Thrombosis risk prediction in lymphoma patients: A multi-institutional, retrospective model development and validation study.

Venous thromboembolism (VTE) poses a significant risk to cancer patients receiving systemic therapy. The generalizability of pan-cancer models to lymphomas is limited. Currently, there are no reliable risk prediction models for thrombosis in patients with lymphoma. Our objective was to create a risk assessment model (RAM) specifically for lymphomas. We performed a retrospective cohort study to develop Fine and Gray sub-distribution hazard model for VTE and pulmonary embolism (PE)/ lower extremity deep vein thrombosis (LE-DVT) respectively in adult lymphoma patients from the Veterans Affairs national healthcare system (VA). External validations were performed at the Harris Health System (HHS) and the MD Anderson Cancer Center (MDACC). Time-dependent c-statistic and calibration curves were used to assess discrimination and fit. There were 10,313 (VA), 854 (HHS), and 1858 (MDACC) patients in the derivation and validation cohorts with diverse baseline. At 6 months, the VTE incidence was 5.8% (VA), 8.2% (HHS), and 8.8% (MDACC), respectively. The corresponding estimates for PE/LE-DVT were 3.9% (VA), 4.5% (HHS), and 3.7% (MDACC), respectively. The variables in the final RAM included lymphoma histology, body mass index, therapy type, recent hospitalization, history of VTE, history of paralysis/immobilization, and time to treatment initiation. The RAM had c-statistics of 0.68 in the derivation and 0.69 and 0.72 in the two external validation cohorts. The two models achieved a clear differentiation in risk stratification in each cohort. Our findings suggest that easy-to-implement, clinical-based model could be used to predict personalized VTE risk for lymphoma patients.

Management of DOAC-related bleeding in cancer patients: a single center-case series.

Venous thromboembolism (VTE) and stroke carry significant mortality and morbidity in cancer patients. Direct oral anticoagulants (DOACs) have been demonstrated to be effective for the treatment of VTE and prevention of stroke in atrial fibrillation (AF). Bleeding rates are variable and are based on the cancer type and the patient's specific risk factors. There are approved specific antidotes for DOAC-associated bleeding. Other strategies are available for bleeding reversal, including the use of prothrombin complex concentrate (PCC). No randomized studies have compared head-to-head the efficacy and safety of reversal agents. We aim to examine the safety and effectiveness of hemostatic agents in cancer patients with DOAC-related major bleeding. A retrospective chart review study of patients at MD Anderson Cancer Center with DOAC-related major bleeding between 2014 and 2019. Bleeding severity and clinical hemostasis were described based on ISTH guidelines and the Sarode criteria, respectively. The rates of thrombotic complications and mortality at 30-day from the index bleeding event were described. We identified 23 patients with DOAC-related major bleeding; 14 patients received PCC and 9 patients received andexanet alfa. The most common sites of bleeding were the gastrointestinal tract and intracranial. Effective hemostasis and 30-day mortality were similar to reported results from other reports of outcomes of reversal agents for DOAC related-bleeding in non-cancer patients. One patient in each treatment group experienced a thrombotic event. Further larger scale studies are needed to confirm our findings in cancer patients.

Mechanical Venous Thrombectomy for Deep Venous Thrombosis in Cancer Patients: A Single-Center Retrospective Study.

PURPOSE: Venous thromboembolism (VTE) is a major contributor to the mortality of cancer patients. Mechanical thrombectomy (MT) is an endovascular technique that physically removes a thrombus without thrombolytics. The purpose of this study was to evaluate safety, efficacy, and clinical outcomes following MT for lower extremity DVT in cancer patients. METHODS: This single-center, retrospective study evaluated outcomes following MT of lower extremity DVT in cancer patients from November 2019 to May 2023. The primary outcome measure was clinical success, defined as a decrease in Villalta score by at least 2 points following the intervention. Secondary outcomes included repeat intervention-free survival and overall survival. Technical success was defined as restoring venous flow with mild (< 10%) or no residual filling defect. RESULTS: In total, 90 patients and 113 procedures were included. Technical and clinical success was achieved in 81% and 87% of procedures performed. Repeat intervention-free survival at 1 month, 3 months, and 6 months post-procedure was 92%, 82%, and 77%, respectively. The complication rate was 2.7%. Pathologic analysis of the extracted thrombus revealed tumor thrombus in 18.4% (18/98) samples. Overall survival for the study cohort was 87% at 1 month, 74% at 3 months, and 62% at 6 months. Patients who were found to have tumor thrombi were noted to have a decreased overall survival compared to patients with non-tumor thrombi (P = 0.012). CONCLUSION: MT is safe and efficacious in reducing cancer patients' VTE-related symptoms. The high rate of tumor thrombus in thrombectomy specimens suggests this phenomenon is more common than suspected.

