scholarly journals Conditioning Intensity and Probability of Live Birth after Blood or Marrow Transplantation (BMT) - a Report from the BMT Survivor Study (BMTSS)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2905-2905
Author(s):  
Nora Balas ◽  
Lindsey Hageman ◽  
Jessica Wu ◽  
Liton F. Francisco ◽  
Elizabeth Schlichting ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Live Birth ◽  
Research Funding ◽  
Conditional Logistic Regression ◽  
Matched Pair ◽  
Same Sex ◽  
Myeloablative Conditioning ◽  
Pair Comparison ◽  
Increased Risk ◽  
Conditioning Intensity

Abstract Background: The observed inter-individual variability in the probability of live birth after BMT is due to exposure to gonadotoxic agents (including total body irradiation [TBI]), age at exposure to gonadotoxic agents, sex of the BMT recipient, and post-BMT morbidity. The last decade has seen an increase in use of non-myeloablative (NMA) conditioning to reduce the risk of early post-treatment mortality. However, the impact of TBI in the context of conditioning intensity (NMA vs. myeloablative conditioning [MAC]) on the probability of post-BMT live birth remains unknown. We addressed this gap by utilizing the BMTSS - a multi-institutional collaborative designed to understand the burden of morbidity after BMT. Methods: This study included 1,607 BMT survivors who underwent BMT between 1974 and 2014 at age ≤45, had survived ≥2y, and were ≥18y of age at study. This study also included pair-matched nearest-age, same-sex biologic siblings (≥18y of age at study) to control for genetic or environmental factors that could affect fertility. Survivors and their siblings completed the BMTSS survey. Sociodemographic characteristics (race/ethnicity, annual household income, availability of health insurance, level of education), chronic health conditions, medical assistance for fertility assistance and details about all pregnancies and their outcomes were retrieved from the BMTSS survey. Clinical characteristics were obtained from the institutional BMT databases and/or participants' medical record. Within survivor analysis: Potential risk factors for not reporting a live birth after BMT were analyzed using multivariable logistic regression. Exposure to TBI and conditioning intensity were consolidated to create four distinct exposure groups: no_TBI/NMA (least intense), TBI/NMA, no_TBI/MAC, TBI/MAC (most intense). Matched-pair comparison with biologic siblings: We matched 172 survivors with their closest-age, same-sex, biological siblings and used conditional logistic regression to determine the failure to report live birth in BMT survivors when compared with their siblings. Results: In this cohort of 1,607 survivors, 599 (37.3%) were autologous BMT recipients, and 765 (47.6%) were female. Median age at BMT was 30y, and at study participation was 45y (IQR: 18-73); median length of follow-up from BMT to study was 14.4y (IQR: 2.4-41.4). The primary indications for BMT included HL/NHL (30.6%), AML/MDS (24.3%), CML (13.4%), ALL (12.2%), and other diagnoses (13.5%). Of the 1,607 survivors, 120 (7.5%) reported one or more live births after BMT. Within survivor comparison: Multivariable analysis (Figure) revealed that receipt of TBI/MAC (OR=2.9, 95%CI: 1.5-5.8; ref: no_TBI/ NMA) was associated with an increased risk of not reporting a post-BMT live birth. Of note, TBI/NMA (OR=1.5, 95%CI, 0.5-5.0), and no_TBI/ MAC (OR=0.9, 95%CI, 0.4-2.0) were at a similar risk of reporting a post-BMT live birth as no_TBI/NMA. Other factors associated with increased risk of not reporting a post-BMT live birth included older age at BMT (>35y: OR=3.5, 95%CI, 1.4-7.9; reference: <12y), lower income ($50k-100k: OR=2.0, 95%CI, 1.1-3.6; <$50k: OR=3.2, 95%CI, 1.6-6.4; reference: >$100k), no medical interventions to facilitate pregnancy (OR=2.7, 95%CI, 1.6-4.6), and history of pre-BMT live birth (OR=2.7, 95%CI, 1.6-4.6). Matched-pair comparison with biologic siblings: Multivariable conditional logistic regression revealed that BMT survivors were less likely to report live birth (OR=0.5, 95%CI: 0.3-0.8) compared to their siblings. However, once pregnant, they were also less likely to report a miscarriage (OR=0.4. 95%CI: 0.2-0.8). Conclusion: While full dose TBI in the setting of myeloablative conditioning is associated with a lower probability of live birth after BMT, lower doses of TBI in the setting of myeloablative or reduced intensity conditioning yield a similar probability of live birth as no TBI. These findings provide evidence for alternative conditioning regimens for patients who wish to have children after BMT. Figure 1 Figure 1. Disclosures Weisdorf: Fate Therapeutics: Research Funding; Incyte: Research Funding. Forman: Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company; Allogene: Consultancy. Arora: Syndax: Research Funding; Pharmacyclics: Research Funding; Kadmom: Research Funding.

