Hussein, Guleid

Abstract Immune checkpoint inhibitor–associated immune thrombocytopenia (ICI-ITP) has been described in case reports and small case series, but comprehensive data on its incidence, risk factors, clinical features, treatment, and outcomes are lacking. We reviewed medical records of all adults initiating ICI therapy between 2016 and 2023 at 29 US hospitals across 7 major cancer centers to identify patients with ICI-ITP. Multivariable logistic regression was used to identify risk factors, and Cox modeling was performed to assess the association between ICI-ITP, its severity, and mortality. Among 86 467 patients, ICI-ITP occurred in 214 (0.25%). Independent risk factors included lower baseline platelet count, combination ICI therapy, stage IV cancer, and additional immune-related adverse events. ICI-ITP occurred at a median of 8 weeks (interquartile range [IQR], 4-18) after ICI initiation, with a median nadir platelet count of 41 × 109/L (IQR, 17 × 109/L to 64 × 109/L). Patients were treated with glucocorticoids (n = 106 [49.5%]), immune globulin (n = 39 [18.2%]), and thrombopoietin receptor agonists (n = 29 [13.6%]). Recovery occurred in 161 patients (75.2%) at a median of 2.3 weeks (IQR, 1.0-5.3). Of 76 patients rechallenged with ICIs, 23 (30.3%) developed recurrent ICI-ITP. ICI-ITP and its severity were associated with higher all-cause mortality, with a nearly threefold increase in risk among patients with severe ICI-ITP than those without ICI-ITP (adjusted hazard ratio, 2.96 [95% confidence interval, 2.14-4.08]). These findings establish ICI-ITP as a rare but clinically significant complication of ICI therapy, provide, to our knowledge, the first large-scale description of its risk factors and clinical course, and underscore the importance of timely recognition and management.

Abstract INTRODUCTION Immune checkpoint inhibitors (ICIs) have emerged as a cornerstone of cancer therapy. However, despite their efficacy, ICIs can cause a unique spectrum of autoimmune toxicities known as immune-related adverse events (irAEs). In contrast to irAEs involving other organ systems, hematologic irAEs such as ICI-associated immune thrombocytopenia (ICI-ITP) are less common. As a result, existing data on ICI-ITP are largely confined to isolated case reports, single-center case series, and pharmacovigilance databases lacking granular clinical data. To address this key knowledge gap, we sought to comprehensively characterize the incidence, risk factors, clinical features, treatments, and outcomes associated with ICI-ITP. METHODS We performed a multicenter cohort study of adult patients who initiated ICI therapy at 29 hospitals across 7 major cancer centers in 11 geographically diverse states in the US between 2016-2023. ICI-ITP was defined as a decline in platelet count to <100 x109/L in the absence of an alternative more plausible etiology of thrombocytopenia. Patients with hematologic malignancies were excluded, as were those who received cytotoxic chemotherapy within 30 days prior to thrombocytopenia onset. For each patient identified as having ICI-ITP, we collected data on demographics, comorbidities, medications, laboratory values, treatments, and outcomes. All data were extracted by manual chart review. To identify risk factors for ICI-ITP and to examine its association with death, for each case of ICI-ITP we also collected data on two control patients who initiated ICI therapy at the same site and in the same year but without development of ICI-ITP. We used multivariable logistic regression to identify independent risk factors for ICI-ITP and its recovery (the latter defined according to criteria established by the ITP International Working Group). We used a multivariable Cox model to examine the association between ICI-ITP and its severity with all-cause mortality. RESULTS We identified a total of 214 patients who developed ICI-ITP among 86,648 examined (0.25%). The incidence was highly consistent across sites (range, 0.15–0.30%). Risk factors for ICI-ITP included simultaneous receipt of two different classes of ICIs, additional irAEs, and a lower baseline platelet count. ICI-ITP developed at a median of 8 weeks (IQR, 4–18) following ICI initiation. The median nadir platelet count was 41 x109/L (IQR, 17–64). Six out of 214 patients (2.8%) developed a major bleed, and 16 patients (7.5%) developed a clinically relevant non-major bleed. Cell-bound anti-platelet antibody testing was positive in 6 of 8 patients (75.0%) for whom it was assessed, and median circulating thrombopoietin levels (201 pg/mL [IQR, 178–295]) were similar to those seen in primary ITP. Treatments used included glucocorticoids (49.5%), immune globulin (18.2%), and thrombopoietin receptor agonists (13.6%). Overall, 161 patients (75.2%) recovered from ICI-ITP at a median of 2 weeks (IQR, 1–5) following ICI-ITP onset. Predictors of recovery included additional irAEs and a higher nadir platelet count. Treatment response was observed in 57.0%, 56.4%, and 58.3% of patients within 60 days following initiation of glucocorticoids, immune globulin, and thrombopoietin receptor agonists, respectively. Of 76 patients rechallenged with an ICI, 23 (30.3%) developed recurrent ICI-ITP at a median of 9 weeks (IQR, 2–15); 17 of these 23 patients (73.9%) recovered. Finally, ICI-ITP and its severity were monotonically associated with a higher risk of death (adjusted hazard ratio 2.96 [95% CI, 2.14–4.08] for those with severe ICI-ITP compared to those without ICI-ITP). CONCLUSION In this multicenter study involving patients treated with ICIs at 29 hospitals across the US, we identified 214 patients with ICI-ITP. For the first time, we characterize in detail the incidence, risk factors, clinical features, treatments, and outcomes of ICI-ITP, a relatively novel disease entity. We found that more than half of patients responded to conventional ITP-directed therapies, and that most patients rechallenged did not develop recurrent ICI-ITP. We also found that ICI-ITP was independently associated with an increased risk of death, including a nearly 3-fold increased risk in those with severe ICI-ITP. These findings highlight ICI-ITP as a rare but clinically significant complication of ICI therapy that hematologists must be equipped to recognize and manage.

