Allogeneic hematopoietic stem cell transplantation (HSCT) has been used as effective therapy for selected non-malignant diseases including aplastic anemia, primary immunodeficiencies and inherited metabolic diseases. Although the therapeutic elements such as donor selection, preparative regimen and GVHD prophylaxis are mutual between HSCT for malignant diseases and HSCT for non-malignant diseases, deciding criterion and adjustment of agents are different. Related donor candidate who diagnosed as disease-carrier should be excluded from donor in certain inherited diseases. Preparative regimens for non-malignant diseases should have enough immunosuppressive effect that enables donor-cell engraftment without loss of fertility. However, even the optimum-conditioning regimen for aplastic anemia is not established until now and under elaboration. Major problems in the HSCT for non-malignant diseases have been considered high rate of graft rejection and mixed hematopoietic chimerism, new autoimmune diseases including autoimmune hemolytic anemia and autoimmune thrombocytopenia become notable complications after cord blood transplantation in recent years.
An 11-year-old girl with late relapse of B-cell precursor acute lymphoblastic leukemia of the bone marrow underwent human leukocyte antigen-1 mismatch (7/8 serotypes) allogeneic bone marrow transplantation (BMT) from an unrelated male donor. She developed gradeⅠ acute graft-versus-host disease (GVHD) , but not chronic GVHD. We observed hyperthyroidism 12 months after BMT and detected anti-thyroid stimulating hormone receptor antibody. Furthermore, she was diagnosed with Basedow's disease and treated with thiamazole. Treatment was successful and thyroid function normalized two months after the start of treatment with thiamazole. Additionally, she had a positive Schirmer test 18 months after being diagnosed with Basedow's disease, and treatment was started. However, 29 months after diagnosis of Basedow's disease, she developed ocular symptoms of chronic GVHD although her ocular symptoms had improved. We speculate that the thyroid gland is the target organ of chronic GVHD; therefore, we need to observe carefully other target organs related to chronic GVHD.
Cord blood is an alternative graft source for patients lacking sibling or unrelated marrow donors, however since there has been no affiliation with cord blood banks overseas, foreign cord blood unit (CBU) is not available in Japan. Here we report the first successful case of cord blood transplantation coordinated through the National Marrow Donor Program (NMDP) for a 34-year-old Filipina of mixed race with AML, weighning 78.5kg. She underwent a conventional preparative regimen and was infused with a 4/6 serologically HLA-matched Asian female CBU with sufficient total nucleated cells and CD34+ cell count. Neutrophil recovery was delayed as late as on 42 days post transplantation. This was caused by a low viability of only 31.5% measured in our facility before infusion, whereas the viability before cryopreservation at the cord blood bank was reportedly 91.0%. The patient developed no fatal complications including graft-versus-host disease. The duration of the coordination process is expected to become shorter with the full collaboration between the cord blood banks in Japan and NMDP. Relatively high nucleated cell number of CBU in NMDP also serves to overcome the difficult task of finding a donor for patients with heavy weight. The great cost is also a major problem.
Typical liver Graft-versus-Host disease (GVHD) is characterized by cholestasis causing bile duct damage. The hepatitic variant of liver GVHD shows marked elevations of blood aminotransferases without significant elevation of biliary tract enzymes. Hepatitic GVHD may account for as many as 36% to 50% of cases of liver GVHD in adults but is rare in children. We describe a 4-year-old girl in whom hepatitic GVHD developed after allogenic hematopoietic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. The pathologic features of liver biopsy specimens were consistent with lobular hepatitis, with marked infiltration of CD8-positive T-cell predominating in portal areas. There was no cholangiolitis or B-cell or plasma cell infiltration, both of which play important roles in autoimmune hepatitis like liver GVHD. The cytokine/chemokine profile showed high expression of monocyte chemotactic protein-1, and macrophage inflammatory protein-1β in liver sample, suggesting that activation of monocytes/macrophages may be related with pathophysiology of hepatitic GVHD.