The role of ursodeoxycholic acid (UDCA) in the prevention of hepatic complications after allogeneic stem cell transplantation was studied in a prospective randomized open-label multicenter trial. A total of 242 patients were allocated to receive (n ‫؍‬ 123) or not to receive (n ‫؍‬ 119) UDCA in the dose of 12 mg/kg/d orally from the day preceding the conditioning until day 90 after transplantation. In the UDCA-treated group a significantly smaller proportion of patients developed a serum bilirubin level exceeding 50 M (18 of 123 versus 31 of 119, P ‫؍‬ .04), and similarly a smaller proportion of patients exceeded the alanine aminotransferase level of 100 U/L. There was no difference in the incidence of veno-occlusive disease of the liver. Compared to the control group, in the UDCA-treated group there was a nonsignificant trend toward a lower overall incidence of acute graft-versushost disease (GVHD) and a significantly lower incidence of grade III to IV acute GVHD (5 of 123 versus 17 of 119, P ‫؍‬ .01), stage II to IV liver and intestinal GVHD, and stage III to IV skin GVHD. There was no difference in the incidence of chronic GVHD or in the relapse rate. Among the patients given UDCA, the survival at 1 year was significantly better, 71% versus 55% (P ‫؍‬ .02), and the nonrelapse mortality rate was lower, 19% versus 34% (P ‫؍‬ .01), than in the control group. There were significantly more deaths in GVHD in the control group. In conclusion, UDCA administration reduced hepatic problems and severe acute GVHD and improved survival. These results suggest a role for UDCA in the prevention of transplantrelated complications in allogeneic transplantation.

Summary:epidemiology and risk factors for IFI is important in identifying subsets of BMT recipients for clinical trials investigating the effects of novel preventive measures, as In order to analyze the incidence and risk factors for invasive fungal infection (IFI) after allogeneic BMT, 142 well as clinical decision-making on the management of patients after allogeneic BMT. consecutive adult BMT recipients (131 sibling donors, 11 unrelated donors) transplanted in 1989-1993 wereIn most previous studies, the role of GVHD and especially the effects of regimens used for GVHD prophyretrospectively analyzed. There were 21 cases with definite or probable IFI (incidence 15%) (Aspergillus, laxis or treatment, have not been evaluated as risk factors for IFI. Due to the increasing age of BMT recipients, wider 15; Candida, four; Fusarium, one; Absidia, one). The median time to the diagnosis of IFI was 136 days after use of unrelated donors, modifications in pre-and posttransplant immunosuppression and antifungal prophylaxis, BMT (range 6-466 days). Only 14% of the IFIs were found during the neutropenic period post-BMT. Of the the incidence of fungal infections, as well as the spectrum of causative agents, may change. We therefore investigated pretransplant characteristics, hematological disease (MDS vs other) (P = 0.001) and unrelated donor (P = the incidence and risk factors for IFI and especially the effects of acute and chronic GVHD and their treatment with 0.01) were risk factors for IFI. Acute GVHD grade III-IV (P = 0.03) and extensive chronic GVHD (P = 0.0002) steroids and antithymocyte globulin, on the risk of IFI in allogeneic BMT recipients transplanted between 1989 and were also found to be significant risk factors. Only three patients with IFI (14%) became long-term survivors.1993. Invasive fungal infections tended to develop late after BMT, were usually caused by Aspergillus sp., and were strongly associated with GVHD and its treatment. BetPatients and methods ter prophylaxis and treatment of IFI are needed. More effective prophylaxis for GVHD might decrease the risk Patients of IFI after allogeneic BMT.One hundred and forty-two adult patients received their first Keywords: invasive fungal infection; BMT; GVHD; risk allogeneic BMT (131 HLA-identical sibling donors, 11 factors; incidence unrelated donors) in the Department of Medicine, Helsinki University Central Hospital between 1989 and 1993. All patient charts were screened for relevant baseline data, Invasive fungal infections (IFI) mainly caused by Candida post-transplant course, occurrence and treatment of GVHD, and Aspergillus species constitute a major problem after as well as invasive fungal infections and their management. allogeneic BMT. Invasive Candida infections have beenThe patients had a median follow-up of 26 months postreported in 10-15% of patients, 1-4 and the incidence of BMT (range 1-82 months). The main pretransplant characAspergillus infections has varied between 3 and 7% in teristics are presented in Table 1. recent series. 2,[5][6][7] ...

Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus- host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan- treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.

We conclude that PCV7 vaccination at 3 months after stem cell transplantation is not inferior to PCV7 vaccination at 9 months after transplantation. Because invasive pneumococcal disease can occur early, we recommend starting the PCV7 vaccination series at 3 months after transplantation to ensure earlier protection against Streptococcus pneumoniae. However, the early vaccination may result in only short-lasting response and may not prime for a 23-valent pneumococcal polysaccharide vaccine boost as efficiently as the late vaccination.