Durvalumab-induced Pure White Cell Aplasia.

Immune checkpoint inhibitors (ICI) have gained approval as a treatment for a wide array of cancers. Their mechanism of action prevents the inactivation of cytotoxic T-cells, allowing for its cytotoxic response. However, the upregulation of the immune system by ICI also leads to many undesired adverse events known as immune-related adverse events (irAEs), ranging from dermatologic manifestations, such as rashes, to inflammation of mucous membranes, to hematologic toxicities. Here, we report a case of ICI-induced pure white cell aplasia, secondary to the agent durvalumab, which responded to treatment with filgrastim, prednisone, and cyclosporine. ICI-neutropenia accounts for 0.6% of all irAEs or 17% of hematologic irAEs. Given the rarity of hematologic irAEs, the available treatment guidelines are based on expert consensus. As ICI becomes more widely used, we can expect an increase in the prevalence of rare irAEs as well. This case report aims to present a rare side effect of ICI and demonstrate its response to immunosuppressive therapy while providing guidance for future clinicians and further elucidating the mechanism behind these irAEs.

Measurement of adherence and health-related quality of life during anticoagulation therapy in cancer-associated venous thromboembolism (VTE): a multicenter quantitative study.

PURPOSE: Therapy for cancer-associated venous thromboembolism (VTE) includes long-term anticoagulation, which may have substantial impact on the health-related quality of life (HRQL) of patients. We assessed patient-reported outcomes to characterize the HRQL associated with VTE treatment and to begin to examine those HRQL elements impacting anticoagulation adherence (AA). METHODS: Participants were adult cancer patients with confirmed symptomatic acute lower extremity deep venous thrombosis. Patients were excluded if there was an indication for anticoagulation other than VTE, ECOG performance status >3, or life expectancy < 3 months. Participants were assessed with a self-reported adherence tool. HRQL was measured with a 6-domain questionnaire using a seven-point Likert scale. Evaluations were performed at 30 days and 3 months after enrollment. For the primary objective, an overall adherence rate was calculated at each time point of evaluation. For the HRQL domains, non-parametric testing was used to compare results between subgroups. RESULTS: Seventy-four patients were enrolled. AA and HRQL at 30 days and 3 months were assessed in 50 and 36 participants, respectively. At 30 days the AA rate was 90%, and at 3 months it was 83%. In regard to HRQL, patients suffered frequent and moderate-severe distress in the domains of emotional and physical symptoms, sleep disturbance, and limitations to physical activity. An association between emotional or physical distress and AA was observed. CONCLUSION: Patients with VTE suffer a substantial impairment of their HRQL. Increased emotional distress correlated with better long-term AA. These results can be used to inform additional research aimed at developing novel strategies to improve AA.

Safety and Effectiveness of Direct Oral Anticoagulants for the Treatment of Gastrointestinal Cancer-Associated Venous Thromboembolism.

BACKGROUND: Patients with gastrointestinal cancer (GICA) are at high risk for venous thromboembolism (VTE). Data from randomized clinical trials in cancer-associated VTE suggest that direct oral anticoagulants (DOACs) conferred similar or superior efficacy but a heterogeneous safety profile in patients with GICA. We compared the safety and effectiveness of DOACs in patients with GICA and VTE at MD Anderson Cancer Center. MATERIALS AND METHODS: This was a retrospective chart review of patients with GICA and VTE receiving treatment with DOACs for a minimum of 6 months. Primary outcomes were the proportion of patients experiencing major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and recurrent VTE. Secondary outcomes were time to bleeding and recurrent VTE. RESULTS: A cohort of 433 patients with GICA who were prescribed apixaban (n = 300), or rivaroxaban (n = 133) were included. MB occurred in 3.7% (95% confidence interval [CI] 2.1-5.9), CRNMB in 5.3% (95% CI 3.4-7.9), and recurrent VTE in 7.4% (95% CI 5.1-10.3). The cumulative incidence rates of CRNMB and recurrent VTE were not significantly different when comparing apixaban to rivaroxaban. CONCLUSION: Apixaban and rivaroxaban had a similar risk of recurrent VTE and bleeding and could be considered as anticoagulant options in selected patients with GICA and VTE.

