scholarly journals Risks and Benefits of Bronchoscopy during the First 100 Days Following Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4500-4500
Author(s):  
Mehrdad Hefazi ◽  
Reona Sakemura ◽  
Saad S. Kenderian ◽  
Mrinal M Patnaik ◽  
William J Hogan ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Lung Biopsy ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Viral Infections ◽  
Diagnostic Yield ◽  
Early Period ◽  
Organizing Pneumonia ◽  
Late Period ◽  
Procedural Complications

BACKGROUND Pulmonary infiltrates are common after allogeneic hematopoietic cell transplantation (HCT) and can have infectious or non-infectious etiologies. Fiberoptic Bronchoscopy (FOB) with bronchoalveolar lavage (BAL) is frequently used to evaluate these patients. However, the diagnostic yield can be highly variable according to patient populations, and the impact on management is not well defined, especially in the era of modern antimicrobial therapies. The aim of this study was to investigate the diagnostic and therapeutic yield of FOB-BAL in adult patients with pulmonary infiltrates during the first 100 days following HCT. METHODS We retrospectively reviewed the medical records of adult HCT patients who underwent FOB-BAL during the first 100 days post HCT between January 2005 and December 2015 at Mayo Clinic, Rochester, MN. The interval from HCT to FOB was stratified into early (days 1-30) vs. late (days 31-100). The finding of progressively more hemorrhagic effluent and/or ≥ 20% hemosiderin-laden macrophages in BAL were considered diagnostic for diffuse alveolar hemorrhage (DAH). Univariate and multivariate logistic regression models were fit to identify clinical and transplant characteristics that may impact the diagnostic yield of FOB-BAL. RESULTS A total of 114 patients (median age 55 years), representing 12% of all HCT patients underwent FOB-BAL. Underlying diagnoses were AML in 36%, MDS in 16%, ALL in 16%, MPN in 12% , CLL in 7%, and other in 13%. Transplants were from matched related donor in 43%, matched unrelated donor in 40%, and other donor/matching status in 17%. FOB-BAL was performed during the early period in 61% and during the late period in 39% of patients. In the early period, FOB-BAL provided a specific diagnosis in 49% of patients (30% DAH and 19% infection). In the late period, FOB-BAL had a diagnostic yield of 55% (14% DAH and 36% infection) (Figure 1). The distribution of bacterial and viral infections identified via BAL were similar during the early period (39% and 38%, respectively), whereas more bacterial than viral infections were identified in the later period (56% vs. 19%, respectively) (Figure 2). Non-invasive testing for respiratory tract infection was performed in 34% of patients. These included nasopharyngeal swab for RSV/Influenza PCR in 16% (all negative), multiplex respiratory pathogen PCR in 5% (1 positive for coronavirus), and sputum culture in 21% (positive in 8 patients). This compares with the identification of an infectious pathogen via BAL in 36% of patients; bacterial in 16%, viral in 11%, and fungal in 10%. Transbronchoscopic lung biopsy biopsies were performed in 8 patients and provided diagnostic information in 3 patients (eosinophilic pneumonia, organizing pneumonia and diffuse alveolar damage each in 1 patient). Procedural complications occurred in 3 patients; 2 after transbronchoscopic lung biopsy (1 bleeding and 1 pneumothorax) and 1 during FOB-BAL (atrial fibrillation with rapid ventricular rate). In a multivariable logistic regression model, the underlying diagnosis, presence of acute respiratory failure, and early vs. later time period after HCT were independently affecting the diagnostic yield of FOB-BAL, with higher likelihood of DAH being diagnosed in patients with AML/MDS and during the early post-HCT period, and higher likelihood of DAH being diagnosed in patients with acute respiratory failure (Table 1). In 40% of patients, FOB-BAL findings lead to treatment changes. These included addition of antimicrobials in 24% and addition of corticosteroids in 22% (17% DAH, 2% idiopathic pneumonia syndrome, and 1% organizing pneumonia) (Figure 3). FOB findings lead to more antimicrobial modifications in the early than in the later period (32% vs. 18%, respectively). Overall survival was poor in all the three groups, although significantly better in patients with non-diagnostic FOB findings (median of 2, 3, and 11 months in patients with DAH, infection, or non-diagnostic FOB finings, respectively) (p = 0.03) (Figure 4). CONCLUSION FOB-BAL provides clinically useful information in the post-transplant period. BAL findings were diagnostic in 51% of patients, and led to management changes in 40% of patients. Transbronchoscopic lung biopsy is associated with higher rates of procedural complications. Further characterization of the underlying diagnosis in patients with non-diagnostic FOB-BAL findings remains an unmet clinical goal. Disclosures Sakemura: Humanigen: Patents & Royalties. Kenderian:Morphosys: Research Funding; Kite/Gilead: Research Funding; Lentigen: Research Funding; Humanigen: Other: Scientific advisory board , Patents & Royalties, Research Funding; Tolero: Research Funding; Novartis: Patents & Royalties, Research Funding. Patnaik:Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees.

