Myelosuppression Research Articles

Impact of administration routes and dose frequency on the toxicology of SARS-CoV-2 mRNA vaccines in mice model.

The increasing use of SARS-CoV-2 mRNA vaccines has raised concerns about their potential toxicological effects, necessitating further investigation to ensure their safety. To address this issue, we aimed to evaluate the toxicological effects of SARS-CoV-2 mRNA vaccine candidates formulated with four different types of lipid nanoparticles in ICR mice, focusing on repeated doses and administration routes. We conducted an extensive analysis in which mice received the mRNA vaccine candidates intramuscularly (50 μg/head) twice at 2-week intervals, followed by necropsy at 2 and 14 dpsi (days post-secondary injection). In addition, we performed a repeated dose toxicity test involving three, four, or five doses and compared the toxicological outcomes between intravenous and intramuscular routes. Our findings revealed that all vaccine candidates significantly induced SARS-CoV-2 spike protein-specific IgG and T cell responses. However, at 2 dpsi, there was a notable temporary decrease in lymphocyte and reticulocyte counts, anemia-related parameters, and significant increases in cardiac damage markers, troponin-I and NT-proBNP. Histopathological analysis revealed severe inflammation and necrosis at the injection site, decreased erythroid cells in bone marrow, cortical atrophy of the thymus, and increased spleen cellularity. While most toxicological changes observed at 2 dpsi had resolved by 14 dpsi, spleen enlargement and injection site damage persisted. Furthermore, repeated doses led to the accumulation of toxicity, and different administration routes resulted in distinct toxicological phenotypes. These findings highlight the potential toxicological risks associated with mRNA vaccines, emphasizing the necessity to carefully consider administration routes and dosage regimens in vaccine safety evaluations, particularly given the presence of bone marrow and immune organ toxicity, which, though eventually reversible, remains a serious concern.

Clinical characteristics and prognostic analysis of prolonged cytopenia after CAR-T cell therapy in LBCL patients

Objective: To investigate the clinical features and prognosis of prolonged cytopenia (PC) in patients with large B-cell lymphoma (LBCL) undergoing anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy. Methods: A retrospective case series study was conducted on LBCL patients who received CAR-T cell therapy with a survival time of over one month at the Hematology Department of Peking Union Medical College Hospital from March 2019 to December 2023. Statistical analyses were performed on hematologic changes at 1, 3, 6, and 12 months post-CAR-T infusion, as well as on the progression-free survival (PFS) and post-treatment adverse events, including infections. Patients were categorized into the PC and non-PC groups based on the occurrence of cytopenia at 90 days post-infusion. Differences between groups were compared, and univariate logistic regression analysis was used to identify risk factors. Results: The median age of 27 LBCL patients receiving CAR-T cell therapy was 58 years (range 27-69 years), with 18 males. Among the 27 LBCL patients who received CAR-T cell therapy, PC was observed in 19 patients (70.4%), with instances of neutropenia (48.1%, 13 cases), anemia (37.0%, 10 cases), and thrombocytopenia (22.2%, 6 cases). Univariate logistic regression analysis revealed that prior chemotherapy sensitivity (OR=18.00, 95%CI 1.56-207.45, P=0.020) and bone marrow suppression (OR=18.00, 95%CI 1.38-235.69, P=0.028) were associated with PC. The median follow-up time was 13.5 months. The PC group exhibited a higher risk of infection within 3 months (9/19 vs. 1/8) and a shorter mean PFS (19.3 months vs. 24.4 months), although the difference was not statistically significant (both P>0.05). Conclusions: PC is common following CAR-T cell therapy and is associated with an increased risk of infection and poorer prognosis. Prior treatment sensitivity and bone marrow suppression may serve as indicators of PC.

Protective environment strategies for hematopoietic stem cell transplantation: progress and prospects.

