Alloimmune Effect May Improve Survival of De Novo Myelodysplastic Syndrome After allogeneic hematopoietic cell transplantaion: A Single Center Analysis of 115 Patients
Authors: Hiramoto Nobuhiro , Tajima Kinuko , Kurosawa Saiko , Yamashita Takuya , Okinaka Kenji , Morikawa Noriyuki , Tada Kohei , Tanaka Takashi , Ueda Ryosuke , Kobayashi Yujin , Shinohara Akihito , Kim Sung-Won , Mori Shin-ichiro , Heike Yuji , Fukuda Takahiro 
Published: October 2019

Abstract
Abstract 2033

Background:
As patients with myelodysplastic syndrome (MDS) tend to be older and to have more comorbidities, reduced-intensity conditioning (RIC) has been more frequently used in allogeneic hematopietic cell transplantation (HCT) for patients with MDS. Although alloimmune effect by donor T-cells is important to control disease especially after HCT using RIC, significance of this effect has not been fully evaluated in patients with MDS.
Patients and Methods: We retrospectively reviewed medical records of 115 patients with de novo MDS or acute myeloid leukemia with multilineage dysplasia (AML-MLD) who underwent first allogeneic HCT at our center between 2000 and 2009.Patients with therapy-related MDS and cord blood transplant recipients were excluded. Karyotypic risk group was stratified according to the International Prognostic Scoring System (IPSS).

Results:
The median age of the patients was 55 yrs (range, 19–68). The median follow-up of surviving patients was 40 months (8–130). FAB classification at diagnosis included RA/RARS (n=45), RAEB (40), CMMoL (4), RAEB-T (12), and AML-MLD (14). Karyotype at diagnosis was good-risk in 45 patients, intermediate-risk in 30, and poor-risk in 40. The IPSS risk at diagnosis was Low in 4 patients, Int-1 in 33, Int-2 in 44, and High in 20. Among the 115 patients with MDS or AML-MLD, 68 (59%) received chemotherapy before HCT. Blast count at HCT was less than 5% in 60 patients, 5–19% in 38 patients, 20% or more in 10 patients, and not evaluable in 7 patients. Fifty-five patients received grafts from a related donor (BM 3, PBSC 52), and 60 patients received BM grafts from an unrelated donor. Conditioning regimens included myeloablative (MAC, n=34) and RIC (n=81). Among the 81 RIC recipients, 23 received low-dose TBI and 26 received ATG. The patients who received RIC were significantly older (median, 57 yrs vs. 46 yrs, p<0.001) and included more patients with poor karyotypic risk (41% vs. 21%, p=0.03) than those who received MAC. The incidence of grade II-IV acute GVHD was 42% and that of grade III-IV acute GVHD was 14%. Among the 107 patients who survived more than 100 days after HCT, 10 developed limited cGVHD (9%) and 48 (45%) developed extensive cGVHD. The OS (47% vs 42% at 4 yrs from HCT, p=0.84), the cumulative incidence of NRM (29% vs 33%, p=0.89), and that of relapse (26% vs. 25%, p=0.97) were not significantly different between the MAC and RIC groups, respectively. A multivariate analysis for OS showed that older patient age (≥50 yrs, HR 2.20, 95%CI 1.11–4.33, p= 0.02), high BM blast at HCT (>20%, HR 3.74, 95%CI 1.73–8.08, p<0.01/ 5%- 20%, HR 1.859, 95%CI 1.04–3.30 0.035), and karyotype (poor-risk, HR 1.88, 95%CI 1.08–3.27, p= 0.02) were associated with a significantly worse OS. The presence of cGVHD seemed to be associated with a better OS (HR 0.54, 95%CI 0.29–1.01, p= 0.054). In a landmark analysis, the OS of the patients with cGVHD was significantly higher than that of those without cGVHD (59% vs. 33%, p=0.02). The OS of 26 patients who received ATG was significantly lower than that of those who did not (21% vs. 51% at 4 yrs, p=0.02). In subgroup analyses according to karyotypic risks, the OS of patients with cGVHD was significantly higher than that of those without cGVHD (54% vs. 12% at 4 yrs, p<0.001) in patients with poor karyotypic risk, whereas the OS was not significantly different between the two groups (62% vs. 47% at 4 yrs, p=0.37) in patients with good/intermediate karyotypic risk (Figure). The OS of the patients with cGVHD was significantly higher than that of those without cGVHD (50% vs. 11% at 4 yrs, p=0.002) in patients with more than 5% BM blast at HCT. The OS of the patients with cGVHD was significantly higher than that of those without cGVHD (54% vs. 17% at 4 yrs, p<0.001) in patients who received RIC, whereas the OS was not significantly different between the two groups in patients who received MAC.

Conclusions:
Our single center analysis of patients with MDS showed that the outcomes after HCT with RIC were similar to those after HCT with MAC. Our data also showed an improvement of OS and especially in patients with more advanced MDS. In the setting of RIC, alloimmune effect by donor T-cells may be more important for prevention of relapse in patients with MDS.

Disclosures:
No relevant conflicts of interest to declare.