Cytomegalovirus Infection Is a Risk Factor for Invasive Aspergillosis in Lung Transplant Recipients

120

106

Summary:Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n ¼ 24) or allogeneic (n ¼ 35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 lmol/g dry weight (7.7 mg/g; range 31-631 lmol/g). In total, 4/32 (12%) patients with HIC o150 lmol/g and 10/27 (37%) with hepatic iron X150 lmol/g showed invasive aspergillosis at autopsy (P ¼ 0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P ¼ 0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.

Section: Discussionmentioning

confidence: 99%

Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis

Altés

Remacha

Sarda

et al. 2004

120

106

“…[45][46][47][48] Nichols et al 49 showed an increased risk particularly for patients during primary infection (D þ /R À ). In our study, HCMV viremia, also without subsequent HCMV disease, seems to be a risk factor for the development of non-viral opportunistic infections.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the COBAS Amplicor HCMV Monitor for early detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation

Lengerke

Ljubicic

Meisner³

et al. 2006

Early diagnosis of human cytomegalovirus (HCMV) infection and the introduction of preemptive antiviral therapy have reduced HCMV-related mortality after allogeneic stem cell transplantation. A critical goal remains stratifying risk profiles and minimizing potential harm owing to antiviral overtreatment. We compared the commercially available standardized COBAS Amplicor CMV Monitor (CACM) to an in-house PCR assay, for the monitoring of HCMV infection. Seventy-two patients were surveyed by an in-house PCR of whole blood, quantitative viral load assessment by CACM and virus culture assays in a prospective and a retrospective study. A high concordance between CACM and PCR was documented. The viral load at onset correlated with the peak viral load (Spearman rank correlation R ¼ 0.634, P ¼ 0.0004). In patients developing HCMV disease, both viral loads were in trend higher (P ¼ 0.823, respectively P ¼ 0.053), and the viremic episodes longer (P ¼ 0.015), as compared to asymptomatically HCMV-infected patients. The serological pre-transplant status was the major risk factor for the development of HCMV disease, showing highest risk for seropositive patients receiving a seronegative graft, whereas donor type (related or unrelated) and graft type (bone marrow or peripheral blood mobilized stem cells) did not have an influence. HCMV infection proved to be a risk factor for the development of non-viral opportunistic infections (P ¼ 0.002).

“…15 Recipient CMV seropositivity is a significant risk factor in bone marrow transplant patients. 7 However, posttransplant CMV infection has not been clearly shown to increase risk for IA.…”

Section: Discussionmentioning

confidence: 99%

Late onset of invasive aspergillus infection in bone marrow transplant patients at a university hospital

Grow

Moreb

Roque

et al. 2002

177

144

Summary:Despite new antifungal treatment strategies, invasive aspergillosis (IA) remains a principal cause of infectious mortality after bone marrow transplantation (BMT). We reviewed the medical records of 93 allogeneic and 149 autologous transplant recipients during a 20 month period, with attention to cases of proven or probable IA. No autologous transplant recipient developed IA, whereas IA was seen in 15.1% of allogeneic recipients (including two of five patients with a prior history of IA despite prophylaxis), for an overall incidence of 5.8%. The median time to occurrence was 92 days post transplant, with no de novo cases developing prior to engraftment. Survival 100 days from diagnosis was 29%. Risk factors for the development of IA included у21 days of corticosteroid therapy of у1 mg/kg/day and post-transplant cytomegalovirus (CMV) infection. These two risk factors were statistically linked. Our data illustrate a shift toward a later occurrence of posttransplant IA, suggesting a need for close, prolonged surveillance in the outpatient environment. The contributory role of protracted corticosteroid use is also highlighted. These data have important implications in an era of alternate donor transplants and more intense immunosuppression. Established strategies implementing newer, less toxic antifungal agents as prophylaxis in high-risk patients are needed. sources and more profound immunosuppression, including T cell depletion techniques, which weaken host defenses in the post-engraftment period. The time of onset in autologous transplant recipients is typically during the preengraftment period, whereas later infections are often also seen in allogeneic recipients. 6 Specific knowledge of the usual time of onset and identifiable risk factors for IA is essential to the development of more effective prevention strategies and the application of new therapeutic techniques. Previously identified risk factors include age, 3,7 unrelated donor, 3,4 transplant outside of a laminar air flow room, 5 low cell dose, 7 recipient CMV seropositivity, 7 persistent or prolonged neutropenia, 5,8 early corticosteroid use for acute graft-versus-host disease (GVHD) prophylaxis, 9 high-grade acute GVHD, 1,3,4 chronic GVHD 4,8 and graft rejection. 10 Decreased risk for IA has been ascribed to housing patients in a high-efficiency particulate air (HEPA) filtered environment. 11 To our knowledge, no data exist comparing the risk for IA using different sources of harvested stem cells (peripheral blood vs bone marrow). Furthermore, the need exists for more data regarding the role of GVHD, as well as duration and dose of corticosteroids as predisposing factors for infection.In this study, we reviewed the current epidemiology of IA in the Bone Marrow Transplant Unit at the University of Florida with specific attention to the time of onset and survival. These findings were compared to those reported in a similar epidemiologic study done at this institution between 1981 and 1985. 11 Such a comparison can illustrate the effects of new tr...