Risks factors and outcomes for isolated catheter-related deep venous thrombosis in patients undergoing allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) require indwelling central venous catheters. The comparative incidence, risk, and outcome of isolated catheter-related deep venous thrombosis (CR-DVT) versus pulmonary embolism/lower-extremity DVT (PE/LE-DVT) remains unclear. MATERIALS AND METHODS: We conducted a retrospective cohort study for patients undergoing allo-HSCT from 2006 to 2019. CR-DVT and PE/LE-DVT outcomes were screened using ICD codes and radiology reports and confirmed by medical record reviews. Cox regression models were used to assess the association between thrombotic outcomes and pertinent baseline and time-varying covariates. The impact of thrombotic events within 1-year post-transplant (time-varying) on overall mortality was also assessed. RESULTS: Among 2879 patients, the cumulative incidence of isolated CR-DVT and PE/LE-DVT at 12 months was 4.2 % and 4.8 %, respectively. The strongest time-varying predictor for onset of CR-DVT and PE/LE-DVT was hospitalization inpatient status (HR 3.71 [95 % CI 2.16-6.37] and 3.99 [95 % CI 2.00-7.99], respectively). Other overlapping variables included lymphoma diagnosis and BMI > 35 kg/m2, whereas acute GVHD grades 2-4 were found to be significantly associated with risk of PE/LE-DVT but not CR-DVT. After adjusting for baseline variables and acute GVHD, the occurrences of CR-DVT and PE/LE-DVT were both independently associated with increased overall mortality (HR 1.58 [95 % CI 1.23-2.02] and HR 1.53 [95 % CI 1.19-1.97], respectively). CONCLUSIONS: We observed a high incidence of both CR-DVT and PE/LE-DVT with overlapping and unique risk factors. CR-DVT was also associated with increased mortality similar to PE/LE-DVT. Standardized strategies targeting high-risk hospitalization periods may help mitigate the development of thrombotic outcomes post-transplant.

Single cell clonotypic and transcriptional evolution of multiple myeloma precursor disease.

Multiple myeloma remains an incurable disease, and the cellular and molecular evolution from precursor conditions, including monoclonal gammopathy of undetermined significance and smoldering multiple myeloma, is incompletely understood. Here, we combine single-cell RNA and B cell receptor sequencing from fifty-two patients with myeloma precursors in comparison with myeloma and normal donors. Our comprehensive analysis reveals early genomic drivers of malignant transformation, distinct transcriptional features, and divergent clonal expansion in hyperdiploid versus non-hyperdiploid samples. Additionally, we observe intra-patient heterogeneity with potential therapeutic implications and identify distinct patterns of evolution from myeloma precursor disease to myeloma. We also demonstrate distinctive characteristics of the microenvironment associated with specific genomic changes in myeloma cells. These findings add to our knowledge about myeloma precursor disease progression, providing valuable insights into patient risk stratification, biomarker discovery, and possible clinical applications.

Phase 1b study of combined selinexor and eribulin for the treatment of advanced solid tumors and triple-negative breast cancer.

BACKGROUND: Selinexor (KPT-330) is a potent inhibitor of exportin 1 (XPO1), in turn inhibiting tumor growth. Selinexor enhances the antitumor efficacy of eribulin in triple-negative breast cancer (TNBC) in vitro and in vivo. Given the unmet medical need in TNBC and sarcoma, the authors explored the safety and efficacy of this combination. METHODS: The authors conducted a phase 1b trial of combined selinexor and eribulin using a 3 + 3 dose-escalation design in patients who had advanced solid tumors and in those who had TNBC in a dose-expansion cohort. RESULTS: Patients with TNBC (N = 19), sarcoma (N = 9), and other cancers (N = 3) were enrolled in the dose-escalation cohort (N = 10) and in the dose-expansion cohort (N = 21). The median number lines of prior therapy received was four (range, from one to seven prior lines). The most common treatment-related adverse events for selinexor were nausea (77%), leukopenia (77%), anemia (68%), neutropenia (68%), and fatigue (48%). One dose-limiting toxicity occurred at the first dose level with prolonged grade 3 neutropenia. The recommended phase 2 dose was 80 mg of selinexor orally once per week and 1 mg/m2 eribulin on days 1 and 8 intravenously every 3 weeks. The objective response rate (ORR) was 10% in three patients. In the dose-escalation cohort, the ORR was 10%, whereas six patients with had stable disease. In the TNBC dose-expansion cohort (n = 18), ORR was 11%, and there were two confirmed partial responses with durations of 10.8 and 19.1 months (ongoing). CONCLUSIONS: Selinexor and eribulin had an acceptable toxicity profile and modest overall efficacy with durable responses in select patients. PLAIN LANGUAGE SUMMARY: Effective therapies for advanced, triple-negative breast cancer and sarcoma represent an unmet need. Exportin 1 is associated with the transport of cancer-related proteins. Preclinical studies have demonstrated tumor growth inhibition and enhanced tumor sensitivity in patients who receive selinexor combined with eribulin. In this phase 1b study, the authors evaluated the safety profile and clinical activity of the combination of selinexor, a potent oral inhibitor of exportin 1, and eribulin in patients with advanced cancers enriched for triple-negative breast cancer or sarcoma. The combination was well tolerated; most adverse events were mild or moderate, reversible, and managed with dose modifications or growth factor support. The combination of selinexor and eribulin produced an antitumor response, particularly in some patients with triple-negative breast cancer. This work lays the foundation for prospective investigations of the role of selinexor and eribulin in the treatment of triple-negative breast cancer.

