Treatment Modifications Research Articles

Challenges in Family Planning and Pregnancy for Women with Rheumatic Diseases

Systemic rheumatic diseases (RDs) often affect women in their reproductive years and may complicate family planning and pregnancy. For women with RD who are not pursuing pregnancy, especially those at the highest risk of maternal morbidity or on teratogenic medications, effective contraception is important. For women with active systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies, oestrogen-containing contraceptive methods are generally not recommended. Emergency contraception and induced abortion are safe for women with RD and should be discussed when clinically appropriate. Women with RD commonly have questions and concerns about the impact of their disease on fertility and conception. RD-associated factors may contribute to difficulties in conceiving and decreased family size. Assisted reproductive technology (ART) is often a safe option for women with RD. However, precautions and specific treatment modifications may be needed, particularly in women with SLE and/or antiphospholipid antibody positivity. SLE and antiphospholipid syndrome (APS) are the RDs associated with the greatest risk of maternal and foetal pregnancy complications. Regardless of the specific RD, having an active disease is a significant risk factor for poor pregnancy outcomes. With appropriate preconception planning and multidisciplinary management during and after pregnancy, most women with RD can have successful pregnancies.

NONCOMPLIANCE TO TREATMENT AND COMMON PRECIPITATING FACTORS IN STAGE C HEART FAILURE

Objectives: The objective of this study was to determine the frequency of non-compliance to treatment and common precipitating factors in stage C heart failure (HF) patients at a tertiary care cardiac hospital of Karachi, Pakistan. Methodology: This descriptive cross-sectional study was conducted at a tertiary care cardiac center of Karachi, Pakistan. Required number of consecutive patients of either gender between 18 to 75 years of age who were diagnosed with stage C HF were included in this study. Data for the study were collected on a pre-defined proforma consisted of demographic characteristics (gender, age), clinical factors, and precipitants of decompensation of HF (duration of disease, non-compliance to the treatment, infection, arrhythmias, uncontrolled hypertension, and anemia). Results: A total of 114 patients with stage C HF were included. Mean age was 56.7 ± 9.9 years with 34.2% (39) patients above 60 years of age. Male patients were 51.8% (59) of the total sample and median duration of disease was 36 [20 to 60] months. Non-compliance to the HF treatment was observed in 48.2% (55), while among other precipitants, infection was observed in 21.9% (25), arrhythmias in 20.2% (23), uncontrolled hypertension in 13.2% (15), and anemia in 18.4% (21). Conclusion: A significant proportion of stage C HF patients were found to be non-adherent to the prescribed treatment. The most commonly observed triggering factor was infection followed by arrhythmias. Routine practice must include an ongoing assessment of compliance to the treatment and lifestyle modifications among HF patients for the proper counseling of non-complying individuals.

Uveitis in spondyloarthropathies

Background: Uveitis is associated with several systemic disorders. It may be the initial presentation or manifestation of a systemic disease. It is the most common ocular complication and is sometimes the earliest manifestation of spondyloarthropathies. This study aimed to review the current literature on spondyloarthropathies and associated uveitis.
 Methods: A narrative review was performed using various combinations of the keywords spondyloarthropathies, seronegative spondylarthritis-related uveitis, and human leukocyte antigen-associated uveitis using PubMed/MEDLINE and Google Scholar from January 1, 2000, to September 30, 2022. We describe the disease mechanisms, genetics, and classification of spondyloarthropathies, the clinical patterns of their related ocular diseases, and the current modalities for the management of their ocular or systemic manifestations.
 Results: Seronegative spondyloarthropathies are a group of rheumatic disorders including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, inflammatory bowel disease-related spondyloarthropathy, juvenile-onset spondyloarthritis, and undifferentiated spondyloarthritis. These are characterized by enthesitis in the absence of serum rheumatoid factor and have a strong association with human leukocyte antigen B27. The clinical courses and features of spondyloarthropathies are remarkably diverse. Ocular inflammation is common in spondyloarthropathies, often precedes the onset or diagnosis of systemic disease, and responds well to topical therapy. Timely diagnosis of systemic diseases may improve quality of life and help avoid ocular and skeletal complications. Recurrence of ocular inflammation is frequent; on occasion, it may be associated with etanercept administration.
 Conclusions: Eye care professionals should be able to recognize spondyloarthropathies, manage ocular disease, and collaborate with related specialties for modification of systemic treatment if associated with ocular complications. Timely referral and early management could attenuate or prevent ocular or systemic morbidities associated with spondyloarthropathies.