572 Background: Neoadjuvant endocrine therapy (NET) is sometimes used to shrink hormone receptor-positive (HR+) breast cancers to improve breast conservation rates and reduce axillary nodal burden. At the beginning of the COVID-19 pandemic, several organizations endorsed NET use to mitigate the harm of surgery delay when cancer operations were less available due to infection transmission concerns. However, the real-world patterns of NET during this period are understudied. This study investigated the alteration of NET utilization patterns during the COVID-19 pandemic in the United States using the National Cancer Database (NCDB). Methods: We identified patients diagnosed with stage I-III invasive HR+/human epidermal growth factor receptor 2-negative (HER2-) breast cancer between 2018-2022 in the NCDB. Estrogen receptor and/or progesterone receptor positivity was required for inclusion in the cohort. Receipt of NET was defined as initiation of endocrine therapy ≥ 14 days before the patient’s first surgical procedure. The study cohort generation and statistical analysis were conducted using Stata and R 4.4.3. A two-tailed p value < 0.05 was considered statistically significant. Results: 495,098 patients were included in the cohort, 195,371 in 2018-2019 (pre-pandemic), 91,686 in 2020 (early pandemic), 106,157 in 2021 (mid-pandemic), and 101,884 in 2022 (late pandemic). NET utilization was increased in the early pandemic compared to the pre-pandemic (seen in 5.8% vs 2.4% of the cohort, Chi-square p value < 0.001), but this use fell back to 3.4% in the mid-pandemic and 3.5% in the late-pandemic. The median (IQR) duration of NET was 15.7 (6.4-26.6) weeks in the pre-pandemic, 9.3 (5.4-18.7) weeks in the early pandemic, 13.2 (5.8-25.7) weeks in the mid-pandemic, and 12.0 (6-24.6) weeks in late pandemic (Kruskal-Wallis p value = 0.001). The transient increase in NET utilization during the early pandemic was more pronounced among patients with tumors < 5 cm and node-negative disease. Conclusions: Our study identified a significant shift in the utilization of NET for HR+/HER2- breast cancer during the COVID-19 pandemic. Pandemic-era NET policies produced a short-lived practice change that was only partially sustained once surgical access normalized. NET utilization (%) by subgroup and year for stage I-III HR+/HER2- breast cancer. Variable Category 2018-2019 2020 2021 2022 Overall NET Use 2.4 5.8 3.4 3.5 Age Group (years old) <50 2.2 4.9 3.9 4.0 >=50 2.4 6.0 3.3 3.4 Tumor Size <5 cm 2.0 5.5 2.9 3.1 >=5 cm 9.0 9.7 11.2 11.6 Histology Subtype Ductal 2.2 5.5 3.3 3.4 Lobular 3.6 7.1 4.4 4.8 Ductal/Lobular 2.6 6.2 4.3 3.6 Other 1.9 6.7 2.5 2.6 KI67 <20% 2.5 6.4 3.4 3.3 >=20% 2.3 5.5 3.5 3.7 Tumor Grade Well differentiated 1.9 5.8 2.4 2.6 Moderately differentiated 2.7 6.1 3.9 3.9 Poorly differentiated/undifferentiated 2.9 4.8 4.3 4.8 Node Positivity Positive 5.2 5.6 9.3 9.5 Negative 2.0 5.8 2.6 2.7

