Thrombotic Outcomes Following Hormonal Treatment of Heavy Menstrual Bleeding in Pediatric Patients Taking Anticoagulation

Introduction: Anticoagulant-associated heavy menstrual bleeding (HMB) is a common and under recognized complication in women who are being treated for venous thromboembolism (VTE), leading to complications such as anemia and decreased quality of life. The appropriate management of HMB in this population is complex and often requires hormonal therapy which may significantly increase the risk for VTE. Additionally, combined oral contraceptives may need to be used to control heavy menstrual bleeding despite contributing to the overall risk for VTE. Due to limited adult and pediatric data, there are currently no expert consensus guidelines for the treatment of anticoagulant-associated HMB. We describe a single institutional experience and thrombotic outcomes following hormonal therapy for anticoagulation-associated HMB in adolescents. Methods: A retrospective cohort of pediatric females ages 9-21 years treated at Children's Healthcare of Atlanta were identified between January 2016 and July 2019. Patients were identified using common ICD codes for both HMB and anticoagulation/thrombosis. Patient demographic information, clinical characteristics, and thrombotic outcomes were abstracted from review of the electronic medical record. Patients receiving anti-platelet therapy with clopidogrel were included due to the reported similarity of bleeding complications compared to anticoagulants. Summary statistics were performed and Student's t test, Fisher's exact test, and Chi square test were used for statistical analysis (SAS v9.4, 2012, Cary, NC, USA). A p value <0.05 was considered statistically significant. Results: The cohort was comprised of 17 adolescent females with confirmed anticoagulation-associated HMB. Among the cohort, 59% identified as White, 35% Black, and 6% Asian. Body Mass Index was normal in 41%, while 24% were obese and 35% were underweight. Indications for anticoagulation included VTE (n=11), pulmonary embolism (n=6), May-Thurner Syndrome with placement of iliac vein stent (n=3), and other vascular anomalies with confirmed stenosis/thrombosis (n=2). The most common risk factor for thrombosis was initiation of combined hormone oral contraceptives within 3 months of the event that led to initiation of anticoagulation (35%). Anticoagulant medications used included lovenox (n=13), clopidogrel (n=3), and lovenox/aspirin (n=1). The median age at initiation of hormonal therapy for HMB was 17.3 years (min-max, 12.6-18.3 years), with a median time between starting anticoagulation and initiation of hormonal therapy of 11 days (min-max, 0-529 days). Medications used to treat HMB included medroxyprogesterone (n=9), norethindrone (n=6), norethindrone-ethinyl estradiol (n=1), and etonogestrel implant (n=1). After initiating hormonal therapy, amenorrhea or menstrual suppression was reported in all but one individual (n=16/17). Following initiation of hormonal therapy with medroxyprogesterone, only one adolescent experienced a new VTE event. This adolescent had the additional risk factors of May-Thurner anatomy, heterozygous FV Leiden and prothrombin gene mutations, and antiphospholipid antibody syndrome. The median length of follow-up from initiation of hormonal therapy was 325 days (min-max, 43-932 days). Statistical differences between groups were not feasible due to small sample size and few outcome events. Conclusions: The proper treatment of anticoagulation-associated HMB using hormonal therapy in the pediatric population is unclear, but our data suggest that treatment with hormonal therapy reduces anticoagulation-associated HMB while adding minimal risk for VTE. The only VTE event that occurred in our cohort was in the setting of multiple strong risk factors for VTE. Larger pediatric studies are required in order to confirm these findings. Disclosures White: National Hemophilia Foundation: Other: Shire Clinical Fellowship Program. Sidonio:Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Kedrion: Research Funding; Uniqure: Membership on an entity's Board of Directors or advisory committees; Biomarin: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Obtaining a Von Willebrand Evaluation at Time of Acute Heavy Menstrual Bleeding Presentation Leads to Overestimation of Von Willebrand Levels

Blood ◽

10.1182/blood-2019-127258 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 627-627

Author(s):

Megan C. Brown ◽

Michael H. White ◽

Robert F. Sidonio

Keyword(s):