With the progress of hematopoietic stem cell transplantation technology, the reduction of pretreatment intensity, the shortening of bone marrow suppression time and the reduction of infection risk, as well as the prominent physical and psychological stress for doctors and patients caused by rigorous protection procedures, the strategies for protective environment need to be reconsidered. Regardless of whether total environment protection is implemented, there is no significant difference in the outcomes of chemotherapy patients with neutropenia. The advantages and disadvantages of total environment protection have been weighed and reviewed for patients receiving hematopoietic stem cell transplantation. The protective environment strategies for hematopoietic stem cell transplantation patients have developed rapidly in the past two decades, from the initial replacement of laminar flow equipment by high-efficiency filtration devices to the development of home care after transplantation. In this article, the progress of protective environment strategies for hematopoietic stem cell transplantation patient was reviewed, and further reflections were posed, providing reference for future improvement.

Safety assessment of Gami-daebo-tang gagambang used for treating stroke sequelae

Objectives: This study aimed to investigate wheter Gami-daebo-tang gagambang, commonly used for treating stroke sequelae, induces acute toxicity or genetoxicity.Methods: Gami-daebo-tang gagambang contains that the root of <i>Angelica gigas Nakai</i> inducing acute headache and weakness, and the rhizome of <i>Cnidium officinale</i> MAKINO, an herb with potential teratogenicity. Teratogenicity is closely associated with genotoxicity. We analyzed whether Gami-daebo-tang gagambang induces acute toxicity and genotoxicity in accordance with Korean non-clinical test standards and OECD test guidelines TG471, TG473, TG474.Results: When male and female rats were given a single dose of Gami-daebo-tang gagambang, no toxic effects or organ damage were observed at dosages reaching 2,500 mg/kg. The bacterial reverse mutation assay showed no evidence of DNA mutations at concentrations up to 5,000 <i>μ</i>g/plate. In vitro studies indicated that Gami-daebo-tang gagambang did not cause structural or numerical chromosomal aberrations at concentrations as high as 2,000 <i>μ</i>g/mL. Moreover, animal studies demonstrated that the substance did not induce bone marrow toxicity or the formation of micronuclei in erythrocytes at doses up to 2,000 mg/kg.Conclusions: The studies conducted with different models showed that Gami-daebo-tang gagambang did not cause acute toxicity or genotoxicity. This study provides evidence for the safety of Gami-daebo-tang gagambang in terms of acute toxicity and genotoxicity, supporting its potential safe application in treating stroke sequelae.

Fatal Feline Leukemia Virus-Associated Enteritis in a Wild Eurasian Lynx (Lynx lynx) in Germany

The Eurasian lynx (Lynx lynx), a widespread wild felid on the Eurasian continent, is currently classified as “critically endangered” in Germany. Understanding the impact of infectious agents is of particular importance for the continued conservation of these animals, especially regarding pathogens with broad host ranges and risk of interspecies transmission. Feline leukemia virus (FeLV) is known to infect wild and domestic felids worldwide, including several species of lynx, but it has not been reported thus far in the Eurasian lynx. In September 2020, a 16-month-old female Eurasian lynx from the Bavarian Forest, Germany, showed a sudden onset of gastrointestinal signs such as anorexia, diarrhea, and vomiting, and died within one week. Macroscopic and histologic examination revealed hemorrhagic-necrotizing enteritis and typhlocolitis, with the degeneration of crypts and crypt abscesses, as well as depleted Peyer’s patches. In addition, the animal showed lymphoid depletion (lymph nodes, thymus, and spleen) and hypocellularity of the bone marrow. FeLV infection was confirmed by immunohistochemistry and next generation sequencing. A secondary bacterial infection with hemolytic Escherichia coli and Clostridium perfringens type A was present in the intestine. This is the first report of FeLV-associated enteritis, lymphoid depletion and bone marrow suppression with associated secondary bacterial infection in a Eurasian lynx.