scholarly journals 578. Infections in Patients Treated with Chimeric Antigen Receptor T-cells (CAR-T) therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S354-S354
Author(s):  
Nikki Tran ◽  
Gregory Eschenauer ◽  
Gianni Scappaticci ◽  
David Frame ◽  
Marisa H Miceli ◽  
...  
Keyword(s):  
T Cells ◽  
Chimeric Antigen Receptor ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Antigen Receptor ◽  
Early Period ◽  
Respiratory Viruses ◽  
Infectious Complications ◽  
Late Period ◽  
Car T

Abstract Background Although chimeric antigen receptor T cells (CAR-T) is a promising novel therapy for the treatment of relapsed or refractory (R/R) B-cell malignancies, data on infectious complications associated with this therapy are limited. Therefore, further assessment of infections after CAR-T therapy is warranted. Methods We retrospectively reviewed and analyzed infectious complications for 6 months following CAR-T therapy infusion (CTI) in 39 adult and pediatric patients with R/R acute lymphoblastic leukemia (ALL) and Non-Hodgkin Lymphoma (NHL) at Michigan Medicine. Results Overall, 20 infections were identified in 16 of 39 patients (41%) following CTI [detailed in Table 1]; 8 (40%) infections occurred in the early period (Day 0–30) and 12 (60%) infections occurred during late period (Day 31–180). The most common infections were viral (n=10, 50%; 80% of viral infections were respiratory viruses), followed by 8 bacterial infections (40%), and 2 fungal infections (10%). More bacterial infections were seen in the early period post-CTI (30% vs. 10%, p = 0.019), whereas viral infections were more common during the late period (40% vs. 10%, p = 0.68). Antimicrobial prophylaxis prior to CTI and following CTI were similar (Table 2). The majority of patients included in the study had NHL (n=32, 82%). Mean age of the cohort was 52 ± 22 years, and 64% were male. 85% of the population developed cytokine release syndrome (CRS) with 67% grade 1–2 and 18% grade 3–5. As shown in Table 2, most baseline characteristics were similar between patients with and without infections post CTI except infected patients were older (63.3 ± 11.3 vs. 44.8 ± 24.2, p = 0.01) and more received steroids for CRS (56% vs 17%, p = 0.02). All-cause mortality within 6 months following CTI was similar in infected and uninfected groups (38% vs 26%, p= 0.50). Table 1 Table 2 Conclusion Infectious complications are common following CAR-T therapy. We found the majority of infections to be caused by various bacteria or respiratory viruses in a cohort of patients with lymphoma as the most common underlying malignancy. Disclosures Marisa H. Miceli, MD, FIDSA, SCYNEXIS, Inc. (Advisor or Review Panel member)

scholarly journals Improved diagnostic yield of transbronchial lung biopsy in peripheral pulmonary lesions using a combination of endobronchial ultrasound and rapid on-site evaluation

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199953
Author(s):  
Chunhua Xu ◽  
Yan Wang ◽  
Wei Wang ◽  
Qi Yuan ◽  
Hui di Hu ◽  
...  
Keyword(s):  
Lung Biopsy ◽  
Diagnostic Yield ◽  
Transbronchial Lung Biopsy ◽  
Endobronchial Ultrasound ◽  
Procedure Time ◽  
Cytologic Diagnosis ◽  
Pulmonary Lesions ◽  
Procedural Complications ◽  
Site Evaluation ◽  
Peripheral Pulmonary Lesions

