Combination of Intra-Bone Marrow–Bone Marrow Transplantation and Subcutaneous Donor Splenocyte Injection Diminishes Risk of Graft-Versus-Host Disease and Enhances Survival Rate

Abstract

The combination of allogeneic bone marrow transplantation (allo-BMT) and donor lymphocyte infusion (DLI) is a useful method for establishing donor chimerism and preventing a relapse of leukemia=lymphoma. However, there is a risk of inducing uncontrollable fatal graft-versus-host disease (GVHD). In fact, allo-BMT plus intravenous (IV)-DLI using donor splenocytes induces fatal GVHD in recipient mice. In this study, we examined the effects of the combination of intra-bone marrow (IBM)-BMT and the subcutaneous injection of donor splenocytes (SC-DLI) on the allo-BMT system. Recipient BALB=c mice were conditioned by sublethal irradiation (5 Gy), followed by IBM-BMT plus IV-DLI or SC-DLI in C57BL=6 mice. The IV-DLI group showed better engraftment of donor hemopoietic cells than the control group (without DLI) but showed fatal GVHD. The SC-DLI group, however, showed good reconstitution and mild GVHD. These results suggest that the combination of SC-DLI and IBM-BMT promotes the reconstitution of hemopoiesis and helps reduce the risk of GVHD.

A nuclear factor-κB inhibitor, dehydroxymethylepoxyquinomicin, ameliorates GVHD in allogeneic bone marrow transplantation

“…As previously described, spleen weight is inversely related to the severity of GVHD Shi et al 2011;Barr et al 2012;Shankar et al 1998). As shown in Fig.…”

“…As we and other researchers have described, the injection of MHC-mismatched donor spleen cells can induce GVHD in mice that have received ABMT, resulting in the weight loss and eventual death of the recipient mice Shi et al 2011). Therefore, the protocol emulated GVHD induced by ABMT and subsequent administration of DLI in human patients.…”

“…This scoring was based on six variables: weight loss, posture, activity, fur texture, skin integrity, and diarrhea (Shi et al 2011;Cooke et al 1996;Kaplan et al 2004). A severity scale of 0-2 was used for each variable, the maximum overall score being 12 (Shi et al 2011). After they had been killed, their spleens were weighed.…”

“…Tissues from the GVHD target organs (liver, intestine, and skin) were embedded in paraffin, sectioned, and stained with hematoxylin and eosin. The sections were examined by pathologists using an Olympus BX61 light microscope (Olympus, Tokyo, Japan) and histological GVHD scores allocated as described (Shi et al 2011).…”

CD4+ T Cell–Depleted Lymphocyte Infusion Impairs Neither the Recovery of Recipient Thymus nor the Development of Transplanted Thymus

“…The severity of GvHD was assessed as previously described (25). In brief, the recipients were scored every 4 or 5 d for six clinical parameters: weight loss, posture, activity, fur texture, skin integrity, and diarrhea.…”