Predicting grade II-IV bone marrow suppression in patients with cervical cancer based on radiomics and dosiomics

Predicting grade II-IV bone marrow suppression in patients with cervical cancer based on radiomics and dosiomics

Efficacy and safety of the combination of decitabine and CHAG priming regimen in the relapsed or refractory acute myeloid leukemia

Efficacy and safety analysis of the combination of decitabine priming followed by CHAG chemotherapy in treatment of relapsed/refractory(r/r) acute myeloid leukemia (AML). Between January 2013 and June 2020, 62 r/r AML patients in our center receiving therapy including combination of decitabine and CHAG pre-excitation regimen were enrolled. Primary objectives were overall response (ORR: complete remission + partial remission), adverse events, overall survival (OS) and relapse-free survival (RFS). There were 46 patients (74.2%) with complete remission (CR), 5 patients (8.06%) with partial remission (PR), ORR was 82.2%. Main adverse events were bone marrow suppression, fever and infection, and no chemotherapy-related deaths occurred. The median RFS time was 4.3 months (0.3 ~ 65 months), and median OS time was 7.75 months (1 ~ 66.3 months). Decitabine priming followed by CHAG regimen is effective and tolerated in patients with r/r AML, and can be used as a salvage treatment for patients with r/r AML.

Analysis of the efficacy of adjusting the dose of imatinib with therapeutic drug monitoring in adjuvant treatment after complete resection of gastrointestinal stromal tumors

Objective: To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors. Methods: This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25-82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2-3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L-1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment. Results: Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6-126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion: The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Clinical efficacy observation of heat-sensitive moxibustion combined with intrapleural perfusion of cisplatin in treatment of malignant pleural effusion

To investigate the clinical efficacy of heat-sensitive moxibustion combined with intrapleural perfusion of cisplatin in comparison with simple intrapleural perfusion of cisplatin on malignant pleural effusion (MPE). Forty patients with MPE, in compliance with the inclusion criteria, were randomly divided into an observation group (20 cases) and a control group (20 cases). In the control group, cisplatin solution (60 mg/m2) was injected into the thoracic cavity after pleural drainage under B-ultrasound positioning, once a week for 4 weeks. In the observation group, based on the intervention as the control group, the heat-sensitive moxibustion was delivered at the back and lumbar region (where Feishu ［BL13］, Pishu ［BL20］ and Shenshu ［BL23］ are located) and the chest-abdomen region (where Danzhong ［CV17］, Guanyuan ［CV4］ and Shuidao ［ST28］ are located), for 30 min to 90 min, once daily (the treatment was discontinued on Saturday and Sunday) and for 4 weeks. Before and after treatment, in the two groups, the pleural effusion volume was detected using B ultrasound, the activity of daily living was evaluated with Karnofsky performance statue (KPS) scale and TCM symptoms with TCM syndrome grading scale. The clinical therapeutic effect was evaluated in the two groups. According to the classification criteria table for acute and subacute toxicity of anticancer drugs made by WHO, the toxic and side reaction was judged. After treatment, the pleural effusion volume was reduced in comparison with that before treatment in the two groups (P<0.01, P<0.001), and the volume in the observation group was lower than that of the control group (P<0.05). KPS score was increased in the two groups after treatment compared with that before treatment (P<0.001), and the score in the observation group was higher than that of the control group (P<0.05). After treatment, the total score of TCM syndromes and the scores for dyspnea, cough and chest pain were lower than those before treatment in the two groups (P<0.001), and the scores in the observation group were lower than those of the control group (P<0.001, P<0.05). The scores for anorexia and lassitude were reduced in comparison with those before treatment in the observation group (P<0.001)；and the scores in the observation group were lower than those in the control group after treatment (P<0.001, P<0.01). After treatment, the effective rate of the observation group was 65.0%(13/20), which was higher than that of the control group (30.0%, 6/20, P<0.05). The incidence of bone marrow suppression in the observation group was 15.0%(3/20), lower than that in the control group (55.0%, 11/20, P<0.05). The incidence of gastrointestinal reactions in the observation group was 30.0%, lower than that in the control group (65.0%, 13/20, P<0.05). Heat-sensitive moxibustion combined with intrapleural infusion of cisplatin is superior to intrapleural infusion of cisplatin in the aspects of the amelioration of pleural effusion, daily-living activity and TCM syndromes in patients with MPE. This combined therapy presents the synergism by cooperating with chemotherapeutics and reduces the incidence of toxic and side effects implicated in chemotherapy so as to attenuate the toxicity of chemotherapeutics.