Objectives To evaluate the value of rapid on-site evaluation (ROSE) during radial probe endobronchial ultrasound transbronchial lung biopsy (rpEBUS-TBLB) for peripheral pulmonary lesions (PPLs). Methods One hundred and six patients with PPLs who received rpEBUS-TBLB were enrolled in this study. One specimen was immediately examined by ROSE and the other was sent to the central laboratory for cytologic diagnosis. The results of ROSE were compared with those of pathological diagnosis. Results The diagnostic accuracy, sensitivity, and specificity of ROSE during rpEBUS-TBLB for PPLs were 82.1%, 89.6%, and 77.1%, respectively. The procedure times and number of biopsies were less for procedures when ROSE was positive compared with those when ROSE was negative (procedure time: 20.5 ± 7.9 vs. 28.3 ± 7.6 minutes; number of biopsies: 1.6 ± 0.9 vs. 2.8 ± 0.6 times). No serious procedural complications were observed. Conclusions ROSE has value for diagnosing PPLs during rpEBUS. It can reduce procedure time, number of biopsies, and complications. ROSE combined with rpEBUS is an effective and safe method for the diagnosis of PPLs.

scholarly journals 630. A 5-mRNA host response whole-blood classifier trained using patients with non-COVID-19 viral infections accurately predicts severity of COVID-19

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S375-S376
Author(s):  
ljubomir Buturovic ◽  
Purvesh Khatri ◽  
Benjamin Tang ◽  
Kevin Lai ◽  
Win Sen Kuan ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Respiratory Failure ◽  
Viral Infections ◽  
Lamp Assay ◽  
Training Data ◽  
Diagnostic Tools ◽  
Severe Respiratory Failure ◽  
Proof Of Concept ◽  
Risk Of Death ◽  
Qpcr Platform

Abstract Background While major progress has been made to establish diagnostic tools for the diagnosis of SARS-CoV-2 infection, determining the severity of COVID-19 remains an unmet medical need. With limited hospital resources, gauging severity would allow for some patients to safely recover in home quarantine while ensuring sicker patients get needed care. We discovered a 5 host mRNA-based classifier for the severity of influenza and other acute viral infections and validated the classifier in COVID-19 patients from Greece. Methods We used training data (N=705) from 21 retrospective clinical studies of influenza and other viral illnesses. Five host mRNAs from a preselected panel were applied to train a logistic regression classifier for predicting 30-day mortality in influenza and other viral illnesses. We then applied this classifier, with fixed weights, to an independent cohort of subjects with confirmed COVID-19 from Athens, Greece (N=71) using NanoString nCounter. Finally, we developed a proof-of-concept rapid, isothermal qRT-LAMP assay for the 5-mRNA host signature using the QuantStudio 6 qPCR platform. Results In 71 patients with COVID-19, the 5 mRNA classifier had an AUROC of 0.88 (95% CI 0.80-0.97) for identifying patients with severe respiratory failure and/or 30-day mortality (Figure 1). Applying a preset cutoff based on training data, the 5-mRNA classifier had 100% sensitivity and 46% specificity for identifying mortality, and 88% sensitivity and 68% specificity for identifying severe respiratory failure. Finally, our proof-of-concept qRT-LAMP assay showed high correlation with the reference NanoString 5-mRNA classifier (r=0.95). Figure 1. Validation of the 5-mRNA classifier in the COVID-19 cohort. (A) Expression of the 5 genes used in the logistic regression model in patients with (red) and without (blue) mortality. (B) The 5-mRNA classifier accurately distinguishes non-severe and severe patients with COVID-19 as well as those at risk of death. Conclusion Our 5-mRNA classifier demonstrated very high accuracy for the prediction of COVID-19 severity and could assist in the rapid, point-of-impact assessment of patients with confirmed COVID-19 to determine level of care thereby improving patient management and healthcare burden. Disclosures ljubomir Buturovic, PhD, Inflammatix Inc. (Employee, Shareholder) Purvesh Khatri, PhD, Inflammatix Inc. (Shareholder) Oliver Liesenfeld, MD, Inflammatix Inc. (Employee, Shareholder) James Wacker, n/a, Inflammatix Inc. (Employee, Shareholder) Uros Midic, PhD, Inflammatix Inc. (Employee, Shareholder) Roland Luethy, PhD, Inflammatix Inc. (Employee, Shareholder) David C. Rawling, PhD, Inflammatix Inc. (Employee, Shareholder) Timothy Sweeney, MD, Inflammatix, Inc. (Employee)

scholarly journals Patient-level and hospital-level variation and related time trends in COVID-19 case fatality rates during the first pandemic wave in England: multilevel modelling analysis of routine data

