scholarly journals 2596. Invasive Fungal Disease in Patients with GATA2 Variant Hematologic Malignancy

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S902-S902
Author(s):  
Tyler D Bold ◽  
Rahul S Vedula ◽  
Matthew P Cheng ◽  
Francisco M Marty ◽  
R Coleman Lindsley

Abstract Background Patients with hematologic malignancies (HM) are at risk of invasive fungal disease (IFD). Identification of those patients at the highest risk for IFD would help optimize prophylactic or preemptive treatment decisions in this population. We previously found that among patients with myeloid malignancies who develop invasive aspergillosis, 15% had a mutation in the gene GATA2. Here, we report the incidence of IFD in a cohort of patients with HM related to a pathogenic sequence variant of GATA2. Methods We identified 6343 patients cared for at Dana-Farber/Brigham and Women’s Cancer Center between January 2014 and August 2018 who underwent a next-generation sequencing assay of 95 genes recurrently mutated in hematologic malignancy. Those found to have a pathogenic GATA2 sequence variant were selected for retrospective chart review with respect to serious infectious complications including IFD. Results We identified 54 patients with a pathogenic GATA2 variant. 5 had a germline mutation related to familial GATA2 deficiency. The other 49 had a HM, mostly (41/49) acute myeloid leukemia or myelodysplastic syndrome. The frequency of the variant GATA2 allele in this group ranged from 2.5 to 92.0% of sequencing reads. 14 patients were excluded due to lack of sufficient follow-up, often related to treatment at another institution. Of the remaining 35 patients, 13 (37%) had proven/probable invasive fungal infection (IFI). Fourteen others had syndromes consistent with possible IFD. In total, 16 of these 35 patients (46%) received antifungal therapy for proven, probable or possible IFD. Four of the patients not treated with antifungals were diagnosed with a serious infection including 2 cases of Staphylococcus aureus bacteremia, and one case of disseminated Mycobacterium avium complex. Conclusion We identified a high incidence of IFD among patients with HM related to a pathogenic sequence variant of GATA2. The wide range of variant allele frequency observed raises the possibility that either inherited or acquired GATA2 dysfunction could incur predisposition to infection. These data suggest that personalized genetic diagnostics of patients with HM may be useful for assessment of infectious risk. Disclosures All authors: No reported disclosures.

2014 ◽  
Vol 6 (1) ◽  
pp. e2014068 ◽  
Author(s):  
Daniel Olson ◽  
Abraham Tareq Yacoub ◽  
Gelenis Domingo ◽  
John Norman Greene

AbstractBackgroundEscherichia coli (E. coli) is a pathogen of great concern in immunosuppressed patients.  While antimicrobial prophylactic therapy has become the standard, the emergence of resistant pathogens has some questioning its use.  This study describes our experience with E.coli as a pathogen in neutropenic patients with a hematologic malignancy, and addresses future directions of treatment for this patient population.MethodsA retrospective chart review of 245 E.coli bacteremia patients at Moffitt Cancer Center from 05/18/02 – 05/15/12 was conducted. Patients were identified via microbiology laboratory computerized records.ResultsThe included patients experienced clinically significant E.coli bacteremia resulting in a median hospital stay of 14.7 days.  Several patients developed severe sepsis requiring the use of pressor and ventilator therapy.ConclusionsE.coli is a major pathogen in these patient populations resulting in extended hospital stays and specialized treatment to overcome their E.coli bacteremia. The data supports the use of fluoroquinolone prophylactic therapy, however, earlier detection and treatment of neutropenic infection is needed.


2020 ◽  
Vol 16 (9) ◽  
pp. 571-578 ◽  
Author(s):  
Mary-Elizabeth M. Percival ◽  
Ryan C. Lynch ◽  
Anna B. Halpern ◽  
Mazyar Shadman ◽  
Ryan D. Cassaday ◽  
...  

In January 2020, the first documented patient in the United States infected with severe acute respiratory syndrome coronavirus 2 was diagnosed in Washington State. Since that time, community spread of coronavirus disease 2019 (COVID-19) in the state has changed the practice of oncologic care at our comprehensive cancer center in Seattle. At the Seattle Cancer Care Alliance, the primary oncology clinic for the University of Washington/Fred Hutchinson Cancer Consortium, our specialists who manage adult patients with hematologic malignancies have rapidly adjusted clinical practices to mitigate the potential risks of COVID-19 to our patients. We suggest that our general management decisions and modifications in Seattle are broadly applicable to patients with hematologic malignancies. Despite a rapidly changing environment that necessitates opinion-based care, we provide recommendations that are based on best available data from clinical trials and collective knowledge of disease states.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Attila Feher ◽  
Rekha Parameswaran ◽  
Eytan M Stein ◽  
Dipti Gupta