Preparation and application of low-cost fibers for efficient adsorption of oil from coal pyrolysis wastewater and establishment of quantitative equation for calculating oil contact angle under water

The removal of oil from coal pyrolysis wastewater persists to be a challenging problem. Thus, this study proposes a new scheme that integrates the adsorption of oil using fibers and subsequent centrifugation or elution to achieve efficient oil–water separation. Based on their stable chemical property, PP and were selected as the substrates for drawing the fibers. In addition, PVDF and PTFE were explored to modify the wettability of PP and PE. The performances of as-prepared fibers were tested for removing oil from wastewater in both batch and continuous modes. Among all the fibers, the PVDF-modified PP fibers exhibited the best performance. For PP-based fibers with 5 wt% PVDF, the saturated oil-removal efficiency reached 92.24 % in case of the simulated wastewater and 81.10 % for the actual wastewater. Given that the oil content in coal pyrolysis wastewater was ~2000 ppm, the residual oil content in the outlet water would be ~380 ppm, which satisfies the requirement of the subsequent treatment process. Furthermore, the PVDF-modified PP fibers exhibited excellent reusability and stability to defy various environmental corrosions. The separation of oil and water based on the adsorption by fibers offers promising prospect to remove oil from coal pyrolysis wastewater. In addition, we derived a formula to calculate the oil contact angle under water based on Young's equation using several measurable parameters. As the calculation results were consistent with real scenarios, this derived formula can provide quantitative guidance for material modification in coal wastewater treatment.

Enhancing Parent-Implemented Functional Communication Training by Assessing Indices of Happiness

Indicators of well-being can be important measures for improving the treatment of challenging behavior and family quality of life. We examined methods for assessing activities associated with indices of happiness (IOH) in a 5-year-old girl with Down syndrome, to mitigate challenging behavior during parent-implemented functional communication training (FCT). During the initial phase treatment (FCT + extinction), challenging behavior persisted, and parents expressed an emerging sense of hopelessness. Treatment modifications informed by the assessments resulted in a > 90% decrease in challenging behavior, promoted reinforcer schedule thinning, improved cooperation with daily routines, and also increased the child’s IOH and parent satisfaction.

Integrated mental health treatment guidelines for prescribers in intellectual and developmental disabilities

AbstractFew healthcare providers receive guidance on the unique needs of persons with intellectual and developmental disabilities and mental healthcare needs. Our aim was to develop a tool for health care providers to use as a guide to address the complex needs of this patient population. The development of the Integrated Mental Health Treatment Guidelines for Prescribers in Intellectual and Developmental Disabilities consisted of five steps: focus groups, draft of the guidelines, evaluation of the guidelines, finalization, and dissemination of the guidelines. The focus groups revealed themes in five domains: (1) relationships, communication, and openness; (2) understanding the person, their environment, and culture; (3) importance of an integrated care and wellness approach; (4) consideration of treatment modifications; (5) recommendations from focus group participants regarding the guidelines. These focus groups informed the development of the guidelines. Forty‐three prescribers evaluated the guidelines noting multiple strengths and some recommendations. Based on this feedback the guidelines were modified as needed, finalized, and disseminated. This paper describes the development of the Integrated Mental Health Treatment Guidelines for Prescribers in Intellectual and Developmental Disabilities. An evidence‐informed, easy‐to‐use, web‐based guide with links to best practice resources. These guidelines incorporate integrated health, other mental health approaches, and the input of patients.

301. Use of a multiplex PCR assay for detection of respiratory co-infections in COVID-19 hospitalized non-ICU patients: an ace up a clinician’s sleeve

Abstract Background Bacterial co-infections in COVID-19 patients represent a significant challenge for clinicians and can impact outcomes. Rapid identification of bacterial co-pathogens improves management, and is crucial to avoid inappropriately administered antimicrobials. We evaluated the use of a multiplex PCR assay in the early detection of respiratory co-infections in COVID-19 hospitalized patients. Methods The study included non-ICU patients with high clinical suspicion of respiratory co-infection. Lower respiratory tract samples (sputum/bronchial secretions), were analyzed using BIOFIRE® FILMARRAY® pneumonia panel plus [(bioMerieux, USA), FA]. Specimens were considered as acceptable based on Gram stain. Conventional cultures were also performed. Results A total of 28 samples from 27 patients (20 males, median age 60 years, IQR 49-71) were analyzed. 8/27 patients were intubated, 5 were treated with high flow nasal canula oxygenation and 11 with high or low oxygen mask. 18 patients received dexamethasone. Co-infection was detected in 17/27 patients (62.9%). 11 specimens were collected in less than 48 hours from admission and no target was identified in 6/11. Detected pathogens and AMR genes, per sample tested, are presented in the table. Bacterial pathogens and any AMR genes were detected in 15 and 4 samples, respectively, leading to modifications of antimicrobial treatment. The semi-quantitative results along with patients’ clinical presentation assisted with differentiation of bacterial colonization versus infection, especially in cases where multiple targets were identified. De-escalation was implemented for 12 patients, for whom no co-infection or a viral co-pathogen (n=2) was detected. One patient was co-infected with another Coronavirus; further analysis, using the FA respiratory panel, detected Human coronavirus HKU-1 along with SARS-CoV-2. Median time until discharge or death was 13.5 days (IQR 9-24). Overall mortality was 33.3%. Detected pathogens, microbial load and AMR genes, per sample tested. Conclusion Implementation of FA assay proved effective for the rapid detection of respiratory co-infections in COVID-19 non-ICU patients. Molecular panel-based assays can contribute to timely adaptation of antimicrobial treatment, benefiting patient management and antibiotic stewardship strategies. Disclosures All Authors: No reported disclosures.