2021 ◽  
pp. bmjqs-2021-012990
Author(s):  
Alex Bottle ◽  
Puji Faitna ◽  
Paul P Aylin
Keyword(s):  
Early Period ◽  
Total Mortality ◽  
Case Fatality ◽  
Routine Data ◽  
Multilevel Modelling ◽  
Primary Diagnosis ◽  
Hospital Death ◽  
Late Period ◽  
Hospital Level ◽  
Patient Level

BackgroundA report suggesting large between-hospital variations in mortality after admission for COVID-19 in England attracted much media attention but used crude rates. We aimed to quantify these variations between hospitals and over time during England’s first wave (March to July 2020) and assess available patient-level and hospital-level predictors to explain those variations.MethodsWe used administrative data for England, augmented by hospital-level information. Admissions were extracted with COVID-19 codes. In-hospital death was the primary outcome. Risk-adjusted mortality ratios (standardised mortality ratios) and interhospital variation were calculated using multilevel logistic regression. Early-wave (March to April) and late-wave (May to July) periods were compared.Results74 781 admissions had a primary diagnosis of COVID-19, with 21 984 in-hospital deaths (29.4%); the 30-day total mortality rate was 28.8%. The crude in-hospital death rate fell in all ages and overall from 32.9% in March to 13.4% in July. Patient-level predictors included age, male gender, non-white ethnic group (early period only) and several comorbidities (obesity early period only). The only significant hospital-level predictor was daily COVID-19 admissions in the late period; we did not find a relation with staff absences for COVID-19, mechanical ventilation bed occupancies, total bed occupancies or bed occupancies for COVID-19 admissions in either period. Just 4 (3%) and 2 (2%) hospitals were high, and 5 (4%) and 0 hospitals were low funnel plot mortality outliers at 3 SD for early and late periods, respectively, after risk adjustment. We found no strong correlation between early and late hospital-level mortality (r=0.17, p=0.06).ConclusionsThere was modest variation in mortality following admission for COVID-19 between English hospitals after adjustment for risk and random variation, in marked contrast to early media reports. Early-period mortality did not predict late-period mortality.

Genesis of the Wuxing Pt–Pd-rich Cu–Ni sulfide deposit in the eastern Central Asian Orogenic Belt: evidences from geochronology, elemental geochemistry, and Sr–Nd–Hf isotopic data

2019 ◽  
Vol 56 (4) ◽  
pp. 380-398 ◽  
Author(s):  
Jing-gui Sun ◽  
Yun-peng He ◽  
Ji-long Han ◽  
Zhong-yu Wang
Keyword(s):  
Crustal Contamination ◽  
Early Period ◽  
Orogenic Belt ◽  
Central Asian Orogenic Belt ◽  
Geochemical Data ◽  
Sulfide Deposit ◽  
Late Period ◽  
Enriched Mantle ◽  
Central Asian ◽  
T Values

The Wuxing Pt–Pd-rich Cu–Ni sulfide deposit in Heilongjiang Province, Northeast China, is located to the northeast of the Dunhua–Mishan fracture of the eastern Central Asian Orogenic Belt. The mafic–ultramafic complex consist of early-period hornblende–olivine pyroxenite, diopsidite, and hornblende pyroxenite and late-period gabbro and diabase units. An early-period hornblende pyroxenite yielded a zircon U–Pb age of 208.2 ± 2.6 Ma and a late-period diabase yielded a U–Pb age of 205.6 ± 1.1 Ma, with zircon εHf(t) values of +1.24 to +8.13. The early- and late-period lithofacies are relatively enriched in LILE (Rb, Ba, and Sr) and LREE, and variably depleted in HFSE (Nb, Ta). The whole-rock and single-mineral analyses of the early-period lithofacies yield (87Sr/86Sr)i ratios of 0.7055–0.7083 and εNd(t) ratios of −7.98–+3.10. These geochemical data suggest that the parental magmas of the Wuxing complex are high-Mg subalkaline basaltic in nature and were derived from an enriched mantle source. The magmas chamber formed after the injection of magma into the crust along with crustal contamination, producing early crystalline minerals and ore-bearing magmas. The rupturing of the magma chamber released evolved magmas, which then ascended and generated Pt–Pd-bearing lithofacies and Cu–Ni sulfide orebodies by fractional crystallization, accumulation, and liquation. During the late period, the residual magma invaded the early lithofacies and Cu–Ni orebodies. The fluids exsolved from the gabbroic magmas concentrated the mineralized metal elements and enhanced the precipitation of Pt–Pd-bearing veinlet-disseminated orebodies and Pt–Pd–Cu–Ni orebodies.