Objective: Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin therapy is not known in thrombocytopenic cancer patients who experience an acute myocardial infarction (AMI). Methods: Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as platelet count <50 cells k/μL within 7 days of AMI. Demographics, aspirin use, survival and bleeding outcomes were collected. T-tests and Fisher exact tests were used to compare continuous and categorical variables. Survival rates were calculated using the Kaplan-Meier product limit method; groups were compared with log-rank statistic. Results: 118 patients with hematologic malignancies had AMI. 58/118 (49%) had sTP. 25/58 (43%) of those with sTP received aspirin. Patients were mostly male (70%, n=83), mean age 69±11 years, mean follow up 3.6 years. Non-Hodgkin’s lymphoma was the most common hematologic diagnosis (36%, n=42). Survival was significantly worse in patients with sTP vs. no sTP (23% vs. 50% at 1 year, log rank p=0.008). When compared to no sTP with AMI, patients with sTP and AMI were less likely to receive aspirin (83% vs 43%, p=0.0001), thienopyridine (27% vs 3%, p=0.0005) and to undergo coronary angiography (30% vs. 5%, p=0.0005) and revascularization (17% vs. 3%, p=0.03). Cancer patients with sTP and AMI who received aspirin had improved survival when compared to those not treated with aspirin, (92% vs. 70% at 7 days, 72% vs. 33% at 30 days and 32% vs. 13% at 1 year, log rank p=0.008). No fatal bleeding events occurred. Thrombolysis in Myocardial Infarction (TIMI) major bleeding occurred in one patient without sTP. Conclusions: In hematologic malignancy patients with AMI and sTP the use of aspirin was associated with improved survival without increase in major bleeding.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2242-2242 ◽  
Author(s):  
Masakatsu Yonezumi ◽  
Mitsutoshi Kurosawa ◽  
Takashi Fukuhara

Abstract Abstract 2242 Poster Board II-219 Invasive aspergillosis (IA) is a common opportunistic infection in hematologic malignancy patients. The diagnosis of IA is difficult and the outcome is poor despite recent progress in treatment. The detection of galactomannan antigen is useful in diagnosis of IA and is defined as one of EORTC/MSG diagnostic criteria. The (1-3)-beta-D-glucan assay is also used in diagnosis of invasive fungal disease, but the sensitivity and specificity of these tests for IA are variable in recent reports. To evaluate the correlation of them, we analyzed retrospectively the results of these tests in IA cases of hematologic malignancy patients. From January 2006 to December 2008, we reviewed 2914 hematologic malignancy patients (AML=492, ALL=198, MDS=284, NHL=1373, HL=92, MM=375) retrospectively who were recieved chemotherapy or stem cell transplantation(SCT). 607 cases received SCT are included in this study. We diagnosed IA according to the EORTC/MSG criteria, and extracted the data of galactomannan antigen and (1-3)-beta-D-glucan assay examined at diagnosis of each case. 43 cases(1.5%) are diagnosed as invasive fungal disease (Aspergillus=24, Candida=9, Mucor=6, Trichosporon=2, Cryptococcus=1, Geotrichum=1). 23 IA cases are analyzed (proven: 3 cases, probable: 20 cases). All cases are positive for galactomannan antigen test(range, 0.5-5.0< ODI, cut-off value:0.5), but only 9 cases for (1-3)-beta-D-glucan assay (range, 24.5-313pg/ml, cut-off value:20). In the three cases of proven IA, only one case are positive for this assay. There is no difference in patient characteristic and prognosis between the positive and negative group. We conclude that the (1-3)-beta-D-glucan assay is not useful tool for diagnosis of invasive aspergillosis. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 661-661
Author(s):  
Sandeep S Voleti ◽  
Nandita Khera ◽  
Carolyn Mead-Harvey ◽  
Sikander Ailawadhi ◽  
Rafael Fonseca ◽  
...  