Evaluation and Clinical Impact of Biofire FilmArray Pneumonia Panel Plus in ICU-Hospitalized COVID-19 Patients.

Microbiological diagnosis by using commercial multiplex quantitative PCR systems provides great advantages over the conventional culture. In this work, the Biofire FilmArray Pneumonia Panel Plus (FAPP+) was used to test 144 low respiratory tract samples from 105 COVID-19 patients admitted to an Intensive Care Unit (ICU), detecting 78 pathogens in 59 (41%) samples. The molecular panel was evaluated by using the conventional culture (CC) as comparator, which isolated 42 pathogens in 40 (27.7%) samples. The overall percentage of agreement was 82.6%. Values of sensitivity (93%), specificity (62%), positive predictive value (50%), and negative predictive value (96%) were obtained. The mean time elapsed from sample extraction to modification of antibiotic treatment was 7.6 h. A change in antimicrobial treatment after the FAPP+ results was performed in 27% of patients. The FAPP+ is a highly sensitive diagnostic method that can be used to significantly reduce diagnostic time and that allows an early optimization of antimicrobial treatment.

The prognostic significance of hematogones in childhood B-cell acute lymphoblastic leukemia.

Recent studies have demonstrated hematogones (HGs) expansion to be associated with favorable outcomes in hematological diseases, especially in patients with acute myeloid leukemia and patients undergoing hematopoietic stem cell transplantation. Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. As of now, minimal residual disease (MRD) remains the most compelling independent prognostic factor in childhood ALL. There is need for more prognostic tools for evaluating relapse risk. The goal of this study was to assess the prognostic value of HGs on relapse-free survival (RFS) and overall survival (OS) in childhood ALL. In this prospective cohort study, a total of 122 subjects with definitive diagnosis of precursor B lymphoblastic leukemia were evaluated. Flow cytometric HG detection was performed in bone marrow aspirates after induction and consolidation therapy. The median follow-up period of patients was 35.5±9.4 (SD) months. Patients who had at least 1.0% HGs had a significantly better RFS (p=.023). Moreover, univariate and multivariate analyses confirmed that positive HGs were independently associated with longer RFS (unadjusted model: hazard ratio=0.33, 95% CI=0.12-0.91, p=.031; adjusted model: hazard ratio=0.30, 95% CI=0.11-0.82, p=.020). Along with the role of MRD, our study shows the significance of HGs as an independent prognostic factor. The results indicate the independent prognostic value of HGs on RFS after adjustment for other prognostic factors, and can be beneficial for risk stratification and treatment modifications amongst pediatric B-cell ALL patients.

S17 Treatment Patterns Among Moderate-to-Severe Ulcerative Colitis Patients in TARGET-IBD

Background: The treatment paradigm for Ulcerative Colitis (UC) is becoming increasingly complex with more treatment options available. There is a growing need to discern patterns of UC treatments in real-world settings. The objectives of this study were to identify a real-world moderate-to-severe UC patient population and estimate the risk of treatment modification (i.e. drug switching, dose escalation, treatment augmentation) among patients initiating advanced or conventional therapies. Methods: TARGET-IBD, a non-interventional cohort of IBD patients enrolled from one of 34 participating academic and community-based gastroenterology US sites, was used to identify the study population. Enrolled patients consented to the collection of up to 3 years of retrospective and 5 years prospective data. Patients were considered moderate to severe if they were ever hospitalized due to UC, received advanced treatments (biologics or Janus kinase inhibitor [JAKi]), an immunomodulator (IMM), or took corticosteroids for >2 months of the year prior to enrollment. To assess treatment modification, patients had to initiate an advanced treatment, or conventional therapy (IMM and 5-aminosalicylic acids) 3 years prior to or after enrollment and have a follow-up duration of at least 1 day. The incidence proportion was defined as the number of patients that experienced a treatment modification in the study period divided by the number of patients at risk. Kaplan Meier curves and cumulative incidence functions were produced for both treatment classes. Fine Gray sub-distribution hazard regression models were used to estimate the unadjusted and multivariable-adjusted hazard rate ratios for treatment modification, with 95% confidence intervals. Results: Out of 1,854 adult UC patients enrolled in TARGET-IBD, 1,332 patients met criteria for moderate to severe UC, of which 1,096 (82%) used an advanced treatment by the date of enrollment. Compared to patients on conventional therapies, patients on advanced treatments were younger (39 vs 50 years old), less likely to be on Medicare (11.6% vs 18.6%), and disproportionately treated at academic sites (70% vs 56%). A total of 660 patients initiated advanced (n=366, 55.5%) or conventional (n=294, 44.5%) therapy during the observation periods and were evaluated for treatment modification. The incidence proportion of treatment modification was lower in patients with advanced treatment compared patients with conventional therapy [47.6% (95% CI = 41.3, 53.8) vs 64.8% (95% CI = 58.3, 71.2), respectively]. Kaplan Meier curve showed that the probability of treatment modification increased with time on treatment for both groups, but was significantly more likely for patients on conventional therapies (median survival = 11.3, 95% CI = 8.80, 13.19) compared to that of patients on advanced treatments (median survival = 13.0, 95% CI = 9.72, 16.90). Both univariate and multivariable models showed that use of an advanced treatment was associated with decreased likelihood of treatment modification (HR = 0.73, 95% CI = 0.56, 0.95). Conclusion(s): In this large, real-world cohort analysis, moderate-to-severe UC patients initiating advanced treatments were significantly less likely to experience treatment modifications than those receiving conventional therapies. This study highlights the importance of therapy selection for patients with moderate-to-severe UC and the need for additional, more efficacious, and durable treatments.

