1729. Profiling Human Neutrophil Functional Responses From Solid-Organ and Stem Cell Transplant Recipients to Candida albicans

Abstract Background Solid-organ (SOT) and stem cell transplant (SCT) recipients are at increased risk of invasive fungal disease despite normal neutrophil counts in peripheral blood. However, the neutrophils function against fungi has not been completely defined. In this study, we measure human neutrophil anti-candida activity in SOT and SCT recipients. Methods SOT and SCT patients were identified and consented from September 2018 until April 2019. Healthy control patients (HC) were identified at primary care clinics. EDTA-anticoagulated peripheral blood was obtained from healthy and transplant patients 2–4 months post-transplant. Neutrophils were isolated by negative selection. C. albicans was incubated for 2 hours with and without human neutrophils at multiplicity of infection (MOI) of 10, 5 and 1. Following neutrophil cell lysis, percent remaining live Candida was measured using a viability dye. In addition, growth inhibition of C. albicans by neutrophil swarming to C. albicans spotted onto glass slide arrays was also assessed by live cell imaging. Results 22 SOT (15 kidneys, 7 livers), 20 SCT (allograft) and 22 HC were enrolled. Neutrophils from SCT and SOT had lower C. albicans killing percentages compared with HC at MOI 10 (HC: 47%, SOT: 29%, SCT 24% P = 0.0041); MOI 5 (HC: 72%, SOT: 35%, SCT 38% P < 0.0001) and MOI 1 (HC: 91%, SOT: 48%, SCT: 45% P < 0.0001). Neutrophil swarming and fungal control of C. albicans spots was significantly inhibited by neutrophils from SCT when compared with SOT and controls (P <0.0001). Analysis of medications, including tyrosine kinase inhibitor (TKI) use, did not demonstrate significant differences of a specific drug class when patient groups are compared (SCT vs. SOT). Conclusion Our study indicates that despite normal circulating numbers, neutrophils from SOT and SCT recipients are dysfunctional and show profoundly impaired anti-Candida activity. There were no medications or laboratory values that predicted functional neutrophil outcome. These data strongly support the use of functional neutrophil profiling to risk stratify those individuals at higher risk for invasive fungal infections. Disclosures All authors: No reported disclosures.

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RhizomucorandScedosporiumInfection Post Hematopoietic Stem-Cell Transplant

Case Reports in Medicine ◽

10.1155/2011/830769 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Dânia Sofia Marques ◽

Carlos Pinho Vaz ◽

Rosa Branca ◽

Fernando Campilho ◽

Catarina Lamelas ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Unrelated Donor ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Increased Risk

Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due toRhizomucor sp.and rhinoencephalitis due toScedosporium apiospermum6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis), its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies).

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β-d-Glucan Testing Is Overused in Patients Without Solid Organ/Stem Cell Transplant or Hematologic Malignancies

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.007 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S74-S74

Author(s):

Theodore Markou ◽

Valeria Fabre ◽

Seema Mehta ◽

Shmuel Shoham ◽

Sara E Cosgrove

Keyword(s):

Stem Cell ◽

False Positive ◽

Stem Cell Transplant ◽

Fungal Infections ◽

Hematologic Malignancies ◽

Johns Hopkins Hospital ◽

Solid Organ ◽

Cell Transplant ◽

Standard Data ◽

Positive Results

Abstract Background The β-d-glucan (BDG) assay aids in diagnosis of some invasive fungal infections (IFI) in at-risk patients. Due to an increase in the number of BDG tests ordered at Johns Hopkins Hospital in patients not at high risk for IFI, we evaluated the appropriateness of testing and conducted a survey to understand providers’ knowledge about the test. Methods From December 2015 to July 2016, we identified inpatients >17 years with at least one BDG test. We did not evaluate patients with solid organ/stem cell transplant or hematologic malignancies as they generally have indications for BDG testing. Using a standard data collection form, one infectious disease (ID) physician reviewed all test for appropriateness; 20% of cases were reviewed by an additional ID physician. Students, housestaff and allied staff from departments of medicine and surgery were surveyed regarding their knowledge of BDG test characteristics including indications and causes of false-positive results. Results 355 patients with at least one BDG were included. 33% (n = 116) had a risk factor for IFI (e.g., AIDS, immunosuppressing medication, malignancy, total parenteral nutrition, and prolonged ICU stay) although only 13% (n = 48) of these had proved or possible IFI. 49% (n = 173) had no indication for testing. Of these, 4% (n = 8) had inappropriate antifungals started based on BDG results. Being at an intensive care unit or having cirrhosis was associated with inappropriate BDG use (P = 0.03). Most of the 47 clinicians surveyed recognized the utility of BDG in the diagnosis of candidiasis (63%) and Aspergillosis (78%) but only 49% recognized its utility in diagnosis of Pneumocystis. Fifty-two percent identified its lack of utility for diagnosis of Cryptococcus infection but only 44% recognized lack of utility for diagnosing Zygomycetes. The majority of those surveyed were unable to identify causes of false-positive results of the assay. Conclusion In patients without solid organ/stem cell transplant or hematologic malignancies, clinicians ordered the BDG assay in the absence of clinical risk or evidence of IFI in almost 50% of patients. Survey results suggest an incomplete understanding of organisms associated with positive BDG tests. Clinicians must be educated about the correct patient population in which a new test should be used. Disclosures All authors: No reported disclosures.