Factor Viii ◽

Board Of Directors ◽

Research Funding ◽

Heavy Menstrual Bleeding ◽

Menstrual Bleeding ◽

Quality Improvement Initiative ◽

Advisory Committees ◽

Von Willebrand ◽

Willebrand Factor

Background: Acute heavy menstrual bleeding (HMB) is common for adolescent females, with about a quarter of menstruating females seeking care for HMB over a 3-year time period (O'Brien et al, Blood 2018). Inherited bleeding disorders are common in this adolescent population, identified in 24.6% referred for hematologic evaluation (Zia et al, Blood 2016). The timing and contents of the hemostatic workup for acute HMB in adolescents is extrapolated from adults, although the causes of acute HMB varies significantly between adult women and adolescents. A consensus statement by the American College of Obstetrics and Gynecology recommends obtaining a variety of hemostatic tests including CBC, von Willebrand studies, factor VIII, prothrombin time, partial thromboplastin time, fibrinogen, and thyroid stimulating hormone at the time of presentation (Committee Opinion 557, ACOG 2011). Factor VIII and Von Willebrand studies are known to be increased in the setting of physiologic stress and supplemental estrogen use, questioning their diagnostic accuracy in the setting of acute bleeding. Repeat testing is often required for diagnosis of von Willebrand disease A von Willebrand factor antigen (VWF:Ag) or von Willebrand factor ristocetin cofactor level over 100IU/dL has been shown to have a negative predictive value (NPV) of 95%.(Doshi et al, ASH 2018). Methods: As part of a quality improvement initiative to improve the evaluation and management of adolescents with HMB at Children's Healthcare of Atlanta (CHOA), we instituted an acute HMB protocol for emergency department (ED) and inpatient use. This protocol was implemented at all CHOA emergency departments in metropolitan Atlanta. Subjects were included if they presented with acute HMB as determined by an adapted Philip Menorrhagia Screening Tool. Subjects with a previously diagnosed bleeding disorder, ITP, active rheumatologic disease, cancer, or anticoagulant use were excluded. Descriptive statistics were used to summarize demographics and clinical characteristics. Patients with a positive Philip screen underwent a uniform bleeding inventory and a standardized set of laboratory tests based on the adult consensus statement. Inpatient and outpatient treatments were standardized by hemoglobin level and symptomology. Follow up with hematology and gynecology was encouraged for all. Data was extracted using various heavy menstrual bleeding ICD-10 codes from January 1, 2017 to December 31, 2018. Individuals with von Willebrand studies at baseline and follow up were identified. T-tests and Wilcoxon rank sum tests were utilized to compare VWF:Ag, VWF:RCo and Factor VIII as baseline and follow up. Results: Over a 2-year period, 232 adolescent girls were seen in CHOA EDs for acute HMB with 88 (37.9%) requiring admission and 6 (2.6%) requiring intensive care. The population was primarily African American (63%) with a median age at presentation of 14.8 years (IQR 13.1-16.7). The majority of adolescents had the core hemostatic labs drawn (55.6%) as described per protocol. Thirty-six individuals had baseline and follow up VWD studies. Those with repeat VWD studies were younger (median 13.2 years vs 15.0 years), more commonly white (44.4% vs 21.2%), were more likely to have been admitted (83.3% vs 29.6%) and more likely to have had a hematology follow up appointment (63.4% vs 7.8%). Mean and median VWF:Ag, VWF:RCo and Factor VIII were significantly higher at presentation with HMB than at follow up. Of those with a baseline VWF:Ag and/or VWF:RCo >100, there was a 96.4% NPV for the diagnosis of VWD. For individuals whose initial VWF:Ag and VCWF:RCo were both >100, there was 100% NPV. Conclusions: Among the adolescents cared for at our institution with acute HMB who had confirmatory VWD testing, initial VWF:Ag and VWF:RCo >100 ruled out VWD based on repeat testing. However, poor adherence with hematology or gynecology follow-up may give false reassurance against a diagnosis of VWD. Further improvements of our quality improvement initiative will include a limited hemostatic workup at presentation with a focus on improved adherence to follow up and subsequent hemostatic evaluation. Disclosures White: National Hemophilia Foundation: Other: Shire Clinical Fellowship Program. Sidonio:Kedrion: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Membership on an entity's Board of Directors or advisory committees; Uniqure: Membership on an entity's Board of Directors or advisory committees.

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Validation Study of the Heavy Menstrual Bleeding Questionnaire in Adolescents

Blood ◽

10.1182/blood-2020-134545 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 45-45

Author(s):

Meghan Pike ◽

Ashley Chopek ◽

Nancy Young ◽

Koyo Usuba ◽

Mark J. Belletrutti ◽

...

Keyword(s):

Quality Of Life ◽

Board Of Directors ◽

Research Funding ◽

Phase 1 ◽

Heavy Menstrual Bleeding ◽

Menstrual Bleeding ◽

Measurement Tool ◽

Phase 2 ◽

Advisory Committees

Introduction Heavy menstrual bleeding (HMB) is a common problem among adolescent girls that affects many aspects of their lives. Estimating the effect of HMB on health-related quality of life (HRQoL) is important but challenging, as there is no instrument that measures menstrual bleeding-specific HRQoL for girls ages < 18 years. Aim To develop and assess the psychometric properties of a menstrual bleeding-specific HRQoL tool adapted for use by girls with HMB aged < 18 years. Methods HMB was defined using a pictorial bleeding assessment chart (PBAC) score >100 and/or hemoglobin >2 SD below age appropriate means. Phase 1 utilized a focus group of girls with HMB to review items of the Menstrual Bleeding Questionnaire (MBQ), validated for use in women ages ≥ 18 years, to generate new items and develop the Adolescent MBQ (aMBQ). In phase 2, participants were divided in two groups: those with and those without HMB. Each participant completed 3 questionnaires (aMBQ, Pediatric Quality of Life core module [PedsQL] and PBAC) at 2 time points. Validity of the aMBQ was measured by Spearman's correlation with the PedsQL. Reliability was calculated using an intra-class correlation (ICC) random effect model in those without HMB who repeated the 3 questionnaires within 30-60 days from baseline. Receiver Operating Characteristic (ROC) curve analysis assessed the ability of the aMBQ to distinguish between participants with and without HMB. Ethics approval and informed consent were obtained prior to participation. Results Phase 1 included 5 girls with previously diagnosed HMB. The MBQ was revised to be appropriate for adolescents by substituting 4 words/phrases that altered 8 of 20 questions (Table 1). With the addition of one new question, a 21-item aMBQ was developed with a score range of 0-77, with 77 representing the worst HRQoL. Phase 2 included 73 participants: 19 with HMB and 56 without HMB. Mean age of participants was 14.7 years (range 11-17 years). The validity of the aMBQ was confirmed by a moderate correlation with PedsQL (rho=-0.61). Test-retest reliability was substantial (ICC=0.71, p=0.03). An aMBQ score of >30 identified those with HMB with excellent discrimination (AUC=0.826, sensitivity 71.4%, specificity 88.0%). Conclusion The aMBQ is a valid and reliable measurement tool to assess HRQoL in adolescents with HMB that is easily implemented in the office setting. Furthermore, it may assist clinicians in identifying those with HMB and aid in the evaluation of treatment effectiveness both in clinical practice and research. Disclosures Belletrutti: Takeda Canada: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk Canada: Membership on an entity's Board of Directors or advisory committees; Bayer Canada: Membership on an entity's Board of Directors or advisory committees; Roche Canada: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees. Matteson:ABOG: Honoraria, Other: Received stipend for being an oral boards examiner.; Myovant: Membership on an entity's Board of Directors or advisory committees; Bayer Ensure: Other: Co-Investigator for longitudinal research study and clinical trial. All funds go to site of research, Research Funding.