Evaluation of factors affecting epidermal growth factor receptor tyrosine kinase inhibitor-induced hepatotoxicity in Japanese patients with non-small cell lung cancer: a two-center retrospective study

BackgroundGefitinib and erlotinib, are epidermal growth factor receptor tyrosine kinase inhibitors, and are currently recommended for non-small cell lung cancer stage IV in the elderly and in patients with decreased performance status in the Japanese Lung Cancer Society Guideline, but they occasionally caused severe hepatotoxicity requiring postponement or modification of treatment. However, little is known about the risk factors for hepatotoxicity in patients receiving gefitinib and erlotinib. In this study, we investigated the factors influencing hepatotoxicity in Japanese non-small cell lung cancer (NSCLC) patients treated with gefitinib or erlotinib monotherapy.MethodsJapanese patients with NSCLC who started gefitinib or erlotinib monotherapy from January 2005 to December 2017 at Kanazawa University Hospital or Kanazawa Medical University Hospital were included in this study. Factors affecting hepatotoxicity were retrospectively investigated by multiple logistic regression analysis.ResultsA total of 102 patients who received gefitinib and 95 patients who received erlotinib were included in the analysis. In the gefitinib group, a body mass index (BMI) ≥ 25 was associated with an increased risk of hepatotoxicity (OR = 4.571, 95% CI = 1.486–14.056, P = 0.008). In the erlotinib group, concomitant use of acid-suppressing medications (AS), namely proton pump inhibitors or histamine-2 receptor antagonists, was associated with a reduced risk of hepatotoxicity (OR = 0.341, 95% CI = 0.129–0.900, P = 0.030).ConclusionsBMI ≥ 25 in patients treated with gefitinib increased the risk of hepatotoxicity. In contrast, AS combination with erlotinib reduced the risk of hepatotoxicity. Thus, because different factors influence the risk of hepatotoxicity, monitoring for adverse events should take into account patient background factors and concomitant medications.

Patellofemoral Anatomical Measurements on MRI in Patient with Suprapatellar Fat Pad Edema and Mass Effect.

To evaluate the impact of patellofemoral joint anatomical measurements of patients with anterior knee pain who were diagnosed with suprapatellar fat pad (SPFP) impingement syndrome (SP-FPIS) by magnetic resonance imaging (MRI). A prospective, descriptivestudy. Goztepe Education and Research Hospital, between March 2015 and June 2019. The study included 34 patients (Group 1) and 34 healthy volunteers (Group 2) who were referred to the radiology clinic with anterior knee pain; they underwent MRI and diagnosed with SP-FPIS. Twenty-three anatomical measurements such as SPFP cranio caudal length (CC), anteroposterior length (AP), oblique length (OBL), patellar length (PL), patellar tendon length (PTL), Insall Salvati Index (ISI), patellar cartilage distal-tibial tubercle (TT), patellar cartilage length (PCL), Modified Insall Salvati Index (MISI), patellotrochlear cartilage length (TCL), lateral trochlear inclination angle (LTI), etc. related to the morphological structure of SPFP and patellofemoral joint were evaluated and compared in both groups. The mean age of groups 1 and 2 was 45.62±10.87 and 41.47±11.98 years, respectively. There was a statistically significant difference in patients with SP-FPIS in PL, PT, TT, PC, MISI, TC, PTI, MF, PHY, PPI, MT, LTI, CC, AP, and OBL measurements compared with the control group (p<0.05). In the logistic regression analysis performed to evaluate the effect of statistically significant parameters on anterior knee pain, the probability of SP-FPIS increases 1.5 times as PTL increases among the groups, while the risk of SP-FPIS decreases 0.78 times as LTI decreases (p<0.05). There is a predisposing effect of PTL increase in SP-FPIS development, while LTI decrease has a protective effect. These results will guide future studies for the development and/or modification of treatment methods. Patellofemoral joint, Suprapatellar fat pad impingement syndrome, Anterior knee pain, Knee magnetic resonance imaging, Knee anatomy.

