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Background: For many inborn errors of metabolism (IEM), allogeneic hematopoietic stem cell transplantation (HSCT) is the only cure., Methods: We report the outcome in 160 patients with inherited diseases, who were treated with HSCT in 3 decades. Median age was 3 years (range 0.1-63). Grafts were from matched related donors (MRDs, 56), matched unrelated donors (MUDs, 66), or HLA-mismatched donors (38)., Results: Graft failure (GF) occurred in 26 patients (16%), severe acute graft-versus-host disease (GVHD) in 9 (6%), and chronic GVHD in 23 (12%). Ten-year survival was 64% before the year 2000 and 86% after that (P = 0.01). Ten-year survival for MRD grafts was 90%, as opposed to 79% for MUD grafts and 56% for HLA-mismatched grafts (P = 0.03). In multivariate analysis, GF was associated with having an HLA-mismatched donor (P < 0.05) or MUD (P = 0.015) and with reduced-intensity conditioning (P < 0.01). Death was associated with year of transplant (P = 0.015), having an HLA-mismatched donor (P < 0.001), and being a male recipient from an immune female donor (P = 0.05)., Conclusions: The outcome after HSCT for IEM depends on HLA match, year and immune female donor.

Background: A recent experimental study in mice shed new light on the controversy as to whether granulocyte colony-stimulating factor (G-CSF) increases graft-versus-host disease (GVHD). Total body irradiation and bone marrow were found to be prerequisites for acute GVHD. This study encouraged us to perform a retrospective clinical study., Methods: We compared 260 patients given G-CSF prophylaxis after allogeneic hematopoietic stem-cell transplantation with 205 controls transplanted between 1993 and 2003., Results: G-CSF hastened the engraftment of neutrophils, but that of platelets was delayed (P<0.0001). The proportion of acute GVHD of grades II to IV was 29% in the G-CSF group and 19% in the controls (P<0.01) and that of chronic GVHD was 54% and 43%, respectively (P=0.019). G-CSF increased acute and chronic GVHD in patients preferentially conditioned with chemotherapy. Unexpectedly, it exacerbated acute GVHD in recipients of peripheral blood stem cells and enhanced chronic GVHD in bone marrow recipients. A multivariable analysis showed that acute GVHD (hazards ratio=1.52, P=0.03) and chronic GVHD (hazards ratio=1.51, P=0.004) were associated with G-CSF. There was no significant difference between study groups regarding nonrelapse mortality, relapse, or survival., Conclusion: G-CSF increased acute and chronic GVHD in patients treated with chemotherapy but did not affect relapse or survival.

There is evolving interest in the use of mesenchymal stem cells (MSC) in solid organ transplantation. Pre-clinical transplantation models show efficacy of MSC in prolonging graft survival and a number of clinical studies are planned or underway. At a recent meeting of the MISOT consortium (MSC In Solid Organ Transplantation) the advances of these studies were evaluated and mechanisms underlying the potential effects of MSC discussed. Continued discussion is required for definition of safety and eventually efficacy endpoints for MSC therapy in solid organ transplantation.

The use of fetal hematopoietic stem cells for in utero transplantation to create permanent hematochimerism represents a new concept in fetal therapy. In one fetus with alpha-thalassemia, one with sickle cell anemia, and one with beta-thalassemia, we have transplanted fetal liver cells obtained from legal abortions in gestational weeks 6-11. The fetus with alpha-thalassemia was transplanted twice during pregnancy, in the 15th (20.4 x 10(8) cells/kg) and in the 31st weeks of gestation (1.2 x 10(8) cells/kg), and is now two years of age. One fetus with sickle cell anemia received its transplant in the 13th week of gestation (16.7 x 10(8) cells/kg), and is now one year old. The fetus with beta-thalassemia was transplanted in 18th week (8.6 x 10(8) cells/kg), and is now three months old. Engraftment was evaluated by chromosomal analysis (sex chromosomes), red cell phenotyping, HLA class I and II typing, and PCR (polymerase chain reaction) for Y chromosome-specific sequences and DNA polymorphisms in cord and peripheral blood. The children with alpha- and beta-thalassemia underwent bone marrow aspirations at 3 and 7 months of age, respectively. In neither of these cases were we able to detect convincing evidence of stem cell engraftment. Thus, the administration of fetal stem cells to fetal recipients after the 12th week of gestation did not result in permanent hematochimerism. It remains to be determined whether the engraftment process can be promoted by earlier transplantations and/or higher cell doses.