Desensitization Therapy for Patients with DSA Receiving Haploidentical (Haplo) Stem Cell Transplantation

Introduction The effect of desensitization therapy on patients with Donor-specific Anti-HLA Antibodies (DSA) for patients receiving Haplo transplantation are unknown. Methods Data of all 51 patients with DSA receiving Haplo transplantation between 11/2010-1/2019 at MD Anderson Cancer Center (N=41) and City of Hope (N=10) were included. Patients received desensitization with plasma exchange (PE), rituximab (R), and IVIg +/- buffy coat (BC) infused on day-1, as previously described by us (Ciurea SO. BBMT.2018:53:521). We analyzed transplant outcomes for DSA treated patients vs. those without DSA receiving Haplo transplant in the same period of time (control; N=345). Results The median age of patients with DSA was 51 years (range 19-69) and 47 years (range 18-72) in control group (p=0.15). There were no significant differences in diagnosis, remission status at transplant, DRI and ABO matching between 2 groups. RIC conditioning was used in 28% and 43% in DSA and control group, respectively (p=0.03) whereas 67% and 82% respectively (p=0.02) received marrow stem cell. Median levels of DSA on single antigen assay before desensitization was 5556 MFI (range 2360-28688). Of 51 patients with DSA, 37 (72.5%) DSA patients received desensitization with PE, R and IVIg, and 27/37 (73%) patients also received BC infusion before transplant. Twenty of 37 (54%) desensitized patients had DSA u003e5000 MFI and 14 out of them had complement binding DSA suggested by a positive C1q assay. Cumulative incidence (CI) of neutrophil engraftment at 28 days for patients who had DSAu003e5000 MFI and received desensitization was 75% compared with 91% in those without DSA (p=0.12) (Figure 1A) while 1-year NRM was 32% vs. 29% (p=0.57) (Figure 1B) and 1-year OS was 54% vs. 58%, respectively (p=0.18) (Figure 1C). The engraftment rate is significantly improved with desensitization treatment as our previous study demonstrated that only 46% of patients with DSAu003e5000 MFI achieved engraftment (Ciurea SO. BBMT.2015;21:1392). Remarkably, patients with DSA 2000-10000 who received treatment had 83% engraftment vs. 91% (p=0.86). Among 14 patients who had C1q+ DSA, 8 patients had persistently positive C1q after desensitization and only 4 engrafted, 2 had primary graft failure and 2 died before engraftment with CI of engraftment at 28 days of 43% (p=0.09 compared with control group). Persistent C1q positivity was associated with significantly higher NRM (37% vs. 29% at 1 year, p=0.01) and lower OS (33% vs. 58% at 1 year, p=0.002) compared with control group (Figure 1D). These significances persisted after adjusting for other factors in multivariable analysis. Conclusions Treatment with PE, R, IVIg and BC infusion is an effective strategy to desensitize patients with DSA before haploidentical transplantation. Patients who remain C1q+ at transplantation have high risk for engraftment failure and should not proceed to transplantation.