CNSC-33. GROUP3 MEDULLOBLASTOMA WITH BONE MARROW AND ABDOMINAL CAVITY METASTASIS:A CASE REPORT

Abstract Medulloblastoma is an infratentorial primitive neuro-ectodermal tumour, which is commonly occurring in childhood. It often spreads through the cerebrospinal fluid pathways with a very low rate of systemic metastases. Extra-central nervous system metastases have a poor prognosis in medulloblastoma. Here, we reported a case of Group3 medulloblastoma with bone marrow and abdominal cavity metastasis. A 10-year-old girl complained of headache, dizziness, vomiting and nausea. Magnetic resonance imaging(MRI) of the brain showed a large mass in the fourth ventricle and obstructive hydrocephalus. The surgery was performed to remove the mass and ventriculoabdominnal shunt was performed for obstructive hydrocephalus. Histological verification was proven classic medulloblastoma and next-generation sequencing confirmed molecular group of Gruop3 with MYC amplication. Radiotherapy was subsequently performed one month after the surgery. During the radiotherapy, brain MRI showed metastasis on the surface of the brain, which confer a poor prognosis. After the radiotherapy According to the therapeutic schedule, She would accept chemotherapy one month after the radiotherapy. But She suffered severe bone marrow suppression manifested as anaemia and thrombocytopenia, which can not be improved by medication and blood transfusion. A bone marrow aspiration was subsequently performed, and bone marrow smear showed large numbers of tumor cells at high magnification and was lack of normal hematopoietic cells. The girl was deteriorating rapidly with jaundice, ascites, hepatosplenomegaly and pancreatitis after the bone marrow aspiration. We found a lot of tumor cells in the bleeding tendency ascites and finally confirmed bone marrow and abdominal cavity metastasis concurrently. Eventually, She died less than a month after the metastasis and the overall survival was only 6 months. This typical case demonstrated severe bone marrow suppression of unknown origin should caused alarm and be performed bone marrow aspiration as soon as possible. The prognosis of medulloblastoma with extra-central nervous system metastases is poor and people may die in months.

NCOG-40. RARE ADVERSE EFFECT OF TEMOZOLOMIDE IN A 65-YEAR-OLD FEMALE WITH GLIOBLASTOMA MULTIFORME: A CASE REPORT

Abstract BACKGROUND Temozolomide, an antineoplastic agent is primarily used to treat certain brain tumors, including glioblastoma multiforme (GBM). Common side effects include nausea, vomiting, constipation, loss of appetite, alopecia (hair loss), headache, fatigue, convulsions and rash. A rare (less than 1%) adverse effect includes aplastic anemia refractory to treatment. Herein we present a case of Temozolomide induced severe bone marrow suppression in a 65-year-old woman with GBM refractory to any treatment CASE PRESENTATION A 65-year-old female presented with dizziness and left-hand numbness. Imaging revealed a right hemisphere mass and she underwent partial resection with pathology showing GBM, IDH wildtype, with CDKN2A/B deletion. She was started on radiation therapy with concurrent temozolomide. After nearly 5 weeks of temozolomide/RT, she developed severe thrombocytopenia/neutropenia with onset of neutropenic fever and severe CMV infection, leading to her demise within a week. DISCUSSION Life threatening refractory cytopenias is a very rare side effect of Temozolomide with a high rate of morbidity/mortality. In the case of our patient, she initially had weekly CBC’s which were stable and hence was switched to a monthly schedule. The patient’s ANC and platelets showed a precipitous drop within a month and ended up with aplastic anemia. The development of this rare complication underscores the importance of increased awareness about this often-fatal adverse event and possibly more frequent monitoring to recognize it early, especially in these patients with an already limited life expectancy. A more tailored approach to monitoring blood work may be needed depending on patient factors. CONCLUSIONS Aplastic anemia refractory to treatment is a rare and life threating adverse effect of temozolomide. The frequency of checking blood work for patients on Temodar has not been definitively established with protocols ranging from once weekly to monthly. Given the potential for this fatal adverse event, it is important to develop better tools to help identify patients in whom more frequent monitoring may be necessary.

