TY - JOUR
T1 - Outcome of very elderly chronic myeloid leukaemia patients treated with imatinib frontline
AU - Crugnola, Monica
AU - Castagnetti, Fausto
AU - Breccia, Massimo
AU - Ferrero, Dario
AU - Trawinska, Malgorzata Monika
AU - Abruzzese, Elisabetta
AU - Annunziata, Mario
AU - Stagno, Fabio
AU - Tiribelli, Mario
AU - Binotto, Gianni
AU - Bonifacio, Massimiliano
AU - Fava, Carmen
AU - Iurlo, Alessandra
AU - Bucelli, Cristina
AU - Mansueto, Giovanna
AU - Gozzini, Antonella
AU - Falzetti, Franca
AU - Montefusco, Enrico
AU - Crisà, Elena
AU - Gugliotta, Gabriele
AU - Russo, Sabina
AU - Cedrone, Michele
AU - Russorossi, Antonella
AU - Pregno, Patrizia
AU - Isidori, Alessandro
AU - Mauro, Endri
AU - Atelda, Romano
AU - Giglio, Gianfranco
AU - Celesti, Francesca
AU - Sora', Federica
AU - Storti, Sergio
AU - D’Addosio, Adam
AU - Galimberti, Sara
AU - Orlandi, Ester
AU - Calistri, Elisabetta
AU - Bocchia, Monica
AU - Cavazzini, Francesco
AU - Rege Cambrin, Giovanna
AU - Orofino, Nicola
AU - Luciano, Luigiana
AU - Sgherza, Nicola
AU - Rosti, Gianantonio
AU - Latagliata, Roberto
AU - Capodanno, Isabella
PY - 2019
Y1 - 2019
N2 - 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%).
AB - 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%).
KW - Chronic myeloid leukaemia
KW - Elderly
KW - Outcome
KW - Tyrosine kinase inhibitor
KW - Chronic myeloid leukaemia
KW - Elderly
KW - Outcome
KW - Tyrosine kinase inhibitor
UR - http://hdl.handle.net/10807/141208
U2 - 10.1007/s00277-019-03767-y
DO - 10.1007/s00277-019-03767-y
M3 - Article
SN - 0939-5555
VL - 98
SP - 2329
EP - 2338
JO - Annals of Hematology
JF - Annals of Hematology
ER -