Survival Outcomes and Prognostic Factors in Therapy-Related Acute Myeloid Leukemia: A SEER Database Study, 2000-2020.

INTRODUCTION: With advances in therapeutics and longer survival across different cancer spectrums, the incidence of therapy-related acute myeloid leukemia (tAML) has continued to rise. This study aims to evaluate the trend of survival outcomes and their association with sociodemographic factors in tAML over the last 20 years. METHODS: We identified tAML patients between 2000 and 2020 from the Surveillance, Epidemiology, and End Results database. Patients were divided into 4 age groups: 18-39, 40-59, 60-69, and >= 70 years, and 4 diagnostic periods: 2000-2005, 2006-2010, 2011-2015, and 2016-2020. Overall survival (OS) was compared using Kaplan Meier and log-rank methods. RESULTS: The 1-year (and 5-year) OS in patients with tAML was 59.3% (33.7%), 48.2% (24.8%), 37.2% (11.1%), and 32.9% (5.5%) in age groups 18-39, 40-59, 60-69, and >=70 years, respectively. The 1-year (and 5-year) OS based on the year of diagnosis was 20.9% (13.2%), 36.8% (15.2%), 41.9% (13.88%), and 40.4% (not reached) for 2000-2005, 2006-2010, 2011-2015, and 2016-2020 respectively. Among the youngest cohort aged 18-39 years, 1-year OS was 35.7%, 57.7%, 66.7%, and 59.6%, respectively, in 4 diagnostic periods, whereas 1-year OS was 10.5%, 23.9%, 32.2%, and 36.9%, respectively, in the oldest cohort aged >=70 years. Age, year of diagnosis, and geographic location were independent prognostic markers of OS. CONCLUSION: Our study demonstrates a significant improvement in the 1-year OS of tAML patients over the last decade, but the long-term prognosis remains dismal. Older patients continue to show improved survival in recent years with the addition of newer intensive and nonintensive options.

Biomarker role of maternal soluble human leukocyte antigen G in pre-eclampsia: A meta-analysis.

INTRODUCTION: Human leukocyte antigen-G (HLA-G) is a non-classical class I HLA molecule shown to regulate the immunomodulation of maternal immune cells to prevent fetal tissue destruction. Low levels of freely circulating maternal soluble HLA-G (sHLA-G) have been observed in pre-eclampsia, however, no pooled evidence exists. This meta-analysis aimed to generate pooled findings on the association of sHLA-G levels with pre-eclampsia and is the first study to perform a trimester-wise comparison of the levels of sHLA-G in preeclamptic cases and normal pregnant controls. METHODS: The databases PubMed, Emba, Web of Science, and Google Scholar through May 31, 2023. Preeclamptic women were defined as cases and normal pregnancies as controls. Data on the level of sHLA-G in cases and controls was extracted and subjected to a meta-analysis using a random-effects model. The pooled effect was expressed in terms of standardized mean difference (SMD). Sensitivity analysis was performed to investigate the effect of the exclusion of each study on the pooled results. Publication bias was assessed statistically. RESULTS: Nine studies with altogether 567 PE cases and 1132 normal pregnancy controls were included in the meta-analysis. The first and third trimester levels of sHLA-G in PE cases were significantly lower than that of normal pregnant controls: (SMD: -0.84 [-1.29; -0.38]; p = .003; I2 = 54%) and (SMD: -0.39 [-0.71; -0.06]; p = .02; I2 = 79%) respectively. Sensitivity analysis revealed significant fluctuations in the pooled findings when few studies were excluded, raising questions on the consistency of results among studies. CONCLUSION: Although we found that first and third-trimester sHLA-G levels in pre-eclampsia are significantly lower, taking into consideration the inconsistent results from the sensitivity analysis, our findings advocate the demand for more studies with larger sample sizes to generate solid ground pooled evidence on the predictive role of sHLA-G in pre-eclampsia.

Oral SERD, a Novel Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer.

Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease. ESR1 mutations have been identified as a common mechanism of endocrine therapy resistance in ER+ breast cancer. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has shown some activity against ESR1 mutant tumors. However, due to its poor bioavailability and need for intramuscular injection, it may not be the optimal therapy for patients. Second-generation SERDs were developed to overcome these limitations. These newer drugs have improved oral bioavailability and pharmacokinetics, making them more convenient and effective for patients. Several oral SERDs are now in phase III trials for early and advanced ER+ breast cancer. This review summarizes the background of oral SERD development, the current status, and future perspectives.

Does Caplacizumab for the management of thrombotic thrombocytopenic purpura increase the risk of relapse, exacerbation, and bleeding? An updated systematic review and meta-analysis based on revised criteria by the International Working Group for thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening condition marked by abnormal blood clotting and organ damage. Caplacizumab is a potential treatment for the TTP management. This systematic review and meta-analysis aimed to assess Caplacizumab's effectiveness and safety in the TTP management. A comprehensive database search identified nine studies, including randomized controlled trials and observational studies. Primary outcomes included TTP exacerbation, relapse, and major bleeding. Major bleeding risk was evaluated using updated definitions recommended by the International TTP Working Group in 2021. Revised criteria proposed by the IWG for TTP recurrence were employed for a comprehensive assessment of Caplacizumab's impact on relapse and exacerbation. Analysis revealed Caplacizumab significantly reduced all-cause mortality in TTP patients. Some studies raised concerns about bleeding risk, but overall, it did not significantly differ from standard treatment. Likewise, there was no significant difference in TTP relapse rates between Caplacizumab and standard care. This study supports Caplacizumab as a potential adjunct therapy for TTP. However, careful consideration of its advantages and risks is crucial in clinical practice. Further research is needed to address concerns related to adverse effects like bleeding risk and relapse rates associated with Caplacizumab in the TTP management. The findings emphasize the importance of weighing potential benefits and risks when considering Caplacizumab as an adjunct therapy for TTP.

