Iron overload is common in patients undergoing allogeneic hematopoietic cell transplantation (HCT) for hematologic disorders. Serum ferritin, a marker of tissue iron overload, was measured immediately before transplant in adult patients undergoing myeloablative HCT from matched sibling or unrelated donors. The effect of elevated pretransplant ferritin (defined as ferritin X1000 ng/ml) on day 100 mortality, overall survival, acute GVHD and infectious complications was assessed. Data on 190 patients were analyzed. In univariate analysis, the highferritin group had increased day 100 mortality (20 vs 9%, P ¼ 0.038), decreased overall survival (log-rank test: P-value ¼ 0.004), increased acute GVHD/death (63 vs 43%, P ¼ 0.009) and increased incidence of blood stream infections (BSIs)/death (60 vs 44%, P ¼ 0.042). In a multivariate analysis, high ferritin was associated with increased risk of death (Cox model: hazard ratio ¼ 2.28, P ¼ 0.004), increased day 100 mortality (generalized linear model (GLM) odds ratio ¼ 3.82, P ¼ 0.013), increased incidence of acute GVHD/death (GLM odds ratio ¼ 3.11, P ¼ 0.001) and increased risk of BSI/death (GLM odds ratio ¼ 1.99, P ¼ 0.032). The results remained similar when serum ferritin was considered a continuous variable. Elevated serum ferritin adversely impacts on overall survival and increases the likelihood of acute GVHD and BSI after allogeneic HCT.
Key Points
The incidence of IFIs during VEN-HMA therapy is low, and the used antifungal prophylaxis approach did not influence the risk of IFIs. The risk of IFIs is higher in nonresponders and those who were treated in the r/r AML setting.
Amphotericin B can be used in low doses as prophylaxis for fungal infections early in the posttransplant course. However, cyclosporine doses need to be monitored to maintain target levels.
Late occurrence of cytomegalovirus (CMV) disease after day 100 after bone marrow transplantation has become an increasing problem; whether a quantitative measurement of CMV DNA in plasma by polymerase chain reaction (P-PCR) could be predictive of such disease was investigated. In a prospective study, 117 subjects undergoing allogeneic marrow transplantation were followed for 120 days with weekly CMV blood cultures, with day 35 bronchoalveolar lavage CMV cultures, with weekly CMV P-PCR, and with clinical follow-up for an additional 1 -2 years. Despite preemptive ganciclovir, CMV disease occurred in 9% of subjects, with a median time of onset of 176 days. Quantitative CMV P-PCR was associated with the late development of CMV disease (P Å .01). Of 43 subjects with positive P-PCR results, 23% developed CMV disease, but no disease occurred in the 74 subjects with negative P-PCR (P õ .001), despite the fact that 22% had CMV isolated from lung lavage fluid and 32% had CMV isolated from blood.
Risk factors for the occurrence of human cytomegalovirusBMT, the presence of CMV DNA in plasma has been associated with risk for disease [3,4, 12] and pulmonary CMV (CMV) -related morbidity after allogeneic bone marrow transplantation (BMT) can be used to guide antiviral therapy [1 -infection [13], but the significance of the quantity of CMV DNA in plasma has not been studied. We evaluated whether 5]. The most important of these factors is the occurrence of asymptomatic CMV reactivation in blood or lung [2], and inquantitative plasma PCR is predictive of late CMV disease. fection of urine or throat has not been as predictive of later disease [1, 2]. In addition, the occurrence of graft-versus-host Methods disease (GVHD), and other factors predisposing to this, such as age ú20 years and HLA mismatch of donor and recipient, Study population. During 1993-1994are important risks for CMV infection and disease [6]. seropositive recipients of allogeneic BMT for hematologic malignancy or severe aplastic anemia were followed for the occurrence With the ability to determine CMV DNA in plasma by polyof CMV infection and disease in a prospective study. CMV infecmerase chain reaction (PCR) [7, 8] persons with CMV pulmonary infection [11]. In allogeneic No clinical decision was made on the basis of CMV P-PCR result. Thirty-six patients (31%) were treated because BAL fluid was positive for CMV; among the 81 BAL fluid CMV-negative subjects, an additional 35 were treated with ganciclovir for positive Received
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