Progress in the Diagnosis and Management of Aspergillosis in Bone Marrow Transplantation: 13 Years' Experience

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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...

Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

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

Grow

Moreb

Roque

et al. 2002

176

144

“…Extensive chronic GvHD, a major risk factor for late infections, 48,54 was a risk factor for LSBI on multivariate analysis, whereas limited GvHD was not. Steroid treatment is also a well-known risk factor for other infections such as invasive aspergillosis [55][56][57] and for other complications including diabetes, growth hormone deficiency or cataract. [58][59][60][61] Aspergillosis and CMV occurred in about 10% of the patients, thus precluding any meaningful analysis of risk factors.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic bone marrow transplantation for acute myeloblastic leukaemia in remission: risk factors for long-term morbidity and mortality

Robin

Guardiola

Dombret

et al. 2003

Summary:In this single-centre retrospective study, we analysed risk factors for nonrelapse long-term morbidity and mortality in patients with acute myeloblastic leukaemia (AML) who had undergone allogeneic transplantation. A total of 112 patients with de novo AML in first complete remission (CR1), n ¼ 90 or second complete remission (CR2, n ¼ 22) who received un-manipulated bone marrow grafts from human leukocyte antigen identical siblings between January 1985 and August 2000 were included. Of these, 97 patients alive and disease-free for at least 100 days after transplant were selected for the purpose of this longterm analysis. The use of an intensified conditioning regimen, Gram-negative bacteriaemia before transplantation, year of transplantation and number of pretransplant chemotherapy courses for patients in CR1 significantly affected the 7-year event-free survival which was 57%. 7-year transplant-related mortality TRM was 22%. Significant predictors for TRM were: bacterial infections before transplantation, major ABO blood group incompatibility, late severe bacterial infections, and chronic (graft-versus-host disease) GvHD. Predictive factors for late severe bacterial infections were infections before transplant, total body irradiation and GvHD. Incidence and risk factors for other late events including, chronic GvHD, late infections, osteonecrosis, cataract, endocrinecardiac-and lung-complications, cancer and performance status at last follow-up were also studied. The analysis strongly suggests that the combination of pretransplant factors such as chemotherapy and conditioning, and post transplant factors such as chronic GvHD had a major impact on late nonrelapse morbidity and mortality.

“…[1][2][3][4] The prognosis of IA is very poor. 5,6 Lungs are the most common site of aspergillosis and are affected in about 90% of patients.…”

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confidence: 99%

Central nervous system aspergillosis in allogeneic stem cell transplant recipients

Jantunen

Volin

Salonen

et al. 2003

Summary:Invasive aspergillosis (IA) is relatively common in allogeneic stem cell transplant (SCT) recipients. Although lungs are the most common site, central nervous system (CNS) involvement is also observed in this setting. We have retrospectively studied 14 cases of CNS aspergillosis found in a cohort of 455 allogeneic SCT recipients (incidence 3%). All patients, except one, had experienced acute graft-versus-host disease treated with high-dose methylprednisolone, and eight patients (57%) had also received ATG. The median time to the diagnosis of CNS aspergillosis was 124 days (range 49-347 days) from SCT. Pulmonary aspergillosis had been diagnosed earlier in four patients (29%). The most common initial symptoms of CNS aspergillosis were convulsions, hemiparesis, and mental alteration. Neuroradiological studies revealed single (two patients) or multiple (seven patients) focal lesions of 0.2-9 cm in diameter. Despite clinical suspicion in many patients, a confirmed diagnosis of CNS aspergillosis was made during life in only one patient. A total of 12 patients (86%) received amphotericin B. Despite therapy, all patients died 0-27 days (median seven days) after the initial CNS symptoms. CNS aspergillosis is not uncommon in allogeneic SCT recipients. Clinical manifestations are usually dramatic and progress quickly. Earlier and more effective treatment of IA is needed to prevent dissemination of infection into the CNS.