Allo- HSCT for Advanced Myelodysplastic Syndrome:MSKCC Vs MDACC
Authors: Tamari Roni , Oran Betul , Hilden Patrick , Papadopoulos Esperanza B , Kongtim Piyanuch , Rondon Gabriela , Jakubowski Ann A. , Andersson Borje S , Devlin Sean M. , Ahmed Sairah , Young James W. , Popat Uday R. , Chen Julianne , de Lima Marcos , O'Reilly Richard J , Giralt Sergio , Champlin Richard E. , Castro-Malaspina Hugo 
Published: November 2019

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only curative treatment for myelodysplastic syndrome (MDS). Relapse, infections and graft-versus-host disease (GvHD) are the main causes of treatment failure. We compared the outcomes of patients receiving T cell depleted (TCD) grafts at Memorial Sloan-Kettering Cancer Center (MSKCC) with patients receiving unmodified grafts at MD Anderson Cancer Center (MDACC) for advanced MDS (RAEB-1 and 2).

Adult patients transplanted between 2001 -2012 were included in this retrospective analysis. All recipients of TCD grafts (N=60) received myeloablative conditioning (MAC) and antithymocyte globulin (ATG) to prevent graft rejection. None of them received post-transplant GvHD prophylaxis. Of the 129 recipients of unmodified grafts, 87 received MAC and 42 reduced intensity conditioning (RIC); GvHD prophylaxis consisted of tacrolimus and mini-dose methotrexate in the majority of patients (N=113). ATG was given to all matched unrelated donor (MUD) recipients. Patients in the unmodified group had more therapy-related MDS (MDS-t), very poor risk cytogenetics by IPSS-R at diagnosis and bone marrow (BM) blast count >5% at transplant. Only the TCD group had mismatched donors (Table 1).

Univariate analysis identified a lower incidence of grade II-IV acute GvHD in the TCD group with 100-day cumulative incidence (CI) of 13.3% vs. 34.1% in the unmodified group (p=0.031). There was no difference in grade III-IV acute GvHD with a 10% CI in both groups at day-100 (p=0.546). The incidence of chronic GvHD was lower in the TCD group with a CI at 3-yrs of 3.4% vs. 44.3% in the unmodified group (p < 0.001). The non-relapse mortality (NRM) in both groups was similar. CIs at day 100, 1yr, and 3 yrs in the TCD group were 8.3%, 20.2% and 32.7% vs. 12.4%, 22.5% and 28.1% in the unmodified group (p=0.628). Relapse was lower in the TCD group, with CI at 1 and 3 yrs of 8.5% and 15.5%, vs. 31.0% and 39.4% in the unmodified group (p=0.002). Since the unmodified recipients had worse disease characteristics, further analyses in patients with good/intermediate risk cytogenetic showed that the relapse incidence was similar between these subgroups, with 3-yr CIs of 7.9% in TCD vs. 18% in unmodified group (p=0.185). The most common causes of death in the TCD group were infections (32%) and relapse (28%), while in the unmodified group it was relapse (55%), GVHD (20%) and infections (13%). Considering the differences in disease characteristics between the groups, multivariate regression models were performed for relapse-free survival (RFS) and overall survival (OS) adjusting for MDS-t, high-risk cytogenetics at diagnosis and high blast count at HSCT. No significant differences were observed between the groups for RFS (HR=1.44, p=0.128) and OS (HR= 1.35, p=0.236) (Table 2). High-risk cytogenetics at diagnosis (very poor risk) was the only significant prognostic factor for RFS (HR=5.32, p<0.001) and OS (HR=4.81, p<0.001).

Allo-HSCT is an effective treatment for patients with MDS with similar long term survival with either unmodified or TCD allografts. TCD is associated with a lower incidence of acute and chronic GVHD and without an increased risk of relapse.

Table 1 Characteristics TCD (N=60) Unmodified (N= 129) p-value Median follow-up, months (range) 43.4 (3.8-119.5) 49.4 (12.2-136.3) Age, years (range) 57.1 (21.9-72.0) 57.0 (19.0-72.0) 0.769 Female gender 34 (56.7%) 45 (34.9%) 0.008 MDS-t 7 (11.7%) 43 (33.3%) 0.003 Cytogenetic risk at diagnosis ( IPSS-R) 0.009 Good 25 (42.4%) 48 (37.2%) Intermediate 15 (25.4%) 19 (14.7%) Poor 11 (18.6%) 15 (11.6%) Very poor 8 (13.6%) 47 (36.4%) Missing 1 Blasts at transplant < 0.001 < 5% 48 (81.4%) 57 (46.3%) 5-9% 11 (18.6%) 35 (28.5%) 10-19% 0 31 (25.2%) Missing 1 6 Donor type < 0.001 MRD 21 (35.0%) 65 (50.4%) MUD 25 (41.7%) 64 (49.6%) MMD 14 (23.3%) 0 Stem cell source 0.002 BM 5 (8.3%) 46 (35.7%) PB 55 (91.7%) 83 (64.3%)

Table 2: Multivariate analysis Variables OS HR (95% CI) RFS HR (95% CI) Disease etiology 0.518 0.511 De novo 1 1 MDS-t 0.87 (0.56-1.34) 0.87 (0.56-1.33) Cytogenetic risk at diagnosis IPSS-R) < 0.001 < 0.001 Good 1 1 Intermediate 1.41 (0.74-2.68) 1.39 (0.73-2.64) Poor 2.06 (1.13-3.73) 2.49 (1.40-4.44) Very poor 4.81 (2.88-8.02) 5.32 (3.22-8.80) Blasts at transplant 0.286 0.502 < 5% 1 1 5-9% 1.11 (0.70-1.77) 1.03 (0.65-1.62) 10-19% 1.57 (0.91-2.71) 1.37 (0.80-2.34) Type of transplant 0.236 0.128 TCD 1 1 Unmodified 1.35 (0.82-2.19) 1.44 (0.90-2.31)

Disclosures

No relevant conflicts of interest to declare.