scholarly journals Utilization Pattern of Traditional Chinese Medicine among Fracture Patients: A Taiwan Hospital-Based Cross-Sectional Study

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Chu-Yao Tseng ◽  
Ching-Wen Huang ◽  
Hsin-Chia Huang ◽  
Wei-Chen Tseng
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Early Period ◽  
Clinic Visit ◽  
Research Database ◽  
Late Period ◽  
Utilization Pattern ◽  
Cross Sectional ◽  
Herbal Products ◽  
Tcm Theory

Traditional Chinese medicine (TCM) divides fracture treatment into three stages. Many TCM herbs and formulas have been used to treat fractures for thousands of years. However, research regarding the Chinese herbal products (CHPs) that should be used at different periods of treatment is still lacking. This study aims to identify the CHPs that should be used at different periods of treatment as well as confirm the TCM theory of fracture periods medicine. We used prescriptions of TCM outpatients with fracture diagnoses analyzed using the Chang Gung Research Database (CGRD) from 2000 to 2015. According to the number of days between the date of the fracture and the clinic visit date, all patients were assigned to one of three groups. Patients with a date gap of 0-13 days were assigned to the early period group; those with a date gap of 14-82 days were assigned to the middle period group; and those with a date gap of 83-182 days were assigned to the late period group. We observed the average number of herbal formulas prescribed by the TCM doctor at each visit was 2.78, and the average number of single herbs prescribed was 6.47. The top three prescriptions in the early fracture period were Zheng-gu-zi-jin-dang, Shu-jing-huo-xue-tang, and Wu-ling-san. In the middle fracture period, the top three formulas were Zheng-gu-zi-jin-dang, Shu-jing-huo-xue-tang, and Zhi-bai-di-huang-wan. In the late fracture period, the top three formulas were Shu-jing-huo-xue-tang, Gui-lu-er-xian-jiao, and Du-huo-ji-sheng-tang. The main single herbs used in the early fracture period were Yan-hu-suo, Gu-sui-bu, and Dan-shen. From the middle to the late period, the most prescribed single herbs were Xu-duan, Gu-sui-bu, and Yan-hu-suo. We concluded that the results showed that the CGRD utilization pattern roughly meets the TCM theory at different fracture periods.

scholarly journals Cryptogenic organizing pneumonia: Case report

2009 ◽  
Vol 137 (11-12) ◽  
pp. 681-683
Author(s):  
Natasa Miladinovic-Djukanovic ◽  
Jelena Djokovic ◽  
Nikola Torbica ◽  
Martin Popevic
Keyword(s):  
Lung Biopsy ◽  
Disease Onset ◽  
Work Capacity ◽  
Open Lung Biopsy ◽  
Organizing Pneumonia ◽  
Cryptogenic Organizing Pneumonia ◽  
Methyl Prednisolone ◽  
Histological Criteria ◽  
Erroneous Diagnosis

Introduction. Cryptogenic organizing pneumonia is a particular form of inflammatory and fibroproliferative lung disease. The disease onset is subacute with cough, dyspnoea, fever, weight loss, and elevation of biological inflammatory markers. Chest imaging usually shows multifocal alveolar opacities predominating in the subpleural regions. Lung biopsy reveals budding connective tissue filling the distal airspaces. Case outline. A 57-year-old electrician complaining of cough, dyspnoea, and fatigue was diagnosed with pneumonia and treated with antibiotics and antihistaminics. After clinical and radiographic progression of the disease, open lung biopsy was performed, some 15 months after the disease onset. The diagnosis of cryptogenic organising pneumonia was made. The patient was treated with oral and inhalatory corticosteroids and finally with cytostatics, which led to a partial improvement of his condition. However, work capacity was lost and the quality of life seriously deteriorated. Conclusion. The diagnosis is established by combining clinical, radiological and histological criteria. Similarities with other disease processes can lead to a delayed or erroneous diagnosis. Most patients respond well to corticosteroid therapy (prednisone or methyl-prednisolone). Relapses are frequent but can generally be controlled.