Abstract Background: Self-reported financial hardship (FH) amongst cancer patients is increasingly becoming a challenge for patients, caregivers, and healthcare providers. FH not only leads to financial struggles, significant lifestyle changes, and emotional distress, but also contributes to treatment noncompliance, affecting clinical outcomes. As treatment costs rise, it is crucial to develop efficient methods to proactively identify and alleviate FH in hematology practice. One potential approach is utilizing automated processes to identify those at highest risk of FH. At Mayo Clinic, screening for FH involves using a single financial strain question 'How hard is it for you to pay for the very basics like food, housing, medical care, and heating?' which all cancer patients answer annually as part of the institution's Social Determinants of Health (SDOH) assessment. Answers are on a five-point scale including not hard at all, not very hard, somewhat hard, hard, and very hard. In this study, we assess the prevalence and predictors for FH (denoted by a response of "Very hard" "Hard" or "Somewhat hard") amongst the Mayo Clinic hematologic malignancy patient population. Our study objective was to determine if this automated process could identify those at risk for FH. Methods: Patients who received care for hematologic malignancies (lymphoma, leukemia, plasma disorders, myelodysplastic/myeloproliferative disorders, and other heme malignancies) at any of the Mayo Clinic cancer centers (Minnesota, Arizona, and Florida) and who had completed the SDOH screen at least once were included in this study. The electronic medical record (EMR) and Mayo Clinic Cancer Registry were utilized to extract demographic and disease variables. Patient's home zip code was used to determine rural/urban residence, distance from cancer center, and the Area Deprivation Index (ADI), a measure of socioeconomic disadvantage based on home zip code (ranging from 1-100, with 100 representing the most disadvantaged). Multivariable logistic regression modeling was used to examine predictor variables for FH in this patient population. Results: The final cohort included 10,024 patients from 2018 to 2020. Median age was 64.6 years (IQR 58.1,73.7), 58% were male, and 79% married. Race/ethnicity composition was 94% White (n=9,268), 2.5% Black (n=246), 0.4% American Indian/Alaskan Native (44), and 4% Hispanic (n=360). Fifty-six percent of patients had Medicare and 41% had commercial insurance. Fifty percent were retired, 40% were working/students, and 72% were urban residents. Mean ADI was 41.2. Fifty-six percent of patients had lymphomas, 23.5% had plasma cell disorders, 8.5% had leukemias, 6.8% had other hematological malignancies, and 5.5% had myelodysplastic/myeloproliferative neoplasms. FH was reported by 12.8% (n=1286) of the patients. Table 1 shows the results of the multivariable model. A significantly higher likelihood of endorsing FH was noted in Hispanic vs non-Hispanics, Black and American Indian/Alaskan Native groups vs whites, Disabled/Unemployed vs working, Medicaid, Medicare, and Self-Pay groups vs commercial insurance, higher ADI (5 th quintile vs 1 st), and myelodysplastic/myeloproliferative disorder and other hematologic malignancy vs lymphoma patients. Older age, being retired, and living farther from the cancer center were associated with significantly less likelihood of endorsing FH. Conclusion: Our study used automated data extraction from the EMR to efficiently identify predictors of FH in hematologic cancer patients. Employing a dichotomized and automated "flag" for FH, particularly if incorporated in the EMR, could ease the identification of SDOH issues, facilitate timely connection to appropriate resources, and help provide better patient-centered care. Figure 1 Figure 1. Disclosures Ailawadhi: Sanofi: Consultancy; Cellectar: Research Funding; Karyopharm: Consultancy; Ascentage: Research Funding; Genentech: Consultancy; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Beigene: Consultancy; GSK: Consultancy, Research Funding; AbbVie: Consultancy; Medimmune: Research Funding; Pharmacyclics: Consultancy, Research Funding; Takeda: Consultancy; Amgen: Consultancy, Research Funding; Xencor: Research Funding. Fonseca: OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; BMS: Consultancy; Mayo Clinic in Arizona: Current Employment; Aduro: Consultancy; AbbVie: Consultancy; GSK: Consultancy; Merck: Consultancy; Juno: Consultancy; Scientific Advisory Board: Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Patent: Prognosticaton of myeloma via FISH: Patents & Royalties; Novartis: Consultancy; Bayer: Consultancy; Celgene: Consultancy; Caris Life Sciences: Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy. Griffin: Exact Sciences: Research Funding.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4628-4628
Author(s):  
Li Gao ◽  
Ren Lin ◽  
Min Dai ◽  
Jing Sun ◽  
Zhiping Fan ◽  
...  