Global distribution of microplastic contaminants in aquatic environments and their remediation strategies.

This review describes the occurrence and distribution of microplastics in freshwater and marine environments in recent years (2017-2022). Use of microplastics often results in contamination of aquatic environments, threatens biodiversity, and creates the need for environmental remediation. Such remediation strategies can involve primary, secondary, and tertiary treatments. Tertiary treatment is a frequent research subject due to its high efficiency and the possibility for advancements and enhancements. This study discusses tertiary treatments with remediation efficiencies of 95% and greater and their advantages, disadvantages, and future perspectives. Biochar-mediated remediation of microplastics is an effective method that may be able to achieve efficiencies approaching 100%. The study concludes by exploring methods of removing microplastics, including constructed wetlands and biochar, which offer high efficiency. PRACTITIONER POINTS: Tertiary treatments are an effective microplastic remediation strategy applicable succeeding secondary or primary treatments or as an individual remediation strategy. Biochar is a highly efficient adsorbent for microplastic remediation from aquatic environment with eco-friendly aspect and reusability. Modifications in tertiary treatments and enhancement in remediation efficiency are still a subject of research for future studies.

Relationship between anti-GBM antibodies and kidney outcomes in patients with anti-GBM disease.

Animal experiments have shown that anti-GBM antibodies play a pathogenic role in anti-GBM disease. However, the relationship between anti-GBM antibody levels and kidney outcomes in patients with anti-GBM disease is unclear. We performed a retrospective analysis of 110 patients diagnosed with anti-GBM disease. We compared their baseline characteristics stratifying on different anti-GBM antibody levels, and used Cox regression analysis to analyze the correlation between antibody levels and kidney survival. We further selected 69 patients to evaluate the modification of antibody titersover 14daysof treatment, then compared kidney survival of patients in the group with antibody level decrease < 48% to those with antibody decrease ≥ 48%. The 110 patients had a median follow-up of 27.1 (Q1-Q3: 7.9-80.1) months, and among them 90 (81.8%) developed kidney failure. Multivariate analysis suggested that anti-GBM antibody level was an independent risk factor for progression to kidney failure in patients with anti-GBM disease (HR 1.08, 95% CI 1.01-1.16). The patients who reduced the antibodies levelsquickly had better kidney survival than those who did not, and multivariate analysis also indicated that antibody decrease rate was related to kidney outcomes. Anti-GBM antibody level is closely related to kidney outcomes in patients with anti-GBM disease, and short-term reduction of antibodies can be beneficial to improving kidney outcomes.

139 Blocking Interleukin-17 in Psoriasis: Real-world Experience from the PsoPlus Cohort

Real-world studies on the use of biologics in psoriasis (Pso) are increasing, but still scarce. Next, interleukin-17 inhibitors (IL-17i) trough concentrations (Ct) seem promising for clinical decision making, however its value in daily practice has yet to be proven. Objectives were to report on IL-17i effectiveness, treatment modifications, and Ct use in our clinic. Data was collected from IL-17i treated Pso patients followed up in the PsoPlus clinic at the Dermatology department, Ghent University Hospital, Belgium.

Food preservation by cold plasma from dielectric barrier discharges in agri-food industries.

Cold plasma (CP) can be defined as partially or wholly ionized gas carrying myriads of highly reactive products, such as electrons, negative ions, positive ions, free radicals, excited or non-excited atoms, and photons at ambient temperature. It is generated at 30-60°C under atmospheric or reduced pressure (vacuum). In contrast to thermal plasma, it requires less power, exhibits electron temperatures much higher than the corresponding gas (macroscopic temperature), and does not present a local thermodynamic equilibrium. Dielectric barrier discharges (DBD) are one of the most convenient and efficient methods to produce CP. Cold plasma technology has the potential to replace traditional agri-food processing purification methods because of its low energy requirements and flexible system design. CP technology works by reducing bacteria levels and removing pests and mycotoxins from your produce at harvest. It can also catalyze physiological and biochemical reactions and modify materials. It can meet microbial food safety standards, improve the physical, nutritional, and sensory characteristics of the products, preserve unstable bioactive compounds, and modulate enzyme activities. This manuscript also discusses the quality characteristics of food components before/after CP treatment. In the past decade, CP treatments of food products have experienced increased popularity due to their potential contributions to non-thermal food processing. There is no doubt that CP treatment is a flexible approach with demonstrated efficacy for controlling many risks across food and agricultural sustainability sectors. In addition, CP technologies also can be applied in food-related areas, including modification of chemical structures and desensitization treatments. There is a need to fully assess the benefits and risks of stand-alone CP unit processes or their integration as a processing chain as soon as the economic, ecological, and consumer benefits and acceptability are considered.

