Donor-Recipient Host-Versus-Graft (HVG) HLA Mismatches and Outcome of Cord Blood Transplants (CBT).
Authors: de Lima Marcos , Patah Poliana A. , Saliba Rima , Couriel Daniel , Chan Kawah , Worth Laura , Giralt Sergio , Kebriae Partow , Khouri Issa , Cooper Laurence , Fernandez-Vina Marcelo , Cano Pedro , Petropoulos Demetrios , McMannis John , Hosing Chitra , Rondon Gabriela , Komanduri Krishna V. , Champlin Richard E. , Shpall Elizabeth J. 
Published: April 2020

The influence of HLA mismatches on outcomes of CBT is yet to be fully defined. We hypothesized that donor-recipient mismatches in the host-versus-graft (HVG) and graft-versus-host (GVH) direction impact engraftment, treatment-related mortality (TRM) and survival after CBT, and addressed the question studying CBT performed in our institution from 3/1996 to June/2006.

Methods: 91 patients (pts) were analyzed. Diagnoses were high-risk hematologic malignancies (n=85; 93%) or non-malignant disorders (n=6; 7%). Conditioning was myeloablative (n=86; 95%), while patients not eligible for high-dose therapy received reduced-intensity (n=5; 5%) regimens. ATG was part of the preparative regimen in 45 cases (49%). GVHD prophylaxis was tacrolimus with (n=83; 91%) or without methotrexate (n=6; 6%), and cyclosporine and MMF (n=2; 2%). Grafts were single (n=70; 77%) or double (n=21; 23%) CB units. 9 pts received ex-vivo expanded grafts. For patients receiving a double CBT, the engrafted unit was used as the reference for this analysis. HLA-A, B (intermediate resolution) and DRB1 typing (high-resolution) was available for all donor-recipient pairs.

Results: Median age was 18 years (1–57); 46 (51%) were younger than 18 yrs old and 50 pts (55%) were males. The patients were heavily pre-treated with 18 (20%) having received prior autotransplants. Disease status at CBT was complete remission (CR; n=43; 47%) and active disease (n=48; 53%). Median number of infused total nucleated cell was 3.45x10E7/kg (0.81–23.6). Numbers of mismatches in the HVG direction were as follows: zero (n=11), 1 (n=37), 2 (n=36), 3 (n=6), and 4 (n=1). Numbers of mismatches in the GVH direction were as follows: zero (n=8), 1 (n=35), 2 (n=41), and 3 (n=7). 78 pts engrafted neutrophils (86%) at a median of 22 days (4–60). 65 pts engrafted platelets (71%) at a median of 42 days(0–133). 13 pts (14%) failed to engraft. Grade II–IV and III–IV acute GVHD rates were 49% and 8%, respectively, and chronic GVHD incidence was 33%. 35 pts are alive with a median follow-up of 25 months. 2-yr actuarial survival is 21%. 100-day and 1-yr NRM is 22%(14–32) and 37% (28–49). The influence of HVG mismatches on NRM, survival and engraftment is shown in the table and figure. The decreasing 2-yr survival and worse NRM associated with increasing number of HVG mismatches was limited to the group of pts &lt;18 yrs old. There was no difference in the proportion of pts in CR, nor in the distribution of infused TNC/Kg across the HVG mismatch subgroups. There was no correlation between mismatches in the GVH direction and NRM or 2-yr survival.

Conclusion: HVG mismatches may influence outcomes of CBT.

Number of Mismatches - HVG direction 1-yr NRM % engrafted Abbreviations: HVG: host-versus-graft; NRM: non-relapse mortality; NS: not significant 0 n=11 21% (CI: 6–74) 100 1 n=36 33% (CI: 20–54) 89 2 n=34 47% (CI: 33–67) 85 3 n=6 33% (CI: 11–100) P=NS 83 Figure Figure