Cytomegalovirus-associated pancytopenia in a four-month-old infant: a case report

Cytomegalovirus (CMV) is a beta-herpes virus causing common infections, often asymptomatic in healthy individuals. However, it poses increased risks to immunocompromised individuals and can cause congenital infections, leading to severe disabilities. CMV infection can cause significant hematological abnormality. A four-month-old female infant was admitted for decreased feeding for two days. She was severely pale, without hepatosplenomegaly. In initial laboratory investigations hemoglobin, platelet count, and white blood cells were decreased. The patient was transfused with whole blood and referred to a tertiary care center. Further workup, including bone marrow biopsy, showed hypocellular marrow. The Urine CMV Polymerase Chain Reaction (PCR) test returned highly positive with a viral load of 1,700,000 copies/mL. This patient was diagnosed with CMV-associated bone marrow suppression, and she was prescribed valganciclovir at a dosage of 16 mg/kg/dose every 12 h for 6 months. She had shown significant hematologic parameter improvement during subsequent follow-up. Pancytopenia in infancy should include a differential diagnosis for CMV infection. The early recognition and correct infection management, including antiviral therapy and symptomatic treatment, yield a better prognosis.

Valacyclovir versus valganciclovir for cytomegalovirus prophylaxis in kidney transplant recipients: a systematic review and comparative meta-analysis.

Valganciclovir (ValG) is the most widely used drug for cytomegalovirus (CMV) prophylaxis in kidney transplant recipients (KTRs). However, it is associated with dose-limiting side effects and considerable costs. Some centers have identified valacyclovir (ValA) as an economically attractive alternative with a lower risk of bone marrow suppression. The comparative effectiveness of these two drugs is not well-established. This study aims to compare the efficacy and safety of ValA and ValG for CMV prophylaxis in KTRs. Searches were conducted of the Medline, Cochrane, Web of Science, Embase, and Ovid databases. Endpoints encompassed the incidence of CMV disease, CMV viremia, acute rejection, leukopenia/neutropenia, and other infections, including BK polyomavirus and non-CMV herpesviruses (HVs). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Six studies, comprising 888 patients (438 receiving ValA), were included. The groups were comparable in CMV viremia incidence (RR, 0.70; 95% CI, 0.31-1.57; P=0.4) and the development of CMV disease (RR, 0.74; 95% CI, 0.09-5.97; P=0.8). No significant differences in acute rejection rates were observed (RR, 0.97; 95% CI, 0.50-1.91; P=0.8). However, the rate of leukopenia/neutropenia was significantly lower in the ValA group (RR, 0.57; 95% CI, 0.42-0.77; P<0.01). No significant differences were noted for BK viremia (RR, 0.67; 95% CI, 0.24-1.87; P=0.4) or other HV infections (RR, 1.43; 95% CI, 0.61-3.38; P=0.4). The drugs demonstrate comparable efficacy in preventing CMV infection following kidney transplantation. However, ValA may have a lower impact on bone marrow suppression.

Clinical Efficacy and Safety of Anlotinib Combined with Immune Checkpoint Inhibitors in the Treatment of Advanced Squamous Cell Lung Cancer: A Retrospective Single-Center Study in China.

