Non-Candida fungal infections after bone marrow transplantation: Risk factors and outcome

Morrison, Vicki A.; Haake, Robert; Weisdorf, Daniel J.

doi:10.1016/0002-9343(94)90088-4

Cited by 191 publications

(120 citation statements)

References 12 publications

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“…Also, although the incidence of fungal infections in this study did not allow us to define statistically significant risk factors, our results support a delayed onset, with invasive aspergillosis occurring mainly after resolution of the neutropenic period, different from that reported after standard allo-SCT. [41][42][43][44] In standard allo-SCT, the transplant period is classically divided into three phases. The first phase is related to the aplastic period, with neutropenia and toxicity of the conditioning regimen favoring a majority of bacterial infections, but also favoring fungal infections.…”

Section: Discussionmentioning

confidence: 99%

“…The first phase is related to the aplastic period, with neutropenia and toxicity of the conditioning regimen favoring a majority of bacterial infections, but also favoring fungal infections. 36,[41][42][43][44] The second phase is characterized by neutrophil recovery, but a major T-cell dysfunction due to the immunosuppressive therapies used for acute GVHD management and thus favoring viral infections, especially CMV. 13,34 A third phase might develop in some long-term surviving patients with several complex immune dysfunctions due to chronic GVHD and/or prolonged immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

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Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen

et al. 2003

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In the setting of reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (allo-SCT), the epidemiology of transplant-related infections is still poorly defined. In 101 high-risk patients who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan and antithymocyte globulin (ATG), we report during the first 6 months a cumulative incidence of positive CMV antigenemia of 42% (95% CI 32-52%), developing at a median of 37 (range 7-116) days without evidence of CMV disease (median follow-up, 434 days). The cumulative incidence of bacteremia was 25% (95% CI 17-33%), occurring at a median of 67 (range 7-172) days, while patients had recovered a full neutrophil count. In all, 65% of the bacteremia (95% CI 49-81%) were gram negative. The cumulative incidence of fungal infections was 8% (95% CI 3-13%), with a median onset of 89 (range 7-170) days. In multivariate analysis, stem cell source (bone marrow; P ¼ 0.0002) was significantly associated with the risk of positive CMV antigenemia, while higher doses of prednisone (42 mg/kg) represented the major risk factor for bacteremia (P ¼ 0.0001). Infectious-related mortality was 5% (95% CI 1-9%), with aspergillosis being the principal cause. Collectively, these results suggest that prospective efforts are warranted to develop optimal antimicrobial preventive strategies after RIC allo-SCT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen

et al. 2003

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“…[1][2][3] It is the most common etiology of non-Candida fungal infections occurring in these patients, and the case-fatality rate for invasive aspergillosis exceeds 80%. Although prolonged neutropenia is a well-established risk factor for Aspergillus infections, the majority of infections in the allogeneic setting become clinically evident well after engraftment, 2 suggesting that cell-mediated immunity plays an important role in protec-tion against this pathogen.…”

mentioning

confidence: 99%

Dendritic cell-mediated stimulation of the in vitro lymphocyte response to Aspergillus

Grazziutti

Przepiorka

Rex³

et al. 2001

Bone Marrow Transplant

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Summary:Lymphocytes play a major role in host defense against Aspergillus, but little is known about the contribution of dendritic cells (DC) to antifungal immunity in humans. We have observed that DC derived from normal volunteers phagocytose heat-killed A. fumigatus conidia. Following 24 h of exposure to the fungus, DC displayed an increase in the mean fluorescence intensity of HLA-DR, CD80, and CD86, and an increase in the percentage of CD54 + cells. These DC also displayed increased production of IL-12. DC derived from CD34 + progenitors or monocytes stimulated autologous lymphocytes to proliferate and produce high levels of interferon-␥, but not interleukin-10, in response to fungal antigen. DC generated from CD34 + progenitors collected prior to autologous or allogeneic stem cell transplantation also partially restored the in vitro antifungal proliferative response of lymphocytes obtained from patients 1 month after transplantation. These results suggest that DC are important to host-response to A. fumigatus, and that ex vivo-generated DC might be useful in restoring or enhancing the antifungal immunity after hematopoietic stem cell transplantation. Bone Marrow Transplantation (2001) 27, 647-652. Keywords: fungi; dendritic cell; immune reconstitution; Candida; AspergillusThe ubiquitous mould Aspergillus rarely causes disease in healthy individuals but poses a serious threat to hematopoietic stem cell transplant recipients. [1][2][3] It is the most common etiology of non-Candida fungal infections occurring in these patients, and the case-fatality rate for invasive aspergillosis exceeds 80%. Although prolonged neutropenia is a well-established risk factor for Aspergillus infections, the majority of infections in the allogeneic setting become clinically evident well after engraftment, 2 suggesting that cell-mediated immunity plays an important role in protec- tion against this pathogen. Indeed, animal studies demonstrated that a Th1 response was associated with resistance to induction of experimental Aspergillus infection, 4 and methods stimulating a Th1 response were successful in inducing anti-Aspergillus immunity. 5 We 6 and others 7 have reported that a substantial proportion of blood and marrow transplant recipients have a deficiency in the number of circulating dendritic cells (DC) in the early post-transplant period. To overcome the potential effects of DC deficiency on immune reconstitution post transplant, DC-based vaccines have been used to induce T cell-mediated immunity to tumor early after transplantation. 8 However, despite the importance of DC in immunity, there is virtually no information regarding the role of human DC in resistance to aspergillosis. We have therefore evaluated the phagocytic capacity of human DC for A. fumigatus conidia, the cytokine response of human DC after exposure to A. fumigatus conidia, and the immunostimulatory competence of A. fumigatus conidia-pulsed DC for autologous lymphocytes from blood stem cell transplant recipients. The results of our studies suggest that DC ...

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“…1,2 Recent reports suggest that the majority of these infections are caused by Aspergillus sp., [1][2][3][4] but invasive Candida infections are also common in allogeneic SCT recipients. [5][6][7] Fluconazole prophylaxis has been widely used in SCT patients due to the results of randomised trials suggesting efficacy.…”

Section: Tion; Treatment Outcomementioning

confidence: 99%

Candidaemia in allogeneic stem cell transplant recipients: low risk without fluconazole prophylaxis

Jantunen

Nihtinen

Volin

et al. 2004

Bone Marrow Transplant

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Non-Candida fungal infections after bone marrow transplantation: Risk factors and outcome

Cited by 191 publications

References 12 publications

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen

Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen

Dendritic cell-mediated stimulation of the in vitro lymphocyte response to Aspergillus

Candidaemia in allogeneic stem cell transplant recipients: low risk without fluconazole prophylaxis

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