scholarly journals Conditioning Intensity and Probability of Live Birth after Blood or Marrow Transplantation (BMT): a BMTSS Report

2021 ◽  
Author(s):  
Nora Balas ◽  
Lindsey Hageman ◽  
Jessica Wu ◽  
Liton Francisco ◽  
Elizabeth Schlichting Ross ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Live Birth ◽  
High Intensity ◽  
Marrow Transplantation ◽  
Conditional Logistic Regression ◽  
Low Intensity ◽  
Exposure Variable ◽  
Total Body ◽  
Conditioning Intensity ◽  
The Impact

We examine the impact of conditioning intensity (low intensity: non-myeloablative/reduced intensity vs. high intensity: myeloablative) and total body irradiation (TBI) on the probability of live birth after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS), and included 1,607 survivors transplanted 1974-2014 at age ≤45, with survival ≥2y post-BMT and age at study ≥18. Closest-age, same-sex biologic siblings (n=172) were 1:1 matched with 172 survivors. Survivors and siblings self-reported information on sociodemographic, chronic health conditions, and pregnancies. Within survivor analysis: The association between the primary exposure variable (No TBI/low-intensity conditioning; 200-800cGy TBI/low-intensity conditioning; No TBI/ high-intensity conditioning; >800cGy TBI/ high-intensity conditioning) and the odds of no post-BMT live birth was examined using multivariable logistic regression, adjusting for clinical and demographic variables. Median age at BMT was 31y (IQR=0-45), and median length of follow-up was 14.3y (IQR=2.4-41.4); 39.3% were autologous BMT recipients and 46.6% were female. Overall, 120 (8.7%) survivors reported post-BMT live births. Receipt of >800cGy TBI/ high-intensity conditioning (OR=3.7, 95%CI=1.9-7.0; ref: no TBI/low-intensity conditioning) was associated with higher odds of reporting no live birth post-BMT. In contrast, 200-800cGy TBI/low-intensity conditioning (OR=1.3, 95%CI=0.5-3.3), and no TBI/high-intensity conditioning (OR=0.9, 95%CI=0.5-1.7) were at similar risk of reporting post-BMT live birth as no TBI/low-intensity conditioning. Comparison with biologic siblings: Using conditional logistic regression, we found that BMT survivors were more likely to report no live birth (OR=2.0, 95%CI: 1.2-3.3) compared with siblings. These findings could inform conditioning intensity options for patients wishing to preserve fertility post-BMT.

scholarly journals Non-Myeloablative Conditioning Regimen before T-Cell Replete Haploidentical Transplantation with Post-Transplant Cyclophosphamide for Advanced Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4614-4614
Author(s):  
Catalina Montes De Oca ◽  
Thomas Pagliardini ◽  
Stefania Bramanti ◽  
Sabine Furst ◽  
Jean Marc Schiano de Collela ◽  
...  
Keyword(s):  
Research Funding ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Research Support ◽  
Myeloablative Conditioning ◽  
Term Survival ◽  
Gvhd Prophylaxis ◽  
Increased Risk ◽  
Low Incidence

