Mismatch of minor histocompatibility antigen contributes to a graft-versus-leukemia effect rather than to acute GVHD, resulting in long-term survival after HLA-identical stem cell transplantation in Japan.

We determined the alleles of five polymorphic molecules including HA-1 and four adhesion molecules for 106 patients transplanted with HLA-identical stem cell grafts and investigated the association of mismatches as correlates of relapse and graft-versus-host disease (GVHD). All 106 recipients underwent stem cell transplantation (SCT) after myeloablative conditioning between 1985 and 2002. Risk status of disease at SCT was standard (n=63) and high (n=42). After SCT, 36, 49 and 33 developed acute GVHD, chronic GVHD and relapsed, respectively. Our patients relapsed at rates of 16.7 and 38.6% with one or more and without incompatibilities (P=0.013). The relapse rates of patients with CD62L, CD31 codon 563, CD31 codon 125, HA-1 and CD49b incompatibilities were 5.9, 11.8, 15.4, 16.0 and 33.3%, respectively. The frequency of acute GVHD did not differ regardless of incompatibilities. In standard-risk group, the accumulated relapse rates of 19 and 44 patients with and without minor histocompatibility antigen incompatibility were 22% and unexpectedly 66%, respectively (P=0.02). The probability of 12-year survival was 88% in the former and 66% in the latter patients (P=0.03). Our data suggest that incompatibility of CD62L, CD31 codon 563 and CD31 codon 125 contributes to a graft-versus-leukemia effect rather than to GVHD, resulting in prolonged survival after HLA-identical SCT.

Retinal damage in hatched chicks induced by formoguanamine. Decrease in ornithine aminotransferase activity and vitamin B6 content.

Subcutaneous injection of formoguanamine (2,4-diamino-s-triazine) induced sightlessness in newly hatched chicks within 28-32 hr. The specific activity of retinal ornithine aminotransferase, localized exclusively in the mitochondria of retinal pigment epithelium, and the retinal vitamin B6 content decreased rapidly after formoguanamine administration. An absorption spectrum of retinal extract showed reduced absorbance at 400 nm in the formoguanamine-treated chicks, but delta 1-pyrroline-5-carboxylate reductase, an enzyme in the retinal cytosol, did not change significantly. A drug-metabolizing enzyme, glutathione transferase, showed an increase in specific activity during a later phase. Histological examination of the formoguanamine-treated chicks revealed characteristic degeneration of pigment epithelium and photoreceptors, acute retinal detachment and a secondary gliosis in the outer nuclear layer. From these findings it may be concluded that formoguanamine primarily damages the physiological functions of retinal pigment epithelium and photoreceptors and results in irreversible retinal detachment in newly hatched chicks.