Abstract Objective To explore the efficacy and safety of micafungin as salvage treatment for invasive fungal disease(IFD) in patients with hematologic malignancies. Methods A retrospective, observational, sequential cohort study was performed between Feb 2012 and June 2015 at southern medical university nanfang Hospital. We selected a group of 51 patients who either refractory or intolerant to first-line antifungal therapies, received micafungin as salvage therapy. Of the 51 patients, IFD was proven in 5 and probable in 46 patients. The predominant cause for treatment switch to micafungin was refractory therapy in 33 patients, followed by intolerance in 15 patients or both in 3 patients. For their first-line antifungal therapies of IFD, 34 patients received voriconazole, 7 patients received itraconazole, 2 patients received amphotericin B,1 patients received caspofungin,1 patients received posaconazole and 6 patients received voriconazole combined amphotericin B. The median duration of antifungal treatment before salvage therapy was 26 days (range, 4 to 57 days). The successful resolution rates、the median time of micafungin treatment, the drug related adverse events and overall survival were assessed. Results All of the patients were treated with 150 mg/d micafungin. The median time of micafungin treatment was 23 days (range,12-72 days). The success rate was 64.7%, including 16 achieved complete response, 17 achieved partial response and 18 patients had no overall response (failure in 9 patients, 2 patient with stable disease and 7 patients died). Only one patient experienced an adverse event. No patient discontinued micafungin therapy due to an adverse event. Conclusions This study demonstrated that micafungin was efficacy and safety as salvage treatment IFD in patients with hematologic malignancies. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nika Maani ◽  
Karen Panabaker ◽  
Jeanna M. McCuaig ◽  
Kathleen Buckley ◽  
Kara Semotiuk ◽  
...  

AbstractNext-generation sequencing (NGS) technologies have facilitated multi-gene panel (MGP) testing to detect germline DNA variants in hereditary cancer patients. This sensitive technique can uncover unexpected, non-germline incidental findings indicative of mosaicism, clonal hematopoiesis (CH), or hematologic malignancies. A retrospective chart review was conducted to identify cases of incidental findings from NGS-MGP testing. Inclusion criteria included: 1) multiple pathogenic variants in the same patient; 2) pathogenic variants at a low allele fraction; and/or 3) the presence of pathogenic variants not consistent with family history. Secondary tissue analysis, complete blood count (CBC) and medical record review were conducted to further delineate the etiology of the pathogenic variants. Of 6060 NGS-MGP tests, 24 cases fulfilling our inclusion criteria were identified. Pathogenic variants were detected in TP53, ATM, CHEK2, BRCA1 and APC. 18/24 (75.0%) patients were classified as CH, 3/24 (12.5%) as mosaic, 2/24 (8.3%) related to a hematologic malignancy, and 1/24 (4.2%) as true germline. We describe a case-specific workflow to identify and interpret the nature of incidental findings on NGS-MGP. This workflow will provide oncology and genetic clinics a practical guide for the management and counselling of patients with unexpected NGS-MGP findings.


2017 ◽  
Vol 23 (4) ◽  
pp. 278-283 ◽  
Author(s):  
Allison R Butts ◽  
Christina Carracedo Bachmeier ◽  
Emily V Dressler ◽  
Meng Liu ◽  
Ann Cowden ◽  
...  

Objective The objective of this study was to determine the clinical impact of time to antibiotic administration in adult inpatients who have hematologic malignancies and develop febrile neutropenia. Methods A retrospective chart review was conducted to screen for all febrile neutropenia events amongst adult hematologic malignancy patients between 1 January 2010 and 1 September 2014. All included patients were admitted to the hospital at the time of fever onset, having been admitted for a diagnosis other than febrile neutropenia. Descriptive statistics and logistic generalized estimated equations were used to analyze the data. Results Two hundred forty-four neutropenic fever events met inclusion criteria. Thirty-five events (14.34%) led to negative clinical outcomes (in-hospital mortality, intensive care unit transfer, or vasopressor requirement), with an in-house mortality rate of 7.4%. The time to antibiotics ranged from 10 min to 1495 min. The median time to antibiotics in the events that led to negative outcomes was 120 min compared to 102 min in the events that did not lead to the negative outcome ( p = 0.93). Conditional order sets were used to order empiric antibiotics in 176 events (72.1%) and significantly reduced time to antibiotics from 287 min to 143 min ( p = 0.0019). Conclusion Prolonged time to antibiotic administration in hematologic malignancy patients who develop neutropenic fever was not shown to be associated with negative clinical outcomes.


2008 ◽  
Vol 6 (2) ◽  
pp. 202-213 ◽  
Author(s):  
Sophia Koo ◽  
Lindsey R. Baden

Immunomodulating monoclonal antibodies are a relatively new addition to the armamentarium of cancer therapeutics and have been shown to improve clinical outcomes in patients with various hematologic malignancies. Because of their targeted nature, these agents are often believed to be less immunosuppressive than standard cytotoxic chemotherapeutic agents. A clear causal association between an immunomodulating therapy and its infectious sequelae is often difficult to discern because of the burden of comorbid illness, intrinsic immunosuppression from the underlying malignancy, use in the salvage setting, and prior and concomitant use of immunosuppressive agents in this patient population. This article evaluates better-established and anecdotal infectious complications associated with major immunomodulating therapies used in hematologic malignancy and hematopoietic stem cell transplantation, including rituximab, alemtuzumab, gemtuzumab ozogamicin, infliximab, dacluzimab, and basiliximab.


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