-Time Polymerase Chain Reaction
Appointments and Schedules
Recurrence

Keywords

  • Minimal residual disease
  • Ph-ALL
  • Prognosis
  • Real-time PCR

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

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. / Pane, Fab; 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, Alessandro; Leoni, Pietro; Volpe, Ettore; Tirelli, Umberto; Liso, Vicencio; Baccarani, Michele; Quarta, Giovanni; Giustolisi, Rosario; Peta, Antonio; Gallamini, Andrea; Castoldi, Gianluigi; Bosi, Alberto; Mozzana, Ruggero; Santini, Gino; Patrone, Franco; De Blasio, Angelo; Nalli, Guilio; Bregni, Marco; Torelli, Guiseppe; Montanaro, Marco; Miraglia, Eustachio; Ferrara, Felicito; Rotoli, Bruno; Mettiver, Vicenzo; Morra, Enrica; Avanzi, Giancarlo; Gabbas, Attilo; Saglio, Guiseppe; Mirto, Salvatore; Mariani, Guglielmo; Citarella, Pietro; Ascari, Edoardo; Martelli, Massimo; Visani, Giuseppe; Fioritoni, Giuseppe; Ricciuti, Francesco; Nobile, Francesco; Gugliotta, Luigi; Mandelli, Franco; Leono, Giuseppe; Amadori, Sergio; Carella, A. Michele; Longinotti, Maurizio; Lauria, Francesco; Mazza, Patricio; Boccadaro, Mario; Gallo, Eugenio; Pizzolo, Giovanni.

In: Leukemia, Vol. 19, No. 4, 04.2005, p. 628-635.

Research output: Contribution to journalArticle

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, 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, AM, Longinotti, M, Lauria, F, Mazza, P, Boccadaro, M, Gallo, E & Pizzolo, G 2005, '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', Leukemia, vol. 19, no. 4, pp. 628-635. https://doi.org/10.1038/sj.leu.2403683
Pane, Fab ; 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, Alessandro ; Leoni, Pietro ; Volpe, Ettore ; Tirelli, Umberto ; Liso, Vicencio ; Baccarani, Michele ; Quarta, Giovanni ; Giustolisi, Rosario ; Peta, Antonio ; Gallamini, Andrea ; Castoldi, Gianluigi ; Bosi, Alberto ; Mozzana, Ruggero ; Santini, Gino ; Patrone, Franco ; De Blasio, Angelo ; Nalli, Guilio ; Bregni, Marco ; Torelli, Guiseppe ; Montanaro, Marco ; Miraglia, Eustachio ; Ferrara, Felicito ; Rotoli, Bruno ; Mettiver, Vicenzo ; Morra, Enrica ; Avanzi, Giancarlo ; Gabbas, Attilo ; Saglio, Guiseppe ; Mirto, Salvatore ; Mariani, Guglielmo ; Citarella, Pietro ; Ascari, Edoardo ; Martelli, Massimo ; Visani, Giuseppe ; Fioritoni, Giuseppe ; Ricciuti, Francesco ; Nobile, Francesco ; Gugliotta, Luigi ; Mandelli, Franco ; Leono, Giuseppe ; Amadori, Sergio ; Carella, A. Michele ; Longinotti, Maurizio ; Lauria, Francesco ; Mazza, Patricio ; Boccadaro, Mario ; Gallo, Eugenio ; Pizzolo, Giovanni. / 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. In: Leukemia. 2005 ; Vol. 19, No. 4. pp. 628-635.
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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.",
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T1 - 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

AU - Pane, Fab

AU - Cimino, G.

AU - Izzo, B.

AU - Camera, A.

AU - Vitale, A.

AU - Quintarelli, C.

AU - Picardi, M.

AU - Specchia, G.

AU - Mancini, M.

AU - Cuneo, A.

AU - Mecucci, C.

AU - Martinelli, G.

AU - Saglio, G.

AU - Rotoli, B.

AU - Mandelli, F.

AU - Salvatore, F.

AU - Foà, R.

AU - Levis, Alessandro

AU - Leoni, Pietro

AU - Volpe, Ettore

AU - Tirelli, Umberto

AU - Liso, Vicencio

AU - Baccarani, Michele

AU - Quarta, Giovanni

AU - Giustolisi, Rosario

AU - Peta, Antonio

AU - Gallamini, Andrea

AU - Castoldi, Gianluigi

AU - Bosi, Alberto

AU - Mozzana, Ruggero

AU - Santini, Gino

AU - Patrone, Franco

AU - De Blasio, Angelo

AU - Nalli, Guilio

AU - Bregni, Marco

AU - Torelli, Guiseppe

AU - Montanaro, Marco

AU - Miraglia, Eustachio

AU - Ferrara, Felicito

AU - Rotoli, Bruno

AU - Mettiver, Vicenzo

AU - Morra, Enrica

AU - Avanzi, Giancarlo

AU - Gabbas, Attilo

AU - Saglio, Guiseppe

AU - Mirto, Salvatore

AU - Mariani, Guglielmo

AU - Citarella, Pietro

AU - Ascari, Edoardo

AU - Martelli, Massimo

AU - Visani, Giuseppe

AU - Fioritoni, Giuseppe

AU - Ricciuti, Francesco

AU - Nobile, Francesco

AU - Gugliotta, Luigi

AU - Mandelli, Franco

AU - Leono, Giuseppe

AU - Amadori, Sergio

AU - Carella, A. Michele

AU - Longinotti, Maurizio

AU - Lauria, Francesco

AU - Mazza, Patricio

AU - Boccadaro, Mario

AU - Gallo, Eugenio

AU - Pizzolo, Giovanni

PY - 2005/4

Y1 - 2005/4

N2 - 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.

AB - 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.

KW - Minimal residual disease

KW - Ph-ALL

KW - Prognosis

KW - Real-time PCR

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