Adenovirus infections following haematopoietic cell transplantation: is there a role for adoptive immunotherapy?

Abstract

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...

Management of multidrug‐resistant viruses in the immunocompromised host

“…One key question to be answered in this setting is whether selected cells offer any real advantage over small doses of unselected donorlymphocytes. Although there is some concern about the possible risk of GvHD, successful application without this complication has been reported (Hromas et al, 1994;Chakrabarti et al, 2000b) and we have similar experience (unpublished observations). Expansion of BK virus-specific T cells is also possible using analogous strategies (Comoli et al, 2003;Blyth et al, 2011) and a number of groups are now evaluating their use, although their clinical experience is not yet published.…”

Polyoma viruria following T-cell-depleted allogeneic transplants using Campath-1H: incidence and outcome in relation to graft manipulation, donor type and conditioning

“…Interestingly, in one patient with viruria for 14 weeks, this cleared after DLI for relapsed leukaemia. 24 Lymphoproliferative responses to polyomaviruses has been demonstrated in post-BMT patients 25 and our observations seem to suggest that the virus is susceptible to cellular immunity.…”

Adenovirus infection in children after allogeneic stem cell transplantation: diagnosis, treatment and immunity

“…19 HAdV secretion disappeared in four SCT recipients, who were treated for a leukaemia relapse after SCT either by tapering of ciclosporin A or by DLI infusion. 20 An additional study in a larger cohort of patients showed a strong association between immune reconstitution and elimination of HAdV infection. 21 Data obtained in ORD/MUD SCT recipients from our retrospective study indicated that patients with a low T-cell count (either CD4 þ or CD8 þ T cells) after SCT are at risk of developing an HAdV infection.…”