There is a relative lack of real-world data regarding the treatment of advanced squamous cell lung cancer (SqCLC) with anlotinib. This study aimed to investigate the clinical efficacy and safety of combining anlotinib with ICIs for the treatment of advanced SqCLC. Sixty patients with advanced SqCLC from December, 2017 to December, 2022, were retrospectively recruited in the final analysis. The overall survival (OS), adverse events (AEs), and short-term clinical effectiveness, including complete remission (CR), partial remission (PR), stable disease (SD), and progression disease (PD) of the study populations, were observed. Objective response rate (ORR) was defined as the combined percentage of CR and PR in all patients. Disease control rate (DCR) was defined as the combined percentage of CR, PR, and SD in all patients. Subgroups were classified based on age (<65 or ≥65), sex (female or male), and the eastern cooperative oncology group (ECOG) score (0-1 or 1-2). The median age of the study population was 65 years, and 41 (68.3%) of the participants were male. ORR was 21.67%, and DCR was 83.33%. The median PFS and OS were 7.5 and 19.5 months, respectively. Furthermore, the Kaplan-Meier curves demonstrated no significant difference (P >0.05) in PFS and OS between different age groups, sex, and ECOG scores. Bone marrow suppression was the most common AE, followed by immune pneumonia. The findings of this study confirmed the effectiveness and safety of anlotinib and ICIs for advanced SqCLC.

Myeloprotective potential of leaves extract fractions of Cnidoscolus aconitifolius in myelo suppression

Chemotherapy has been associated with myelosuppression. Myeloprotection is the main remedy to myelosuppression. Nature has been endowed with natural molecules rich in therapeutic components and one of such nature is Cnidoscolus aconitifolius (CA) which has been reported to be rich in antioxidants. The aim of the study was to investigate myelo-protective potential of CA in myelo-suppressed animal model. Albino rats (n = 32) were divided into 8 groups of 4 rats each labelled A-H out of which 7 groups (B-H) were induced intraperitoneally for myelosuppression with cyclophosphamide (CP) and only 6 groups (C-H) were treated with CA extracts for four weeks. Group A served as normal control, groups B-H was induced for myelosuppression with cyclophosphamide. Group B served as myelo-suppressed control, groups C, D and E, received 100mg/kg body weight (bw) methanol fractions of CA while groups F, G and H received 200mg/kg body weight methanol fractions of CA. Two milliliters of blood were collected into ethylenediaminetetraacetic acid containers for total white blood cell count and absolute granulocyte count on days 3, 12 and 21 using mindray auto analyser BC-360. On day 30, bone marrow (BM) was harvested from one rat per group for BM examination and cellularity. Following administration of (CP), myelosuppression set in as observed in significant decreased (P &lt; 0.05) in total white blood cell (TWBC) count and absolute granulocyte count. Extract fractions of CA caused significant increase (P &lt; 0.05) in TWBC count and absolute granulocyte count in all the treated groups on days 12 and 21 compared with baseline. Bone marrow cellularity of all the treated groups revealed normal myeloid erythroid ratio indicating normal marrow cellularity. The findings in this study suggested myelo-protection by Cnidoscolus aconitifolius against cyclophosphamide induced myelosuppression.

The efficacy and safety of anlotinib combined with chemotherapy in treatment of advanced soft tissue sarcoma