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Patients with Immune Thrombocytopenia (ITP) Frequently Experience Severe Fatigue but Is It Under-Recognized By Physicians: Results from the ITP World Impact Survey (I-WISh)

Blood ◽

10.1182/blood-2018-99-112378 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2273-2273 ◽

Cited By ~ 4

Author(s):

Caroline Kruse ◽

Alexandra Kruse ◽

Shirley Watson ◽

Mervyn Morgan ◽

Nichola Cooper ◽

...

Keyword(s):

Platelet Count ◽

Board Of Directors ◽

Research Funding ◽

Signs And Symptoms ◽

Likert Scale ◽

High Impact ◽

Heavy Menstrual Bleeding ◽

Menstrual Bleeding ◽

Advisory Committees ◽

Advisory Boards

Abstract Background: ITP has a multifaceted impact on patients' (pts) lives but there are limited data on which signs and symptoms treating physicians (MDs) and pts perceive as having the greatest impact, especially on pt quality of life (QoL). As in many chronic autoimmune diseases, fatigue can significantly affect QoL in ITP pts. Aims: I-WISh studied the burden of ITP and its impact on QoL, especially fatigue, using a global pt and MD sampling frame. This analysis reports pt vs MD perception of frequency and severity of signs and symptoms. Methods : I-WISh is a cross-sectional survey of ITP pts, recruited via MDs and pt support groups, and also of MDs, recruited via local fieldwork agencies. Participants (pts and MDs) completed a 30-minute online survey that included demographics, signs and symptoms, impact of symptoms, and pt-MD relationships. A steering committee of expert MDs and pt advocacy ITP specialists designed and endorsed survey materials. Results: 1491 pts from 12 countries completed the survey; 65% female, with a mean (SD) age of 47 (16) yrs. 472 MDs from 13 countries completed the survey, with a mean (SD) ITP pt caseload of 34 (50) and a mean (SD) of 18 (36) newly-diagnosed pts in the past yr. The most frequent pt-reported signs and symptoms at diagnosis and at survey completion (Figure A,B) were petechiae (65%; 31%), bruising (64%; 30%), fatigue (58%; 50%), and anxiety around a stable platelet count (34%; 32%). The most common signs and symptoms MDs reported at diagnosis and overall (ie at any stage) were similar to those reported by pts, with petechiae (82% overall; 83% at diagnosis), purpura (74%; 73%), bleeding of the gums (69%; 70%), and epistaxis (69%; 70%) being the most common; there were few differences between diagnosis and overall. By contrast, fatigue was under-reported by MDs (31% overall; 30% at diagnosis) compared with pt-reported data (58% diagnosis; 50% survey completion). Pts rated the severity of their current symptoms. Fatigue was one of the most severe pt-reported symptoms, ie scored ≥5 on a 7-point Likert scale (7=worst imaginable severity), both at diagnosis (74%) and survey completion (65%), and remained consistently frequent and severe over time (Figure A,B). Of pts experiencing heavy menstrual bleeding (84%; 63%) and anxiety around a stable platelet count (78%; 65%) these were also reported as severe, although less so at survey completion. Thrombosis, while not common, was considered severe (62%; 74%; Figure A,B). When asked to consider their current symptoms, the three symptoms pts would most like to resolve were heavy menstrual bleeding (75%, n=118/158), thrombosis (74%, n=25/34), and fatigue (73%, n=544/743). MDs perceived several signs and symptoms as having a high impact on pt QoL (scored ≥5 on a 7-point Likert scale; 7=a great deal), with blood in urine/stool (81%), profuse bleeding during surgery (79%), and menorrhagia (78%) considered the most impactful; 59% believed fatigue has a high impact. Overall, 80% of MDs felt ITP symptoms reduce QoL (scored ≥5 on a 7-point Likert scale; 7=a great deal), and 66% believed that ITP-related fatigue reduces QoL. 46% of MDs believe fatigue is severe (scored ≥5 on a 7-point Likert scale; 7=completely fatigued) and believe fatigue increases as platelet levels decrease (Figure C). Pts are generally satisfied (79% satisfaction) with their MD's management of their disease, and overall satisfaction between pts and MDs was high regarding communication (80% vs 88%), management (79% vs 86%), and understanding of treatment goals (77% vs 90%). Summary/conclusions: The pt-reported symptom with highest frequency and greatest severity both at diagnosis and survey completion was fatigue. MDs who participated were experienced with treating ITP and believed fatigue would greatly affect pts, nonetheless MDs did not consider fatigue to be as substantial a problem as pts did. Pts were also concerned about platelet count stability, heavy menstrual bleeding, and thrombosis. Likelihood of fatigue increased as platelet count reduced suggesting fatigue may be intrinsically related to disease activity and could be alleviated by increasing the platelet count. These results indicate that pts and MDs align on overall symptom burden in ITP but highlight that improved understanding and awareness of the relationships between fatigue, platelet count, and QoL is needed. Disclosures Kruse: Novartis/ITP: Consultancy; Rigel/ITP: Honoraria; Amgen/ITP: Consultancy. Watson:Novartis: Membership on an entity's Board of Directors or advisory committees. Cooper:Amgen, Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Ghanima:Amgen, Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer, BMS, Novartis: Research Funding. Provan:Amgen, Novartis: Honoraria, Research Funding. Arnold:Amgen: Consultancy, Research Funding; UCB: Consultancy; Bristol Myers Squibb: Research Funding; UCB: Consultancy; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Consultancy, Research Funding. Santoro:Bayer, CSL, Novo Nordisk, Pfizer, Shire, Sobi: Other: advisory boards, Speakers Bureau; Grifols, Gilead: Other: advisory boards; Amgen, Glaxo: Speakers Bureau. Tomiyama:Sysmex Corporation: Consultancy; Chugai Pharmaceutical Co., Ltd.: Honoraria; Novartis Pharma Co., Ltd.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kyowa Hakko Kirin Co., Ltd.: Honoraria. Waller:Novartis: Consultancy. Taylor-Stokes:Novartis: Consultancy. Bailey:Novartis: Consultancy. Stankovic:Novartis: Employment. Bussel:Novartis: Consultancy, Research Funding; Uptodate: Honoraria; Rigel: Consultancy, Research Funding; Momenta: Consultancy; Protalex: Consultancy; Amgen Inc.: Consultancy, Research Funding; Prophylix: Consultancy, Research Funding.