Introduction: allogeneic transplantation (allo-HSCT) is a curative treatment for patients with advanced lymphoma. Haploidentical (haplo-SCT) transplantation extended the accessibility to allo-HSCT, overcoming the issue of donor availability. However, alternative donor allo-HSCT is still considered at higher risk of non-relapse mortality due to the HLA disparity and thus an anticipated higher incidence of GVHD. In this context, the use of a non myeloablative conditioning (NMAC) regimen combined with post transplantation cyclophosphamide (PT-Cy) based GVHD prophylaxis may reduce procedure related toxicity. The aim was to evaluate the toxicity and efficacy of haplo-SCT using NMAC with PT-Cy in advanced lymphoma patients. Methods: We here report the retrospective experience of a bicentric transplantation program. We analyzed a cohort of lymphoma patients undergoing Haplo-SCT and homogeneously receiving NMAC and PT-Cy. Inclusion criteria were: 1) first allo-HSCT for advanced lymphoma between 2009 and 2018; 2) haploidentical donor; 3) NMAC (fludarabine cyclophosphamide and 2 gray TBI GVHD prophylaxis consisted of PT-Cy day+3 and +4 , cyclosporine A and MMF starting from day +5. Multivariate analyses included age, disease type (NHL vs HL), HCT-CI (< vs ≥ 3), graft source (PBSC vs BM), disease status at haplo-SCT (CR vs other). Results: One hundred forty seven patients (73 NHL; 74 HL) with a median age of 46 years (range: 19-71) were included. PBSC (peripheral blood stem cell) was used as graft source in 96 patients (65%). Patients received a median number of 3 conventional chemotherapy lines before haplo-SCT (1-8). Sixty-five (44%) had relapse after Auto-HCT. At the time of haplo-SCT, 96 patients (66%) were in complete remission. The cumulative incidences of day+100 grade 2-4 and 3-4 acute GVHD were 30% and 3%, respectively. The cumulative incidences of 2-year chronic and moderate or severe chronic GVHD were 13% and 8%, respectively. With a median follow up of 39 months (6-114), 2-year NRM was 14%, with a trend for higher risk in patients with HCT-CI ≥ 3 (HR 0.39, 95CI [0.15-1.04] p = 0.061) while age was not associated with an increased risk of NRM (HR 1.01, 95CI [0.98-1.05], p = 0.450). Two-year cumulative incidence of relapse (CIR) was 21% and 18% in HL and NHL patients, respectively. Disease status at the time of haplo-SCT was strongly associated with relapse (HR 2.99, 95CI [1.41-6.35], p = 0.004) In HL patients, 2-year PFS, OS and GRFS were 65%, 77% and 57%, respectively, while corresponding values in NHL patients were 65%, 69% and 55%, respectively. Two-year PFS and GRFS were significantly higher in patients who underwent haplo-SCT in CR (PFS: CR vs. no CR: 72% vs. 55%, p=0.045; GRFS: CR vs. no CR: 63% vs. 42%, p=0.010). There was a trend for better 2-year OS in CR (OS: CR vs. no CR: 78% vs. 63%, p=0.063. Conclusion: We confirm the feasibility of haplo-SCT using NMAC and PT-Cy with low incidence of GVHD (notably severe forms) and NRM. In addition, we observed a relatively low incidence of relapse (19%) in this cohort of heavily pretreated patients, underlining a potent graft-versus-lymphoma effect after haplo-SCT, leading to promising survivals, including high rate of GRFS (>50%), suggesting a preserved long term quality of life in survivors. We conclude that NMAC haplo-SCT with PT-Cy should be considered as a valuable curative option for advanced lymphoma patients, with a favorable toxicity profile and promising long term survival. Figure Disclosures Stoppa: celgene: Other: travel fees, lecture fees; takeda: Other: travel fees. Carlo-Stella:MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Boehringer Ingelheim: Consultancy; Genenta Science sr: Consultancy; Sanofi: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; Servier: Consultancy, Honoraria, Other: Travel, accommodations; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Other: Travel, accommodations; Janssen Oncology: Honoraria; AstraZeneca: Honoraria. Chabannon:EBMT: Other: Working Party Chair, Board member; Fresenius Kabi: Other: research support; Miltenyi Biotech: Other: research support; Terumo BCT: Other: speaker's fees; Celgene: Other: speaker's fees; Novartis: Other: speaker's fees; Gilead: Other: speaker's fees, hospitalities; Sanofi SA: Other: research support, speaker's fees, hospitalities. Santoro:Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; BMS: Consultancy. Blaise:Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria; Molmed: Consultancy, Honoraria; Pierre Fabre medicaments: Honoraria.

scholarly journals 455Association of interpregnancy interval and preterm births: what does a sibling-matched study indicate?

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Gizachew Tessema ◽  
M Luke Marinovich ◽  
Siri E Håberg ◽  
Mika Gissler ◽  
Jonathan A Mayo ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Birth Outcomes ◽  
Meta Analysis ◽  
Conditional Logistic Regression ◽  
Preterm Births ◽  
Adverse Birth Outcomes ◽  
Interpregnancy Interval ◽  
Insufficient Evidence ◽  
Increased Risk ◽  
Matched Study

Abstract Background Most evidence for interpregnancy interval (IPI) and adverse birth outcomes come from between-women (unmatched) studies that are prone to incomplete control for confounders that vary between women. Comparing pregnancies to the same women (sibling-matched) can address this issue. Methods We conducted an international longitudinal study of births from Australia, Finland, Norway, and United States (California) covering over three decades (1980-2017). We included 5,523,914 births to 3,849,737 women, and within each country, we first investigated the associations between IPI and preterm birth (PTB), spontaneous PTB using logistic regression (unmatched analyses). Second, we used conditional logistic regression comparing IPIs in the same women (sibling-matched analyses), with 2,908,907 births to 1,234,730 women having at least two IPIs. Random effects meta-analysis was used to calculate pooled effect estimates. Results Compared to an IPI of 18-23 months, there was insufficient evidence of association between IPI &lt;6 months and overall PTB (adjusted odds ratio (aOR)=1.08, 95%CI 0.99-1.18) but increased odds of spontaneous PTB (aOR=1.38, 95%CI 1.21-1.57). We observed elevated odds of both birth outcomes associated with IPI ≥60 months. In comparison, between-women analyses showed elevated odds of adverse birth outcomes for &lt;12 month and &gt;24 month IPIs. Conclusions We found consistently elevated odds of PTB following long IPIs. IPI shorter than 6 months were associated with elevated risk of spontaneous PTB, but there was insufficient evidence for increased risk of overall PTB. Key message Current recommendations of waiting at least 24 months to conceive after a previous pregnancy, may be unnecessarily long in high-income countries.