BackgroundTo evaluate the efficacy and safety of anlotinib combined with chemotherapy in the treatment of advanced soft tissue sarcoma (STS).MethodsA total of 14 patients with advanced STS consisting of 4 liposarcoma, 3 undifferentiated polymorphous sarcoma, 2 synovial sarcoma, 1 Extraosseous ewing sarcoma, 1 spindle cell sarcoma, 1 Sarcomatoid malignant mesothelioma, 1 hemangiosarcoma, and 1 fibrosarcoma, were treated with anlotinib plus chemotherapy. The anlotinib was combined with chemotherapy as the first-line treatment in 13 patients, and as second-line treatment in 1 patient. Chemotherapy regimens were based on anthracyclines and ifosfamide, and other drugs included paclitaxel, and so on. Efficacy and safety were evaluated every 2 treatment cycles.ResultsAccording to the stage of AJCC, 9 patients were stage III and 5 patients were stage IV. The average cycle of treatment is 3.86. Among the 14 patients, 2 cases had received surgical treatment after neoadjuvant chemothrapy, 5 cases had partial response (PR), 7 cases had stable disease (SD), and 2 cases had progressive disease (PD). The overall response rate (ORR) was 35.7% (5/14). Patients who had not underwent surgical treatment were with a disease control rate (DCR) of 83.3% (10/12). The median progression free survival (PFS) was 8.25 months. The common treatment-related adverse effects included bone marrow suppression, nausea, vomiting and hypertension. Three patients had severe adverse effect, which was febrile neutropenia. No treatment-related death was found.ConclusionsAnlotinib combined with chemotherapy in the treatment of STS is effective and tolerable, which is a promising strategy. It is worthy of further clinical research.

Ziltivekimab for anemia and atherosclerosis in chronic kidney disease: a new hope?

Anemia of chronic kidney disease is a multifactorial condition secondary to various etiologies, including nutritional deficiencies, chronic inflammation, erythropoietin deficiency or resistance, bone marrow suppression, iron deficiency and adverse drug effects. The major therapeutic intervention for anemia among chronic kidney disease patients is erythropoiesis-stimulating agents. However, a limitation of erythropoiesis-stimulating agents is the risk for thromboembolic events, hypertension, seizures, solid organ malignancies and hyporesponsiveness. A novel interleukin-6 monoclonal antibody, ziltivekimab, has been evaluated for managing anemia in chronic kidney disease patients in pilot clinical trials with promising outcomes, including an improvement in hemoglobin levels and reduction of inflammatory parameters. These trials have shown that ziltivekimab does not increase the risk for cytopenia or infectious complications as has been described for other interleukin-6-targeting monoclonal antibodies, like tocilizumab. Furthermore, potentially beneficial effects on serum lipid profile have been reported, leading to the hypothesis of a favorable impact of the drug on atherosclerotic complications. In addition, ziltivekimab has shown efficacy in improving anemia parameters, including hemoglobin levels and iron studies. Ziltivekimab deserves full scale clinical development, and to this aim, large-scale clinical trials are under way.

Hematological Side Effects of Psychiatric Drugs

This review article focuses on hematological disorders caused by psychiatric drugs, including neutropenia, leukopenia, leukocytosis, and anemia. Most major psychiatric drugs induce neutropenia and thrombocytopenia through various mechanisms, such as toxic bone marrow suppression and drug-dependent antineutrophil antibodies against hematopoietic precursors. Among these, agranulocytosis associated with phenothiazines is a well-discussed hematological side effect. Although rare, agranulocytosis is a dangerous and often fatal complication that may go unnoticed until infection occurs. We conducted a comprehensive literature search from 1977 to 2021, identifying 64 relevant articles. Our study aims to analyze outcomes related to pancytopenia, leucopenia, neutropenia, agranulocytosis, thrombocytopenia, and other hematological complications leading to hospitalization.

Efficacy and safety of anlotinib combined with S‑1 as a third‑ or later‑line treatment for advanced non‑small cell lung cancer in China: A systematic review and meta‑analysis.

