Abstract

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   
Blasts at transplant   < 0.001 
< 5% 48 (81.4%) 57 (46.3%)  
5-9% 11 (18.6%) 35 (28.5%)  
10-19% 31 (25.2%)  
Missing  
Donor type   < 0.001 
MRD 21 (35.0%) 65 (50.4%)  
MUD 25 (41.7%) 64 (49.6%)  
MMD 14 (23.3%)  
Stem cell source   0.002 
BM 5 (8.3%) 46 (35.7%)  
PB 55 (91.7%) 83 (64.3%)  
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   
Blasts at transplant   < 0.001 
< 5% 48 (81.4%) 57 (46.3%)  
5-9% 11 (18.6%) 35 (28.5%)  
10-19% 31 (25.2%)  
Missing  
Donor type   < 0.001 
MRD 21 (35.0%) 65 (50.4%)  
MUD 25 (41.7%) 64 (49.6%)  
MMD 14 (23.3%)  
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   
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   
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%   
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   
Unmodified 1.35 (0.82-2.19)  1.44 (0.90-2.31)  
Variables OS HR (95% CI) RFS HR (95% CI) 
Disease etiology  0.518  0.511 
De novo   
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   
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%   
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   
Unmodified 1.35 (0.82-2.19)  1.44 (0.90-2.31)  

Disclosures

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.