Issue link: https://ahint.epubxp.com/i/574474
15 ASHI Quarterly Third Quarter 2015 While continuous monitoring of HLA antibody status of the recipient is the norm in solid organ transplantation, it is not a common practice in bone marrow hematopoietic stem cell transplantation (BMT/HSCT) This is because transplantation of HLA-mismatched BMT/HSCT is not very common, unlike solid organ transplantation However, related haploidentical BMT/ HSCT is being practiced in many centers and, also, there are occasions when mismatched related or unrelated BMT/HSCT is the only option for some patients In addition, even in unrelated HLA-A,B,Cw,DR,DQ (10/10) matched cases, there is a possibility of DP disparity in about 10% of the cases Similar to patients waiting for solid organ transplantation, patients waiting for BMT/ HSCT transplants are also likely to be allo-sensitized due to prior pregnancies, blood transfusions, or previous transplants In such mismatched BMT/HSCT cases, presence of pre-existing donor- specific HLA antibodies (DSA) in the recipients has been shown to reduce successful engraftment Because the donor immune system replaces the recipient's immune system after transplant, plasma cells that are carried over by the allograft that are specific for the mismatched recipient antigens could make antibodies against the recipient, potentially causing antibody mediated graft vs host disease (GVHD) Pre-existing HLA DSAs in BMT/HSCT Recipients and its Implications in the Engraftment Process Several studies in the recent past have shown that the presence of pre-existing donor-specific HLA antibodies in patients undergoing mismatched hematopoietic stem cell transplantation represents a considerable risk factor for primary graft failures 1-6 The studies were done in unrelated SCT 1,2 cord blood transplantation 3,4 or HLA-haploidentical BMT/HSCT from related family members 5,6 Spellman et al 1 evaluated pre-transplant sera from 37 allogenic BMT/HSCT patients with graft failure and a matched case- control cohort of 78 subjects to determine the role of DSAs in unrelated donor SCT Among the 37 failed transplants, 9 (24%) recipients possessed DSAs against donor HLA-A, -B, and/or -DP, compared with only 1 (1%) of 78 controls who were matched for "disease, disease status, graft type, patient age, and transplantation year " Based on the odds ratio of 22 84 with a 95% confidence interval, the authors concluded that the presence of DSAs was significantly associated with graft failures (P< 001) A similar study on unrelated BMT/HSCT by Ciurea et al 2 showed the detrimental effect of DSA to donor HLA-DP in causing engraftment failure (As we know, DP mismatching in the 10/10 HLA-matched unrelated donor/recipient pair is not infrequent) The presence of anti-HLA antibodies before transplantation was determined in 592 recipients with matched unrelated donors (MUD) using mixed-screen beads in a solid-phase fluorescent assay DSA identification was performed using single-antigen beads containing the donor's corresponding HLA-mismatched antigens Anti-HLA antibodies were detected in 116 patients (19 6%), including 20 patients (3 4%) with anti-DPB1 Graft failure occurred in 19/592 (3 2%) and 16/19 of them did not have any HLA antibodies However, the remaining three patients who had graft failure were among the eight patients with HLA- DP DSA (37 5%) By multivariate analysis, the authors affirmed that DSAs were the only factor highly associated with graft failure (P= 0001; odds ratio=21 3) And, as one would expect, anti-HLA antibodies were generally higher in women than in men (30 8% vs 12 1%; P< 0001) and higher in women with one (P= 008) and two or more pregnancies (P= 0003) Most cord blood transplantations (CBTs) have HLA mismatches Takanashi et al, 3 Japanese Red Cross Tokyo Blood Center, retrospectively investigated the effects of pre-transplant anti-HLA antibodies on the outcome of CBTs with sensitive solid-phase assays Among 386 single unit CBTs for first myeloablative stem cell transplantations for malignancies, 89 patients had HLA antibodies In 69 of these 89 patients, there were no DSAs (the Non-DSA) while 20 patients had antibodies specific toward the cord blood HLA (DSA + ) The authors evaluated the neutrophil recovery in these antibody negative (297), DSA - (69) and DSA + (20) recipients The results showed a significant low recovery of neutrophils in DSA + : 32% (95% CI, 13%-53%, P<0 0001, Gray test) compared to antibody negative group (83% (95% confidence interval [CI])), and Non-DSA Ab + : 73% (95% CI, 61%-82%) The results indicated potential engraftment and recovery problems for patients undergoing CBT in the presence of pre-transplant anti- HLA antibodies Cutler et al 4 studied the effect of preformed DSAs on outcomes in double umbilical cord blood transplantation and found that pre-existing DSAs were associated with an increased incidence of graft failure (5 5% vs 18 2% vs 57 1% for none, 1, or 2 DSAs; P=0 0001), Prolonged time for neutrophil engraftment was also noted in DSA positive patients (21 vs 29 days for none vs any DSA; P=0 04) These authors also recommended antibody screening for DSAs in umbilical cord blood recipients to avoid the use of units with DSA-specific HLA antigens C U R R E N T L I T E R A T U R E R E V I E W HLA Antibody Testing of Recipients and Donors for Bone Marrow/Hematopoietic Stem Cell Transplantation (BMT/HSCT) Siva Kanangat, PhD, D(ABHI)