Comparative Analysis of T CELL Depleted Matched Vs Mismatched Unrelated DONOR Transplants in Patients with Hematologic Malignancies

Background: T cell depletion (TCD) of HSC grafts has been shown to reduce the incidence and severity of graft vs host disease (GvHD) without increasing relapse in appropriately selected patients. As an alternative to cord blood (CB) grafts, it makes transplantation an option for patients who lack a matched donor.  We retrospectively reviewed a 13-year experience of TCD HSC transplants for patients who received grafts from mismatched unrelated donors (MMUD) as treatment for hematologic malignancies.

Methods: Under an IRB approved waiver of authorization, 140 adult patients were identified who received TCD HLA MMUD grafts during 2000-2013. All HLA typing was by molecular methods. TCD of BM was by soybean agglutination & sheep RBC rosetting (sRBCr) and for PB by automated CD34+ selection +/- sRBCr. Conditioning regimens were ablative and all included ATG. Patients were in remission or had a low volume of disease. No pharmacologic GvHD prophylaxis was given. For different levels of mismatch, overall (OS) and disease-free survival (DFS) were compared using Kaplan-Meier curves and the logrank test. Cumulative incidence functions and Gray's test compared the incidence of grade 2-4 aGvHD and cGvHD.  Results were compared with 169 TCD HLA matched unrelated donor (MUD) grafts during the same period.

Results: Table 1 lists demographics. Several subgroups had limited numbers of patients. Table 2 shows cumulative incidence (CI) for outcomes, and Figure 1 survival curves to 5 yrs.  There was no difference in outcomes for 1 loci MMUD vs. MUD grafts. There was no statistical difference in outcomes for a single C vs. any single non C mismatch. Nearly all acute GVHD was 2-3, and there were only 4 limited chronic GVHDs. OS and DFS were lower for >1 loci MMUD transplants.

Conclusion:  These results support the use of TCD MMUD grafts as alternatives for patients lacking a MUD or ineligible for a CB graft.

 

 

 

 

 

 

 

Table 1: Demographics

 

 

 

 

 

 

Table 2: Transplant Outcomes for MMUD vs MUD Grafts

* As appropriate, logrank or Gray's test p-value comparing outcomes for single DQB1, Single C and Single class 1 or DRB1 to MUD transplants. Similarly, outcomes were compared across 8/10 loci, 9/10 loci and 10/10 loci MUD transplants.   

 

Figure 1: Kaplan Meier Curves for DFS and OS