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the clonal proliferation of myeloid precursors and rapid progression. Historically consisting of intensive chemotherapy, AML management has evolved significantly due to advances in molecular diagnostics and risk stratification. This review discusses current therapeutic paradigms in AML, emphasizing the growing role of personalized medicine across age and risk groups. For younger, fit patients, intensive regimens such as the “7 + 3” protocol remain the standard, often enhanced by targeted agents like FMS-like tyrosine kinase 3 (FLT3) and IDH inhibitors. Older or unfit individuals benefit from low-intensity treatments such as hypomethylating agents combined with venetoclax, now considered a frontline standard of care. The use of liposomal chemotherapy (CPX-351), measurable residual disease (MRD) monitoring, and maintenance therapy further refine post-remission strategies. Emerging therapies, including menin inhibitors, antibody–drug conjugates, and immunotherapies like CAR-T cells and vaccines, offer additional options, especially in relapsed/refractory settings. This comprehensive review outlines the current landscape and future directions in AML therapy, emphasizing the transition toward individualized, mutation-driven treatment strategies.

Key Clinical MessageStone heart syndrome has a complex interaction with digoxin toxicity, where, theoretically, the administration of intravenous calcium can worsen a patient's condition. Research on this subject is conflicting, so it is imperative to approach it cautiously.

Blood transfusion is a common therapeutic intervention in hospitalized patients. There are numerous indications for transfusion, including anemia and coagulopathy with deficiency of single or multiple coagulation components such as platelets or coagulation factors. Nevertheless, the practice of transfusion in critically ill patients has been controversial mainly due to a lack of evidence and the need to consider the appropriate clinical context for transfusion. Further, transfusion carries many risk factors that must be balanced with benefits. Therefore, transfusion practice in ICU patients has constantly evolved, and we endeavor to present a contemporary review of transfusion practices in this population guided by clinical trials and expert guidelines.

e23537 Background: Follicular Dendritic Cell Sarcoma (FDCS) is a rare, indolent, low-grade sarcoma known for local recurrences managed primarily by surgery. The role for adjuvant therapy has not been established for either radiation or chemotherapy. We aimed to comprehensively analyze clinical and epidemiological profiles and responses to treatment in these patients. Methods: This is a retrospective study using the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Result (SEER) database. Cases of FDCS between 2001 to 2022 were identified utilizing the International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9758/3. Only adults > 18 years of age and diagnosed by positive histology or cytology were included. Descriptive statistics were used to describe demographic and tumor characteristics. Logistic regression was used to identify the factors influencing survival. Kaplan-Meier method was used to plot survival based on different treatment regimens and stages. Results: A total of 168 patients with FDCS were identified, with more than 50% of the patients ≥ 50 years of age. The mean age at diagnosis was 52.6 years, 56% were female, and 74.4% were white. Most of the patients had localized disease (63.7%), 17.9% had distant disease, and the remaining had unknown stages. About 90% of the patients underwent surgery, with 41% receiving local tumor excision. In Univariate analysis, older age, and distant disease were found to have poor outcomes. Surgery, irrespective of stage, was found to improve overall Survival (Table 1). While chemotherapy and distant disease had poor outcomes in univariate analysis, they were not statistically significant in multivariate analysis. The majority of the patients who received chemotherapy alone without surgical intervention had distant disease, explaining the poor outcome seen in univariate analysis. Among 107 patients with localized disease, 41 patients (41.1%) underwent only surgery and 43 patients (40.1%) received adjuvant therapy (either chemotherapy or radiation vs both) along with surgery. 5-year overall survival was significantly lower in patients who received adjuvant therapy. (88.4% vs 68.4%, p = 0.001). Conclusions: In conclusion, FDCS has a fair overall 5-year survival with surgery alone. Patients with localized disease, who received adjuvant therapies had poor survival outcomes as compared to the surgery-only group owing to disease burden. Large prospective studies are required to properly evaluate the benefit of adding chemotherapy or radiotherapy in resectable disease.

