No abstract

Summary:We retrospectively evaluated 75 allogeneic stem cell transplant recipients to ascertain the incidence, risk factors and outcome of infection with Clostridium difficile. Ten patients (13%) had Clostridium difficile infection at a median of 38 days (range day −6 to day +72) following the transplant. There was no difference in the duration or severity of diarrhoea in patients with Clostridium difficile infection compared to the uninfected patients and no relationship to the prior antibiotic or chemotherapy usage, age, gender, underlying disease, donor type, CMV serostatus, total body irradiation or time to engraftment. The incidence of viral infections was increased in patients infected with Clostridium difficile (7/10 vs 15/65, P = 0.005, odds ratio 7.7), but the strongest association was with GVHD Ͼgrade 2 (5/10 vs 6/65 uninfected patients, P = 0.004, odds ratio 9.8). Patients infected with Clostridium difficile also suffered a higher non-relapse mortality with 7/10 patients succumbing to either GVHD or infections, compared to 19/65 patients in the uninfected group (P = 0.02, odds ratio 5.6). Thus Clostridium difficile infections in our study had a strong association with GVHD and increased non-relapse mortality. It is possible that Clostridium difficile toxin might predispose to increased severity of GVHD leading to an adverse outcome. Bone Marrow Transplantation (2000) 26, 871-876.

1, Observations have been made by light and electron microscopy of the development of peritoneal adhesions in lhe rat following abdominal surgery.2. Essentially the changes which occurred were those which are seen in healing by fibrosis, except that in many areas of adhesions numerous eosinophils were observed by electron microscopy. In areas where eosinophils were numerous little profijeration of fibroblasts was seen. Conversely in sites where fibroplasia and collagen formation were well advanced no eosinophils were seen.3. The role of the eosinophil in the development of adhesions is discussed and it is suggested that the presence of eosinophiis with their associated antihistamine activity may hold in check the proliferation of' fibroblasts while a new mesothelium is formed and thus prevent adhesion formation.

Summary:Adenovirus has been recognised as an important pathogen in BMT recipients, especially in patients with GVHD and those receiving T cell-depleted allografts. We report adenovirus infections from an ongoing surveillance study in four patients after a non-myeloablative transplant and their improved outcome following withdrawal of immunosuppression in two patients and donor lymphocyte infusion for relapsed disease in the others. We discuss the control of adenovirus infections following immune manipulations and the feasibility of adoptive immunotherapy for post-transplant adenovirus infections. Bone Marrow Transplantation (2000) 26, 305-307. Keywords: adenovirus; immunosuppression; donor lymphocyte infusion Adenovirus infections have been increasingly recognized as an important cause of morbidity and mortality in allogeneic stem cell transplant recipients.1-3 Most of the serious infections are reported in patients with GVHD or T celldepleted graft recipients.1-3 Despite its emergence as a lifethreatening pathogen treatment of adenovirus infections remains difficult. Anti-viral drugs have been used with variable results. 4 Immunotherapy has been used with success in other viral infections, 5 but has not yet been seriously explored in the context of adenovirus infections.We are currently carrying out a viral surveillance study, examining stool, urine and throat specimens from BMT recipients weekly for 6 months after transplantation. We report the effects of immunological interventions carried out after transplant for control of the primary disease on adenovirus infections in four patients from this surveillance study. Case reports Patient 1A 38-year-old female received an allogeneic stem cell transplant from a matched sibling donor in July 1998 for refractory AML. She was given pre-transplant conditioning with Campath 1H (anti-CD52 antibody), fludarabine, and melphalan with cyclosporin A as GVHD prophylaxis. She engrafted with full donor chimerism on day +16 post transplant. At the same time, adenovirus type 2 (Ad2) was identified from the stool sample on electron microscopy (EM) and culture. Although she was asymptomatic, 14 consecutive stool samples continued to grow adenovirus on culture. Polyomavirus (BK virus) was persistently identified in the urine by EM. Twelve weeks following the transplant she had early evidence of relapsed leukemia. Cyclosporin A was stopped. This was followed 1 week later by donor lymphocyte infusion (DLI) of 3 × 10 7 CD3 + cells/kg. Adenovirus was eradicated from the stool 4 weeks after the DLI and six subsequent stool specimens were negative for 5 weeks until she succumbed to progressive leukaemia 23 weeks after transplant without any evidence of GVHD. The polyomavirus was also cleared from the urine 6 weeks after the first DLI. Patient 2A 50-year-old female received an allogeneic stem cell transplant from a matched sibling donor in July 1998 because of refractory AML. She was given identical pretransplant conditioning and GVHD prophylaxis as patient 1. She engrafted on day +14 pos...

Summary:Infections with the paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus (PIV) can result in serious morbidity and mortality after haemopoietic stem cell transplant (HSCT). Once pneumonia develops, the outcome of these infections is often poor despite anti-viral therapy. Aerosolised ribavirin has been evaluated as pre-emptive therapy for post-transplant RSV infections with some success. Due to the financial and logistic burden involved with the use of aerosolised ribavirin, we explored the efficacy and toxicity of oral ribavirin for pre-emptive therapy of post-transplant RSV and PIV infections in a dose escalating schedule (15-60 mg/kg/day). Five episodes each of RSV and PIV were treated in seven patients. Five patients were receiving treatment for GVHD and two acquired the infection in the pre-engraftment period. All the episodes of RSV infection improved with oral ribavirin with dose escalation to 30-45 mg/kg in three of them. On the other hand, only two of the five PIV infections improved with oral ribavirin. Of the three non-responders, two infections were acquired in the pre-engraftment period with one death from PIV pneumonia. Reversible anaemia was the only side-effect noted in patients treated for over 2 weeks. Thus, the use of oral ribavirin was well tolerated in the post-transplant period with no untoward toxicities. There was a trend towards better response in RSV infections, which needs to be further explored in controlled studies. Bone Marrow Transplantation (2001) 28, 759-763.