2: Donor-Recipient Host-Versus-Graft Human Leukocyte Antigen Mismatches and Outcome of Cord Blood Transplants

Digitalitzat per Artypla

Donor-Recipient Host-Versus-Graft (HVG) HLA Mismatches and Outcome of Cord Blood Transplants (CBT)

Abstract 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 <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 Figur