Therapeutic plasma exchange (TPE) is a treatment paradigm used to remove harmful molecules from the body. In short, it is a technique that employs a process that functions partially outside the body and involves the replacement of the patient’s plasma. It has been used in the ICU for a number of different disease states, for some as a first-line treatment modality and for others as a type of salvage therapy. This paper provides a brief review of the principles, current applications, and potential future directions of TPE in critical care settings.

Introduction Acute chest syndrome (ACS) is a clinical presentation of fever, chest pain, pulmonary symptoms, and new infiltrates on lung imaging. It affects nearly 50% of patients with sickle cell disease during their lifetime and often leads to hospitalization. The mortality rate is variable ranging from 3 to 9 %. and depends on several factors. We aimed to identify the clinical and epidemiological characteristics of patients admitted with ACS on a national scale and factors affecting clinical outcomes in inpatient setting. Methods: We utilized the National Inpatient Sample (NIS) database 2019 for the purpose of this study. Using this database, we identified patients with a principle diagnosis of ACS using International Classification of Diseases (ICD-10) codes. Data on demographic characteristics such as age, sex, race, insurance type were collected. Additionally, we selected clinically significant medical comorbidities such as asthma, chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD), chronic kidney disease (CKD), heart failure, hypertension, diabetes mellitus (DM), sepsis, obesity, and others. The primary endpoint of this study was to identify factors influencing all-cause mortality, while the secondary endpoint was to identify factors influencing mechanical intubation, in-patient blood transfusion, and length of stay. We used multivariate logistic regression analysis to adjust for confounders. A p value of ≤0.05 considered statistically significant. Results: Baseline Characteristics Our analysis consisted of 22,459 patients who were admitted with principal diagnosis of ACS. 49.5% were female and 50.5% were male. Mean age was 30.5 years. African American race was predominant (92%) with sickle cell Hb-SS disease (87%). Major insurance payer was Medicaid (47%) followed by Medicare (27%) and then private insurance (21%). Asthma was the most common comorbidities (24%) and majority of patient had Charlson Comorbidity Index (CCI) score of zero (55%). The details of clinical and epidemiological characteristics are shown in Table 1. Clinical outcomes and factors influencing mortality Only 0.89% patient died of ACS. Average length of stay was 6.86 days. 34% of the patient required packed red blood cell (pRBC) transfusion. 3.2% needed mechanical ventilation. In multivariate analysis, factors associated with mortality included age of patient, CCI and sepsis. Younger patient had higher odds of mortality however this was not statistically significant. There was no difference in mortality with sex, race and insurance status of the patients. Factors affecting inpatient transfusion, mechanical ventilation and length of stay Female, higher CCI score and sepsis on admission were associated with higher needs of inpatient pRBC transfusion. Within race, White (OR 3.16, CI 1.44-6.93, P &lt;0.01) and Hispanics (OR 2.68, CI 1.59-4.51, P&lt;0.01) had higher odds of receiving transfusion compared to African Americans (OR 1.84, CI: 1.17-2.89, P &lt;0.01). Similarly patient with sepsis, supraventricular tachycardia had more odds of needing mechanical ventilation. Patient's insurance status was also related to increased odds of intubation. Comorbidities such as asthma and CAD were not associated with need of mechanical ventilation and in fact our study shows they had less odd of needing mechanical ventilation. Length of stay was influenced by several of epidemiological and clinical comorbidities. Females had less odds of longer length of stay compared to male (OR: 0.65, P &lt;0.01). Comorbidities such as asthma, heart failure, CAD, DM2 and hypertension did not increase the length of stay while patients with sepsis and high CCI score had higher odds of hospitalization for extended period of time. The details are in Table 2. Conclusion We found mortality was 0.89% in patients admitted with ACS compared to 3 to 9% previously reported. Sepsis and CCI were one of the predictors for odds of having higher mortality, need of blood transfusion, mechanical ventilation and increased length of stay in patient with ACS. Female, White and Hispanic had higher odds of needing transfusion then African Americans. Comorbidities such as asthma, heart failure, CAD, DM 2 and hypertension did not increase the odds of prolonged hospital stay.

