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...

Summary:GVHD is a life-threatening complication of allogeneic BMT. It can be either acute (aGVHD) or chronic (cGVHD), In our BMT Unit, we have observed a high frequency with the latter form behaving like an autoimmune disease. of skin rash associated with fever and other clinical finClassically, GVHD is thought to be the response of donor dings during engraftment of autologous BM and/or lymphocytes to the foreign histocompatibility antigens of PBSC. Thirty patients with breast cancer and 12 the recipients. 1 Recent studies in humans, however, indicate patients with Hodgkin's or non-Hodgkin's lymphoma, that aGVHD-like syndrome can occur after BMT perfortreated with the same regimen, were analyzed retromed between identical twins (syngeneic) or after ABMT. 2-7 spectively or prospectively to characterize the clinicalIn fact, an incidence of 8% of this aGVHD is reported in syndrome, its frequency, and its clinical course, as well autologous or syngeneic BMT recipients. 8 These early as to define the factors affecting its incidence. In reports were met with skepticism because they challenged patients developing skin rash, the median and range for the universal concept that histocompatibility differences time to onset of skin rash and for time to increase in between donor and host are absolute requirements for the WBC after reinfusion of stem cells were identical (8 induction of GVHD, as once postulated by Billingham. 1 days, range 5-13) and did not differ significantly (P = More recent reports suggest that GVHD may include a dis-0.533). Twenty-three patients (55%) had skin rash, 18 regulation of self-nonself discrimination or a failure of both patients had fever. Other, less frequent manifestations central and peripheral mechanisms that govern self-tolerinclude platelet transfusion refractoriness (PTR), ance. 9 Several studies have shown that the induction of diarrhea, diffuse alveolar hemorrhage, and autoimmune syngeneic/autologous GVHD requires (1) the inhibition of thrombocytopenia or hemolytic anemia. A higher prothymic-dependent clonal deletion of autoreactive T cells by portion of breast cancer patients developed the syncyclosporine, and (2) the elimination of the peripheral regudrome in comparison to lymphoma patients (67% vs latory mechanism by the preparative regimen before 25%, P = 0.051). Acute GVHD grade I-II was estab-BMT. [10][11][12][13] The absence of this peripheral regulatory system lished histologically in six patients with the syndrome.creates a permissive environment for the activation and Comparison of the incidence of the syndrome by differexpansion of the autoreactive effector T lymphocytes. ent variables using Fisher's exact test revealed signifiSimilar mechanisms may be responsible for the cance for disease category (P = 0.02) and number of cutaneous eruptions seen frequently in immunocomproprevious treatment regimens (P = 0.002) as predictive mised patients undergoing intensive chemotherapy in the factors for developing the autoaggression syndrome. In treatment of malignancies. 14,15 In a ...

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