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Risk Factors Associated with the Development of Infusion-Related Reactions in Patients with Chronic Lymphocytic Leukaemia Treated with Anti-CD20 Monoclonal Antibodies: Analysis of the CLL11 Study Dataset

Blood ◽

10.1182/blood.v124.21.3339.3339 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3339-3339 ◽

Cited By ~ 4

Author(s):

Ciara Louise Freeman ◽

Mark Dixon ◽

Richard Houghton ◽

Kathryn Humphrey ◽

Gunter Fingerle-Rowson ◽

...

Keyword(s):

Risk Factors ◽

Monoclonal Antibodies ◽

Board Of Directors ◽

Research Funding ◽

Lymphocytic Leukaemia ◽

Signs And Symptoms ◽

Leukemic Cells ◽

Tumour Burden ◽

Advisory Committees ◽

Anti Cd20

Abstract Background: The administration of anti-CD20 monoclonal antibodies (mAb) in patients with B-cell lympho-proliferative disorders is frequently accompanied by a constellation of signs and symptoms that have been labelled as infusion-related reactions (IRR). The pathophysiology of IRR remains poorly understood as do predictors of risk, which may relate to the mechanism of action of the anti-CD20, disease-related factors such as tumour burden or host factors such as polymorphisms of Fc gamma receptor 3A (FcγRIIIA). In the CLL11 trial (NCT01010061), patients with previously untreated chronic lymphocytic leukaemia and comorbidities were randomised to receive either rituximab (type I anti-CD20 mAb) or obinutuzumab (type II and glycoengineered anti-CD20 mAb) in combination with chlorambucil for six cycles. Obinutuzumab led to faster depletion of B cells and achieved an improvement in outcome parameters such as response and progression-free survival compared with the rituximab arm, but was also associated with a higher rate and increased severity of IRR. To better understand the profile of risk for IRR in patients with CLL, we performed an exploratory analysis on data obtained from patients treated with either one of the two antibodies given in combination with chlorambucil. Methods: Patients from the prospective, randomized Phase III CLL11 study who received a first infusion of obinutuzumab (N=331) or rituximab (N=326) were included. Baseline pre-treatment risk factors thought to play a possible role in the development of IRR were identified a priori and included patient demographics, concurrent conditions and premedications, parameters of disease burden, prognostic factors, laboratory variables and FcγR genotype. Baseline values for mean fluorescence intensity (MFI) of CD20, gated on the circulating CLL clone, and MFI of CD16, gated on the natural killer (NK) cell population (CD56+16+) in peripheral blood were also available for N=510 patients. The primary outcome, development of an IRR with the first infusion, was defined as the occurrence of related signs and symptoms during or within 24 hours of administration of antibody. Due to the short-term nature of the initial IRR a multivariate logistical regression analysis was performed rather than a time to event analysis. Internal validation of this model, derived from a single dataset, was conducted using the established resampling technique of bootstrapping. This assessed the proportion of times each variable retained significance at α=0.10 when the model was fitted to bootstrapped samples of the dataset. Results: Patients that appeared to be at greater risk of developing any grade of IRR with the first infusion of rituximab or obinutuzumab were those treated with obinutuzumab, those with higher surface expression CD20 on CLL cells (MFI CD20) and greater FcγRIIIA (MFI CD16) on NK cells in peripheral blood, those with higher affinity FcγRIIIA genotype (VV), more pronounced neutropenia and splenomegaly at baseline (Table 1). Higher baseline absolute lymphocyte count and the presence of respiratory comorbidity also appeared to increase risk. All variables significant for inclusion in the model are shown in Table 1. Looking at those patients treated with obinutuzumab only, the most important determinant of risk was MFI CD20 (OR 3.6 95% CI 1.6-7.9). The impact of glucocorticoid premedication in reducing risk in obinutuzumab treated patients was not sufficient to reach significance, however, patients were not randomised to this intervention. Conclusion: This work identifies novel disease- and patient-specific biological variables that appear to play a role in the development of IRR in patients with CLL treated with anti-CD20 mAb, although the treatment received (obinutuzumab >rituximab) confers greatest risk. In addition to parameters of tumour burden, target antigen expression and gene polymorphisms of FcγR also appear to contribute to the risk of developing an IRR. Our results support the hypothesis that higher rates of IRR seen with the administration of obinutuzumab may result from stronger activation upon binding to CD20 on leukemic cells and subsequent enhanced cross-linking between CD20 expressing leukemic cells and FcγRIIIA bearing effector cells. Further studies involving obinutuzumab in this patient population will be needed to externally validate the results of this exploratory analysis. Disclosures Freeman: Roche Pharmaceuticals: clinical research fellowship supported by Roche Pharmaceuticals (secondment from Bart's) Other. Dixon:Roche Pharmaceuticals: Employment. Houghton:Roche Pharmaceuticals: Employment. Humphrey:Roche: Employment. Fingerle-Rowson:Roche Pharmaceuticals: Employment. Kreuzer:Roche Pharmaceuticals: Research Funding. Engelke:Roche: Travel grants Other. Hallek:Roche Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau. Goede:Bristol Myers Squibb: Honoraria; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grants Other.

