Post-transplant complications Polyoma viruria following T-cell-depleted allogeneic transplants using Campath-1H: incidence and outcome in relation to graft manipulation, donor type and conditioning S Chakrabarti 1 , H Osman 2 , K Collingham 2 and DW Milligan 1 1 Departments of Haematology, Birmingham Heartlands Hospital, Birmingham, UK; and 2 Public Health Laboratory Birmingham Heartlands Hospital, Birmingham, UK Summary: Haemorrhagic cystitis (HC) is an important cause of morbidity following stem cell transplantation (SCT) and has been associated with polyoma virus infection. We studied the incidence and outcome of polyoma virus infection in 58 T-cell-depleted SCT patients. T-cell depletion was carried out using Campath-1H, either 10 or 20 mg in vitro (n ¼ 33) or 50 or 100 mg in vivo (n ¼ 25) following conventional (n ¼ 35) or nonmyeloablative con- ditioning (n ¼ 23). A total of 21 patients (36%) had polyoma viruria at a median of 35 days (5–114); 30% among patients receiving Campath in vitro and 44% among those given in vivo. The only risk factor for polyoma viruria was graft-versus-host disease GVHD grade X2. The onset of polyoma viruria coincided with Cytomegalovirus (CMV) reactivation in all six patients who reactivated both viruses. Prolonged viruria (defined as polyoma viruria 42 weeks) was documented in 10 patients (17%) and this was associated with GVHD Xgrade 2. HC occurred in four patients. Prolonged viruria was associated with HC only in patients receiving unrelated donor grafts following conventional condition- ing. HC was not observed following nonmyeloablative conditioning despite a higher incidence of prolonged viruria. Thus, HC was uncommon in patients with polyoma viruria following T-cell depletion with Campath, particularly after reduced intensity conditioning. Bone Marrow Transplantation (2003) 31, 379–386. doi:10.1038/sj.bmt.1703847 Keywords: polyomavirus; T-cell depletion; transplantation Polyoma viruses (BK and JC viruses) are ubiquitous and 90% of children sero-convert by 10 years of age. 1 Following primary infection the virus establishes latency particularly in the kidneys. 1 They are known to reactivate during immunosuppressed states, such as solid organ transplantation, AIDS and BMT. 1 Reactivation following BMT has been reported to be associated with haemorrhagic cystitis (HC). 2–9 HC is a serious post-transplant complica- tion associated with significant morbidity. However, the relation between HC and polyoma virus remains conten- tious because not all patients who reactivate the virus develop HC. 10,11 Recently, Leung et al 12 have correlated BK viruria quantitatively with the occurrence of HC. However, the impact of donor type and conditioning treatment was not apparent in this study because of small patient cohorts. It is not known whether the incidence or outcome of polyoma viruria is likely to be different after reduced-intensity conditioning. If reactivation of polyoma virus is related to a deficiency in the cellular immune system, T-cell depletion might be associated with increased virus load. Again, if higher viral load is the key factor in the occurrence of HC, then T-cell depletion should lead to an increase in the incidence of HC irrespective of the conditioning regimen. Indeed, increased morbidity and mortality have been reported with polyoma-related HC following T-cell-de- pleted transplants. 13 We investigated the incidence and outcome of polyoma viruria in 58 consecutive patients, T- cell depleted, with Campath in vivo or in vitro following both conventional and reduced-intensity conditioning. Patients and methods We evaluated 58 T-cell-depleted allograft recipients who were treated in the BMT unit at Birmingham Heartlands Hospital between June 1998 and September 2001 for evidence of polyoma virus infection. All the patients were nursed in single rooms with high-efficiency particulate air (HEPA) filters. Conditioning treatment and T-cell depletion All patients and donors, both related and unrelated were fully matched at both class I (A, B, C) and II loci (DR, DP, DQ). Conventional conditioning consisted of cyclopho- sphamide (n ¼ 23) or etoposide (n ¼ 12) and total body irradiation (n ¼ 32) or busulfan (n ¼ 3). The nonmyeloa- blative transplant (NMT) conditioning schedule (n ¼ 23) consisted of fludarabine and melphalan. T-cell depletion was carried out with Campath (anti-CD52) antibodies Received 14 June 2002; accepted 12 August 2002 Correspondence: Dr S Chakrabarti, Bone Marrow Transplant Unit, Bristol Royal Hospital for Sick Children, Bristol, BS2 8BJ, UK Bone Marrow Transplantation (2003) 31, 379–386 & 2003 Nature Publishing Group All rights reserved 0268-3369/03 $25.00 www.nature.com/bmt