Allo- HSCT for Advanced Myelodysplastic Syndrome:MSKCC Vs MDACC

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. | 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% | | 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%) | | | | Stem cell source | | | 0.002 | | BM | 5 (8.3%) | 46 (35.7%) | | | PB | 55 (91.7%) | 83 (64.3%) | | Table 1 | 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) | | Table 2: Multivariate analysis Disclosures No relevant conflicts of interest to declare.