Early Detection of Isohemagglutinin From Donor Lymphocytes Has Impact On Acute Graft-Versus-Host Disease After Minor ABO-Incompatible Hematopoietic Stem Cell Transplantation.

ABO-incompatibility is not generally considered to be a risk factor of hematopoietic stem cell transplantation (HSCT). However, in our single-institute study of 568 patients, the incidence of acute GVHD was higher in minor-ABO incompatible HSCT than others (45.3% vs 35.2%, p=0.019). We made a hypothesis that there is a potential association between donor-derived isohemagglutinin (IH) and the outcomes of minor-ABO incompatible HSCT.

There were 1052 patients undergone HSCT between 1988 and 2009 at Komagome hospital. We analyzed 130 of 1052 patients (12.4%), who had received minor- ABO incompatible HSCT. Blood type and anti-A/B antibody titers were evaluated at least weekly in first one month after HSCT, and were repeated monthly until blood type had completely changed to the donor type. Our analysis was especially focused on the impact of IH on the outcome of minor-ABO incompatible HSCT.

Minor ABO-incompatible HSCT were 130 cases that included AML (n=40), ALL (n=28), CML (n=27), MDS (n=15), SAA (n=9), NHL (n=7), MM (n=2) and ATL (n=2). Median age was 37 (range: 16-67) years old. Seventy-seven patients were male, 53 were female. Stem cell sources were bone marrow (n=96), peripheral blood (n=16) and umbilical cord blood (n=18). Eleven cases were HLA-matched and 9 were HLA-mismatched transplants. Anti-host IgG and IgM IH had been detected in 20 of 130 transplants undergoing minor ABO-incompatible HSCT (15.4%). Median time to IH detection was 13 days after HSCT (12-39days). There was a higher incidence of IH production in the HLA-mismatched group than in the HLA-matched group (p=0.007).There was also a higher incidence of IH production in the unrelated transplants group than in the related transplants group. (p=0.021). None of 18 patients receiving umbilical cord blood transplantation showed evidence of IH production. The incidence of grade II-IV acute GVHD was significantly higher (90% vs 60%, p <0.001) and the severity of target organs was higher in the group with IH (IH group). Onset of acute GVHD was significantly earlier (median: 9 days vs 20 days, p<0.001) in IH group compared to non-IH group. The incidence of chronic GVHD was higher in IH group (69% vs 55%, p=0.036). No statistically significant differences were observed between IH group and non-IH group in time to engraftment, transplantation related mortality (63% vs 65%, p=0.666), disease-free survival (49.5% vs 37.6%,p=0.277) and overall survival (44.9% vs 37.6%,p=0.348). Immune hemolysis called passenger lymphocyte syndrome occurred in 2 cases of IH group. Their onset of acute GVHD was on Day 7 and 8 after HSCT, and IH was detected on Day 11 and 12 that were almost at the same time as hemolysis. Their WBC engraftment occurred on Day14 and 15. In both of 2 cases, hemolysis was resolved without specific treatment.

Our study showed that IH production had association with HLA-mismatched and unrelated transplants in minor-ABO incompatible HSCT. We also showed that early detection of IH was related with the onset of grade II-IV acute GVHD. These findings indicate that strong allo-immunity induces not only severe acute GVHD caused by T lymphocytes but also antibody-production by B lymphocytes. In conclusion, we suggest that early detection of IH has impact on severity of acute GVHD.

No relevant conflicts of interest to declare.