Adenovirus Viremia and Disease: Comparison of T Cell–Depleted and Conventional Hematopoietic Stem Cell Transplantation Recipients from a Single Institution

Abstract

Background ADV (adenovirus) is an important cause of viral mortality in hematopoietic stem cell transplantation (HSCT). T-cell depleted (TCD) HSCT are at increased risk of viral infections. We compared the rates and outcomes of ADV viremia and disease between TCD and conventional (CONV) HSCT at our institution. Methods This was an observational study of 624 adult and pediatric recipients of myeloablative HSCT at Memorial Sloan-Kettering Cancer Center from January 1, 2006, through March 11, 2011. Viral cultures and ADV polymerase chain reaction (PCR) were ordered as clinically indicated. ADV viremia by a quantitative PCR assay was defined as ≥1 positive value ≥1,000 copies/mL or ≥2 consecutive values at any value. Competing risk regression analyses were used to identify predictors for ADV viremia. Results Eight percent TCD and 4.0% CONV were noted to have ADV viremia at 1 year after HSCT (P=.041). Among TCD, 15% of children compared with 5% of adults developed ADV viremia (P=.008). Young age (Hazard Ratio [HR] 3.0; P<.001) and acute graft-versus-host-disease (GVHD) (HR 3.2; P=.001) were risk factors for ADV viremia. ADV viremia was a predictor of mortality (HR 6.0; P<.001). ADV disease developed in 3.5% TCD and 0.4% CONV HSCT (P=.022) with attributable mortality of 27%. Among TCD, grade 2–4 GVHD was a risk factor for ADV disease (HR 13; P<.001); age was not significant. More than 90% ADV disease cases had a viral load of ≥ 10,000 copies/mL. Conclusions Rates of ADV disease were 10-fold higher in TCD compared with CONV HSCT, predominantly in patients who developed acute GVHD. The benefit of preemptive therapy for ADV viral load ≥ 10,000 copies/mL for prevention of ADV disease in recipients of TCD grafts should be evaluated in prospective clinical trials.

Outcomes of acute leukemia patients transplanted with naive T cell–depleted stem cell grafts

“…A rationale for our approach was that the transfer of T M would improve immune reconstitution relative to pan-TCD, which results in prolonged lymphopenia and an increase in opportunistic infections (10)(11)(12). T cell numbers recovered much earlier after T N -depleted HCT relative to patients that received TCD HCT (33), and EBV reactivation and post-HCT lymphoproliferative disease (PTLD), which occur in 18% and 2% of TCD HCT recipients, respectively (7,33), were not observed at all after T N -depleted HCT, consistent with transfer of protective EBV-specific immunity.…”

“…GVHD can be substantially reduced by nonselective removal of T cells from the stem cell graft or by early in vivo administration of T cell-depleting antibodies (7)(8)(9). Unfortunately, pan-T cell depletion (TCD) is complicated by delayed immune reconstitution and an increased frequency of opportunistic infections (10)(11)(12).…”

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

“…More specifically, the most prominent risk factors include allogeneic transplantations with in vivo and/or ex vivo T-cell depletion, grafts from unrelated donors or cord blood, treatment with the anti-CD52 antibody alemtuzumab (Campath) or anti-thymocyte globulin (ATG), and the presence of graft-versus-host disease (GvHD) grades III and IV associated with the use of immunosuppressive agents (129)(130)(131)(132)(133)(134)(135)(136). Additionally, severe lymphopenia, with CD3 ϩ cell counts of Ͻ300 per l peripheral blood (PB), and an absence of HAdV-specific T cells play an important role in the development of viral disease (122,124,(137)(138)(139)(140)(141).…”

“…However, the thresholds suggested by different authors are highly divergent, ranging from 10 2 (in individuals with high risk) to Ͼ10 6 copies/ml (130,135,172,175,186,204,205), and it is difficult therefore to draw generally applicable conclusions. Moreover, the measured absolute values are, at least to some extent, dependent on the individual technique used, and in the absence of appropriate interlaboratory standardization, the values cannot readily be adopted by or exchanged between centers.…”

Disseminated Adenovirus Infection in Cancer Patients Presenting with Focal Pulmonary Consolidation

“…T-cell depletion has been identified as a risk factor for ADV disease. Additional risk factors for ADV viremia in SCT recipients are young age and acute graft-versus-host disease (GVHD) (10). In addition, high doses of sequential chemotherapy may induce severe lymphocyte depletion (11).…”