scholarly journals Interpregnancy intervals and adverse birth outcomes in high-income countries: An international cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0255000
Author(s):  
Gizachew A. Tessema ◽  
M. Luke Marinovich ◽  
Siri E. Håberg ◽  
Mika Gissler ◽  
Jonathan A. Mayo ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cohort Study ◽  
Birth Outcomes ◽  
Meta Analysis ◽  
Conditional Logistic Regression ◽  
The United States ◽  
High Income ◽  
Adverse Birth Outcomes ◽  
Insufficient Evidence ◽  
Increased Risk

Background Most evidence for interpregnancy interval (IPI) and adverse birth outcomes come from studies that are prone to incomplete control for confounders that vary between women. Comparing pregnancies to the same women can address this issue. Methods We conducted an international longitudinal cohort study of 5,521,211 births to 3,849,193 women from Australia (1980–2016), Finland (1987–2017), Norway (1980–2016) and the United States (California) (1991–2012). IPI was calculated based on the time difference between two dates—the date of birth of the first pregnancy and the date of conception of the next (index) pregnancy. We estimated associations between IPI and preterm birth (PTB), spontaneous PTB, and small-for-gestational age births (SGA) using logistic regression (between-women analyses). We also used conditional logistic regression comparing IPIs and birth outcomes in the same women (within-women analyses). Random effects meta-analysis was used to calculate pooled adjusted odds ratios (aOR). Results Compared to an IPI of 18–23 months, there was insufficient evidence for an association between IPI <6 months and overall PTB (aOR 1.08, 95% CI 0.99–1.18) and SGA (aOR 0.99, 95% CI 0.81–1.19), but increased odds of spontaneous PTB (aOR 1.38, 95% CI 1.21–1.57) in the within-women analysis. We observed elevated odds of all birth outcomes associated with IPI ≥60 months. In comparison, between-women analyses showed elevated odds of adverse birth outcomes for <12 month and >24 month IPIs. Conclusions We found consistently elevated odds of adverse birth outcomes following long IPIs. IPI shorter than 6 months were associated with elevated risk of spontaneous PTB, but there was insufficient evidence for increased risk of other adverse birth outcomes. Current recommendations of waiting at least 24 months to conceive after a previous pregnancy, may be unnecessarily long in high-income countries.

scholarly journals Reduced Intensity Vs. Non-Myeloablative Conditioning Regimens for Haploidentical Transplantation in Complete Remission Acute Myeloid Leukemia: A Study from the ALWP of the EBMT

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 9-9
Author(s):  
Raynier Devillier ◽  
Jacques-Emmanuel Galimard ◽  
Myriam Labopin ◽  
Didier Blaise ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Advisory Committees ◽  
Significant Difference ◽  
Conditioning Regimens ◽  
Conditioning Intensity ◽  
Reduced Intensity