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Clinical and Biomarker Predictors for Avascular Necrosis in Sickle Cell Disease

Blood ◽

10.1182/blood-2021-147829 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3091-3091

Author(s):

Michael Rabaza ◽

Maria Armila Ruiz ◽

Liana Posch ◽

Faiz Ahmed Hussain ◽

Franklin Njoku ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Board Of Directors ◽

Avascular Necrosis ◽

Sickle Cell ◽

Research Funding ◽

Medical Attention ◽

Cell Disease ◽

Advisory Committees ◽

Early Management

Abstract Introduction Sickle cell disease (SCD) affects 1 in 365 African Americans and approximately 25 million people world-wide. A common skeletal system complication is avascular necrosis (AVN), which can cause substantial pain and a reduced quality of life. While early management of AVN is focused on increasing range of motion with physical therapy and pain relief, there are no clear predictors for who is more likely to develop AVN and earlier institution of these preventive measure could help decrease disease progression. Vascular endothelial growth factor (VEGF) is a biomarker of endothelial injury and may indicate reduced vascular supply to the femoral or humeral head. Here we describe potential risk factors and biologic pathways for AVN in SCD, as understanding these may lead to improvements in future monitoring, early detection, and early intervention practices. Methods We investigated clinical and laboratory risk factors associated with AVN in a cohort of 435 SCD patients from our center. Blood samples, clinical, and laboratory data were collected at the time of enrollment during a clinic visit. Genotyping for alpha thalassemia was performed by PCR and the serum concentration of VEGF was measured by ELISA. AVN status was confirmed by review of the medical record and available imaging. We conducted a cross-sectional analysis comparing categorical and linear variables by AVN status using the chi-square and Kruskal-Wallis test, respectively. The independent association of the clinical and laboratory variables with AVN status was determined by logistic regression analysis. The initial model included variables with a P-value < 0.1 on univariate analysis and the final model was ascertained by stepwise forward and backward selection. Median values and interquartile range (IQR) are provided. Results The median age of the cohort was 32 (IQR, 24 - 43) years, 57% (250/435) were female, and 46% (198/435) were on hydroxyurea. AVN was observed in 34% (149/435) of SCD patients. SCD patients with AVN were older, had more frequent vaso-occlusive crises requiring medical attention, and had a higher body mass index (Table I) (P ≤ 0.002). We measured VEGF in 241 of the SCD patients with serum samples available at the time of enrolment. Serum VEGF concentrations trended higher in SCD patients with versus without AVN (420 vs. 359 pg/mL, respectively; P = 0.078). In the multivariate analysis model, AVN was independently associated with increased number of vaso-occlusive crises (OR 1.1, 95% CI: 1.0 - 1.14; P = 0.02), AST concentration (natural log OR 0.5, 95% CI: 0.2 - 0.9; P = 0.03), VEGF concentration (natural log OR 1.4, 95% CI: 1.0 - 1.9; P = 0.047), and tobacco use (OR 1.9, 95% CI: 0.9 - 3.7; P = 0.078). Discussion In conclusion, we demonstrate a high prevalence of AVN in an adult cohort of SCD patients. The presence of AVN was independently associated with a greater frequency of vaso-occlusive pain episodes, which may demonstrate a shared pathophysiology between AVN and vaso-occlusion that merits further investigation. We demonstrate that serum VEGF concentrations are higher in SCD patients with AVN and may be a clinical tool to identify those at high-risk and for earlier intervention for this complication. Figure 1 Figure 1. Disclosures Gordeuk: Modus Therapeutics: Consultancy; Novartis: Research Funding; Incyte: Research Funding; Emmaus: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; CSL Behring: Consultancy. Saraf: Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Bleeding Complications in Patients with Cancer and COVID 19- Analysis from the COVID 19and Cancer Consortium (CCC19) Registry

Blood ◽

10.1182/blood-2021-154314 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4997-4997

Author(s):

Surbhi Shah ◽

Shuchi Gulati ◽

Ang Li ◽

Julie Fu ◽

Vaibhav Kumar ◽

...

Keyword(s):

Mechanical Ventilation ◽

Board Of Directors ◽

Stock Options ◽

Research Funding ◽

Tumor Board ◽

Bleeding Complications ◽

Advisory Committees ◽

Icu Admission ◽

Patients With Cancer ◽

Privately Held

Abstract Background : Patients (pts) with COVID-19 are reported to have increased risk of venous thromboembolism yet bleeding has been an under recognized complication. Rates of bleeding remain unexamined in all patients especially in pts with cancer and COVID-19. Aim: To estimate the incidence of bleeding complication in patients with cancer and COVID 19 Methods: The CCC19 international registry (NCT04354701) aims to investigate complications of COVID-19 in pts with cancer. Our aim was to investigate the frequency of bleeding in hospitalized adult pts with cancer andCOVID-19, enrolled between March 16, 2020 and Feb 8, 2021. The incidence of bleeding complications was captured as defined by CCC19 and included both major and non major bleeding . Associated baseline clinic-pathologic prognostic factors and outcomes such as need for mechanical ventilation, intensive care unit (ICU) admission and mortality rates were assessed Results :3849 pts met analysis inclusion criteria. Bleeding was reported in 276 (7%) pts with median age of 70years; incidence was 6.6 % in females and 7.6 % in males, 6.5% in non-Hispanic white pts, 8.2 % in non-Hispanic Black pts, and 7.8 % in Hispanic pts. 74% had solid cancer and 29% had hematologic malignancies, 33% had received anti-cancer therapy in preceding 30 days, and 8% had surgery within 4weeks. In pts taking antiplatelet or anticoagulant medications at baseline, 7.2% developed bleeding. Need for mechanical ventilation, ICU admission, 30-day mortality, and total mortality were significantly higher in those with bleeding complications compared to those without, p<0.05 Conclusion : We describe the incidence of bleeding in a large cohort of pts with cancer and COVID-19. Bleeding events were observed in those with adverse outcomes including mechanical ventilation, ICU admission, and high mortality; the overall mortality of 43% in patients with bleeding complications is especially notable. This important complication may reflect underlying COVID-19 pathophysiology as well as iatrogenic causes. Figure 1 Figure 1. Disclosures Kumar: Diagnostica Stago: Honoraria. Zon: AMAGMA AND RLZ: Consultancy, Current holder of individual stocks in a privately-held company. Byeff: Pfizer, BMS, Takeda,Teva, Merck, United health: Consultancy, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Nagaraj: Novartis: Research Funding. Hwang: astrazaneca,Merck,bayer, Genentech: Consultancy, Research Funding. McKay: Myovant: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Exelixis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Calithera: Membership on an entity's Board of Directors or advisory committees; Tempus: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tempus: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Dendreon: Consultancy; Caris: Other: Serves as a molecular tumor board ; Vividion: Consultancy; Sorrento Therapeutics: Consultancy; Bayer: Research Funding. Warner: Westat, Hemonc.org: Consultancy, Current holder of stock options in a privately-held company. Connors: Pfizer: Honoraria; CSL Behring: Research Funding; Alnylam: Consultancy; Bristol-Myers Squibb: Honoraria; takeda: Honoraria; Abbott: 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.