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The Number of Leukoreduced RBC and Platelet Transfusions Does Not Increase the Incidence of aGVHD in Allogeneic Peripheral Blood Stem Cell Transplant Recipients

Blood ◽

10.1182/blood.v128.22.1460.1460 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1460-1460

Author(s):

Robert A. DeSimone ◽

Ruchika Goel ◽

Ronit Reich-Slotky ◽

Adrienne Phillips ◽

Usama Gergis ◽

...

Keyword(s):

T Cells ◽

Stem Cell ◽

Peripheral Blood ◽

Blood Cells ◽

Stem Cell Transplant ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Cell Transplant ◽

Increased Risk ◽

Donor T Cells

Abstract INTRO: The pathophysiology of acute graft versus host disease(aGVHD) after stem cell transplant has been described as a three-phase process. The first involves damage to host tissue by inflammation. In the second, both recipient and donor antigen-presenting cells and inflammatory cytokines trigger activation of donor T cells which expand into effector T cells. In the third phase, activated donor T cells mediate cytotoxicity against host cells by multiple mechanisms. Known risk factors for aGVHD include: stem cell source, graft type, unrelated donor, HLA mismatched donor, older age of donor, multiparous female donor, older age of recipient, GVHD prophylaxis and certain conditioning regimens. The transfusion (Tx) of red blood cells (RBC) and platelets (PLT) expose the recipient to additional white blood cells and cytokines, even in leukoreduced products. Potentially, ABO-non identical (ABO-NI) RBC and PLT Tx could further increase the release of cytokines. This study investigated whether more Tx, or more ABO-NI RBC or PLT Tx, were associated with an increased risk of aGVHD. METHODS: All ABO-identical allogeneic peripheral blood stem cell transplants at our center since 2012 were included. Primary outcome was development of Grade I-IV aGVHD (skin, liver or gastrointestinal tract). Any patient who received more than 1 transplant or did not have aGVHD status documented in the transplant database was excluded. Adjustment was performed for recipient age and gender. The following parameters were evaluated for an association with aGVHD: combined number of RBC and PLT Tx, number of RBC Tx, number of PLT Tx, number of ABO-NI RBC Tx, and number of ABO-NI PLT Tx. Only Tx within 1 year after transplant and prior to development of aGVHD or relapse (if applicable) were included. Statistical analysis (logistic regression and chi-square) was performed using STATA 14.1. RESULTS: Eighty-four patients were included. Forty-one percent were MUD and 59% were MRD. Thirty-six patients developed aGVHD (43.4%). Twenty-seven percent of platelet Tx were ABO-NI (99.9% major ABO incompatible). ABO-NI (all minor ABO incompatible) accounted for 2.5% of RBC Tx. Patients who developed aGVHD received an average of 4 RBC (0 ABO-NI) and 6 PLT (3.7 ABO-NI) per patient. Patients who did not develop aGVHD received an average of 4.6 RBC (0.4 ABO-NI) and 5.6 PLT (2.7 ABO-NI) per patient. There was no association seen between the number of RBC+PLT (p=0.88), RBC (p=0.57), PLT (p=0.65) and development of aGVHD. Receiving any ABO-NI RBC or PLT did not put a patient at increased risk of aGHVD and total number of transfusions received (RBC p=0.19; PLT p=0.13). CONCLUSION: An increased number of RBC or PLT transfusions, or receiving ABO non-identical RBC or PLT transfusions, did not increase the risk of aGVHD after allogeneic peripheral blood stem cell transplant. Additional studies are needed to evaluate whether patients receiving ABO minor incompatible platelets have an increased risk of aGVHD. Disclosures Phillips: Kyowa Kirin: Research Funding; Celgene: Speakers Bureau; Takeda: Speakers Bureau.

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