Background: In the context of a haploidentical stem cell transplantation (Haplo-SCT) platform with post transplantation cyclophosphamide (PT-Cy) for acute myeloid leukemia (AML) patients, the optimal conditioning regimen remains unknown. A non-myeloablative conditioning (NMAC) regimen (cyclophosphamide + fludarabine + 2Gy TBI [CyFluTBI]) was initially reported by the Johns Hopkins group as a safe approach in this setting, notably to treat patients of advanced age and/or with comorbid conditions. However, relapse incidence after NMAC Haplo-SCT remains high in AML where it can reach 45%. Alternatively, a reduced intensity conditioning (RIC) regimen containing an antileukemic drug combination like thiotepa and reduced-dose busulfan in addition to fludarabine (TBF) may decrease AML relapse. However, this anticipated benefit may be counterbalanced by a higher incidence of toxicity, graft-versus-host disease (GVHD) and non-relapse mortality (NRM). To date, no study comparing TBF vs. CyFluTBI has been published in complete remission (CR) AML. We performed this retrospective comparison on behalf of the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). Methods: We retrospectively analyzed 398 patients from the EBMT registry database with the following inclusion criteria: 1) adult patient in CR1 or CR2 AML; 2) T-replete Haplo-SCT with PT-Cy; 3) no in vivo depletion using antithymocyte globulin or alemtuzumab; and 4) receiving either TBF RIC (equivalent of 2-day iv busulfan dose) or CyFluTBI NMAC regimen. We compared separately TBF vs. CyFluTBI in patients younger (n=170, 82 TBF vs. 88 CyFluTBI) and older (n=228, 141 TBF vs. 87 CyFluTBI) than 60 years. Results: In patients younger than 60 years, the 2-year cumulative incidence of relapse (CIR) was significantly lower in the TBF group compared with the CyFluTBI group (TBF vs. CyFluTBI: 14% vs. 43%, p&lt;0.01). No significant increase in 2-year NRM was observed (TBF vs. CyFluTBI: 22% vs. 16%, p=0.15). This led to a significantly higher 2-year leukemia-free survival (LFS) probability in the TBF group (64% vs. 41%, p=0.03). After adjustment in multivariate analysis, CyFluTBI was associated with a higher risk of relapse (hazard ratio [HR] 3.4, 95%CI [1.4-6.9], p&lt;0.01), lower LFS (HR 1.8, 95%CI 1.1-3.0, p=0.03) and lower overall survival (OS) (HR 1.8, 95%CI 1.1-3.1, p=0.02), without significant impact of conditioning regimen on incidence of GVHD and NRM. In patients older than 60 years, univariate analysis did not show any significant difference in outcome according to the type of conditioning regimen (2-year NRM: TBF vs. CyFluTBI: 33% vs. 25%, p=0.23; 2-year CIR: TBF vs. CyFluTBI: 23% vs. 28%, p=0.20; 2-year LFS: TBF vs. CyFluTBI: 44% vs. 47%, p=0.96). Multivariate analysis showed a significant reduction in the risk of NRM after CyFluTBI (HR 0.5, 95%CI [0.2-0.9], p=0.04), while a non-significant increase in the risk of relapse was observed (HR 1.9, 95%CI [0.8-4.2], p=0.13). Finally, there was no significant difference in LFS (HR 0.9, 95%CI [0.5-1.5], p=0.67) and OS (HR 0.9, 95%CI [0.5-1.5], p=0.67). Conclusion: Our study suggests that in CR AML patients aged younger than 60 years, the use of TBF RIC provides better outcomes than NMAC CyFluTBI due to lower incidence of relapse, without significant increase in the risk of NRM. Conversely, it seems that older patients do not benefit from such conditioning intensification, due to a significantly higher risk of NRM after TBF RIC. Thus, in CR AML patients who will not receive a truly myeloablative regimen prior to PT-Cy Haplo-SCT, age could be used for determining the conditioning intensity from the wide variety of reduced toxicity conditioning regimens. Beyond the patient age, further prospective trials should assess patient-based parameters that may be useful for a fine tuning of conditioning intensity in a more individualized approach. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Blaise:Jazz Pharmaceuticals: Honoraria. Bug:Sanofi: Other: Travel; Neovii: Other: Travel; Jazz: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Hexal: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Eurocept: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel. Mohty:Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Plasmatic Extracellular Vesicles in Acute Graft-Versus-Host Disease after Haplo-Identical Allografting with Post-Transplant Cyclophosphamide

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 598-598
Author(s):  
Giuseppe Lia ◽  
Clara Di Vito ◽  
Marta Tapparo ◽  
Stefania Bruno ◽  
Elisa Zaghi ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Extracellular Vesicles ◽  
Graft Versus Host Disease ◽  
Research Funding ◽  
Regression Models ◽  
Logistic Regression Models ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Acute Graft

INTRODUCTION: Acute Graft-versus-Host-Disease (aGVHD) is a frequent complication where the endothelium may play a pivotal role. We recently investigated the potential role of extracellular vesicles (EVs) as novel biomarkers of aGVHD (Lia G. et al. Leukemia 2018). In this study we further investigated the correlation of plasma EVs and their content in miRNAs with the risk of developing aGVHD in the setting of post-transplant cyclophosphamide (PTCY) haploidentical-stem cell transplantation (Haplo-SCT). METHODS: Thirty-two patients who underwent a Haplo-SCT were included. Plasma samples were collected from peripheral blood at given time-points (pre-transplant, on day 0, 3, 7, 14, 21, 28, 35, 45, 60, 75 and 90 after transplant). EVs were extracted by a protamine-based precipitation method and were characterized by Nano-tracking Particle Analysis (Nanosight). EVs were then analyzed by flow-cytometry (Guava EasyCyte Flow Cytometer) with a panel of 14 antibodies (CD44, CD138, CD146, KRT18, CD120a, CD8, CD30, CD106, CD25, CD26, CD31, CD144, CD86, and CD140a). MiRNAs were extracted from EVs by miRNeasy Mini Kit (Qiagen) and retrotranscribed by miScript II RT Kit (Qiagen). Three miRNAs (miR100, miR194, miR155) were studied and quantified by qRT-PCR using the miScript SYBR Green PCR Kit (Qiagen). Concomitant plasma concentrations of human Tumor Necrosis Factor Receptor I (TNFR1) and human ST2 were also evaluated using a commercially available sandwich enzyme-linked immunosorbent assay (DualSET® ELISA R&D Systems). The risk of aGVHD was evaluated by logistic regression models and Odds Ratios (ORs) were estimated as absolute levels and as proportional changes compared with pre-transplant baseline levels of each marker. Moreover, among biomarkers significantly associated with a higher risk of aGVHD, a multivariable logistic regression model using Akaike's information criteria (AIC) was estimated to define a biomarker combination. Ors were reported for 1-unit increase of standardized variables. RESULTS: AGVHD (grade II-IV) was observed in 7/32 patients (22%) at a median of 41 (range 33-90) days after transplant. Logistic regression models showed that CD146 fluorescence was associated with a significantly increased risk of acute GVHD (OR 2.93 p&lt;0.001) as well as expression changes in miR100, miR155 and miR194 (OR 3.90 p&lt;0.001; OR 1.84 p=0.008; OR 2.68 p&lt;0.001, respectively). Concentrations of plasmatic hTNFR1 and ST2 were also confirmed to be associated with increased risk of aGVHD (OR 1.47 p=0.04; OR 1.55 p=0.05, respectively) as previously described. Of note, all biomarkers associated with risk of aGVHD showed a consensual change in signal levels before the onset of aGVHD (Figure 1). By applying a backward selection on a multivariable logistic model using the AICapproach, we found that the combination of CD146-miR100-TNFR1 with an individual AUROC of 0.858, 0.923, and 0.794, respectively, increased their discrimination ability to predict aGVHD (multivariable AUROC = 0.987). CONCLUSIONS: This study, in the setting of haplo-transplant, confirms the association of CD146, a cell adhesion molecule, and the risk of aGVHD suggesting an important role of endothelium damage in the pathogenesis of aGVHD. The association of miRNA100, miRNA155 and miRNA194, carried by EVs, and aGVHD was also significant. Interestingly, MiRNA100 was reported to regulate inflammatory neovascularization during GvHD while miR-155 plays a role in donor T cell expansion. We have also found that using three markers in combination (CD146-miR100-TNFR1) could greatly improve aGVHD predictivity. To translate our results into an in vivo model, we have recently designed preclinical mouse models to evaluate if a) antagomir (against miRNA100 and/or miRNA155) injections or b) pre-emptive treatments with endothelium protective agents such as defibrinotide or OMS721 (Anti-Masp2) may reduce the risk of aGVHD. Figure1 a) Signal variation from baseline level (preTx) of CD146 fluorescence, miR100 expression, and TNFR1 concentration before aGVHD onset. Disclosures Boccadoro: Sanofi: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding.