Combination of Thrombopoietin Receptor Agonist and Recombinant Human Thrombopoietin for Treating Cancer Therapy Induced Thrombopenia

Background Cancer therapy induced thrombopenia (CTIT) refer to thrombopenia caused by various anti-cancer therapy which include chemotherapy, radiotherapy, targeted therapy and immunotherapy. Chemotherapy-induced thrombopenia (CIT) could increase the risk of bleeding, modification of treatment, cost of treatment and even influence overall survival. Recombinant human thrombopoietin (rhTPO) was approved for CIT by national medical products administration (NMPA). However, certain patients still could not benefit from these agents. Hetrombopag, a new orally active small molecule thrombopoietin receptor agonist (TPO-RA), acts through binding to thrombopoietin receptor to stimulate multiple intracellular signaling pathways, including JAK/STAT, PI3K/AKT and ERK1/2. This will stimulate the proliferation and differentiation of megakaryocytes and promote platelet production. Combination of TPO-RA and rhTPO is anticipated to improve the outcome compared with rhTPO alone for treating CTIT in cancer patients. Methods Between January 2021 and June 2022, we conducted a retrospective analysis of patients (18 - 80 years) with cancer therapy induced thrombopenia (platelet count < 50 x 109/L) treated with rhTPO (subcutaneous injection, 300 U/kg/d) alone or combination of rhTPO and hetrombopag (oral, 5 mg/d) at Beijing Luhe Hospital, Capital Medical University. Treatment will discontinue when platelet count increased more than 50 x 109/L or platelet count doubled than baseline. The maximum treatment was 14 days. Results In total, 58 patients were included for analysis (28 patients received rhTPO plus hetrombopag and 30 patients received rhTPO alone). The baseline characteristics were generally similar between two groups. Patients with baseline platelet count less than 30 x109/L were 28.6% vs 10% in rhTPO plus hetrombopag group and rhTPO alone group, respectively. There were 21 patients (75.0%) vs 9 patients (30.0%) achieved response (platelet count increased more than 50 x 109/L or doubled than baseline or reached more than 100 x 109/L without platelet transfusion) within 7-day treatment in rhTPO plus hetrombopag group and rhTPO alone group, respectively. Furthermore, 11 patients (39.3%) and 3 patients (10.0%) reached platelet count ≥100 x 109/L in rhTPO plus hetrombopag group and rhTPO alone group (Table 1). The median platelet count at baseline in two groups were similar. The platelet count of post treatment in two groups were both increased. While the platelet count increase in rhTPO plus hetrombopag group were higher than rhTPO group in day 3, day 5, day 7 and day 9 after treatment (Figure 1). Median time of treatment was 6.5 days (range 4-13) for rhTPO plus hetromnopag group and 9.5 days (range 5-14) for rhTPO group (P < 0.0001). One patient (3.3%) in rhTPO group reported bleeding (WHO bleeding grade 2) while no bleeding events were reported in rhTPO plus hetrombopag group. Five patients (16.7%) and three patients (10.7%) in rhTPO group and rhTPO plus hetrombopag group received platelet transfusion. Cancer patients treated with rhTPO or rhTPO plus hetrombopag were well tolerated, the treatment related adverse events were mainly alanine aminotransferase/aspartate aminotransferase increase or total bilirubin increased (all grade 1/2). The incidence of such adverse event was not significantly different between two groups. Conclusion Compared with rhTPO, combined rhTPO with hetrombopag for treating cancer therapy induced thrombopenia showed faster and deeper response without raise the safety concern. Further study needed to consolidate this result. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Single Institutional Experience Using Romiplostim to Manage Treatment Related Thrombocytopenia in Pediatric Solid Tumor Patients

