Graft rejection and hyperacute graft‐versus‐host disease in stem cell transplantation from non‐inherited maternal antigen complementary HLA‐mismatched siblings

Abstract

Graft rejection occurred in the SAA patient who was conditioned with a fludarabine-based regimen. Grade III and grade IV acute GVHD developed in patients with AML on day 8 and day 11 acute GVHD respectively, and became a direct cause of death in one patient. The findings suggest that intensive conditioning and immunosuppression after stem cell transplantation are needed in NIMA-mismatched SCT even if donor and recipient microchimerisms is detectable in the donor and recipient before SCT.

Prediction of Reactivity to Noninherited Maternal Antigen in MHC-Mismatched, Minor Histocompatibility Antigen-Matched Stem Cell Transplantation in a Mouse Model

“…Presence of fetomaternal tolerance was expected by expression of MMc (2), and it was believed and applied to the clinical studies to date (13); nevertheless, severe acute GVHD developed even if MMc was detected (14,15). Indeed, NIMA allografts have been shown to accept better than noninherited paternal Ag allografts in vivo (3), and in vitro T cell response to NIMA is significantly reduced in IL-2 and IFN-g production (2).…”

“…However, in non-TCD BMT from a NIMA-mismatched donor, 10% of patients still experienced severe acute GVHD (13). Furthermore, graft rejection and hyperacute GVHD in HSCT from NIMA-mismatched siblings were observed despite detecting of maternal microchimerism (MMc) (14). In contrast, Kanda et al (15) described that a substantial proportion of long-term survivors after NIMA-mismatched HSCT could discontinue administration of immunosuppressive agents despite the frequent occurrence of moderate to severe chronic GVHD.…”

Major and Minor Histocompatibility Antigens to Non-Inherited Maternal Antigens (NIMA)

“…Although detection of MMc was clinically used for an indication of probable tolerance to NIMA, severe acute cases of GVHD developed (Okumura, Yamaguchi et al 2007;Kanda, Ichinohe et al 2009). Studies indicate that NIMA allografts do better than NIPA allografts in vivo (Burlingham, Grailer et al 1998), and in vitro T-cell responses to NIMA are significantly reduced in IL-2 and IFN-γ production assays, compared with NIPA (Andrassy, Kusaka et al 2003).…”

“…T-cell replete HSCT, without GVHD, could be accomplished by using this phenomenon of feto-maternal tolerance. Unfortunately, graft rejection and hyperacute GVHD have been reported in HSCT from NIMA-mismatched siblings, despite detecting of MMc (Okumura, Yamaguchi et al 2007). Therefore, development of a predictable method for GVHD in NIMA-mismatched HSCT is needed.…”

A feasibility study on the prediction of acute graft-vs.-host disease before hematopoietic stem cell transplantation based on fetomaternal tolerance

“…5,7,21 However, it is difficult to predict severe acute GVHD prior to transplantation. Our recent clinical trial has addressed this issue.…”