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Hypercholesterolemia In Imatinib Intolerant/Resistant CML-CP Patients Treated With Nilotinib: A Retrospective Analysis

Blood ◽

10.1182/blood.v122.21.1503.1503 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1503-1503 ◽

Cited By ~ 9

Author(s):

Devendra K. Hiwase ◽

David T Yeung ◽

Lisa Carne ◽

David Ross ◽

Andrew Grigg ◽

...

Keyword(s):

Risk Factors ◽

Lipid Profile ◽

Retrospective Analysis ◽

Board Of Directors ◽

Research Funding ◽

Lipid Profiles ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Advisory Committees ◽

Before And After

Abstract Background CML patients (pts) enjoy prolonged leukaemia-free survival with tyrosine kinase inhibitor (TKI) treatment. Addressing common non-CML causes of morbidity and mortality such as cardiovascular disease (CVD) and its associated risk factors is therefore increasingly important. Anecdotal evidence suggests a possible association between nilotinib (NIL) therapy and vascular events though there is little good quality evidence in this regard. The incidence of hyperlipidaemia and hyperglycaemia is higher in NIL-treated pts compared to imatinib- (IM) treated pts; conversely IM treatment may retard development of dyslipidaemia and hyperglycaemia. This retrospective analysis assessed the lipid profile of CML-CP pts before and after changing from IM to NIL therapy. Method Plasma lipid profile (total cholesterol, LDL, HDL and triglycerides), TKI exposure, and CVD risk factors before and after switchover to NIL of chronic phase CML pts were analysed. Baseline measurements were done during IM treatment or within 2 weeks of changing from IM to NIL. Follow-up results were obtained at least 1 month after starting NIL. Results Thirty-one CML pts were switched to NIL (median dose 400mg bd) after a median of 27 (1-96) months of IM therapy, predominantly for intolerance (16/31, 52%) or for failure to achieve deep molecular responses (13/31, 42%). Median age at NIL start was 51 (17-80) years (Table I). After switching to NIL, three pts had new onset PVD/IHD and one patient had multiple recurrences of PVD. Antihypertensive and hypoglycaemic medications were started in one additional patient each after switching over to NIL. Three pts were excluded from further analysis because of lack of data (n=2) or pre-existing dyslipidemia (n=1). The remaining pts had 90 TC assays, 72 of which were full lipid profiles whilst on NIL. Observations were censored at the time of statin commencement. Median time to 1st lipid measurement on NIL was 108 days (28-633) after switching. Median TC on IM was 4.7mM (2.1-6.4), compared to 6.1mM on NIL (3.1-8.5). Median peak TC on NIL was 6.8mM. Full fasting lipid profiles available for 11 pts before and after switching showed significantly increased LDL to be the major contributor to the increase in TC (Fig. 2). Thirteen pts had a fasting TC >5.5 mM (210 mg/dL) whilst on NIL, peaking at 312 days (medians). Eight of 13 pts started statins treatment for dyslipidemia whilst on NIL; (all retrospectively confirmed to be appropriate according to Australian National Heart Foundation guidelines, using a composite measure of CVD risk); whilst the other 5 were offered lifestyle modifications only. Of note, 2 pts had dyslipidaemia prior to starting IM treatment, discontinued statins whilst on IM, and had recurrence of dyslipidaemia after switching to NIL necessitating resumption of statin treatment. In addition, the 2 pts with PVD were also offered statins (total starting statin n=10) Discussion This retrospective analysis showed a high incidence of dyslipidemia in a cohort of CML pts treated with second-line NIL after IM therapy; 10/31 pts required lipid lowering agent. While the epidemiological association between nilotinib and CVD remains controversial, the increase in TC may have a contributing effect. Monitoring lipid levels in NIL-treated pts is prudent, along with screening for and minimisation of concomitant CVD risk factors, especially in pts previous treated with IM which may mask underlying metabolic syndromes. # DKH DTY and LC contributed equally to this work. Disclosures: Hiwase: Novartis Pharmaceuticals: Research Funding. Yeung:Novartis: Honoraria, Research Funding; BMS: Honoraria. Hughes:Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding.

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Major Bleeding Complications Among Patients Treated with Ibrutinib and Concomitant Antiplatelet, Anticoagulant, or Supplemental Therapy

Blood ◽

10.1182/blood.v128.22.4387.4387 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4387-4387 ◽

Cited By ~ 4

Author(s):

Aaron Pavlik ◽

Hallie Barr ◽

Emily Dotson ◽

John C. Byrd ◽

Kristie A. Blum ◽

...

Keyword(s):

