Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation

Björklund, Andreas; Aschan, J; Labopin, Myriam; Remberger, Mats; Ringdén, Olle; Winiarski, Jacek; Ljungman, Per

doi:10.1038/sj.bmt.1705856

Cited by 82 publications

(71 citation statements)

References 53 publications

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“…The Bone Marrow Transplantation Registry has reported that fatal infections are a prevalent cause of late mortality, with risk factors for infectious death including acute GVHD, chronic GVHD, CMV infection, mismatched or unrelated donor and TBI. 5,13 Chronic GVHD has been identified as the primary isolated risk factor for late infections after HSCT in adult patients. 14 These infections have been attributed to functional asplenia, 14 impaired T and B cell reconstitution and the immunosuppressive therapy used to treat chronic GVHD.…”

Section: Study Populationmentioning

confidence: 99%

“…2 In survivors of allogeneic HSCT, relapse of the primary disease and chronic GVHD are the most frequent causes of late mortality in adults. 3,5 Relapsed disease and second malignancies are the main causes of late mortality after autologous HSCT. 6,7 However, as the distribution of cancers, for which HSCT is indicated differs between adults and children, 4 the contribution of relapse to late mortality in children may not mirror that seen in adult cohorts.…”

Section: Introductionmentioning

confidence: 99%

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Late mortality after hematopoietic SCT for a childhood malignancy

Schechter

Pole

Darmawikarta

et al. 2013

Bone Marrow Transplant

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Hematopoietic SCT (HSCT) has been used as a curative therapy for pediatric malignancies. Survivors of HSCT are at risk for disease recurrence, late morbidity and mortality. We assessed late mortality (X2 years post-HSCT) in a population-based cohort of children who underwent HSCT for a malignancy. Mortality outcomes were determined by linking a clinical transplant database with the Canadian province of Ontario's pediatric cancer mortality files. Seven hundred and fifty-four children underwent HSCT (371 allogeneic, 383 autologous). Of the 479 (63.5%) who were alive X2 years post HSCT, 98 (20.5%) suffered a late death. Late mortality in the allogeneic HSCT group was 14.9% (median follow-up 10.0 years; range: 2.0-25.6 years), mainly due to relapse of the primary malignancy (64.7%). Chronic GVHD and second malignancies were not major causes of late mortality. A total of 25.5% suffered a late death following autologous HSCT (median follow-up 6.7 years; range: 2.0-22.2 years). Recurrence of the primary malignancy accounted for 87.5% of these deaths. Recurrence of the primary malignancy is the predominant cause of late mortality after HSCT. In contrast to studies of adult patients, non-relapse mortality is less common in children, and death due to chronic GVHD and secondary malignancies is uncommon.

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Section: Study Populationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Late mortality after hematopoietic SCT for a childhood malignancy

Schechter

Pole

Darmawikarta

et al. 2013

Bone Marrow Transplant

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“…Due to the therapies preventing and treating graft-versus-host-disease (GVHD) and cytopenia, HSCT recipients have a high risk of acquiring invasive fungal infection (IFI) (Jantunen et al, 1997;Bjorklund et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years

Shi

Pei

Luo

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:Invasive fungal infection (IFI) is a growing cause of morbidity and mortality among patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively reviewed the records of 408 patients undergoing allo-HSCTs during the period November 1998 to December 2009, analyzed the incidence and risk factors of IFI, and examined the impact of IFI on overall survival. A total of 92 (22.5%) episodes suffered proven or probable IFI (4 patients were proven, 88 patients were probable). Candida was the most common pathogen for early IFI, and mold was the most frequent causative organism for late IFI. A prior history of IFI, human leukocyte antigen (HLA) mismatch, long-time neutropenia, and acute graft-versus-host-disease (GVHD) were risk factors for early IFI. A prior history of IFI, corticosteroid therapy, cytomegalovirus (CMV) disease, and chronic GVHD were risk factors for late IFI. IFI-related mortality was 53.26%. The 12-year overall survival (OS) rate for IFI was significantly lower than that of patients without IFI (41.9% vs. 63.6%, P<0.01).

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“…Infectious complications represent an important cause of non-relapse morbidity and mortality even more than ten years after allogeneic stem cell transplantation. 26,27 Extensive chronic graft-versus-host disease (GVHD), cytomegalovirus (CMV) status, unrelated donor transplantation, irradiation in conditioning regimen and age have been established as important risk factors for late infections, [28][29][30] but there are no objective parameters to define a dysfunction of the immune system in long-term survivors. Therefore, we investigated the association between serum MBL levels and the occurrence of severe infections during different periods after transplantation in a single center cross-sectional study of a unique cohort of very long-term survivors.…”

Section: Introductionmentioning

confidence: 99%

Mannose-binding lectin levels and major infections in a cohort of very long-term survivors after allogeneic stem cell transplantation

Osthoff¹,

Rovó²,

Stangel³

et al. 2010

Haematologica

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BackgroundLife-threatening infections are a major cause of death after allogeneic stem cell transplantation. Complement Mannose-binding lectin is a key component of innate immunity. Functional deficiency of mannose-binding lectin due to genetic polymorphism is frequent. Previous reports showed conflicting results with respect to the influence of functional mannose-binding lectin deficiency on infectious risk after allogeneic stem cell transplantation. The aim of this study was to clarify the impact of low mannose-binding lectin levels on infectious risk in a unique cohort of very long-term survivors after stem cell transplantation. Design and MethodsIncidence of major infections was evaluable in 43 out of 44 very long-term survivors (over ten years) and studied retrospectively in relation to mannose-binding lectin serum concentrations. ResultsRecipients with mannose-binding lectin levels below 1,000 ng/mL were at increased risk to suffer from one or more major infections (P=0.002) during entire follow up. Infectious susceptibility was increased after neutrophil recovery, particularly until 24 months (Hazard Ratio 3.4) with sustained effects afterwards (Hazard Ratio 2.9). Mannose-binding lectin serum concentrations below 1,000 ng/mL were independently associated with major infections after neutrophil recovery (P=0.009). In subgroup analyses occurrence of severe herpes virus infections in particular was associated with significantly lower mannose-binding lectin levels (P=0.02). ConclusionsOur findings indicate that low mannose-binding lectin levels may predict markedly increased susceptibility to severe infections with sustained effects even late after allogeneic stem cell transplantation. Determinations of mannose-binding lectin status should therefore be included into pre-transplantation risk assessment.Key words: stem cell transplantation, MBL levels, life-threatening infections. geneic stem cell transplantation. Haematologica 2010;95(8):1389-1396. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Osthoff M, Rovó A, Stern M, Danner D, Gratwohl A, Tichelli A,and Trendelenburg M. Mannose-binding lectin levels and major infections in a cohort of very long-term survivors after allo Mannose-binding lectin levels and major infections in a cohort of very long-term survivors after allogeneic stem cell transplantation

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Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation

Cited by 82 publications

References 53 publications

Late mortality after hematopoietic SCT for a childhood malignancy

Late mortality after hematopoietic SCT for a childhood malignancy

Invasive fungal infection in allogeneic hematopoietic stem cell transplant recipients: single center experiences of 12 years

Mannose-binding lectin levels and major infections in a cohort of very long-term survivors after allogeneic stem cell transplantation

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