Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors. A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (Gitmo)

Federica Sora', Simona Sica, Robin Foa, Anna Candoni, Alessandro Rambaldi, Renato Fanin, Andrea Velardi, William Arcese, Fabio Ciceri, Davide Lazzarotto, Federico Lussana, Jacopo Olivieri, Giovanni Grillo, Matteo Parma, Benedetto Bruno, Paolo Bernasconi, Riccardo Saccardi, Robin Foà, Mariarosa Sessa, Paola BrescianiFabio Giglio, Alessandra Picardi, Alessandro Busca, Katia Perruccio, Elisa Zucchetti, Elisa Diral, Anna Paola Iori, Anna Amelia Colombo, Stefano Tringali, Stella Santarone, Giuseppe Irrera, Stefano Mancini, Francesco Zallio, Michele Malagola, Francesco Albano, Angelo Michele Carella, Attilio Olivieri, Cristina Tecchio, Alida Dominietto, Adriana Vacca, Roberto Sorasio, Enrico Orciuolo, Antonio Maria Risitano, Salvatore Leotta, Agostino Cortelezzi, Sonia Mammoliti, Elena Oldani, Francesca Bonifazi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

4 Citazioni (Scopus)

Abstract

Abstract PURPOSE: We performed a nationwide registry-based analysis to describe the clinical outcome of adults patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a TKI-based treatment. PATIENTS AND RESULTS: A total of 441 patients were included in the study. The median age at HSCT was 44 years (range 18-70). All the 441 patients (100%) received TKI before the HSCT (performed between 2005 and 2016). Of these patients, 404 (92%) were in cytologic complete remission (CR), while the remaining 37 (8%) had an 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 cases. The prevalent source of stem cells was peripheral blood (70%). The conditioning regimen was myeloablative in 82% of cases (TBI-based in 50%) and included ATG in 51% of cases. With a median follow-up after HSCT of 39.4 months (range: 1-145), the overall survival (OS) probability 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 with CR and MRD-negative at the time of transplant compared with those of patients with CR but MRD-positive (50% OS not reached vs. 36 months, P=0.015; 50% PFS not reached vs. 26 months, P=0.003). The subgroup of MRD-negative patients both at HSCT and at 3 months after HSCT had a better outcome (5 years OS rate 70%). Conversely, the 37 patients who underwent a HSCT with active Ph+ ALL had a median OS and PFS of 7 and 5 months, respectively. The 5 years cumulative incidence of relapse was significantly lower in MRD-negative patients (19.5% vs. 35.4%, P=0.001). The non-relapse mortality (NRM) after 1, 2 and 5 years was 19.1% (95%CI: 15.5-22.9), 20.7% (95%CI: 17-24.7) and 24.1% (95%CI: 20-28.5), respectively. The NRM was significantly lower with a mEBMT risk score of 0-2 compared with mEBMT risk score of ≥ 3 (15% vs. 25%, P=0,016). CONCLUSIONS: The median OS for Ph+ ALL patients who underwent a TKI-based treatment followed by an allograft, 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 patients MRD-negative both at HSCT and at 3 months after HSCT (5 year OS 70%).
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaBiology of Blood and Marrow Transplantation
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • Allogeneic Hematopoietic Stem Cell Transplantation
  • Philadelphia Positive Acute Lymphoblastic Leukemia
  • Tyrosine Kinase Inhibitors

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