Opportunities and Challenges for a Histology-Agnostic Utilization of Trastuzumab Deruxtecan.

PURPOSE OF REVIEW: This review delves into the prospects and challenges offered by a potential pan-histological utilization of trastuzumab deruxtecan (T-DXd) in patients with advanced solid tumors. RECENT FINDINGS: The HER2-targeted antibody-drug conjugate (ADC) T-DXd has shown broad activity across cancer types, with current indications for patients with biomarker-selected breast, gastric, and non-small-cell lung cancer and relevant activity observed in multiple histology-specific trials. Moreover, two recently reported phase 2 trials (DESTINY-Pantumor02 and HERALD) have supported the potential for a pan-cancer utilization of this ADC in patients with advanced cancers expressing HER2 or with HER2 amplifications. By improving the delivery of cytotoxic chemotherapy, ADCs have allowed for meaningful clinical advantages in broad populations of cancer patients, often leading to survival advantages over conventional chemotherapy. Notably, the broad spectrum of activity of certain ADCs has led to the hypothesis of a histology-agnostic utilization based on detecting specific biomarkers, similar to what is already established for certain targeted treatments and immunotherapy. To date, T-DXd has shown the broadest activity across cancer types, with current approvals in breast, gastric, and lung cancer, and relevant antitumor activity observed in a multiplicity of additional cancer types. The optimization of the drug dose, identification of predictive biomarkers, and clarification of mechanisms of resistance will be critical steps in view of a pan-histological expansion in the use of T-DXd.

An Unusual Case of ST-Elevation Myocardial Infarction (STEMI) Mimicker: Pneumopericardium Secondary to Gastro-Pericardial Fistula.

Pneumopericardium is defined as the collection of air inside the pericardium. Gastro-pericardial fistula is one of its rarest etiologies. We are presenting a case of pneumopericardium due to gastro-pericardial fistula secondary to gastric cancer presented with an inferior ST-elevation myocardial infarction (STEMI)-like picture. Our case is a 57-year-old male with a past medical history of metastatic gastric cancer status post chemotherapy and radiotherapy who presented to the emergency with acute onset severe burning chest pain with radiation to his back. He was diaphoretic, saturating 96% on room air, and hypotensive with a blood pressure of 80/50 mmHg, and his EKG showed sinus rhythm with a heart rate of 60 BPM and ST elevation in inferior leads meeting STEMI criteria. The patient was transferred for an emergency coronary angiogram with possible percutaneous intervention. Surprisingly, no significant lesions in his epicardial vessels would corroborate his clinical presentation and EKG changes. The decision was to obtain CT angiography to exclude aortic dissection and pulmonary embolism. His CT chest revealed a large pneumopericardium with a gastric-pericardial fistula. A nasogastric tube was placed with suctioning of gastric contents. Given his tamponade physiology, it was decided to do emergent pericardiocentesis draining only 20 cc of gastric contents and a significant amount of air. After the procedure, the patient was transferred to the ICU with stable hemodynamics. The case was discussed with surgery, but given his inoperable cancer, a palliative team was involved. Acknowledging his very poor prognosis, the patient requested discharge to home with home hospice. As reported in the literature, pneumopericardium is rare, and gastro-pericardial fistula associated with gastric cancer is even rarer. Clinical presentation is variable and can be confusing. Providers should be aware of how a patient with gastric cancer can be complicated with pneumopericardium, and they should have a lower threshold of suspicion in patients having risk factors. CT scan is the most sensitive tool for diagnosis.

Real-World Effectiveness of Tixagevimab and Cilgavimab (Evusheld) in Patients With Hematological Malignancies.

Background: Immunocompromised individuals with hematological malignancy have increased risk for poor outcomes and death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This special population may mount a suboptimal response to vaccination. We assessed the effectiveness of tixagevimab and cilgavimab (Evusheld), a monoclonal antibody combination against SARS-CoV-2, in conjunction with standard preventative measures, at preventing symptomatic incident infection. Methods: Patients aged 18 years and older with hematological malignancy consented to receive Evusheld. Patients were followed longitudinally for development of symptomatic incident SARS-CoV-2 infections. Adverse events were monitored. Results: Two hundred and three patients (94 female) with hematological malignancies and mean age 72 ± 10 years were included. Of the patients, 99.5% had received at least one mRNA vaccination against SARS-CoV-2. Average time of follow-up was 151 ± 50 days. Nineteen patients (9.3%) developed incident symptomatic SARS-CoV-2 infection, with only one (0.5%) requiring hospitalization. During the same follow-up period, local incident rate of infection was 84,123 cases (11.3% of population). Of those, 3,386 cases (4%) of SARS-CoV-2 required hospital admission. The incidence rate ratio was 0.79. No serious adverse events occurred following administration of Evusheld. Conclusion: Patients with hematological malignancy who received Evusheld infrequently developed symptomatic infections or require hospitalization. The high-risk cohort incidence was at least as comparable to the average risk general population. Evusheld appears effective and is well tolerated, and may be administered in conjunction with vaccination and standard prevention measures, at decreasing incident SARS-Co-V2 cases in this high-risk population.