scholarly journals Long-Term Experience with Large Granular Lymphocytic Leukemia Evolving after Solid Organ and Hematopoietic Stem Cell Transplantation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1226-1226
Author(s):  
Hassan Awada ◽  
Reda Z. Mahfouz ◽  
Jibran Durrani ◽  
Ashwin Kishtagari ◽  
Deepa Jagadeesh ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Viral Infections ◽  
De Novo ◽  
Post Transplantation ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Stat3 Mutations

T-cell large granular lymphocyte leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes (CTL). T-LGLL mainly manifest in elderly and is associated with autoimmune diseases including rheumatoid arthritis (RA), B cell dyscrasias, non-hematologic cancers and immunodeficiency (e.g., hypogammaglobulinemia). LGL manifestations often resemble reactive immune processes leading to the dilemmas that LGLs act like CTL expansion during viral infections (for example EBV associated infectious mononucleosis). While studying a cohort of 246 adult patients with T-LGLL seen at Cleveland Clinic over the past 10 years, we encountered 15 cases of overt T-LGLL following transplantation of solid organs (SOT; n=8) and hematopoietic stem cell transplantation (HSCT; n=7). Although early studies reported on the occurrence of LGL post-transplant, these studies focused on the analysis of oligoclonality skewed reactive CTL responses rather than frank T-LGLL. We aimed to characterize post-transplantation T-LGLL in SOT and HSCT simultaneously and compare them to a control group of 231 de novo T-LGLL (cases with no history of SOT or HSCT). To characterize an unambiguous "WHO-defined T-LGLL" we applied stringent and uniform criteria. All cases were diagnosed if 3 out of 4 criteria were fulfilled, including: 1) LGL count >500/µL in blood for more than 6 months; 2) abnormal CTLs expressing CD3, CD8 and CD57 by flow cytometry; 3) preferential usage of a TCR Vβ family by flow cytometry; 4) TCR gene rearrangement by PCR. In addition, targeted deep sequencing for STAT3 mutations was performed and charts of bone marrow biopsies were reviewed to exclude other possible conditions. Diagnosis was made 0.2-27 yrs post-transplantation (median: 4 yrs). At the time of T-LGLL diagnosis, relative lymphocytosis (15-91%), T lymphocytosis (49-99%) and elevated absolute LGL counts (>500 /µL; 93%) were also seen. Post-transplantation T-LGLL were significantly younger than de novo T-LGLL, (median age: 48 vs. 61 yr; P<.0001). Sixty% of post-transplantation T-LGLL patients were males. Fifteen% of patients had more cytogenetic abnormalities compared to de novo T-LGLL, had a lower absolute LGL count (median: 4.5 vs. 8.5 k/µL) and had less frequent neutropenia, thrombocytopenia and anemia (27 vs. 43%, 33 vs. 35% and 20% vs. 55%; P=.01). TCR Vb analysis identified clonal expansion of ≥1 of the Vb proteins in 60% (n=9) of the patients; the remaining 40% (n=6) of the cases had either a clonal process involving a Vb protein not tested in the panel (20%; n=3) or no clear expansion (20%; n=3). Signs of rejection were observed in 20% (n=3/15) and GvHD in 13% (n=2/15) of the patients. Post-transplantation, 27% of cases presented with neutropenia (absolute neutrophil count <1.5 x109/L; n=4), 33% with thrombocytopenia (platelet count <150 x109/L; n=5) and 25% with anemia (hemoglobin <10 g/dL; n=3). T-LGLL evolved in 10 patients (67%; 10/15) despite IST including cyclosporine (n=5), tacrolimus (n=4), mycophenolate mofetil (n=5), cyclophosphamide (n=1), anti-thymocyte globulin (n=1), and corticosteroids (n=6). Lymphadenopathy and splenomegaly were seen in 13% (n=2) and 33% (n=5) of the patients. Other conditions observed were MGUS (20%; n=3) and RA (7%; n=1). Conventional cytogenetic showed normal karyotype in 89% (n=11, tested individuals 13/15). Somatic STAT3 mutations were identified in 2 patients. Sixty% of cases (n=9) were seropositive for EBV when tested at different time points after transplant. Similarly, 53% (n=8) were seropositive for CMV, of which, 5 were positive post-transplantation and 3 pre-/post-transplantation. The complexity of T-LGLL expansion post-transplantation might be due to several mechanisms including active viral infections, latent oncogenic viral reactivation and graft allo-antigenic stimulation. However, in our cohort graft rejection or GvHD was encountered in a few patients (2 allo-HSCT recipients). Autoimmune conditions were present in 50% of SOT recipients (n=4/ 8, including RA, ulcerative colitis, systemic lupus erythematosus). Some of our patients also had low immunoglobulin levels. Overt EBV (post-transplant lymphoproliferative disorder) and CMV reactivation was diagnosed in only 27% (4/15) of the patients. In sum we report the long term follow up of a cohort of T-LGLL and emphasize the expansion of T-LGLL post-transplant highlighting the difficulty in assigning one unique origin of LGLL. Disclosures Hill: Genentech: Consultancy, Research Funding; Takeda: Research Funding; Celegene: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Honoraria; Amgen: Research Funding; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Research Funding; AstraZeneca: Consultancy, Honoraria. Majhail:Atara Bio: Consultancy; Mallinckrodt: Honoraria; Nkarta: Consultancy; Anthem, Inc.: Consultancy; Incyte: Consultancy. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Maciejewski:Alexion: Consultancy; Novartis: Consultancy.

