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BCR/ABL Studies

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 volume 19, pages 628–635 (2005)Cite this article

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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Author information

Authors and Affiliations

  1. CEINGE – Biotecnologie Avanzate and Dipartimento di Biochimica e Biotecnologie Mediche, University ‘Federico II di Napoli’, Italy

    F Pane, B Izzo, C Quintarelli & F Salvatore

  2. Dipartimento di Biotecnologie Cellulari ed Ematologia, University ‘La Sapienza’, Rome, Italy

    G Cimino, A Vitale, M Mancini, F Mandelli & R Foà

  3. Divisione di Ematologia, University ‘Federico II di Napoli’, Italy

    A Camera, M Picardi & B Rotoli

  4. Divisione di Ematologia, University of Bari, Italy

    G Specchia

  5. Dipartimento di Scienze Biomediche e Terapie Avanzate, University of Ferrara, Italy

    A Cuneo

  6. Dipartimento di Medicina Clinica e Sperimentale, Universiy of Perugia, Italy

    C Mecucci

  7. Istituto di Ematologia ‘L&A Seragnoli’, University of Bologna, Italy

    G Martinelli

  8. Dipartimento di Scienze Biomediche ed Oncologia Umana, University of Turin, Italy

    G Saglio

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for the GIMEMA group

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Correspondence to F Pane.

Additional information

Supported by Associazione Italiana per la Ricerca sul Cancro (AIRC), and COFIN, Ministero della Salute (Roma), Ministero dell'Istruzione e Ricerca Scientifica (MIUR), Regione Campania, Intas (Brussel), EurLeukemiaNet (Brussel), Biogem (Avellino).

Appendix A1

Appendix A1

Participating centers and physicians in the GIMEMA study were Alessandro Levis, Ospedale SS Antonio e Biagio, Alessandria; Pietro Leoni, Nuovo Ospedale Torrette, Ancona; Ettore Volpe, AOSG Moscati, Avellino; Umberto Tirelli, CRO Unita' Operativa Leucemia, Aviano; Vincenzo Liso, Ematologia-Universita' degli Studi, Bari; Michele Baccarani, Istituto di Ematologia L&A Seragnoli, Bologna; Giovanni Quarta, Azienda Ospedaliera ‘A: Di Summa’, Brindisi; Rosario Giustolisi, Ospedale Ferrarotto, Catania; Antonio Peta, Ospedale A Pugliese, Catanzaro; Andrea Gallamini, Ospedale S Croce, Cuneo; Gianluigi Castoldi, Arcispedale S Anna, Ferrara; Alberto Bosi, Ematologia-Policlinico di Careggi, Florence; Ruggerro Mozzana, Ospedale S Antonio Abate, Gallarate, Gino Santini, Ospedale S Martino, Genoa; Franco Patrone, Ematologia-Universita' degli Studi, Genoa; Angelo De Blasio, Ospedale S Maria Goretti, Latina; Giulio Nalli, Ospedale Maggiore, Lodi; Marco Bregni, Istututo di Ricerca e Cura a Carattere Scientifico San Raffaele, Milan; Giuseppe Torelli, Universita' degli Studi, Modena; Marco Montanaro, Ospedale Civile, Montefiascone; Eustachio Miraglia, Ospedale S Giovanni Bosco, Napoli; Felicetto Ferrara, Ospedale A Cardarelli, Napoli; Bruno Rotoli, Universita' Federico II, Napoli;Vincenzo Mettiver, Divisione TERE-Ospedale A Carderelli, Napoli; Enrica Morra, Ospedale Niguarda ‘Ca' Grande’, Milan; Giancarlo Avanzi, Ospedale Maggiore della Carita', Novara; Attilio Gabbas, Ospedale S Francesco, Nuoro; Giuseppe Saglio, AOS Luigi Gonzaga, Orbassano-Turin; Salvatore Mirto, Ospedale Cervello, Palermo; Guglielmo Mariani, Universita' degli Studi, Palermo; Pietro Citarella, Universita' degli Studi, Palermo; Edoardo Ascari, IRCCS S Matteo, Pavia; Massimo Martelli, Policlinico Monteluce; Perugia, Giuseppe Visani, Ospedale S Salvatore, Pesaro; Giuseppe Fioritoni, Ospedale Civile, Pescara; Francesco Ricciuti, Ospedale S Carlo, Potenza; Francesco Nobile, AO Bianchi-Melacrino-Morelli, Reggio Calabria; Luigi Gugliotta, Arcispedale S Maria Nuova, Reggio Emilia; Franco Mandelli, Universita' ‘La Sapienza’, Rome; Giuseppe Leone, Universita' Cattolica del Sacro Cuore, Rome; Sergio Amadori, Ospedale S Eugenio, Rome; A Michele Carella, Ospedale Casa Sollievo Della Sofferenza, San Giovanni Rotondo; Maurizio Longinotti, Universita' degli Studi, Sassari; Francesco Lauria, AOA Sclavo, Siena; Dr Patrizio Mazza, Ospedale SS Annunziata, Taranto; Mario Boccadoro, Ospedale S Giovanni, Turin; Eugenio Gallo, Opsedale ‘le Molinette’, Turin and Giovanni Pizzolo, Policlinico GB Rossi, Verona; Italy.

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Pane, F., Cimino, G., Izzo, B. et al. 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 19, 628–635 (2005). https://doi.org/10.1038/sj.leu.2403683

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