Anlotinib is presently used as a third-line treatment for non-small cell lung cancer. However, it is not yet reported whether combining anlotinib with S-1 as a third- or later-line treatment offers superior outcomes compared with anlotinib alone. The present meta-analysis aimed to address this question by systematically searching the PubMed, Embase, Web of Science, Cochrane Library, CMB and China National Knowledge Infrastructure databases for eligible studies published from the establishment of the database to January 10, 2024. Primary outcomes of interest included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and the incidence of adverse effects, which were presented as hazard ratios and 95% CIs. The present analysis included 5 retrospective studies with a total of 317 patients and compared the outcomes of patients treated with a combination of anlotinib and S-1 (experimental group) compared with anlotinib alone (control group). The combination treatment significantly improved PFS, OS, ORR and DCR in the experimental group compared with the control group. Bone marrow suppression and fatigue were significantly higher in the experimental group compared with the control group. However, incidences of hypertension, proteinuria, gastrointestinal adverse reactions, hepatic and renal insufficiency and functional hand-foot syndrome were higher in the control group compared with the experimental group, but there was no statistical significance. In summary, combining anlotinib with S-1 may be more effective compared with anlotinib alone for treating advanced non-small cell lung cancer. Despite the higher incidence of adverse reactions with the combination therapy, these reactions could be considered manageable and controllable.

8675 Dosing of Radioactive Iodine for Papillary Thyroid Cancer in Advanced Chronic Kidney Disease

Abstract Disclosure: C. Cheatham: None. D. Beckman: None. INTRO Radioactive Iodine (RAI) ablation is an important treatment for patients diagnosed with papillary thyroid carcinoma. Most studies completed on RAI in renal dysfunction were focused on End Stage Renal Disease (ESRD) patients on dialysis to establish protocols on timing of dialysis to allow desired clinical response to RAI without increased risks and minimizing exposure of dialysis staff to radiation dose. The ideal RAI dosing and monitoring of patients with advanced chronic kidney disease (CKD) stage 4 or 5 not requiring dialysis has not been systematically reviewed. CASE 26 year-old female with CKD stage 4/5 secondary to chronic hydronephrosis from vesicoureteral reflux with baseline eGFR 15-20 mL/min/1.73 m2 was diagnosed with papillary thyroid cancer. She underwent total thyroidectomy with central and left lateral neck dissection, resulting in pathologic stage I, pT2 N1b M0 disease, high risk for recurrence according to the 2015 American Thyroid Association guidelines due to 17 positive lymph nodes from left level II-IV and VI, multiple with extranodal extension, as well as 1 vessel angioinvasion. She was referred for adjuvant RAI ablation after withdrawal from thyroid hormone. Decision was made to proceed with a 50% dose reduction and close monitoring of radioactivity clearance as an inpatient given decrease of eGFR to 10-12 mL/min/1.73 m2. She was cleared for discharge 4 days after RAI dose of 74.8mCi when activity level dropped to &amp;lt;2mR/hr. Post-ablation whole body scan showed activity in the thyroid bed and parasternal notch without evidence of metastatic disease. Post-treatment non-stimulated thyroglobulin 6 weeks later was 0.4 ng/mL down from 269.7 ng/mL. DISCUSSION Given RAI is predominately renally cleared, decreased renal function affects clearance rates and associated exposure to radiation. Risks with decreased RAI clearance include bone marrow toxicity and prolonged isolation requirements. In a 2017 retrospective review, patients with eGFR &amp;lt;30 mL/min/1.73 m2 had delayed clearance leading to a mean proportional reduction of exposure rate at 48 hours of -67.2% compared to -94.3% in healthy controls. While protocols exist for patients on hemodialysis, no such protocols have been established for patients with advanced CKD not requiring dialysis. For this patient, after multidisciplinary discussion with nuclear medicine, health physics, and nephrology in setting of further eGFR reduction during hormone withdrawal, decision was made to reduce the intended dose by 50% with inpatient monitoring and backup to dialyze if no significant decrease in radiation activity level was seen or if she were to progress to anuric or oliguric renal failure. This case highlights the need for established protocols and long-term studies to evaluate risk and treatment response in relation to dosing of RAI in this population, but a 50% dose reduction appears to be effective without adverse event. Presentation: 6/2/2024