Outbreaks of infectious diseases in stem cell transplant units: a silent cause of death for patients and transplant programmes.

Following the closure of the National Blood and Bone Marrow Transplant Unit in Dublin, because of an outbreak of vancomycin-resistant enterococcal infection, a survey was carried out by the EBMT to investigate the occurrence of outbreaks of infection in SCT units and the impact on patient morbidity, mortality and the administration of the transplant programme over a 10-year period from 1991 to 2001. A total of 13 centres reported 23 outbreaks of infection involving 231 patients: 10 bacterial, eight viral and five fungal outbreaks were reported and 56 deaths were attributed to infection. All fungal and bacterial deaths and the majority of viral deaths occurred in allograft recipients. In all outbreaks, the infection was reported to be hospital acquired and in all the viral, and half the bacterial infections, cross-infection was a major factor. All viral, four of 10 bacterial and three of five fungal outbreaks occurred in HEPA filtered rooms. A total of 12 SCT units reported a partial or total closure. The introduction of mandatory quality management systems such as JACIE should result in a change in attitude to 'incident reporting' and together with future surveys should reduce the incidence of infectious outbreaks in SCT units.

Hepatitis C virus infection and liver failure in patients undergoing allogeneic bone marrow transplantation.

The role of hepatitis C virus (HCV) infection in severe liver failure (LF) following bone marrow transplantation is still uncertain. We therefore decided to determine the presence of HCV-RNA in 31 patients who died of severe LF after BMT and in 26 matched BMT controls who did not develop LF. HCV-RNA was identified by polymerase chain reaction and anti-HCV by second generation enzyme-linked immunoassay and by 4-band recombinant immunoblotting assay in serum samples obtained before and after BMT. Biochemical and clinical parameters of liver disease were obtained by reviewing clinical records. LF developed at a median interval of 80 days (20-570) from transplantation and was clinically assessed as VOD (n = 7), liver GVHD (n = 5) or hepatitis (n = 19). HCV-RNA was detected, respectively, in 15/31 (48%) and in 12/26 (46%) of LF patients and controls (P = 0.9). Conversely, the risk of dying of LF was 62% and 53% (P = 0.5) respectively, for HCV-RNA positive and negative patients. Anti-HCV profile did not correlate with viremia, nor with type of liver disease. These findings indicate that, despite a 47% prevalence of HCV infection in our series, HCV-RNA positivity was neither a predictor of VOD nor a marker for life-threatening liver disease.

Ovarian recovery after total body irradiation and allogeneic bone marrow transplantation: long-term follow up of 79 females.

Seventy-nine females undergoing allogeneic BMT following conditioning with total body irradiation (TBI), were prospectively followed between March 1983 and March 1992 with regular gynaecological examinations, including plasma levels of luteinising hormone (LH), follicle stimulating hormone (FSH), 17-beta oestradiol (E2) and pelvic ultrasonography. The end-points of this study were the following: (1) early and late effects of TBI on ovarian function, (2) compliance and results of hormonal replacement therapy (HRT), and (3) predictive events for ovarian recovery. During the first year post-BMT most adult women complained of vasomotor and/or genitourinary tract symptoms. These were associated with decreased E2 and increased LH-FSH plasma levels and a deterioration in their sexual life (94% of sexually active women). Forty-nine adult females were selected to receive systemic hormonal replacement therapy (HRT), consisting of cyclic transdermal oestrogens plus medroxyprogesterone acetate (MPA) or cyclic oral therapy with low doses of conjugated oestrogens and MPA: these patients were selected on the basis of age (< 45 years), absence of medical contraindications or subjective refusal. Compliance and tolerability were overall good: most women (65%) never stopped HRT; this was discontinued in 14 patients for medical reasons and in 3 because of refusal. Forty-three females completed 6 months of HRT: vasomotor symptoms disappeared in 91% of 58 women who previously referred these symptoms. Improvement of genitourinary symptoms was seen both with local and systemic hormonal therapy. However sexual symptoms were reduced in 21 of 26 women (81%) given HRT compared with 8 of 19 (42%) women given local treatment (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatitis C virus infection in patients undergoing allogeneic bone marrow transplantation.

Antibody to the recently identified hepatitis C virus was investigated in sera of 128 patients treated with allogeneic bone marrow transplantation, to determine the prevalence of HCV infection and its role in post-transplant liver complications. The overall prevalence of anti-HCV positivity was 28.6% (38/128 patients). The presence of pretransplant anti-HCV positivity (in 10/35 tested patients) did not seem to predict a more severe liver disease. In fact 8/10 anti-HCV+ and 15/25 anti-HCV- patients had elevated transaminases at BMT, and posttransplant liver failure (due to VOD or subacute hepatitis), and post-BMT rises in transaminases occurred regardless of anti-HCV serology (P = 0.6 and 0.2, respectively). In patients tested for anti-HCV after BMT (n = 128), only two (one anti-HCV+ and one anti-HCV-) experienced VOD; the number of patients in whom liver failure contributed to death was comparable in anti-HCV-positive and anti-HCV- negative patients (P = 0.4). Among 17 patients with documented posttransplant seroconversion (from anti-HCV- to anti-HCV+) the appearance of anti-HCV was concomitant with hepatitis exacerbation in 9 (53%). Histologic changes demonstrated a more severe liver damage in anti-HCV+ patients: a chronic hepatitis was diagnosed in 9/11 anti-HCV+ versus 1/7 anti-HCV- cases. Based on these observations, we conclude that hepatitis C virus has a role in liver disease in such patients, although its evaluation by the anti-HCV test is still of limited accuracy, due to low sensitivity and incomplete specificity.

Allogeneic bone marrow transplantation (BMT) for acquired severe aplastic anaemia (SAA) in children.

The SAA Registry of the EBMT now contains data on 171 children younger than 15 years of age with acquired SAA and undergoing BMT between 1970 and 1988. The overall actuarial survival is 63% at 10 years. In a multivariate Cox analysis, the year of transplant was the most important prognostic factor with a significant advantage for children grafted in 1984-88 (81%) vs 1981-83 (67%) and 1970-80 (41%) (p = 0.02). Cyclosporine A given for GVHD prophylaxis, no treatment before transplant and an interval less than 90 days from diagnosis to BMT were all favourable variables in univariate analysis. As regard to transplant procedures, the better results were obtained using Cyclophosphamide and Cyclosporine A (78%) followed by Cyclophosphamide plus irradiation plus Cyclosporine A (77%). Sex, etiology and the severity of the aplasia had no impact on survival in both uni and multivariate analysis.