scholarly journals Targeted Treatment and Survival Following Relapse after Allogeneic Hematopoietic Cell Transplantation for Acute Leukemia and MDS in the Contemporary Era

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4567-4567
Author(s):  
Sanghee Hong ◽  
Lisa Rybicki ◽  
Donna Corrigan ◽  
Betty K. Hamilton ◽  
Ronald Sobecks ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Treatment Strategies ◽  
Targeted Agents ◽  
Advisory Committees ◽  
Survival After Relapse ◽  
Grade Ii

Introduction: Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). While transplant-related mortality has decreased substantially over the last few decades, little progress has been made in outcomes and no standard of care exists for patients (pts) with post-alloHCT relapse. In the recent era, several new therapies, including targeted agents, have been approved for ALL, AML, and MDS. We conducted a study to evaluate outcomes of pts with these diseases who relapse after alloHCT in the contemporary period with routine availability of these newer therapeutic agents. Methods: We performed a single-institution retrospective cohort study to review treatment strategies and outcomes of relapse post-alloHCT. We identified 420 adult pts who received their first alloHCT in 2010-2018 using any conditioning regimen or donor source. Overall, 115 (27%) pts experienced relapse (ALL=17/64 [27%], AML=67/242 [28%], MDS=31/114 [27%]) and were included in the analysis. Results: Myeloablative (54%) matched-unrelated donor grafts (50%) were the most common types of HCTs. Peripheral blood stem cell graft (49%) and bone marrow graft (48%) were used the most. Median time from alloHCT to relapse was 5 (range 1-65) months, and 83% of relapses occurred within the first year. Only 24% and 11% of pts experienced grade II-IV acute and any chronic GVHD prior to relapse, respectively. Seven of 17 pts had Philadelphia chromosome positive ALL. Mutation panel was tested in 56% of AML and MDS. Median follow-up period after relapse was 19 (range 6-80) months. The estimated survival after relapse for all diseases was 32% (95% CI 24-41%) at 6 months, 21% (14-28%) at 12 months, and 14% (8-21%) at 24 months (Fig 1). Excluding pts treated with supportive care only, the majority received a combination of different treatments; pts with ALL received median 3 (range 1-5), pts with AML received median 2 (1-4), and pts with MDS received median 1 (1-3) agent. Targeted therapies used for ALL pts included blinatumomab (n=5) and BCR-ABL targeting tyrosine kinase inhibitors with (n=2) or without (n=4) chemotherapy. Among AML pts, targeted agents were used in 15 pts (sorafenib [n=7], 2 each with enasidenib, gemtuzumab ozagamicin, and ivosidenib, and 1 each with venetoclax and SEL24 [a dual pan-PIM/FLT3 inhibitor]). One pt each was treated with enasidenib, gemtuzumab ozagamicin, and PTC299 (an inhibitor of VEGFA mRNA translation) followed by SEL24 for MDS. Second alloHCTs (n=5) were performed median 5 (range 1-16) months after first HCT and median 1 month (range 0-5 months) after relapse. Two pts received no bridging therapy, while 3 pts received chemotherapy (n=2) or donor lymphocyte infusions (DLI [n=1]) prior to the second transplant. DLI without second transplant was used in 25 pts at a median of 20 (range 3-18) months after ALL relapse, median 2 (range 0-13) months after AML relapse, and median 3 (range 1-5) months after MDS relapse. Following DLI, 53% pts developed GVHD. Targeted therapy was associated with a trend towards better survival compared to other therapies (Fig 2, HR 0.65, 95% CI 0.41-1.03, p=0.06). Based on multivariable analysis, matched unrelated (vs. matched sibling, HR 1.70, p=0.027) or haploidentical donor grafts (HR 2.69, p=0.003), presence of grade II-IV acute GVHD before relapse (HR 2.46, p<0.001), and less than 12 months from HCT to relapse (<6 vs. >12 months, HR 6.34, p<0.001; 6-12 vs. >12 months, HR 3.16, p=0.005) were adverse prognostic features with survival after relapse post-alloHCT (Table 1). Conclusion: Outcomes of pts with ALL, AML, and MDS who relapse following alloHCT remain poor in the contemporary era when several newer therapies, including targeted agents, are available for their treatment. Targeted agents were used only in a minority of post-alloHCT relapses likely due to the combination of pt status, absence of the target mutation, the agents' availability, and other factors. Pts who developed grade II-IV acute GVHD and had shorter "disease-free" duration from unrelated or haploidentical donor grafts had the significantly shorter survival following relapse. More innovative treatment strategies to prevent and treat relapse post-alloHCT are needed. Disclosures Hill: Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celegene: Consultancy, Honoraria, Research Funding; Amgen: Research Funding; TG therapeutics: Research Funding; Genentech: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding. Anwer:In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Majhail:Atara Bio: Consultancy; Anthem, Inc.: Consultancy; Nkarta: Consultancy; Mallinckrodt: Honoraria; Incyte: Consultancy.