Clinical Trial ◽

Board Of Directors ◽

Major Bleeding ◽

Research Funding ◽

Bleeding Event ◽

Antiplatelet Agents ◽

Bleeding Complications ◽

Bleeding Events ◽

Advisory Committees ◽

Major Bleeding Events

Abstract Background: Ibrutinib, an orally bioavailable small molecular inhibitor of Bruton's tyrosine kinase (BTK), is an approved therapy for chronic lymphocytic leukemia (CLL), relapsed mantle cell lymphoma (MCL) and Waldenstrӧm's macroglobulinemia (WM). Beyond B lymphocytes, BTK signaling is important for collagen-mediated platelet activation, and BTK inhibition has been associated with primary hemostatic bleeding events (Levade et al Blood 2014). Although serious bleeding events have been uncommon (1-5%) in clinical trial populations, there is limited data describing the potential for increased serious bleeding incidence when ibrutinib is co-administered with other agents affecting the clotting cascade or platelet function. Methods: We conducted a retrospective cohort study to evaluate the incidence of major bleeding in patients receiving ibrutinib concomitantly with antiplatelet agents (non-steroidal anti-inflammatory agents, ADP inhibitors), anticoagulants (heparins, warfarin, novel oral anticoagulants), or supplements with potential anticoagulant activity (vitamin E and fish oil). Major bleeding events were identified using criteria developed by the International Society on Thrombosis and Haemostasis (Schulman et al J Thromb Haemost 2005). Patients 18-89 years of age and treated with ibrutinib for CLL, MCL, or WM between March 1, 2010 and March 1, 2015 were included. The primary endpoint of this study was the incidence of major bleeding events, but we also sought to identify risk factors associated with the development of major bleeding, focusing on potential drug interactions. Based on the historic prevalence of major bleeding in ibrutinib clinical studies, we calculated that at least 20 major bleeding events would need to be identified in order to perform blinded multinomial regression on the collected data of an estimated 400 patients. Results: 437 eligible patients were included in the analysis. Patients were overwhelmingly male (71.4%) and white (94.8%), with a mean age of 67.1 years (range: 29-89). 53.1% received ibrutinib as participants of a clinical trial, and the remainder received standard-of-care ibrutinib treatment. The table (upper panel) summarizes use of concomitant antihemostatic agents by presence or absence of major bleeding events. Characteristics of the major bleeding events are further detailed in the lower panel. The most commonly observed concomitant antihemostatic medication was aspirin, with 147 patients (33.6%) being exposed to aspirin within the study period. Fourteen instances of major bleeding were observed, corresponding to an overall incidence of 3.2%. These major bleeding events all occurred in CLL patients receiving ibrutinib at the standard dose of 420 mg daily. Two patients had platelet counts less than 50 k/µL at time of the bleeding event. One-half of the major bleeding events were observed in the absence of an antihemostatic medication, and 2 of the observed major bleeding events resulted in death (1 received concomitant warfarin). Fourteen patients (3.3%) in the group without major bleeding were on anticoagulation, 4 being warfarin. The most common sites of major bleeding were gastrointestinal (50%), intracranial (14.3%) and thoracic (14.3%). While most patients developing major bleeding permanently discontinued ibrutinib (57.1%), approximately one third of the patients who developed major bleeding subsequently resumed ibrutinib following resolution of the bleeding event. Subsequently, these patients did not experience a recurrent major bleeding event. The rate of major bleeding did not meet power to detect statistical differences in bleeding events when comparing concomitant therapy, Conclusions: Our observed incidence of major bleeding is consistent with previous controlled clinical trials, suggesting similar safety profile when ibrutinib is used outside of a controlled setting. Major bleeding events were uncommon despite the frequent co-administration of antiplatelet agents. However, because we modified practice early to avoid therapeutic anticoagulation during ibrutinib therapy whenever possible, the number of patients receiving such drugs in combination was small and precludes inferences regarding safety. Table Table. Disclosures Blum: Pharmacyclics: Research Funding. Awan:Innate Pharma: Research Funding; Pharmacyclics: Consultancy; Novartis Oncology: Consultancy. Woyach:Acerta: Research Funding; Karyopharm: Research Funding; Morphosys: Research Funding. Christian:Pharmacyclics: Research Funding; Janssen: Research Funding. Jones:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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Efficacy and Safety of Primary Thromboprophylaxis for the Prevention of Venous Thromboembolism in Patients with Cancer and Central Venous Catheter: A Systematic Review and Meta-Analysis

Blood ◽

10.1182/blood-2021-146904 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2139-2139

Author(s):

Allen Li ◽

Willem Brandt ◽

Cameron Brown ◽

Tzu-Fei Wang ◽

Rick Ikesaka ◽

...

Keyword(s):

Venous Thromboembolism ◽

Board Of Directors ◽

Major Bleeding ◽

Research Funding ◽

Venous Catheter ◽

Bleeding Complications ◽

Efficacy And Safety ◽

Central Venous ◽

Advisory Committees ◽

Patients With Cancer

Abstract Background Venous thromboembolism (VTE) is a leading cause of mortality in patients with cancer and is associated with significant morbidity and healthcare expenditure. The risk of VTE is also increased following the insertion of a central venous catheter (CVC) for chemotherapy deliverance and supportive care. The risks and benefits of primary thromboprophylaxis in patients with cancer and newly inserted CVC are unclear. Objective We sought to assess the rates of VTE and major bleeding complications to determine the safety and efficacy of primary thromboprophylaxis in adult patients with cancer and a CVC. Methods A systematic search of MEDLINE, EMBASE, and all EBM was conducted. Randomized controlled trials (RCTs) of adult patients with cancer and a CVC receiving primary thromboprophylaxis or observation/placebo were included. The primary efficacy and safety outcomes were total VTE and major bleeding episodes, respectively. Results A total of 9 RCTs (3155 patients) were included in the analysis. The total rates of VTE were significantly lower in patients receiving primary thromboprophylaxis compared to those not receiving primary prevention (7.6% vs. 13%; Odds Ratio (OR) 0.51, 95% CI 0.32 to 0.82, p < 0.01, I² = 52%) (Figure 1). The rate of major bleeding complication was not increased in patients receiving thromboprophylaxis (0.9% vs. 0.7%; OR 1.12, 95% CI 0.29 to 4.40, p = 0.87, I² = 32%) (Figure 2). Conclusions Primary thromboprophylaxis significantly reduced the risk of VTE without increasing the risk of major bleeding complications in patients with cancer and CVC. Future studies are needed to confirm these findings. Figure 1 Figure 1. Disclosures Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding. Ikesaka: LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wells: Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; BMS/Pfizer: Research Funding; Servier: Honoraria. Carrier: Servier: Honoraria; Boehringer Ingelheim: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aspen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Prolonged Lymphopenia and Infection Risk Is Mitigated By Antimicrobial Prophylaxis in Patients with Indolent Non-Hodgkin Lymphoma (iNHL) Treated with Bendamustine +/- Anti-CD20 Antibody: The Australasian Lymphoma Alliance Experience

Blood ◽

10.1182/blood-2020-138642 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 47-49

Author(s):

Kate Manos ◽

Masa Lasica ◽

Andrew Grigg ◽

Pietro R Di Ciaccio ◽

Jonathan Wong ◽

...

