Overall Survival Improvement Following ALLO-SCT in Patients Older THAN 60 YEARS: A Gruppo Italiano Trapianto DI Midollo Osseo (GITMO) Registry Study
Authors: Malagola Michele , Polverelli Nicola , Martino Massimo , Rubini Vicky , Lupo Stanghellini Maria Teresa , Patriarca Francesca , Fanin Renato , Bruno Benedetto , Giaccone Luisa , Faraci Danilo Giuseppe , Grillo Giovanni , Bramanti Stefania , Castagna Luca , Bernasconi Paolo , Colombo Anna Amelia , De Gobbi Marco , Nicoli Paolo , Natale Annalisa , Santarone Stella , Terruzzi Elisabetta , Olivieri Attilio , Scortechini Ilaria , Chiusolo Patrizia , Metafuni Elisabetta , Carella Angelo Michele , Merla Emanuela , Casini Marco , Cavattoni Irene M , Arpinati Mario , Nozzoli Chiara , Cutini Ilaria , Mazza Patrizio , Mazzone Annamaria , Bassi Simona , Onida Francesco , Saporiti Giorgia , Canale Filippo Antonio , Vacca Adriana , Piras Eugenia , Galieni Piero , Falcioni Sadia , Luppi Mario , Debbia Giulia , Iori Anna Paola , La Rocca Ursula , Pavone Vincenzo , Mele Anna , Skert Cristina , Carobolante Francesca , Carluccio Paola , Borghero Carlo , Elice Francesca , Proia Anna , Fanelli Fulvia , Selleri Carmine , Sacchi Nicoletta , Mammoliti Sonia , Oldani Elena , Ciceri Fabio , Bonifazi Francesca , Russo Domenico 
Published: November 2021

Abstract
The upper age-limit for patients with hematological malignancies eligible for allo-SCT progressed to 70-75 years. As a consequence, an increase of older patients submitted to allo-SCT has been observed worldwide and in Italy as well.
This registry-based retrospective study on behalf of GITMO (GITMO AlloEld) describes the transplant activity among elderly patients in Italy, between 2000 and 2017. Thiry GITMO Centers participated to the Study. 2061 allo-SCTS in patients older than 60 years were exported from PROMISE database and 1996 first transplants were analysed.
The median age of the patients at transplant was 63,5 years (59,5-77,8). The most commonly transplanted diseases were acute leukemias and myelodisplastic syndromes (67,5%). 28% and 27% of the patients showed a HCT-CI of 1-2 or grater than 3, respectively. The KPS was 100% in 27,2% and 90% in 42,9% of the cases. 32% of the patients received a myeloablative conditioning regimen and 55% of the patients received an in vivo T-cell depletion (either post transplant cyclophosphamide or ATG).
With a median follow up of 10,4 years, the OS at 5 years significantly improved during time, moving from 28% between 2000-2005 to 37% between 2012-2017 (p=0,012). This was related to a significant reduction in RI (45% vs 30%, p&lt;0,0001), whereas NRM remained stable over time (33% vs 35%, p=0,5).
The following significant differences were observed across the years of the present study:
1) a longer 5 years OS in patients younger than 65 years (34%) vs those older than 70 years (19%) between 2000 and 2011 only (p=0,003) (Figure 1A and 1B);
2) a longer 5 years OS (p&lt;0.001) and a reduced NRM (p=0.02) for HCT-CI 0 vs 1-2 vs &gt;3 between 2000-2011 only (Figure 2A and 2B);
3) a different 5 years OS according to donor type between 2000 and 2011 only (19% for haplo vs 31% for sibling vs 33% for mismatch UD and 38% for MUD; p&lt;0,0001) (Figure 3A and 3B);
4) a reduction in the incidence of extensive cGVHD at 1 year (15,6% between 2000 and 2005 vs 10,3% between 2012 and 2017, p=0,004) (Figure 4).
Comparing 2000-2005 vs 2012-2017, the major significant differences of the patients regard: the baseline disease (more AL/MDS: 40% vs 77%; p&lt;0,001); the disease status at SCT (more CR: 29% vs 54%, p&lt;0,0001), the intensity of conditioning (MAC in 14% vs 42%, p&lt;0,001), the use of alkylator-base conditioning regimen (49% vs 91%; p&lt;0,001) and the use of in vivo T-cell depletion (17% vs 43%, p&lt;0,0001). Moreover, the percentage of patients with HCT-CI &gt; 3 moved from 10% to 30% (p&lt;0,001), in parallel with an increase in patients with KPS 100 (10% vs 30%; p&lt;0,001)
By multivariate analysis MUD donor or UCB, no response at the time of SCT and male recipient significantly impaired OS, whereas HCT-CI &lt;1, KPS 90-100 and transplant between 2011-2017 significantly improved OS.
These retrospective data showed that the transplant procedure for elderly patients became safer and more effective over time, for a reduction of the RI related to a better selection of patients (more acute leukemias in CR) and a better selection of conditionings (more MAC and more alkylators). Nowdays, the HCT-CI score is probably not sufficient for estimate elderly patients probability of OS and NRM.
Figure 1 Figure 1.

Disclosures
Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Ciceri: IRCCS Ospedale San Raffaele: Current Employment.