Allo- HSCT for Advanced Myelodysplastic Syndrome:MSKCC Vs MDACC

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 1CharacteristicsTCD (N=60)Unmodified (N= 129)p-valueMedian 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)0.769Female gender34 (56.7%)45 (34.9%)0.008MDS-t7 (11.7%)43 (33.3%)0.003Cytogenetic risk at diagnosis ( IPSS-R)0.009Good25 (42.4%)48 (37.2%)Intermediate15 (25.4%)19 (14.7%)Poor11 (18.6%)15 (11.6%)Very poor8 (13.6%)47 (36.4%)Missing1Blasts at transplant< 0.001< 5%48 (81.4%)57 (46.3%)5-9%11 (18.6%)35 (28.5%)10-19%031 (25.2%)Missing16Donor type< 0.001MRD21 (35.0%)65 (50.4%)MUD25 (41.7%)64 (49.6%)MMD14 (23.3%)0Stem cell source0.002BM5 (8.3%)46 (35.7%)PB55 (91.7%)83 (64.3%)Table 2:Multivariate analysisVariablesOS HR (95% CI)RFS HR (95% CI)Disease etiology0.5180.511De novo11MDS-t0.87 (0.56-1.34)0.87 (0.56-1.33)Cytogenetic risk at diagnosis IPSS-R)< 0.001 < 0.001 Good11Intermediate1.41 (0.74-2.68)1.39 (0.73-2.64)Poor2.06 (1.13-3.73)2.49 (1.40-4.44)Very poor4.81 (2.88-8.02)5.32 (3.22-8.80)Blasts at transplant0.2860.502< 5%115-9%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 transplant0.2360.128TCD11Unmodified1.35 (0.82-2.19)1.44 (0.90-2.31) DisclosuresNo relevant conflicts of interest to declare.