Emergency Department Visits Prior to Suicide and Homicide

Crisis ◽  
2016 ◽  
Vol 37 (1) ◽  
pp. 5-12 ◽  
Author(s):  
Julie Cerel ◽  
Michael D. Singleton ◽  
Margaret M. Brown ◽  
Sabrina V. Brown ◽  
Heather M. Bush ◽  
...  
Keyword(s):  
Risk Factors ◽  
Emergency Department ◽  
Logistic Regression ◽  
Conditional Logistic Regression ◽  
Emergency Department Visits ◽  
Matched Pair ◽  
Surveillance Systems ◽  
Wide Range ◽  
Psychiatric Conditions ◽  
Zip Code

Abstract. Background: Emergency departments (EDs) serve a wide range of patients who present at risk of impending suicide and homicide. Aims: Two statewide surveillance systems were probabilistically linked to understand who utilizes EDs and then dies violently within 6 weeks. Method: Each identified case was matched with four randomly selected controls on sex, race, date of birth, resident zip code, and date of ED visit vs. date of death. Matched-pair odds ratios were estimated by conditional logistic regression to assess differences between cases and controls on reported diagnoses and expected payment sources. Results: Of 1,599 suicides and 569 homicides in the 3-year study period, 10.7% of decedents who died by suicide (x = 13.6 days) and 8.3% who died by homicide (x = 16.3 days) were seen in a state ED within 6 weeks prior to death. ED attendees who died by suicide were more likely to have a diagnosis of injury/ poisoning diagnosis or mental disorder and more likely to have Medicare. Those who died by homicide were more likely to have a diagnosis of injury/poisoning and less likely to have commercial insurance. Conclusion: It is essential for research to further explore risk factors for imminent suicide and homicide in ED patients who present for psychiatric conditions and general injuries.

scholarly journals Increased Risk of Thrombosis in Patients with Myeloproliferative Neoplasms Compared with the General Population Hospitalized with COVID-19

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1508-1508
Author(s):  
Orly Leiva ◽  
Umberto Campia ◽  
Julia Snyder ◽  
Briana Barns ◽  
Samantha Rizzo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Logistic Regression ◽  
Research Funding ◽  
Myeloproliferative Neoplasms ◽  
Multivariable Analysis ◽  
Philadelphia Chromosome ◽  
Advisory Committees ◽  
Multivariable Logistic Regression ◽  
Increased Risk ◽  
Thrombotic Complications

