Work

Comparison of Double Unit Cord Blood Transplants (dCBT) with 8/8 HLA-Allele Matched Related (MRD) or Unrelated Donor (MUD) T-Cell Depleted (TCD) Transplants in Adults with Myeloid Malignancies: Comparable Progression-Free Survival (PFS)

Year: 2019

Type: article

Abstract: Background TCD is being investigated as a CNI-free strategy for GVHD prophylaxis (BMT CTN 1301) & dCBT has previously been associated with PFS comparable to 8/8 MUD TCD transplants with low rates of relapse. However, how outcomes of MRD TCD, MUD TCD, & dCB transplants compare when adjusted for aaHCT-CI & rDRI is not established. Methods We compared dCBT (Cy/ Flu/ Thio/ TBI 400 & CSA/ MMF) with MRD or MUD (Bu/Mel/Flu, Cy/Thio/TBI1375 or Flu/Thio/TBI1375) CD34+ selected transplants. Eligible patients (pts) were 1st allograft recipients 21 - 60 years transplanted 1/2012 - 8/2017 for myeloid malignancies [AML/ MDS/ MPD (< 10% blasts at workup)]. Results Of 206 pts (Table 1), 76 received dCB, 52 MRD, 78 MUD transplants. Pts had similar age, gender, weight, recipient CMV+ status, & aaHCT-CI/ diagnosis distribution. Each group differed according to donor age. rDRI also differed by graft source with fewer dCBT pts having low risk disease. Significantly more MRD/ MUD transplants received high dose TBI & there were marked differences in graft dose & donor-recipient HLA-match. While the incidence of engraftment at day 45 was lower in dCBT (96%) than MRD & MUD pts (both 100%, p < 0.001), no dCB, 2/52 MRD & 3/78 MUD pts received stem cell boosts/ 2nd transplants for secondary graft failure/ poor graft function. dCBT pts had a higher incidence of day 100 aGVHD: grade 2-4 was 83% (72-90) in dCBT, 17% (8-29) in MRD, & 21% (12-30) in MUD pts (p < 0.001), & grade 3-4 was 17% (10-26) in dCBT, 0% in MRD, & 3% (0.4-8) in MUD pts (p < 0.001). 1-yr cGVHD was 1% (1-6) in dCBT, 6% (1-14) in MRD & 5% (2-12) in MUD pts, p = 0.40. 3-yr TRM was not different between groups: 20% (11-30) dCBT, 12% (5-23) MRD, & 8% (3-15) MUD, p = 0.20. 3-yr relapse was also not different: 12% (6-21) dCBT, 32% (19-45) MRD, 24% (15-35) MUD, p = 0.08. With a median 3.1 yr (range 1-6.4) survivor followup, the 3-yr PFS was 70% (60-81) in dCBT, 63% (51-78) in MRD, & 68% (58-79) in MUD pts, p = 0.70 (Figure 1A). In multivariate analysis (Table 2), aaHCT-CI of > 3 was associated with higher TRM whereas graft source was not significant. High/ V. High rDRI was associated with higher relapse. Also, MRD pts had a higher relapse risk than dCBT pts. Both > 3 aaHCT-CI & High/ V. High rDRI had worse PFS whereas donor type was not significant. In a subset analysis of the 132 (64%) pts with an aaHCT-CI of 0-3, the 3-yr PFS was 76% (65-90) in dCBT, 61% (46-80) in MRD, & 79% (68-91) in MUD pts (Figure 1B). Conclusions This data supports dCBT in pts without promptly available MRD or MUD donors. dCBT pts had a low incidence of relapse supporting a potent GVL effect. Relapse after dCBT was significantly lower than after MRD transplants, & this finding was despite more than half of MRD pts receiving high dose conditioning. New strategies to further lower TRM in dCBT recipients may translate to dCBT being a preferred therapy over TCD MRD in the future especially in pts with low aaHCT-CI.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2018.12.137