Borderline Donor Specific Antibodies Are Safe In Haploidentical Transplantation

BackgroundIn haploidentical hematopoietic stem cell transplantation (HCT), the presence of recipient pre-transplant Donor Specific Antibodies (DSA) is a strong risk factor for impaired engraftment. However, the impact of borderline pre-transplant DSA levels is not well defined. We performed a retrospective study on borderline DSA levels in 38 haplo-HCT.Subjects and MethodsIn this single center, retrospective study, we analyzed 38 patients (median age= 59.0 years; range=28-77). All patients were screened for the presence of pre-transplant HLA antibodies and each recipient: donor pair underwent T- and B-cell flow cytometry crossmatch (FCM). DSA levels were assigned as negative (MFI<1500; negative FCM), or borderline (MFI=1,700-4,200; negative FCM). Degree of HLA matching, graft source, donor demographics, ABO compatibility, length of time to engraftment and adverse events were reviewed.Results33 haplo-HCT recipients were both DSA (MFI<1500) and FCM negative; 5 were transplanted with borderline DSA levels (MFI=1,700-4,200) and negative FCM. All borderline DSA recipients received PBSC grafts. Borderline DSA patients achieved ANC≥500 at median day 21 (range=15-28), platelet engraftment at median day 25 (range=18-31) and all demonstrated 100% donor CD3 and 100% CD33 chimerism at days 30 and 100 respectively. None of the borderline DSA patients had grade 2-4 aGVHD but one had extensive cGVHD. Progression occurred in one patient (25%). Overall survival for the borderline DSA group was 4/5 (80%). In comparison, the DSA negative group achieved ANC≥500 at median day 20 (range=14-33) and platelet engraftment at median day 28 (range=15-393). Full (>95%) donor chimerism at day 30 and 100 was 26/30 (87%) and 25/27 (93%) for CD3; 30/31 (97%) and 26/28 (93%) for CD33 respectively. Twelve patients (36%) experienced grade 2-4 aGVHDand 4/33 (12%) had extensive cGVHD. Disease progression was observed in 9/33 (27%) patients, with an overall survival of 67% (22/33).ConclusionsThe presence of pre-transplant borderline levels of DSA does not appear deleterious for haplo-HCT outcomes using PBSC grafts. In haploidentical hematopoietic stem cell transplantation (HCT), the presence of recipient pre-transplant Donor Specific Antibodies (DSA) is a strong risk factor for impaired engraftment. However, the impact of borderline pre-transplant DSA levels is not well defined. We performed a retrospective study on borderline DSA levels in 38 haplo-HCT. In this single center, retrospective study, we analyzed 38 patients (median age= 59.0 years; range=28-77). All patients were screened for the presence of pre-transplant HLA antibodies and each recipient: donor pair underwent T- and B-cell flow cytometry crossmatch (FCM). DSA levels were assigned as negative (MFI<1500; negative FCM), or borderline (MFI=1,700-4,200; negative FCM). Degree of HLA matching, graft source, donor demographics, ABO compatibility, length of time to engraftment and adverse events were reviewed. 33 haplo-HCT recipients were both DSA (MFI<1500) and FCM negative; 5 were transplanted with borderline DSA levels (MFI=1,700-4,200) and negative FCM. All borderline DSA recipients received PBSC grafts. Borderline DSA patients achieved ANC≥500 at median day 21 (range=15-28), platelet engraftment at median day 25 (range=18-31) and all demonstrated 100% donor CD3 and 100% CD33 chimerism at days 30 and 100 respectively. None of the borderline DSA patients had grade 2-4 aGVHD but one had extensive cGVHD. Progression occurred in one patient (25%). Overall survival for the borderline DSA group was 4/5 (80%). In comparison, the DSA negative group achieved ANC≥500 at median day 20 (range=14-33) and platelet engraftment at median day 28 (range=15-393). Full (>95%) donor chimerism at day 30 and 100 was 26/30 (87%) and 25/27 (93%) for CD3; 30/31 (97%) and 26/28 (93%) for CD33 respectively. Twelve patients (36%) experienced grade 2-4 aGVHDand 4/33 (12%) had extensive cGVHD. Disease progression was observed in 9/33 (27%) patients, with an overall survival of 67% (22/33). The presence of pre-transplant borderline levels of DSA does not appear deleterious for haplo-HCT outcomes using PBSC grafts.