Abstract Background: Coronavirus disease-2019 (COVID-19) is an inflammatory, multisystem infectious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) and is associated with increased risk of thrombosis, particularly among critically ill patients. The myeloproliferative neoplasms (MPNs) include Philadelphia chromosome-negative (Ph-negative) MPNs polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF), and Philadelphia-chromosome positive chronic myeloid leukemia (CML). Patients with MPNs, especially PH-negative, have increased risk of thrombotic complications. Given the increased propensity of thrombosis and prognostic significance of thrombosis in both COVID and MPNs, defining the risk of thrombotic complications in this patient population compared to the general population is important. Methods: Using an institutional database within the Mass General Brigham integrated health network, we retrospectively analyzed 63 consecutive patients with MPN who were ≥ 18 years old and tested positive for SARS-COV-2 infection based on polymerase chain reaction (PCR) testing from March 1, 2020 to January 1, 2021. We compared patients admitted to the hospital in our "MPN cohort" with patients admitted to the hospital from a separate COVID-19 (non-MPN cohort) Mass General Brigham registry of 1114 consecutive patients who tested positive for SARS-COV-2 infection based on PCR testing from March 13, 2020 to April 3, 2020. Care was taken to ensure the cohorts were mutually exclusive. The 90-day primary outcome for MPN cohort was a composite of all-cause death, any thrombosis (composite of arterial and venous thromboembolism [VTE]), International Society on Thrombosis and Haemostasis (ISTH) defined major and clinically relevant non-major bleeding. To identify risk factors for primary outcome in MPN cohort we used a multivariable logistic regression using age, sex, hospital admission status, MPN type, cytoreduction for MPN, hypertension, smoking status, baseline anticoagulation (AC), prior thrombosis (stroke, myocardial infarction or VTE) as co-variables. The 90-day outcomes of interest in our MPN vs non-MPN cohort analysis were any thrombosis, death, ISTH major and clinically relevant non-major bleeding and readmission for any reason. To assess impact of MPN status in hospitalized patients in our MPN vs non-MPN comparison, we used a multivariable logistic regression using age, sex, race, Hispanic ethnicity, ICU admission, treatment with steroids and/or Remdesivir, baseline AC and aspirin use, prior thrombosis (stroke, myocardial infarction or VTE), diabetes, heart failure, admission hematocrit, platelet count and D-dimer as co-variables. Continuous variables were compared using student t-test and categorical variables were compared using Fischer's Exact Test with a p value of &lt; 0.05 considered significant. Results: Of the 63 patients with MPN (23 with PV, 17 ET, 4 PMF, 15 CML, 4 other), 27 (43%) were admitted to the hospital for COVID-19 and 5 (8%) required ICU admission. The mean age of all MPN patients was 66, 84% were White, 8% Black and 10% Hispanic. Primary 90-day outcome occurred in 12 (19%) of MPN patients. In multivariable analysis, only admission to hospital was associated with increased odds of composite (aOR 21.11, 95% CI 2.38 - 546.40), Figure 1A. In patients with (n = 27) and without MPN (n = 399) who were admitted to the hospital, patients with MPN were older (mean age 70 vs 61, p = 0.0076), more likely to be White (89% vs 54%, p = 0.0004) and less likely to be Hispanic (7% vs 29%, p = 0.0158), less likely to be admitted to the ICU (19% vs 43%, p = 0.0138), and more likely to be treated with corticosteroids (30% vs 14%, p = 0.025) or remdesivir (41% vs 13%, p &lt; 0.0001). After multivariable logistic regression, diagnosis of MPN was significantly associated with increased odds of thrombosis (aOR 5.38, 95% CI 1.15-25.38) and readmission (aOR 6.28, 95% CI 1.60-24.88), but not bleeding (aOR 3.51, 95% CI 0.62-18.87) or death (aOR 4.29, 95% CI 0.95-18.99), Figure 1B. Conclusions: Thrombotic complications are common in patients with MPN and COVID-19, particularly if hospitalized for COVID-19. After multivariable analysis, MPN patients admitted for COVID-19 had a significantly increased risk of thrombotic complications compared with non-MPN patients. Figure 1 Figure 1. Disclosures Al-Samkari: Dova/Sobi: Consultancy, Research Funding; Novartis: Consultancy; Argenx: Consultancy; Rigel: Consultancy; Amgen: Research Funding; Agios: Consultancy, Research Funding; Moderna: Consultancy. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees. Fathi: Agios/Servier: Consultancy, Other: Clinical Trial Support; BMS: Consultancy, Other: Clinical Trial Support; AbbVie: Consultancy, Other: Clinical Trial Support; Pfizer: Consultancy; Trillium: Consultancy; Kura: Consultancy; Blueprint Medicines Corporation: Consultancy; Genentech: Consultancy; Novartis: Consultancy; Trovagene: Consultancy; Daiichi Sankyo: Consultancy; Novartis: Consultancy; Morphosys: Consultancy; Kite: Consultancy; Foghorn: Consultancy; Takeda: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy; NewLink Genetics: Consultancy; Forty Seven: Consultancy; Ipsen: Consultancy. Goldhaber: Bayer: Consultancy, Research Funding; Boehringer-Ingelheim: Consultancy, Research Funding; BMS: Research Funding; Boston Scientific BTG EKOS: Research Funding; Daiichi: Research Funding; Janssen: Research Funding; Pfizer: Consultancy, Research Funding; Agile: Consultancy. Piazza: Portola: Research Funding; Bayer: Research Funding; Amgen: Research Funding; BMS: Research Funding; Janssen: Research Funding; BSC: Research Funding. Hobbs: Celgene/Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Merck: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding; Bayer: Research Funding; Incyte Corporation: Research Funding; AbbVie.: Consultancy.

