No Influence of Post-Transplant Anti-HLA Antibodies on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Mismatched Unrelated Donors

Introduction: Although anti-HLA Antibodies (Abs) are considered an important factor of graft failure in solid organ transplants, their role in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still undiscovered. Large polymorphism and immunogenicity of HLA-antigens and heterogeneity of anti-HLA Abs warrant the need of such investigation. The purpose of this study was to define the presence of anti-HLA Abs after allo-HSCT from HLA-mismatched unrelated donors and their impact on outcomes of allo-HSCT.

Material and methods: 68 HLA-mismatched donor/recipient pairs entered the study. Indication for allo-HSCT was: ALL, AML, CML, SAA, PNH, MDS and CLL. Preparative regimen was myeloablative in 66(97%)pts and reduced in 2(3%)pts. Standard GVHD prophylaxis consisted of cyclosporine, methotrexate and pre-transplant anti-thymocyte globulin (67pts) or Alemtuzumab (1pt). HLA A,B,C,DR,DQ alleles were PCR-typed. Single HLA-antigen was mismatched in 44pts, single HLA-allele in 16pts, double antigens or alleles in 2 pts and another 2 pts had combined antigenic/allelic HLA mismatches. Anti-HLA A,B,C,DR,DQ,DP Abs were identified in sera collected at +30, +100 days and 1 year post-transplant with use of automated DynaChip assay utilizing microchips bearing purified class I and class II HLA antigens. Post-transplant chimerism was analyzed using STR-PCR method at 30, 100-days and 1-year after allo-HSCT.

Results: Anti-HLA Abs were detected post-transplant in 49(72.1%) patients at least at one of three examined time-points. They were directed against HLA class I, II or both in: 22(32.4%), 7(10.3%) or 20(29.4%) patients, respectively. In 3 (4.4%) patients antibodies for many specificities were detected. Anti-HLA antibodies detected during the first year after transplantation did not impact the donor's chimerism. Full donor's chimerism was observed in 22/48 (46%) patients without versus 7/18 (39%) patients with anti-HLA Abs, p=0.615). Anti-HLA Abs present after transplantation also did not impact the risk of developing aGVHD, grades neither I-IV (36/49, 73% in positive versus 17/19, 89% in negative group, p=0.270), nor II-IV (15/49, 31% in positive versus 8/19, 42% in negative group, p=0.372). Chronic GVHD and extensive cGVHD also were not influenced by anti-HLA Abs detected post-transplant (23/49, 47% versus 10/19, 53%, p=0.676) and (13/49, 27% versus 5/19, 26%, p=0.986), respectively.

Post-transplant anti-HLA Abs did not influence the recurrence of the disease, which was observed in 9/49 (18.3%) patients with versus 1/19 (5.2%) patients without anti-HLA antibodies, p=0.323, nor the overall survival at 3-years (54% in anti-HLA Abs positive versus 46% in anti-HLA Abs negative patients, p=0.207).

Conclusions: Our results indicate, that anti-HLA Abs can be detected post-transplant in HLA-mismatched allo-HSCT recipients. Presence of anti-HLA antibodies detected after allo-HSCT was not associated with occurrence of aGVHD, cGVHD, relapse nor overall survival.