Introduction: Vitamin B12 deficiency is a common nutritional issue associated with mild anemia and neurological deficits. While rare, hemolytic anemia and low platelet count can be complications of this deficiency, often misdiagnosed as thrombotic microangiopathy (TMA), specifically thrombotic thrombocytopenic purpura (TTP). Pseudo TMA features can occur with B12 deficiency and can be effectively treated with vitamin B12 supplementation. In contrast, true TMA requires plasmapheresis. This systematic review aims to differentiate between pseudo TMA and TMA cases through an analysis of published case reports, providing valuable insights to avoid unnecessary treatments. Methods: We performed systematic review from Pubmed, Web of Science, and Scopus database. Twin independent reviewers (SY and BL) performed the screening using Covidence. Search keywords included “((hemolytic anemia) AND (vitamin B12 deficiency)) OR ((cobalamin deficiency) AND (hemolytic anemia)) Filters: English” for Pubmed, “(((ALL=(Cobalamin deficiency)) OR ALL=(vitamin B12 Deficiency))) AND ALL=(hemolytic anemia) Filter: English” for Web of Science and “( vitamin AND b12 AND deficiency OR cobalamin AND deficiency ) AND hemolytic AND anemia AND ( LIMIT-TO ( LANGUAGE , ”English“ ))” from Scopus. Only case reports in English with full-text availability and adult subjects were selected. Cases without final clinical outcome after treatment were excluded. After a comprehensive review, we identified 43 case reports and series with a total 53 patients that fulfilled our criteria. The details of selection process is illustrated in the prisma diagram (Figure 1). Results: The majority of cases involved males with low hemoglobin and platelet counts upon admission. Evidence of hemolysis was observed, indicated by increased lactate dehydrogenase (LDH), undetectable haptoglobin, and elevated or normal total and direct bilirubin levels. Peripheral blood films confirmed the presence of hemolytic anemia. Due to the co-occurrence of thrombocytopenia and hemolytic anemia, some cases were initially diagnosed as TTP, leading to the initiation of plasmapheresis. In 16 out of 53 reported case reports/series, patient received plasmapheresis. However, low reticulocyte index and normal ADAMTS 13 suggested an alternative diagnosis. Once ADAMTS 13 levels were normal, plasmapheresis was discontinued as TTP was ruled out. Diagnosis of B12 deficiency was confirmed by low B12 levels and elevated methylmalonic acid (MMA) levels. Leading cause for B12 deficiency were pernicious anemia in 28/53 cases, followed by dietary deficiency, and malabsorption due to surgery. Some patients also exhibiting concurrent iron deficiency anemia and folate deficiency. Treatment with subcutaneous B12 injections showed improvement in hemolysis as early as one week. Conclusion: Many cases of Vitamin B12 deficiency presenting with hemolytic anemia and thrombocytopenia are mistakenly diagnosed as TTP, leading to unnecessary and expensive plasmapheresis. Routine B12 level checks should be performed in all patients with hemolytic anemia, as B12 deficiency can be rapidly diagnosed and effectively treated, avoiding misdiagnoses and unnecessary interventions associated with TTP. The short turnover time for B12 levels (hours) compared to ADAMTS 13 activity (1-2 days) further supports the importance of routine B12 assessment in these patients.