scholarly journals Development of a Web-Based System for Exploring Cancer Risk With Long-term Use of Drugs: Logistic Regression Approach

10.2196/21401 ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e21401
Author(s):  
Hsuan-Chia Yang ◽  
Md Mohaimenul Islam ◽  
Phung Anh Alex Nguyen ◽  
Ching-Huan Wang ◽  
Tahmina Nasrin Poly ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cancer Risk ◽  
Drug Exposure ◽  
Conditional Logistic Regression ◽  
Population Based ◽  
Research Database ◽  
Web Based ◽  
Increased Risk ◽  
Web Based System

Background Existing epidemiological evidence regarding the association between the long-term use of drugs and cancer risk remains controversial. Objective We aimed to have a comprehensive view of the cancer risk of the long-term use of drugs. Methods A nationwide population-based, nested, case-control study was conducted within the National Health Insurance Research Database sample cohort of 1999 to 2013 in Taiwan. We identified cases in adults aged 20 years and older who were receiving treatment for at least two months before the index date. We randomly selected control patients from the patients without a cancer diagnosis during the 15 years (1999-2013) of the study period. Case and control patients were matched 1:4 based on age, sex, and visit date. Conditional logistic regression was used to estimate the association between drug exposure and cancer risk by adjusting potential confounders such as drugs and comorbidities. Results There were 79,245 cancer cases and 316,980 matched controls included in this study. Of the 45,368 associations, there were 2419, 1302, 662, and 366 associations found statistically significant at a level of P<.05, P<.01, P<.001, and P<.0001, respectively. Benzodiazepine derivatives were associated with an increased risk of brain cancer (adjusted odds ratio [AOR] 1.379, 95% CI 1.138-1.670; P=.001). Statins were associated with a reduced risk of liver cancer (AOR 0.470, 95% CI 0.426-0.517; P<.0001) and gastric cancer (AOR 0.781, 95% CI 0.678-0.900; P<.001). Our web-based system, which collected comprehensive data of associations, contained 2 domains: (1) the drug and cancer association page and (2) the overview page. Conclusions Our web-based system provides an overview of comprehensive quantified data of drug-cancer associations. With all the quantified data visualized, the system is expected to facilitate further research on cancer risk and prevention, potentially serving as a stepping-stone to consulting and exploring associations between the long-term use of drugs and cancer risk.

scholarly journals Identifying Household Level Risk Factors for Unintentional House Fire Incidents, Injuries and Fatalities

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Samantha Turner ◽  
Sarah Rodgers ◽  
Ronan Lyons
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Large Scale ◽  
Conditional Logistic Regression ◽  
Household Composition ◽  
Health Concern ◽  
Logistic Regression Models ◽  
Household Level ◽  
Increased Risk ◽  
The Uk

ABSTRACTObjectivesUnintentional house fire incidents, injuries and deaths are a serious public health concern in the UK, which disproportionally affect certain groups in the population. Whilst house fires have decreased in recent years; growing financial pressures in the Fire and Rescue Services (FRSs) have resulted in funds dedicated to fire preventative activities becoming increasingly limited. To ensure ever limiting resources are targeted towards those households at greatest risk, it is essential the FRSs’ are accurately informed about the types of household at increased risk. The aim of this project is to undertake a large-scale case-control study, to identify the distinguishing household level risk factors associated with unintentional house fire incidents, injuries and deaths. ApproachUnintentional house fire incidents reported to the Welsh FRS between the years 2003-2008, were anonymised and incorporated into the Secure Anonymised Information Linkage (SAIL) Databank at the Farr Institute, Swansea University. 6943 case households (households which reported a fire to the FRS) were time-matched to 347,150 control households (case:control ratio 1:50). Individuals registered as living at these properties on the date of the fire were established using the Welsh Demographic Service (WDS) dataset. Household level variables will be created by linking case and control households to other demographic, health, educational and environmental datasets in SAIL. Conditional Logistic Regression will be used to estimate matched odds ratios and 95% confidence intervals. ResultsPotential risk factor variables were selected on the basis of a systematic review and theoretically plausible variables. Covariates include: household composition (e.g. age and gender of residents), socioeconomic status, educational attainment, smoking, alcohol consumption, mental health conditions, other health related conditions, mobility and sensory impairments and property related characteristics. Fire related circumstances (e.g. fire ignition source, presence of a smoke alarm) will also be investigated in logistic regression models exploring risk factors for injury and death. Results will be presented at the conference. ConclusionThis is the first large-scale analysis of risk factors for unintentional house fire incidents, injuries and deaths. The findings from this project will be translated into comprehensible infographics, designed to support the FRSs, other partner organisations and the general public, recognise high risk households in need of preventative interventions.

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