Refractory and 17p-deleted chronic lymphocytic leukemia: improving survival with pathway inhibitors and allogeneic stem cell transplantation |
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| Institution: | 1. Division of Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;2. Department of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;3. Strategic Research Program on CLL, Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele, Milan, Italy;4. Department of Oncology, SSCVD Trapianto di Cellule Staminali, AOU Città della Salute e della Scienza di Torino and Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy;5. Department of Medical Area (DAME), University Hospital, DAME, University of Udine, Udine, Italy;6. Department of Hematology, Niguarda Cancer Center, Niguarda Hospital, Milano, Italy;7. Division of Hematology, AOU Città della Salute e della Scienza di Torino, Torino, Italy;8. Division of Hematology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy;9. Department of Hematology, Azienda Sanitaria Universitaria Integrata S. Maria della Misericordia, Udine, Italy;10. BMT Center, Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy;11. Division of Medical Oncology and Hematology, Istituto Clinico Humanitas, Humanitas Cancer Center, Rozzano, Italy;12. Division of Hematology, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy;13. Hematology Unit and Transplant Center, Guglielmo da Saliceto Hospital, Piacenza, italy;14. Division of Hematology, Fondazione IRCCS Ca'' Granda Ospedale Maggiore Policlinico, Milano, Italy;15. Division of Hematology, Azienda Socio Sanitaria Territoriale dei Sette Laghi-Ospedale di Circolo di Varese, Varese, Italy;16. Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy |
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| Abstract: | Refractory/early relapsed and 17p deletion/p53 mutation (del(17p)/TP53mut)-positive chronic lymphocytic leukemia (CLL) has been conventionally considered a high-risk disease, potentially eligible for treatment with allogeneic stem cell transplantation (alloSCT). In this multicenter retrospective analysis of 157 patients, we compared the outcomes of patients with high-risk CLL treated with alloSCT, a B-cell receptor pathway inhibitor (BCRi), and both. Seventy-one patients were treated with BCRis, 67 patients underwent reduced-intensity conditioning alloSCT, and 19 received alloSCT with a BCRi before and/or after transplantation. Inverse probability of treatment weighting analyses were performed to compare the alloSCT and no-alloSCT groups; in the 2 groups, 5-year OS, PFS, and cumulative incidence of nonrelapse mortality (NRM) and relapse were 40% versus 60% (P = .096), 34% versus 17% (P = .638), 28% versus 5% (P = .016), and 38% versus 83% (P = .005), respectively. Patients treated with alloSCT plus BCRi had a 3-year OS of 83%. The 3-year OS and NRM by year of alloSCT, including patients treated with BCRi, were 53% and 17% in 2000 to 2007, 55% and 30% in 2008 to 2012, and 72% and 18% in 2013 to 2018. In conclusion, the combination of pathway inhibitors and alloSCT is feasible and may further improve the outcome of high-risk CLL patients. |
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