Background: Therapy related thrombocytopenia (TRT), particularly chemotherapy induced thrombocytopenia (CIT), is a common toxicity encountered by pediatric solid tumor patients. It is associated with both reduced relative dose intensity of chemotherapy treatment as well as increased platelet transfusion requirements. Given the utility of thrombopoietin receptor (TPO-R) agonists in adult CIT and the reassuring safety profile in pediatric immune thrombocytopenia (ITP), romiplostim has been widely used in our department for management of TRT. This study describes our single institution experience of the off-label use of romiplostim for TRT in pediatric solid tumor patients. Methods: This study retrospectively evaluated solid tumor patients (sarcomas, high-risk neuroblastoma, and CNS tumors) treated at Memorial Sloan Kettering Cancer Center between 2010-2022 who received romiplostim during their cancer therapy for TRT. TRT was defined as thrombocytopenia attributed to cancer-directed therapy that persisted despite adequate recovery time and/or resulted in treatment modifications. Baseline data (Table 1) was collected on patient demographics, tumor types, cancer therapy, and dosing and duration of romiplostim administration. The primary endpoint was impact of romiplostim on TRT measured through (1) the median platelet count throughout romiplostim treatment, (2) the time-to-platelet count recovery after initiation of romiplostim (defined by platelet count of ≥75 µ/L), (3) the median number of platelet transfusions while on romiplostim. Safety data was also collected on incidence of venous thromboembolism (VTE) development during romiplostim treatment. Results: A total of 62 patients were included with mean age 8.5 years (range: 1.0 to 30.0 years). The overall median time on romiplostim was 17 weeks (range 1-95). The median starting dose ranged from 1-5 mcg/kg, with the majority (81%) starting at 3 mcg/kg and a median maximum dose of 8mcg/kg. There was an upward trend of platelet counts over time with a sustained response measured 30 days post-romiplostim discontinuation (Figure 1). Disease subgroup was a predictor of platelet counts while on romiplostim as the patients with sarcomas had higher counts compared to the other histologic subgroups (p < 0.001). Within the neuroblastoma cohort, there appears to be a difference in platelet response depending on type of cancer-directed therapy, with chemo and immunotherapy groups exhibiting a higher response than the radionuclide group. Of the total 62 patients, 48 (77%) experienced a platelet recovery and the median measured time-to-recovery was 45 days; with the sarcoma patients experiencing the earliest time-to-recovery with a median time of 8 days (p < 0.001). In assessing incidence of adverse events, of the 62 studied patients, 2 (3%) were noted to be on anticoagulation for a documented VTE while on romiplostim. Conclusions: Given such paucity of available data in pediatrics, the purpose of this retrospective study was to provide insight into the off-label use of romiplostim in pediatric oncology patients. From the analysis of the 62 patients treated with romiplostim during their cancer treatment course, it appears that romiplostim was well tolerated and exhibited potential in providing clinical benefit. While the length of romiplostim treatment varied depending on the specifics of a patient's cancer-directed therapy, overall, the median time on romiplostim was approximately 4 to 5 months with some patients being notably treated for > 1 year. Future, prospective studies are warranted to study the efficacy of using TPO-R agonists in pediatric oncology patients for the indication of TRT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Improvement of Platelet Count after Helicobacter Pylori Screening and Eradication in Immune Thrombocytopenia Patients: A Randomized Open-Label Study

Background:Helicobacter pylori (HP) has been known as a secondary cause of immune thrombocytopenia (ITP). Previous studies have demonstrated platelet count improvement after HP eradication in ITP. However, the impact of HP screening in adults with ITP remains unclear. Methods: We conducted a randomized open-label study to evaluate the benefit of HP screening to improve platelet count in ITP patients. Persistent or chronic ITP patients with ≥ 18 years of age who had platelet count below 150 x109/L were eligible. Patients were excluded if there were HIV or hepatitis C virus infection, active cancer, history of HP eradication within 1 year, or antibiotics/bismuth use within one month before enrollment. Patients were allocated in a 3:1 ratio to the HP screening arm or non-screening arm. Patients in the HP screening arm underwent 2 methods of HP screening: urea breath test (UBT) and HP serology test (Assure® H. pylori Rapid Test). Patients who had positive HP results by either test were received HP eradication with a 14-day course of proton pump inhibitor-based triple therapy. Treated patients were subsequently confirmed HP eradication by stool antigen test at 1 month. Dose modifications of treatments for ITP were allowed according to the treating physician's decision. Platelet count and 3-month cumulative dose of prednisolone were measured at baseline, 3 months, and 6 months. Quality of life using the Thai version of EQ-5D-5L was assessed at baseline and 6 months. The primary outcome was the mean difference in platelet count at 6 months. Key secondary outcomes were the prevalence of HP infection in adult ITP patients and improvement of EQ-5D-5L score at 6 months. Other outcome was the diagnostic accuracy of the HP serology test. Results: A total of 64 patients were enrolled. Forty-nine patients were assigned to the HP screening arm and 15 patients to the non-screening arm. Mean age was 47.2 years (SD 15.7). Fifty patients (78%) were female. Forty patients (62.5%) were using prednisolone with a mean dose of 8.5 mg/day. Mean platelet count at baseline was 73.8 x109/L (SD 29.5). Baseline characteristics were balanced (Table 1). All of the patients, except one, in the HP screening arm completed 2 methods of screening. Twenty-three of 48 patients had HP positive results by UBT, as a result, the prevalence of HP was 47.9%. All HP-positive patients completed an HP eradication course. One patient had a positive result of stool antigen test after HP eradication, which was successfully eradicated with levofloxacin-based treatment. At 6 months follow-up, patients in the HP screening arm had a significant improvement in platelet count as compared to baseline with a mean difference of 21.8 x109/L (95% CI 22.2 - 41.3, p=0.030) (Table 2). In addition, the EQ-5D-5L score revealed a significant improvement at 6 months as compared to baseline in the HP screening arm with a mean difference of 4.2 points (95% CI 0.8 - 7.6, p=0.016) (Table 2). Patients in the non-screening arm had no significant changes in platelet count or EQ-5D-5L score. A 3-month cumulative dose of prednisolone and dose adjustments of concomitant ITP treatments at 6 months in both arms were not significantly changed. Of 23 UBT-positive patients, only 11 patients had positive results with HP serology. All 25 UBT-negative patients also had negative results with HP serology. The sensitivity and specificity of the HP serology test were 47.8% and 100%, respectively. Conclusion: The prevalence of HP infection in adult Thai ITP patients was 47.9%. HP screening is effective in the improvement of platelet count and quality of life at 6 months in adult ITP patients with platelet count below 150 x 109/L. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Fast-Track Measurable Residual Disease Detection By Multiparametric Flow Cytometry in Acute Myeloid Leukemia before Allogeneic Hematopoietic Cell Transplantation

