Outcome of 673 Patients with Hematologic Malignancies Surviving at Least 8 YEARS Post- Allogeneic Transplants: Risk Factors and Quality of Life
Authors: Sapienza Giuseppe , Lamparelli Teresa , Dominietto Alida , Raiola Anna Maria , Di Grazia Carmen , Gualandi Francesca , Sica Simona , Metafuni Elisabetta , Angelucci Emanuele , Bacigalupo Andrea 
Published: November 2019

Background : Allogeneic hemopoietic stem cell transplantation (HSCT) has been widely used in hematologic malignancies for over 4 decades. One important question is the longterm outcome of these patients, in terms of leukemia control and quality of life.
Aim of the study. Assess the outcome of patients surviving at least 3000 days post allogeneic HSCT, and identify risk factors for failure.
Methods. We used our transplant relational database, in which patients' clinical and laboratory data are prospectively recorded during each outpatient visit or during admission. We identified 673 patients who were seen between 8 and 30 years post-transplant. The median follow up was 17.5 years (range 8.2-36.6), median age was 34 years (range1-65). The diagnosis was AML (n=205), ALL (n=97) CML (n=208), MDS (n=51), Lymphoma (n=45), Myelofibrosis (n=19), other (n=48).
The stem cell source was bone marrow (BM)(n= 488), peripheral blood (PB) (n=154), cord blood (CB) (n=31). The disease was in remission (n=553) or in relapse (n=120).
Result . The overall actuarial survival at 20 years was 86% (95%CI 83%-89%). The CI of TRM at 20 years was 9.4% and the CI of relapse related death (RRD) was 4.6% . Leading causes of death were second tumours (3.2%), chronic GvHD (2.8%) relapse (2.8%). In univariate analysis negative predictors of survival were the following : severe cGvHD (RR 5.0, p=0.002) compared to n0 cGvHD, the use of PB compared to BM as a stem cells source (RR 2.6, p<0.00001), patients age over 40 (RR 3.1, p<0.0001), donors age over 40 (RR 2.4, p=0.0001), advanced disease (RR 2.0, p=0.005), conditioning without TBI (RR 2.1, p=0.0007). The actuarial survival at 20 years of patients grafted from BM or PB was 89% vs 75% (p<0.0001), with a CI of TRM at 20 years of 7% vs 17% respectively (p=0.001) and a CI of RRD of 3% vs 7% (p=0.008). The actuarial 20 year survival for patients </> 40 years was 91% vs 80% (p<0.0001). Survival according to the severity of cGvHD is shown in Figure 1.
Multivariate analysis. In a multivariate Cox analysis, negative predictors of survival, were severe cGvHD (RR 5.0, p=0.0003), patients age over 40 (RR 2.4, p=0.001) , PB grafts versus BM (RR 1.8, p=0.002).
Conclusions. Patients surviving 8 years post HSCT have a 9% risk of transplant related death and a 4% risk of relapse related death. Chronic GvHD remains the strongest negative predictor of survival , together with patients age , and PB as a stem cell source. The impact of cGvHD 10-20 years post transplant strongly calls for preventing meaures to be adopted early in the transplant course, and or with a preferential use of BM as a stem cell source.

Disclosures
Angelucci: Novartis: Honoraria, Other: Chair Steering Committee TELESTO protocol; Celgene: Honoraria, Other: Participation in DMC; BlueBirdBio: Other: Local advisory board; Jazz Pharmaceuticals: Other: Local advisory board; Roche: Other: Local advisory board; Vertex Pharmaceuticals Incorp., and CRISPR Therapeutics: Other: Participation in DMC.