Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors: A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (GITMO) |
| |
| Institution: | 1. Hematology and SCT Unit, Università di Udine, Azienda Sanitaria-Universitaria Integrata Santa Maria Misericordia, Udine, Italy;2. Department of Oncology-Hematology, Universita'' degli Studi di Milano e Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy;3. Hematology and Clinical Immunology, Università di Perugia, Perugia, Italy;4. Rome Transplant Network, Università Tor Vergata, Roma, Italy;5. Hematology and BMT Unit, San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Milano, Italy;6. Department of Oncology-Hematology, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Bergamo, Italy;7. Department of Hematology Oncology, Ospedale Niguarda Ca'' Granda, Milano, Italy;8. Clinica Ematologica e Centro Trapianto di Midollo, Ospedale San Gerardo, Monza, Italy;9. Dipartimento di Biotecnologie Molecolari e Scienze per la Salute, Università di Torino,Torino, Italy;10. Dipartimento di Oncologia, Presidio Molinette-AOU Città della Salute e della Scienza, Trapianto Allogenico di Cellule Staminali, Torino, Italy;11. Istituto di Ematologia, Fondazione Policlinico Universitario A. Gemelli, Roma, Italy;12. Centro Trapianti SC Ematologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;13. Centro Trapianti di Midollo Osseo, Careggi University Hospital, Firenze, Italy;14. Hematology, Department of Translational and Precision Medicine, Sapienza University, Policlinico Umberto I, Roma, Italy;15. Institute of Hematology L. and A. Seragnoli, University Hospital S. Orsola-Malpighi, Bologna, Italy;16. Section of Hematology, University of Modena and Reggio Emilia, Modena, Italy;17. UOS Trapianto di Midollo, AOR Villa Sofia-Cervello, Palermo, Italy;18. Dipartimento di Ematologia, Medicina Trasfusionale e Biotecnologie, Ospedale Civile, Pescara, Italy;19. Centro Unico Regionale Trapianto Cellule Staminali e Terapie Cellulari A. Neri, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy;20. Centro Trapianti di Cellule Staminali, Azienda Ospedaliera San Camillo Forlanini, Roma, Italy;21. Unità Trapianti Midollo, Azienda Ospedaliera S. Antonio e Biagio, Alessandria, Italy;22. Unit of Blood Diseases and Stem Cell Transplantation, University of Brescia, ASST-Spedali Civili, Brescia, Italy;23. Dipartimento Emergenza e Trapianti di Organi, University of Bari, Bari, Italy;24. UO Ematologia e Centro Trapianti TMO, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy;25. Hematology and Bone Marrow Transplantation, University of Marche-Ospedali Riuniti, Ancona, Italy;26. Hematology-Bone Marrow Transplant Unit, University of Verona, Verona, Italy;27. UO Ematologia e Centro Trapianti, IRCCS Ospedale Policlinico San Martino, Genova, Italy;28. UO Ematologia-CTMO, PO Roberto Binaghi, Cagliari, Italy;29. SC Ematologia, Azienda Ospedaliera S Croce e Carle, Cuneo, Italy;30. UO Ematologia, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy;31. BMT Unit, Department of Clinical Medicine and Surgery, Università di Napoli, Napoli, Italy;32. Programma di Trapianto Emopoietico, Azienda Policlinico-Vittorio Emanuele, Catania, Italy;33. Università degli Studi e Ospedale Maggiore Policlinico di Milano, Milano, Italy;34. GITMO Clinical Trials Office, Genova, Italy |
| |
| Abstract: | We performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a tyrosine kinase inhibitor (TKI)-based treatmentA total of 441 patients were included in the study. The median age at HSCT was 44 years (range, 18 to 70 years). All 441 patients (100%) received TKI before HSCT (performed between 2005 and 2016). Of these 441 patients, 404 (92%) were in cytologic complete remission (CR), whereas the remaining 37 (8%) had active disease at the time of HSCT. Molecular minimal residual disease (MRD) was negative in 147 patients (36%) at the time of HSCT. The donor was unrelated in 46% of patients. The most prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (total body irradiation-based in 50%) and included antithymocyte globulin in 51% of patients. With a median follow-up after HSCT of 39.4 months (range, 1 to 145 months), the probability of overall survival (OS) at 1, 2, and 5 years was 69.6%, 61.1% and 50.3%, respectively, with a median OS of 62 months. Progression-free survival (PFS) at 1, 2, and 5 years was 60.2%, 52.1% and 43.7%, respectively. OS and PFS were significantly better in patients who were in CR and MRD-negative at the time of HSCT compared with patients who were in CR but MRD-positive (50% OS not reached versus 36 months; P = .015; 50% PFS not reached versus 26 months, P = .003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5-year OS, 70%). Conversely, the 37 patients who underwent a HSCT with active Ph+ ALL had a median OS of 7 months and a median PFS of 5 months. The 5-year cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% versus 35.4%; P = .001). Nonrelapse mortality (NRM) after 1, 2, and 5 years was 19.1% (95% confidence interval CI], 15.5% to 22.9%), 20.7% (95% CI, 17% to 24.7%), and 24.1% (95% CI, 20% to 28.5%), respectively. NRM was significantly lower with a modified European Society for Blood and Marrow Transplantation (mEBMT) risk score of 0 to 2 compared with ≥3 (15% versus 25%; P = .016). The median OS for Ph+ ALL patients who underwent a TKI-based treatment followed by an allogeneic HSCT, in recent years at the GITMO centers, was 62 months. Evaluation of the mEBMT risk score can be useful to predict NRM. Our data confirm that HSCT is a potentially curative treatment for Ph+ ALL with an excellent outcome for the subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT (5-year OS, 70%). |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