scholarly journals A Lower Level of Post-Vaccinal Antibody Titer against Influenza Virus A H1N1 May Protect Patients with Autoimmune Rheumatic Diseases from Respiratory Viral Infections

Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 76
Author(s):  
Milomir S. Milanovic ◽  
Djordje M. Kadijevich ◽  
Ljudmila Stojanovich ◽  
Branislav Milovanovic ◽  
Aleksandra Djokovic
Keyword(s):  
Logistic Regression ◽  
Influenza Virus ◽  
Antibody Titer ◽  
Rheumatic Diseases ◽  
Disease Duration ◽  
Viral Infections ◽  
Binary Logistic Regression ◽  
Influenza Virus A ◽  
Autoimmune Rheumatic Diseases ◽  
Respiratory Viral Infections

Background and Objectives: The concentration of antibodies against virus influenza A H1N1 in the titer (≥1:32) positively correlates with resistance to flu in healthy persons. In elderly and immune-compromised patients, an influenza vaccine may be less immunogenic. Hypothesis: A lower post-vaccinal antibody titer (≥1:16) may be sero-protective against respiratory viral infections in patients with autoimmune rheumatic diseases. Materials and Methods: Fifty patients with autoimmune rheumatic diseases (Systemic Lupus Erythematosus—24; Rheumatoid Arthritis—15; and Sjögren’s Syndrome—11), who were at least 65 years old or whose relative disease duration (disease duration/age) was greater than 1/8, were examined. Thirty-four of them were vaccinated with a trivalent inactivated non-adjuvant influenza vaccine. The antibody concentration against influenza virus A H1N1 was measured using the standardized hemagglutination inhibition test and patients who got any respiratory viral infection were registered. To test the hypothesis, a correlative analysis was applied, followed by a binary logistic regression that included potential confounding variables, such as age, disease duration and therapy (personal/health-related conditions). Results: Vaccinated patients were significantly less affected by respiratory viral infections (21% vs. 75%). The lower titer considered (≥1:16) was significantly present more often among vaccinated patients (68% vs. 6%). The correlation between its presence/absence and that of respiratory viral infections was –0.34 (p < 0.05). The binary logistic regression evidenced the relevance of this correlation, confirming the hypothesis. Vaccination was associated with the 87.3% reduction in the likelihood of getting respiratory viral infections, whereas the lower antibody titer (≥1:16) was associated with the 77.6% reduction in the likelihood of getting respiratory viral infections. The vaccine was well tolerated by all patients and after vaccination no exacerbation of the underlying disease was observed. Conclusions: A lower antibody titer (≥1:16) against influenza virus A H1N1 could be protective against respiratory viral infections for certain autoimmune rheumatic diseases patients, which confirms the clinical effectiveness of influenza vaccination.

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