Prospective evaluation of a combination of fungal biomarkers for the diagnosis of invasive fungal disease in high-risk haematology patients

AbstractPatients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at high risk of acquiring tuberculosis (TB) due to a status of immunosuppression. We conducted a nested case control study to investigate the incidence and risk factors for TB after allo-HSCT. Between 2012 and 2017, 730 consecutive allo-HSCT recipients were enrolled, and 14 patients (1.92%) were diagnosed with TB. Relatively, 54 allo-HSCT recipients were selected as control. Patients who suffered TB had a significantly higher 3-year non-relapse mortality rate than the control group (30.36% vs 5.39%, P < 0.01). In multivariate analysis, invasive fungal disease (HR 4.87, 95% CI 1.39–17.09), treatment with a relatively high dose of prednisone (HR 10.34, 95% CI 1.12–95.47) and treatment with tacrolimus (HR 4.79, 95% CI 1.18–19.44) were identified independent risk factors for TB occurrence post allo-HSCT (P < 0.05). Meanwhile, donor type, dose and type of anti-thymocyte globulin (ATG) administrated, as well as treatment intensity, did not alter the incidence of TB. Therefore, allo-HSCT recipients with unexplained fever, especially those who suffer from invasive fungal disease and ongoing immunosuppression with a relatively high dose of prednisone or tacrolimus, are at a high-risk of developing active TB. Closely Monitoring TB occurrence, making a timely diagnosis and administering the proper treatment may be beneficial to those high-risk patients.

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Clinical impact of enhanced diagnosis of invasive fungal disease in high-risk haematology and stem cell transplant patients

Journal of Clinical Pathology ◽

10.1136/jcp.2008.058354 ◽

2008 ◽

Vol 62 (1) ◽

pp. 64-69 ◽

Cited By ~ 77

Author(s):

R A Barnes ◽

P L White ◽

C Bygrave ◽

N Evans ◽

B Healy ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplant ◽

Invasive Fungal Disease ◽

Fungal Disease ◽

Clinical Impact ◽

Cell Transplant ◽

Transplant Patients

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Recipient And Donor PTX3 rs2305619 Polymorphisms Increase The Susceptibility To Invasive Fungal Disease Following Haploidentical Stem Cell Transplantation: A Prospective Study

10.21203/rs.3.rs-770441/v1 ◽

2021 ◽

Author(s):

Chen Zhao ◽

Xiao-Su Zhao ◽

Lan-Ping Xu ◽

Xiao-Hui Zhang ◽

Xiao-Jun Huang ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Scoring System ◽

Invasive Fungal Disease ◽

Fungal Disease ◽

Chinese Han ◽

Haploidentical Stem Cell Transplantation ◽

Increased Risk

Abstract Background Invasive fungal disease (IFD) is a severe complication after haploidentical stem cell transplantation (haplo-HSCT) and has a poor prognosis. It has been shown that genetic polymorphism may be one possible reason for the increased risk of IFD. This study aimed to assess the role of genetic polymorphisms in the level of susceptibility to IFD in after haplo-HSCT. Methods In this study, we prospectively enrolled 251 patients who received haplo-HSCT at the Peking University Institute of Hematology from to 2016-2018. Forty-three single nucleotide polymorphisms (SNPs) of the genomic DNA were genotyped in blood samples from both recipient and donor. Results Twenty-two patients (8.8%) were diagnosed with proven or probable IFD. The independent risk factors for IFD were grades 3-4 acute graft-versus-host disease, cytomegalovirus reactivation, and recipient and donor rs2305619 (PTX3) (P<0.05) in multivariate analysis. Meanwhile, we combined the variables to develop the IFD risk scoring system and stratified patients into low- (0), intermediate- (1-2), and high-risk (3-4) groups. The 30-day and 100-day cumulative incidence of IFD in the low-, intermediate-, and high-risk groups were 0.1%, 2.4%, 10.2% and 4.5%, 4.1%, 20.3%, respectively (P=0.015). Conclusions PTX3 rs2305619 polymorphisms increase the susceptibility of IFD after haplo-HSCT in the Chinese Han population, and the IFD scoring system could be considered as a new standard for risk stratification for IFD after HSCT.

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Somatic GATA2 mutations define a subgroup of myeloid malignancy patients at high risk for invasive fungal disease

Blood Advances ◽

10.1182/bloodadvances.2020002854 ◽

2020 ◽

Vol 5 (1) ◽

pp. 54-60

Author(s):

Rahul S. Vedula ◽

Matthew P. Cheng ◽

Christine E. Ronayne ◽

Dimitrios Farmakiotis ◽

Vincent T. Ho ◽

...

Keyword(s):

High Risk ◽

Gene Mutations ◽

Invasive Fungal Disease ◽

Fungal Disease ◽

Antifungal Prophylaxis ◽

Cell Transplant ◽

Myeloid Malignancy ◽

Somatic Gene ◽

Treatment Complication ◽

Gata2 Deficiency

Abstract Invasive fungal disease (IFD) can be a severe treatment complication in patients with myeloid malignancies, but current risk models do not incorporate disease-specific factors, such as somatic gene mutations. Germline GATA2 deficiency is associated with a susceptibility to IFD. To determine whether myeloid gene mutations were associated with IFD risk, we identified 2 complementary cohorts of patients with myeloid malignancy, based on (1) the diagnosis of invasive aspergillosis (IA), or (2) the presence of GATA2 mutations identified during standard clinical sequencing. We found somatic GATA2 mutations in 5 of 27 consecutive patients who had myeloid malignancy and developed IA. Among 51 consecutive patients with GATA2 mutations identified in the evaluation of myeloid malignancy, we found that IFD was diagnosed and treated in 21 (41%), all of whom had received chemotherapy or had undergone an allogeneic stem cell transplant. Pulmonary infections and disseminated candidiasis were most common. The 90-day mortality was 52% among patients with IFD. Our results indicate that patients with somatic GATA2 mutations are a vulnerable subgroup of patients with myeloid malignancy who have high risk for treatment-associated IFD and suggest that a focused approach to antifungal prophylaxis be considered.

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