Keyword(s):

Risk Factors ◽

Board Of Directors ◽

Research Funding ◽

Antimicrobial Prophylaxis ◽

Advisory Committees ◽

Cd20 Antibody ◽

Grade 3 ◽

Anti Cd20 ◽

The Relationship

Background: Bendamustine +/- anti-CD20 antibody is a highly effective regimen for iNHL. Though initially favoured for its toxicity profile, subsequent analyses demonstrate profound and prolonged lymphopenia and the landmark phase III GALLIUM study showed a grade 3-5 infection rate of 20-26% in the bendamustine arms (Hiddemann JCO 2018). The relationship between severity and duration of lymphopenia and infection, and the role of antimicrobial prophylaxis (ppx), are not fully characterised. We performed a multicentre, retrospective analysis of bendamustine-treated iNHL patients (pts) to define the type and onset of infections, identify concomitant risk factors and evaluate the role of ppx. Methods: iNHL pts aged ≥18 yrs, treated with bendamustine +/- anti-CD20 in 1st-3rd line from 2011-2019, were identified from 9 Australian centres. HIV, prior transplant and long-term immunosuppression were excluded. Demographics, treatment, lymphocyte counts, infections and ppx were collected from baseline to 24 months post end of bendamustine treatment (EOT) or subsequent lymphoma therapy. Association between potential risk factors and infection was evaluated by logistic regression (odds ratio, OR) and negative binomial regression (incidence rate ratio, IRR) with Stata 16.1. Results: 302 pts were eligible. Baseline and treatment characteristics are summarised in Table 1. 252 infection episodes occurred across 134 pts (44%), equally divided between during therapy and after EOT (Figure 1A, Table 2). Infections on treatment occurred in 30% of pts (n=92) with 18% hospitalised (n = 54; n = 20 with febrile neutropenia (FN)) and dose delay /modification/ discontinuation in 11%. Late infections post EOT occurred in 23% of pts (n=70) with 11% hospitalised (n = 32; n = 12 with FN); infection post EOT was more common in pts on maintenance anti-CD20 (infection rate 49% v 16%, OR 5.1 p<0.001). Opportunistic infections (OI) occurred in 21 pts: VZV (n=9; 4 on treatment, 5 post EOT, 1 on ppx); HSV (n=5, all on treatment without ppx); PJP (n=1, on treatment without ppx); nocardiosis (n=1, on treatment); other fungal infections (n=3, all on treatment); PML (n=1, 1-yr post EOT); CMV (n=1, at EOT). Lymphopenia was near universal and prolonged; 98% of pts became lymphopenic (53% grade 3, 9% grade 4) with a median nadir of 0.4x109/L (range 0-2.3). Median time to recovery (>1x109/L) was 10 months post EOT; 39% of pts remained lymphopenic (4% grade 3/4) at 2 yrs (Figure 1B). However, neither lymphopenia nadir nor duration correlated with infection post EOT (OR 0.53 p=0.26 and 0.97 p=0.29 respectively) and the relationship between lymphocyte nadir and OI was not significant (OR 0.09 p=0.053). VZV/HSV and PJP ppx were prescribed to 42% and 54% respectively during treatment and continued for a median of 3 months post EOT (range 0-27, cessation date unknown in 60%). PJP ppx (sulfamethoxazole/trimethoprim) was associated with fewer bacterial infections (OR 0.44 p=0.003) but did not reduce the incidence of FN (OR 0.83 p=0.63). Antiviral ppx (aciclovir/valaciclovir) was associated with fewer VZV/HSV infections (OR 0.10 p=0.026). More ppx was prescribed in 2018-2019 (post GALLIUM) than 2011-2017 (PCP ppx - OR 5.19 p<0.001; VZV ppx - OR 3.76 p<0.001; Figure 2) with an associated fall in the number of infections per pt (IRR 0.55, p=0.011). Factors independently associated with an increased number of infections (during and post EOT) were obinutuzumab vs rituximab (IRR 2.76, p<0.001), maintenance anti-CD20 (IRR 3.43 p<0.001), and stage III/IV disease (IRR 2.55, p=0.002). Factors specifically associated with infection post EOT were maintenance (OR 5.10 p<0.001) and obinutuzumab (OR 3.51 p=0.001). ECOG, hypogammaglobulinaemia, comorbidity index, treatment line and disease subtype were not associated with infections during or post treatment. Conclusion: iNHL pts receiving bendamustine are at high risk of prolonged lymphopenia and infectious complications extending beyond treatment completion, with half of infections occurring post treatment cessation. Lymphopenia duration and nadir did not correlate with infection. PJP and antiviral ppx reduced risk of bacterial and VZV/HSV infections respectively, though rates of PJP and VZV/HSV were low. Prolonged ppx to mitigate the risk of late infections should be considered, particularly in pts with additional risk factors such as concomitant obinutuzumab and anti-CD20 maintenance. Disclosures Manos: Bristol-Myers Squibb: Other: Travel. Di Ciaccio:Jansen: Honoraria, Other: travel and accomodation grant. Hamad:Abbvie: Honoraria; Novartis: Honoraria. Gregory:Janssen: Consultancy; F. Hoffmann-La Roche, Genentech, Inc., MSD, AbbVie, BeiGene, AstraZeneca, Celgene, BMS: Research Funding; F. Hoffmann-La Roche, Novartis, Sandoz, Gilead, AbbVie, MSD: Honoraria; F. Hoffmann-La Roche, Novartis, AbbVie: Speakers Bureau; F. Hoffmann-La Roche, Novartis, Sandoz, Gilead: Membership on an entity's Board of Directors or advisory committees. Gangatharan:Roche: Other: Travel grant. Hawkes:Merck Sharpe &Dohme: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding, Speakers Bureau; BMS celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck KgA: Research Funding; takeda: Speakers Bureau.

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