Introduction In acute myeloid leukemia (AML), measurable residual disease (MRD) becomes more and more important for individualized treatment decisions. The MRD status at the time of allogeneic hematopoietic cell transplantation (alloHCT) provides prognostic information beyond baseline risk features. Peri-transplant treatment strategies and conditioning intensity can be stratified according MRD-levels. However, therapeutic interventions (e.g. conditioning intensity) usually require the prompt availability of reliable information on the MRD status. We assessed the prognostic value of a standardized, reproducible, and fast turnover multiparametric flow cytometry (MFC) approach that has been validated at the end of intensive induction therapy to monitor MRD before alloHCT (Röhnert, Leukemia 2022). This approach allows for the simultaneous detection of MRD by the leukemia-associated immunophenotype (LAIP) and the different from normal (DfN) method. Methods Between October 2016 and March 2020, bone marrow (BM) aspirates of patients (pts) with AML were analyzed for the presence of MRD immediately before the start of conditioning. therapy with the aim of analyzing to predictive value of this fast-track parameter. Pts receiving sequential regimens (re-induction chemotherapy followed by reduced-intensity conditioning) were excluded. Briefly, the LAIP-based DfN analysis is based on a hierarchical gating strategy with fixed gates and encompasses the antigens CD34, CD117, HLA-DR (backbone markers), CD13, CD33 (myeloid markers), CD7 and CD56 (lymphoid markers). Within less than 5 minutes, the analysis checks for the presence of the aberrant categories i) deficiency of myeloid markers and ii) cross-lineage expression of lymphoid markers. Reference values for 32 immunophenotypically defined populations were established on BM aspirates of 90 leukemia free controls. An aberrant category already detectable at diagnosis on ≥10% of myeloid progenitors/ monocytes was termed aberrant LAIP (aLAIP) and a de-novo appearance (after chemotherapy) post-treatment DfN (ptDfN). In conclusion this approach is very fast and provides high reproducibility. Results We identified 58 pts with a median follow-up of 33.3 months after alloHCT (Table 1 with pts characteristics). Response assessment was performed in median 8 days before alloHCT. Most of the patients were in morphologic complete remission (CR n=37). A subset of 21 patients had refractory disease with a median BM blast count of 6.5%. Samples at AML diagnosis were available for 48/58 (83%) pts, of whom 34/48 (71%) showed at least one aLAIP at initial diagnosis. Before start of conditioning, 44/58 (76%) patients were MRDpos. The proportion of MRDpos in responders was lower compared to non-responders: 24/37 (65%) vs. 20/21 (95%) (p=0.0106). MRDpos was designated by aLAIPonly, ptDfNonly and aLAIP+ptDfN in 18%, 48% and 34% of cases, respectively. Noteworthy, 8 of 21 pts classified MRDpos by ptDfNonly had no sample available at diagnosis and therefore could not be assessed for aLAIP persistence. Amongst 37 pts in CR before alloHCT, 12/24 (50%) of MRDpos pts relapsed compared to 3/13 (23%) of MRDneg pts. TRM in these patients did not differ (13% vs. 8%). In a univariable Cox regression analysis, the 1-year Overall survival (OS) rate of MRDpos cohort was significantly shorter compared to MRDneg pts (64% vs. 93%, Hazard ratio (HR) 10.5, p=0.004). MRD was detected by ptDfNonly in 23/44 (52%) of MRDpos pts. The OS of these pts was comparable to MRDpos by aLAIP with or without ptDfN (Figure 1). As expected, the MRDpos cohort was enriched for non-responders. However, when the analysis was restricted to pts in CR (n=37), MRD status preserved its prognostic significance (HR 7.9, p=0.019). And even in the subpopulation of pts in first CR, MRDpos was associated with a significantly reduced OS compared to MRDneg (HR 6.3, p=0.043). Interestingly, a single non-responder was classified as MRDneg and showed a long-term OS. Conclusions Our fast-track LAIP-based DfN approach provides relevant prognostic information prior to conditioning for allo HCT. On top of the classical LAIP approach, the ptDfN analysis gives additional prognostic information. The LAIP-based DfN approach might be a suitable tool for fast-track and reliable MRD assessment before starting the preparative regimen for alloHCT and might help to guide potential treatment modifications. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal