Hematologic Events Research Articles

Effect of Segmental Abutting Esophagus-Sparing Technique to Reduce Severe Esophagitis in Limited-Stage Small-Cell Lung Cancer Patients Treated with Concurrent Hypofractionated Thoracic Radiation and Chemotherapy

To evaluate the effect of segmental abutting esophagus-sparing (SAES) radiotherapy to reduce severe (G3+) acute esophagitis from 20% to 5% in patients with limited-stage small cell lung cancer (LS-SCLC) treated with concurrent chemoradiotherapy. Patients with a clinical target volume (CTV) ≤1 cm close to the esophagus were enrolled in the experimental arm (45 Gy in 3 Gy daily fractions in 3 weeks) of an ongoing phase III randomized clinical trial (NCT02675088), which enrolled patients with histologically confirmed SCLC and clinically staged as LS or I-IIIB (AJCC 7th). This trial was designed to determine whether HYPO TRT (45 Gy in 3 Gy QD, experimental arm) has the same efficacy as CF TRT (60 Gy in 2 Gy QD, controlled arm) in patients with LS-SCLC. The whole esophagus was divided into the involved esophagus and abutting esophagus (AE) to receive different dose limitations according to the distance from the edge of the CTV. The primary endpoint was grade ≥ 3 acute esophagitis. From 1 May 2021 to 30 April 2022, 30 patients were enrolled and completed four cycles of planned chemotherapy and radiotherapy. Our patient population was predominantly male (66.7% men vs. 33.3% women), with a median age of 62 years. A majority of patients presented with Stage N2-3 (90.0%) and T2-4 (76.7%), in which 4 patients had ultracentral-located primary tumors. With the SAES technique, all dosimetric parameters were significantly reduced for the whole esophagus and AE. The maximal and mean dose of the esophagus (47.4±1.9 Gy and 13.5 ± 5.8 Gy, respectively) and AE (42.9±2.3 Gy and 8.6 ± 3.6 Gy, respectively) in the SAES plan were significantly lower than those (esophagus 48.0±1.9 Gy and 14.7± 6.1 Gy, AE 45.1±2.4 Gy and 9.8± 4.2 Gy, respectively) in the non-SAES plan. After the follow-up of more than 7 months (range, 7.0-18.1 months) for all patients, only one patient (3.3%, 95% CI 0.1%-17.2%) experienced grade 3 acute esophagitis and no grade 4-5 acute esophagitis happened (Table 3). For late toxicities, one patient suffered sustained grade 1 late esophagitis and all others had no symptoms of esophagitis. The rate of radiation pneumonitis was very low, with one grade 3 event and no grade 4-5 event. Twelve (40.0%) patients had G3+ hematologic toxic events, including 2 patients with febrile neutropenia. The 1-year OS, LRFS, DMFS and PFS was 96.4%, 88.7%, 78.4% and 64.3%, respectively. No patient developed local recurrence in the abutting esophagus-sparing region. SAES radiotherapy has significant dosimetric advantages compared with standard radiotherapy, which are successfully translated into clinical benefits for patients with LS-SCLC treated with 45 Gy in 3 Gy daily fractions. This may facilitate dose escalation for TRT in LS-SCLC patients.

Hematological Events Potentially Associated with CDK4/6 Inhibitors: An Analysis from the European Spontaneous Adverse Event Reporting System.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are a recent targeted therapy approved for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer. Abemaciclib, palbociclib and ribociclib demonstrated great efficacy and safety during clinical studies. However, differences in their adverse-event profiles have been observed. This work aims to describe the suspected adverse drug reactions (ADRs), such as leukopenia and thrombocytopenia, reported for each CDK4/6 inhibitor in the EudraVigilance (EV) database. Data on individual case safety reports (ICSRs) were obtained by accessing the European spontaneous reporting system via the EV website. Information on concomitant drug therapy, including fulvestrant, letrozole, anastrozole and exemestane, was also analyzed. A total of 1611 ICSRs were collected from the EV database. Most reports of palbociclib and ribociclib were classified as serious cases for both suspected leukopenia and thrombocytopenia ADRs. However, most patients had their leukopenia and thrombocytopenia recovered/resolved. On the contrary, reports of abemaciclib were mostly characterized as non-serious cases. Abemaciclib and palbociclib were often combined with fulvestrant, while ribociclib was generally associated with letrozole. Pharmacovigilance studies are crucial for the early identification of potential ADRs and to better differentiate the toxicity profile of the different CDK4/6 inhibitors, particularly in a real-world setting.

Long-term incidence of haematological cancer after bariatric surgery or usual care in the Swedish Obese Subjects study: a prospective cohort study

Bariatric surgery in people with obesity is associated with a reduced overall cancer risk. Retrospective studies indicate that bariatric surgery specifically might reduce the risk of haematological cancers, but there is an absence of data from long-term, prospective studies. We therefore studied the association between bariatric surgery and haematological cancer in the Swedish Obese Subjects study. The prospective controlled Swedish Obese Subjects study was designed to compare overall mortality in people who underwent bariatric surgery (n=2007) and usual care (n=2040). Participants were recruited through campaigns in mass media and at 480 primary health-care centres all over Sweden. The inclusion criteria were an age of 37-60 years and a BMI of 34 kg/m2 or more in men and 38 kg/m2 or more in women before or at the time of the examination. Haematological cancer events, including malignant lymphoma, myeloma, myeloproliferative neoplasms, as well as acute and chronic leukaemias, were captured from the Swedish Cancer Registry. The main outcome of this study was haematological cancer incidence and mortality. This study is registered with ClinicalTrials.gov (NCT01479452) and is ongoing. A total of 4047 individuals with obesity were enrolled between Sept 1, 1987, and Jan 31, 2001. Overall, 34 participants in the surgery group and 51 participants in the usual care control group were diagnosed with haematological cancer during follow-up (hazard ratio [HR] 0·60; 95% CI 0·39-0·92; p=0·020). Moreover, there were three deaths by haematological cancer in the surgery group and 13 deaths in the control group (0·22; 0·06-0·76; p=0·017). Surgery was also associated with a reduced incidence of lymphoma (0·45; 0·23-0·88; p=0·020). A significant difference in treatment effect between men and women was found; bariatric surgery was associated with reduced incidence of haematological cancer in women (0·44; 0·26-0·74; p=0·002), but not in men (1·35; 0·58-3·17; p=0·489; interaction p=0·031). Bariatric surgery is associated with a reduced incidence of haematological cancer, specifically in women. Health-care providers and policy makers working in the field of cancer prevention should consider bariatric surgery a primary prevention resource for people with obesity. The Swedish Research Council, the Swedish State under the agreement between the Swedish Government and the county councils, the Avtal om Läkarutbildning och Forskning agreement, the Health & Medical Care Committee of the Region Västra Götaland, the Swedish Heart Lung Foundation, Gothenburg Medical Society, and the Adlerbert Research Foundation. For the Swedish translation of the abstract see Supplementary Material section.

Phase I study evaluating the Fc-optimized FLT3 antibody FLYSYN in AML patients with measurable residual disease

BackgroundAbout half of AML patients achieving complete remission (CR) display measurable residual disease (MRD) and eventually relapse. FLYSYN is an Fc-optimized antibody for eradication of MRD directed to FLT3/CD135, which is abundantly expressed on AML cells.MethodsThis first-in-human, open-label, single-arm, multicenter trial included AML patients in CR with persisting or increasing MRD and evaluated safety/tolerability, pharmacokinetics and preliminary efficacy of FLYSYN at different dose levels administered intravenously (cohort 1–5: single dose of 0.5 mg/m2, 1.5 mg/m2, 5 mg/m2, 15 mg/m2, 45 mg/m2; cohort 6: 15 mg/m2 on day 1, 15 and 29). Three patients were treated per cohort except for cohorts 4 and 6, which were expanded to nine and ten patients, respectively. Primary objective was safety, and secondary efficacy objective was ≥ 1 log MRD reduction or negativity in bone marrow.ResultsOverall, 31 patients were treated, of whom seven patients (22.6%) experienced a transient decrease in neutrophil count (two grade 3, others ≤ grade 2). No infusion-related reaction or dose-limiting toxicity was observed. Adverse events (AEs) were mostly mild to moderate, with the most frequent AEs being hematologic events and laboratory abnormalities. Response per predefined criteria was documented in 35% of patients, and two patients maintained MRD negativity until end of study. Application of 45 mg/m2 FLYSYN as single or cumulative dose achieved objective responses in 46% of patients, whereas 28% responded at lower doses.ConclusionsFLYSYN monotherapy is safe and well-tolerated in AML patients with MRD. Early efficacy data are promising and warrant further evaluation in an up-coming phase II trial.Trial registration This clinical is registered on clinicaltrials.gov (NCT02789254).

Hematological and Extra-Hematological Manifestations of Parvovirus B19 Disease

Abstract Objective Parvovirus B19 (PVB19) is a virus that can present with many hematological and extra-hematological findings. Its prognosis is relatively good in immunocompetent patients, but severe disease may develop in immunocompromised patients. We retrospectively reviewed a series of children who presented with PVB19 during a 6-year period at our institution. Methods Nine children with positive polymerase chain reaction and serological test results for PVB19 were studied. Their demographic data, atypical clinical and laboratory findings, treatment regiments, clinical course, and prognosis were noted. Results The hematological abnormalities associated with PVB19 were anemia, neutropenia, and thrombocytopenia, and the extra-hematological abnormalities were systemic lupus erythematosus-like syndrome, hemophagocytic lymphohistiocytosis, and acute kidney injury. All patients had good outcomes with no significant sequelae. Conclusion This case review suggests that clinicians should not consider PVB19 only as a cause of hematological events; they should also be alert to the possibility that it may cause extra-hematological diseases.

Evaluation of Bivalirudin During Adult Extracorporeal Membrane Oxygenation: A Retrospective Characterization of Dosing, Efficacy and Bleeding.

Objective: Although heparin is the current standard anticoagulant during venoarterial (VA) and venovenous (VV) extracorporeal membrane oxygenation (ECMO), factors including heparin-induced thrombocytopenia, heparin resistance and drug shortages necessitate alternative anticoagulants such as direct thrombin inhibitors. The aim was to characterize dosing, safety, and efficacy of bivalirudin during ECMO support. Methods: This retrospective single-center study included 24 adults on ECMO support who received ≥6 hours of bivalirudin. The primary endpoint was dose to first therapeutic activated partial thromboplastin time (aPTT). Secondary endpoints included evaluating dosing between ECMO modes, incidence of bleeding and thrombotic events, and time in therapeutic range (TTR). Results: The dose at time of first therapeutic aPTT was bivalirudin 0.05 [0.05-0.1] mg/kg/hour. Bivalirudin dosing requirements were lower in VAECMO compared to VV-ECMO patients and were not impacted by continuous venovenous hemofiltration. Time to therapeutic aPTT was 5.5 [2-13] hours for VA-ECMO and 4.5 [2-8.6] hours for VV-ECMO patients. During any mode of ECMO TTR was 58.3% [39.6-73.1]. Thrombotic events occurred in 3 (13%) patients and major bleeding occurred in 12 (50%) patients. Conclusions: Our findings demonstrated variable bivalirudin dosing requirements based on mode of ECMO and dosing modifications may not be required during CVVH. Factors including mode of ECMO, indication for bivalirudin and concomitant antiplatelet therapy may impact hematologic events. Application of this data can assist with developing a bivalirudin ECMO protocol which provides less variability in initial dosing and TTR.

Nanoparticle Albumin‑Bound Paclitaxel and Solvent-Based Paclitaxel as Chemotherapy Options for Patients With Advanced Gastric Cancer: A Systematic Review and Meta-Analysis.

The aim of this study is to assess and compare the effectiveness and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) and solvent-based PTX (sb-PTX) as treatment options for advanced gastric cancer.This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We carried out a comprehensive search of PubMed, Google Scholar, and EMBASE from inception to June 15, 2023. The search strategy included the following keywords: "Nanoparticle albumin-bound paclitaxel," "solvent-based paclitaxel," and "advanced gastric cancer," along with their synonyms and medical subject heading (MeSH) terms.In this meta-analysis, the primary outcome was the comparison of overall survival and progression-free survival between the two groups. For safety purposes, we compared the risk of hematological and non-hematological events between the two groups. Four studies were included in this meta-analysis enrolling 1052 patients (483 received nb-PTX and 569 received sb-PTX).In terms of efficacy, nab-PTX showed favorable trends in overall survival and progression-free survival, despite no statistically significant differences being reported.The subgroup meta-analysis showed that nab-PTX seemed to have a better effect on peritoneal metastasis compared to sb-PTX.Regarding safety, the number of patients with neutropenia and leucopenia was significantly higher in the nab-PTX group compared to the sb-PTX group. However, the difference was statistically insignificant.Future research should focus on conducting more robust studies to further validate these findings and establish a stronger evidence base for the use of nab-PTX in this patient population.

Evaluation of Epirubicin, Cyclophosphamide and Paclitaxel-based Chemotherapy Response for Treatment of Breast Cancer Patients as Neo-Adjuvant: A Case-Series in a Tertiary Care Hospital in Bangladesh

Background: Breast cancer is the most common cancer among women across the world. Various treatment modalities in terms of radiotherapy, chemotherapy or surgery along with several neoadjuvant or adjuvant therapies are already established for the better survival of the patients. New modalities are still under research every other day for improvement of quality of life of cancer victims. Objective: This case series was conducted to assess the efficacy and safety profile of primary breast cancer patients by adding Paclitaxel to the established regimen of Epirubicin and Cyclophosphamide. Methods: This was performed during January 2019 to January 2021 with 9 cases of clinically diagnosed breast cancer patients at Combined Military Hospital, Dhaka. Patients included in our study received Epirubicin in the dose of 75-100 mg/m2 dl, Cyclophosphamide 600 mg/m2 dl, every 3 weeks for a total of 4 cycles followed by Paclitaxel at a dose of 175 mg/m2, every 3 weeks for a sum of 4 cycles. After every cycle of neoadjuvant chemotherapy and at the end of it, response was assessed by ultrasound. Results: The findings revealed 6 out of 9 patients showed pathological complete response at the end of this neoadjuvant regimen. The remaining 3 cases showed partial response. Toxicity was minimal and well-managed. 5 patients developed leukopenia in terms of haematological events, whereas for other effects, nausea and fatigue was commonly encountered. Conclusion: Overall, this treatment modality turned out to be feasible and a good option for neoadjuvant therapy in terms of efficacy and safety profile for the breast cancer patients.

Development of Real-world Data-based Medication Instruction Sheet for Acute Myeloid Leukemia Patients Receiving High-dose Cytarabine Consolidation Therapy.

For quick and accurate monitoring of potential adverse events (AEs) during concurrent chemotherapy, we had previously developed innovative medication instruction sheets (MIS) for a variety of chemotherapy regimens. However, it is still unclear whether these sheets correctly predict the type and time course of the onset and recovery of AEs. Therefore, we monitored AEs in patients with acute myeloid leukemia (AML) receiving high-dose cytarabine (HD-AraC) using the original MIS. Patients who received HD-AraC following remission induction chemotherapy were included in this study. Data obtained from AE monitoring were evaluated, and the original MIS was modified as appropriate. Among 41 patients, a total of 203 AEs (139 non-hematological and 64 hematological) were observed after chemotherapy. By contrast, all but one patient (97.6%) experienced 102 AEs (43 non-hematological and 59 hematological) before chemotherapy. The AEs that appeared after chemotherapy were all predicted items described in the original MIS; however, their onset and duration were not consistent with the predicted data, in which the prediction accuracy was 69.1% for non-hematological AEs and 1.6% for hematological events. Based on these monitoring data, the original MIS was revised, which led to an increase in the prediction accuracy to 94.2% for nonhematological events and 100% for hematological events. Preexisting AEs should be considered when preparing MIS for consolidation therapy with HD-AraC. The modified MIS based on AE monitoring exhibited a sufficiently high prediction accuracy.

A phase II study of tinostamustine in patients (pts) with advanced solid tumours.

3021 Background: The novel multi-action alkylating deacetylase inhibitor tinostamustine improves drug access to DNA strands within cancer cells, breaks them and counteracts damage repair. Tinostamustine was well tolerated with signals of efficacy during dose escalation in pts with advanced solid tumours (Mita et al. Cancer Res 2019;79[13 Suppl]:CT023). Methods: This was an open-label Phase I/II trial of single agent tinostamustine in pts with advanced solid tumours (NCT03345485). The Phase II primary endpoint was objective response rate (ORR: complete response + partial response [PR]) and the rate of stable disease ≥4 mo duration following the recommended Phase II dose (RP2D; 80 mg/m2 over 1 h on Day 1 & 15 of each 4-wk treatment cycle). Secondary endpoints included progression-free (PFS) and overall survival (OS), and duration of response. Eligible pts were ≥18 y with life expectancy ≥3 mo, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2, histologically confirmed diagnosis of advanced/metastatic soft tissue sarcoma (STS), small-cell lung (SCLC), triple-negative breast (TNBC), ovarian (OvCa) or endometrial cancer, progression following ≥1 prior line of therapy, with no other standard therapy with proven clinical benefit available or recommended. Results: 36 pts were enrolled and evaluable for response; mean ± SD age 59.6 ± 11.2 y, 83.3% female, 80.6% Caucasian, all ECOG PS ≤1, median of 3 (range 1–9) lines of prior therapy. At data cut-off (30 November 2022) pts had received a median of 2 (range 1–8) cycles of tinostamustine. 19 pts (52.8%) discontinued treatment due to progressive disease. One pt with synovial sarcoma (STS cohort; n=10) and one pt with OvCa (n=12) achieved a PR. Overall, 14 pts (38.9%) had stable disease ≥4 mo (0/4 SCLC; 3/10 STS; 3/4 TNBC; 5/12 OvCa; 3/6 endometrial cancer); Clinical Benefit Rate, 44.4% (95% CI: 27.9%, 61.9%). Median PFS and OS for all treated pts were 2.2 mo (95% CI 1.8, 3.3 mo) and 5.5 mo (95% CI 4.1, 15.0 mo), respectively. All pts experienced ≥1 treatment-emergent adverse event (TEAE), with 56.7% of events considered related to tinostamustine. Serious tinostamustine-related AEs were reported in 30.6% of pts (13 haematological events); 10 (27.8%) pts discontinued treatment due to TEAEs (platelet count decreased: 5 events in 3 pts, including 2 Grade 3 and 1 Grade 4; all other events n=1). Two pts experienced fatal TEAEs; n=1 each of intra-abdominal haemorrhage (considered related to study drug), hypoxia/dyspnoea (not study drug related). Conclusions: Tinostamustine demonstrated modest signals of efficacy, with 2 pts achieving a PR, and manageable tolerability in pts with advanced solid tumours for whom no other standard therapy with proven clinical benefit was available or recommended. Further studies are needed to fully explore the benefits of tinostamustine in solid tumours. Clinical trial information: NCT03345485 .

Hematologic adverse events reported after COVID-19 vaccination in the Philippines: A national database study.

Vaccination is the most important strategy in preventing COVID-19. Vaccine efficacy and safety have been established in clinical trials but real-world data are useful to determine occurrence of adverse events in a population with heterogeneous characteristics. Knowledge on the hematologic events associated with different COVID-19 vaccines would be beneficial for patients as well as hematologists who oversee the care of these patients. This study aimed to determine the rates and outcomes of hematologic adverse events after COVID-19 vaccination in the Philippines. In this self-controlled case series, there were 268 individuals reported to have hematologic adverse events. Most received Comirnaty at 29.85%. Majority (62.31%) reported hematologic adverse events following the first dose of the vaccine. The overall event rate was 0.0182 per 10,000 vaccine doses; and lymphadenopathy was the most common hematologic adverse effect with a rate of 0.011 per 10,000 vaccine doses, followed by anemia at 0.0034 per 10,000 vaccine doses and thrombocytopenia at 0.0017 per 10,000 vaccine doses. Autoimmune cytopenias were also reported with an event rate of 0.0007 per 10,000 vaccine doses for ITP. One-hundred thirty two (49.25%) were fully recovered and 23.88% were recovering from hematologic adverse events as of the time of writing. The study showed a low rate of hematologic adverse events post COVID-19 vaccination with the seven different vaccine brands administered in the Philippines.

PO-05-004 CAUSES AND OUTCOMES OF EARLY READMISSIONS AFTER VENTRICULAR TACHYCARDIA ABLATION

Patients with ventricular tachycardia (VT) who require VT catheter ablation are a population at high risk for readmissions. The contemporary causes and outcomes of readmission after VT ablation are not well-established. This study aimed to identify the causes and outcomes of readmission within 30 days after VT ablation procedure. Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged 18 years or older who underwent VT catheter ablation between 2017 and 2019. On the basis of the International Classification of Diseases, Tenth Revision, Clinical Modification, we identified and categorized the causes of readmissions by organ systems and analyzed their outcomes. Out of 3,170 patients who underwent VT ablation, 446 (14.1%) patients were readmitted within 30 days of the procedure. The most common cause of readmission was cardiac (n=326, 73.1%), followed by infectious (n=31, 7.0%), neurological (n=15, 3.4%), renal (n=13, 2.9%), gastrointestinal (n=9, 2.0%), respiratory (n=9, 2.0%), vascular (n=9, 2.0%), endocrinological (n=5, 1.1%) and hematological (n=5, 1.1%) events. Among the cardiac causes-related readmission, recurrent VT (65.0%), and congestive heart failure (CHF) (18.1%) were the most common etiologies. Among these causes of readmissions, patients readmitted due to CHF had the highest rate in readmission mortality (8.47%), prolonged length of hospital stay for more than 7 days (42.37%), non-home discharge (33.9%), and the highest cost of hospitalization. Recurrent VT was the most common cause of early readmission after VT ablation procedure. However, early readmission due to CHF had the poorest outcome with the highest mortality rate during the readmission.

Clinical impact of reducing the frequency of clozapine monitoring: controlled mirror-image cohort study.

To minimise infection during COVID-19, the clozapine haematological monitoring interval was extended from 4-weekly to 12-weekly intervals in South London and Maudsley NHS Foundation Trust. To investigate the impact of this temporary policy change on clinical and safety outcomes. All patients who received clozapine treatment with extended (12-weekly) monitoring in a large London National Health Service trust were included in a 1-year mirror-image study. A comparison group was selected with standard monitoring. The proportion of participants with mild to severe neutropenia and the proportion of participants attending the emergency department for clozapine-induced severe neutropenia treatment during the follow-up period were compared. Psychiatric hospital admission rates, clozapine dose and concomitant psychotropic medication in the 1 year before and the 1 year after extended monitoring were compared. All-cause clozapine discontinuation at 1-year follow-up was examined. Of 569 participants, 459 received clozapine with extended monitoring and 110 controls continued as normal. The total person-years were 458 in the intervention group and 109 in the control group, with a median follow-up time of 1 year in both groups. During follow-up, two participants (0.4%) recorded mild to moderate neutropenia in the intervention group and one (0.9%) in the control group. There was no difference in the incidence of haematological events between the two groups (IRR = 0.48, 95% CI 0.02-28.15, P = 0.29). All neutropenia cases in the intervention group were mild, co-occurring during COVID-19 infection. The median number of admissions per patient during the pre-mirror period remained unchanged (0, IQR = 0) during the post-mirror period. There was one death in the control group, secondary to COVID-19 infection. There was no evidence that the incidence of severe neutropenia was increased in those receiving extended monitoring.

Efficacy of Pemetrexed or Gemcitabine Combined with Cis-platinum on Patients with Advanced Non-small-cell Lung Carcinoma and Its Effect on Serum miR-365

Objective: To determine the efficacy of pemetrexed or gemcitabine combined with cis-platinum on patients with advanced non-small-cell lung carcinoma (NSCLC) and its effect on serum miR-365. Methods: A total of 183 patients with NSCLC were enrolled and assigned to a pemetrexed + cis-platinum group (PC group) and a gemcitabine + cis-platinum group (GC group) according to their chemotherapy regimens. The two groups were compared in general data, therapeutic effect, drug-associated toxicity, life quality, 3-year survival outcome, and serum miR-365. Results: There was no significant difference between the two groups in remission rate and disease control rate, and the PC group experienced notably less hematological events including thrombocytopenia than the GC group, but had no significant difference with the latter in nausea, vomiting, constipation, abnormal liver function, esophageal injury and peripheral neurotoxicity. Additionally, there was no significant difference between the two groups in the improvement rate of Karnofsky performance scale, increased appetite, body mass gain, 3-year overall survival and progression-free survival, while the PC group showed better grade 3-4 toxicity-free survival outcome than the GC group. Moreover, serum miR-365 was up-regulated in cases with NSCLC, and decreased in both groups after treatment, while it was lower in the PC group than in the GC group over the same period after treatment. Conclusion: Both pemetrexed or gemcitabine combined with cis-platinum can strongly mitigate advanced NSCLC and suppress serum miR-365, but the former is safer.

5593300 INVESTIGATIONS OF KIDNEY DYSFUNCTION-RELATED GENE VARIANTS IN SICKLE CELL DISEASE PATIENTS IN CAMEROON (SUB-SAHARAN AFRICA)

Background: Renal dysfunctions are associated with increased morbidity and mortality in sickle cell disease (SCD). Early detection and subsequent management of SCD patients at risk for renal failure and dysfunctions are essential, however, predictors that can identify patients at risk of developing renal dysfunction are not fully understood. Aims: the aims of the study were: to employ a multi-factorial approach to investigate genetic factors and also to explore the contribution of socio-demographic, anthropometric, clinical and haematological variables associated to renal abnormalities in SCD patients in Cameroon. Methods: In this study, we have investigated the association of 31 known kidney dysfunctions-related variants detected in African Americans from multi-ethnic genome wide studies (GWAS) meta-analysis to kidney-dysfunctions in a group of 413 Cameroonian patients with SCD. Systems level bioinformatics analyses were performed, employing protein-protein interaction networks to further interrogate the putative associations. Results: Up to 61% of these patients had micro-albuminuria, 2.4% proteinuria, 71% glomerular hyperfiltration, and 5.9% had renal failure. Six variants are significantly associated with the two quantifiable phenotypes of kidney dysfunction (eGFR and crude-albuminuria): A1CF-rs10994860 (P = 0.02020), SYPL2-rs12136063 (P = 0.04208), and APOL1 (G1)-rs73885319 (P = 0.04610) are associated with eGFR; and WNT7A-rs6795744 (P = 0.03730), TMEM60-rs6465825 (P = 0.02340), and APOL1 (G2)-rs71785313 (P = 0.03803) observed to be protective against micro-albuminuria. We identified a protein-protein interaction sub-network containing three of these gene variants: APOL1, SYPL2, and WNT7A, connected to the nuclear factor NF-kappa-B p105 subunit (NFKB1), revealed to be essential and might indirectly influence extreme phenotypes. Interestingly, clinical variables, including body mass index (BMI), systolic blood pressure, vaso-occlusive crisis (VOC), and haemoglobin (Hb), explain better the kidney phenotypic variations in this SCD population. Conclusion: This study highlights a strong contribution of haematological indices (Hb level), anthropometric variables (BMI, blood pressure), and clinical events (i.e., vasoocclusive crisis) to kidney dysfunctions in SCD, rather than known genetic factors. Only 6/31 characterised gene-variants are associated with kidney dysfunction phenotypes in SCD samples from Cameroon. The data reveal and emphasise the urgent need to extend GWAS studies in populations of African ancestries living in Africa, and particularly for kidney dysfunctions in SCD. Keywords: sickle cell disease, kidney dysfunctions, gene variants, cameroon, Africa

Valproate-related neutropenia and lithium-related leukocytosis in patients treated with clozapine: a retrospective cohort study

BackgroundNeutropenia is a noteworthy side effect of clozapine, which might warrant this drugs’ discontinuance for safety. Studies have revealed that the risk of neutropenia increases with concurrent administration of valproate, but the evidence was limited. Conversely, lithium may have an ameliorating effect on clozapine-induced neutropenia. This study explored the effects of valproate and lithium on white blood cell counts in patients treated with clozapine.MethodsWe retrospectively investigated the electronic medical records from one tertiary psychiatric hospital in Taiwan and enrolled patients discharged between January 1, 2006, and December 31, 2017, with clozapine prescriptions. We scrutinized their demographic data, medications, and hematological results at discharge and during follow-up outpatient clinic visits over the subsequent 3 years. Patients were classified into four groups: clozapine only (CLO), clozapine and valproate (CLO + VAL), clozapine and lithium (CLO + Li), and clozapine, valproate, and lithium (CLO + VAL + Li). We also identified hematological events (neutropenia or leukocytosis) of these patients during outpatient follow-ups.ResultsOf the included 1084 patients, 55(5.1%) developed neutropenia. Concurrent valproate use (odds ratio [OR] = 3.49) and older age (p = .007) were identified as risk factors. Moreover, 453 (41.79%) patients developed leukocytosis. Younger age; male sex; and concurrent use of lithium (OR = 3.39, p < .001), clozapine daily dosage, and benzodiazepines were the risk factors for leukocytosis.ConclusionConcurrent valproate use and older age are associated with the development of neutropenia in patients treated with clozapine. Concurrent lithium usage, younger age, male sex, and concurrent benzodiazepine use might be related to leukocytosis.

Analysis of hematologic adverse events reported to a national surveillance system following COVID-19 bivalent booster vaccination.

Hematologic complications, including vaccine-induced immune thrombotic thrombocytopenia (VITT), immune thrombocytopenia (ITP), and autoimmune hemolytic anemia (AIHA), have been associated with the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. However, on August 31, 2022, new formulations of the Pfizer-BioNTech and Moderna vaccines were approved for use without clinical trial testing. Thus, any potential adverse hematologic effects with these new vaccines remain unknown. We queried the US Centers for Disease Control Vaccine Adverse Event Reporting System (VAERS), a national surveillance database, through February 3, 2023, all reported hematologic adverse events that occurred within 42days of administration of either the Pfizer-BioNTech or Moderna Bivalent COVID-19 Booster vaccine. We included all patient ages and geographic locations and utilized 71 unique VAERS diagnostic codes pertaining to a hematologic condition as defined in the VAERS database. Fifty-five reports of hematologic events were identified (60.0% Pfizer-BioNTech, 27.3% Moderna, 7.3% Pfizer-BioNTech bivalent booster plus influenza, 5.5% Moderna bivalent booster plus influenza). The median age of patients was 66years, and 90.9% (50/55) of reports involved a description of cytopenias or thrombosis. Notably, 3 potential cases of ITP and 1 case of VITT were identified. In one of the first safety analyses of the new SARS-CoV-2 booster vaccines, we identified few adverse hematologic events (1.05 per 1,000,000 doses), most of which could not be definitively attributed to vaccination. However, three reports of possible ITP and one report of possible VITT highlight the need for continued safety monitoring of these vaccines as their use expands and new formulations are authorized.

Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone.

Daratumumab, pomalidomide, and dexamethasone (DPd) is an effective option for treatment of patients with relapsed/refractory multiple myeloma (RRMM). In this study, we sought to analyze the risk of hematological and non-hematological toxicities in patients who responded to DPd treatment. We analyzed 97 patients with RRMM who were treated with DPd between January 2015 and June 2022. The patients and disease characteristics, as well as safety and efficacy outcomes were summarized as descriptive analysis. The overall response rate for the entire group was 74% (n = 72). The most common grade III/IV hematological toxicities in those who responded to treatment were neutropenia (79%), leukopenia (65%), lymphopenia (56%), anemia (18%), and thrombocytopenia (8%). The most common grade III/IV non-hematological toxicities were pneumonia (17%) and peripheral neuropathy (8%). The incidence of dose reduction/interruption was 76% (55/72), which was due to hematological toxicity in 73% of the cases. The most common reason for discontinuing treatment was disease progression in 61% (44 out of 72 patients). Our study revealed that patients who respond to DPd are at high risk of dose reduction or treatment interruption because of hematological toxicity, typically due to neutropenia and leukopenia leading to increased risk of hospitalization and pneumonia.

P393 Effect of filgotinib on anaemia in patients with Ulcerative Colitis in SELECTION

Abstract Background Patients with ulcerative colitis (UC) often have anaemia owing to inflammation and/or blood loss.1 Filgotinib (FIL) is a once-daily, oral, Janus kinase (JAK) 1 preferential inhibitor approved for the treatment of UC, which may be associated with fewer haematological events than pan-JAK inhibitors. In the phase 2b/3 SELECTION trial (NCT02914522),2 FIL 200 mg (FIL200) was well tolerated and effective vs placebo (PBO) in patients with UC. This post hoc analysis of SELECTION data compared haematological events across the FIL and PBO treatment arms. Methods In SELECTION, adults with moderately to severely active UC were randomized 2:2:1 to receive FIL200, or FIL 100 mg, or PBO once daily for 11 weeks during induction. FIL responders (clinical remission or a Mayo Clinic Score response at week 10 [W10]) were rerandomized to continue their induction FIL dose or PBO in the 47-week Maintenance (MNT) Study. PBO responders continued PBO during MNT. This analysis evaluated the proportions of patients with haematological events (anaemia, leukopenia, lymphopenia, neutropenia and thrombocytopenia) at baseline (BL), W10 and W58. Haematological events were defined based on the relevant laboratory parameters being below the lower limit of normal. For anaemia at W10 and W58, patients were further stratified by rectal bleeding (RB) status (no: RB subscore=0; yes: RB subscore ≥1) at W10 and W58, respectively. Results At BL, ~50% of patients had anaemia in all treatment arms. Among these patients, the proportion without anaemia at W10 was similar across the FIL and PBO arms (25.0–30.7%; Table 1). Among patients without BL anaemia, the proportion with anaemia at W10 was also similar across all arms (12.1–17.3%). Among patients without RB at W10, the proportion of patients with a change in anaemia status from BL to W10 was also similar across arms. At W58, the proportion of patients with anaemia was similar across all arms, although ~40% of patients overall had missing data (Table 2). At BL, &amp;lt;5% of patients had leukopenia across all treatment arms (Tables 3 and 4). Lymphopenia, neutropenia and thrombocytopenia were also uncommon at BL (&amp;lt;10%, &amp;lt;4%, and &amp;lt;1% of patients, respectively). Among patients without these four haematological events at BL, &amp;lt;5%, &amp;lt;6%, 4% and ~1%, respectively, had them at W10. Conclusion Treatment with JAK1-preferential FIL up to W58, was not associated with anaemia, thought to occur via JAK2 inhibition, in patients overall and in those without RB at W10, compared with PBO. The small numbers of patients with haematological events excluding anaemia at BL limit rigorous inter-arm comparison. 1. Malesza IJ et al. Nutrients 2022;14:3478. 2. Feagan BG et al. Lancet 2021;397:2372–84.

Hematological Questions in Personalized Management of COVID-19 Vaccination.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been causing a worldwide pandemic since 2019. Many vaccines have been manufactured and have shown promising results in reducing disease morbidity and mortality. However, a variety of vaccine-related adverse effects, including hematological events, have been reported, such as thromboembolic events, thrombocytopenia, and bleeding. Moreover, a new syndrome, vaccine-induced immune thrombotic thrombocytopenia, following vaccination against COVID-19 has been recognized. These hematologic side effects have also raised concerns about SARS-CoV-2 vaccination in patients with preexisting hematologic conditions. Patients with hematological tumors are at a higher risk of severe SARS-CoV-2 infection, and the efficacy and safety of vaccination in this group remain uncertain and have raised attention. In this review, we discuss the hematological events following COVID-19 vaccination and vaccination in patients with hematological disorders.