External validation of a novel electronic risk score for cancer-associated thrombosis in a comprehensive cancer center.

Venous thromboembolism (VTE) is a significant complication for cancer patients undergoing systemic therapy. We performed an independent external validation for a recently derived and validated a novel electronic health record (EHR) VTE risk score in a comprehensive cancer center. Adult patients with incident cancer diagnoses were identified from MD Anderson Cancer Center Tumor Registry 1/2017-1/2021. Baseline covariates extracted at the time of first-line systemic therapy included demographics, cancer site/histology, stage, treatment, complete blood count, body mass index, recent prolonged hospitalization, and history of VTE or paralysis. VTE was ascertained using an institution-specific natural language processing radiology algorithm (positive predictive value of 94.8%). The median follow-up for 21 142 cancer patients was 8.1 months. There were 1067 (5.7%) VTE within 6 months after systemic therapy. The distribution of the novel score for 0-, 1, 2, 3, 4, 5+ was 5661, 3558, 3462, 3489, 2918, and 2054; while the corresponding 6-month VTE incidence was 1.3%, 3.1%, 5.4%, 7.3%, 9.3%, and 13.8%, respectively (c statistic 0.71 [95% CI 0.69-0.72] with excellent calibration). In comparison, the Khorana score had a c statistic of 0.64 [95% CI 0.62-0.65]. The two risk scores had 80% concordance; the novel score reclassified 20% of Khorana score (3530 low-to-high with 9.0% VTE; 734 high-to-low with 3.4% VTE) and led to a 25% increment in VTEs captured in the high-risk group. In conclusion, the novel score demonstrated consistent discrimination and calibration across cohorts with heterogenous demographics. It could become a new standard to select high-risk populations for clinical trials and VTE monitoring.

Secondary erythrocytosis.

INTRODUCTION: Erythrocytosis is associated with an elevation of the hemoglobin level above 16.5 g/dL in men and above 16 g/dL in women and an elevation of the hematocrit level above 49% in men and > 48% in women. In primary erythrocytosis, the defect is a clonal disorder in the myeloid compartment of the bone marrow, leading to an increased red cell production. Secondary erythrocytosis is the result of external stimuli to the bone marrow, leading to the production of red cells in excess. Secondary erythrocytosis is more common than primary erythrocytosis and has a broad differential diagnosis. AREAS COVERED: This review will discuss secondary erythrocytosis, its causes, clinical presentation, and both diagnostic and therapeutic approaches. EXPERT OPINION: Although secondary erythrocytosis is more common than PV, there are still challenges and difficulties associated with the distinction between these two conditions. Moreover, there is a paucity of data and guidance when it comes to the management of certain congenital and acquired conditions. A pragmatic approach is recommended in order to identify the cause for this condition. Treatment should be directed at the management of the underlying cause.

Heparin-Induced Thrombocytopenia at the Emergency Department Due to Intermittent Heparin Flush in a Patient Undergoing Stem Cell Transplant.

Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin products, but not warfarin. HIT usually occurs 5‒10 days after exposure to heparin. Here, we report a case of HIT with multiple thrombotic events and severe thrombocytopenia resulting from intermittent intravenous heparin flushes for maintenance of a newly placed subclavian central venous catheter (CVC) for stem cell transplant. The patient is a woman in her forties with multiple myeloma who presented to the emergency department (ED) with dyspnea, pleuritic-type chest pain, hemoptysis, and worsening left-leg swelling. Heparin had been used to flush the CVC. Her platelet count began dropping approximately one week after insertion. The patient was receiving other medications known to cause thrombocytopenia. She had undergone multiple platelet transfusions. In the ED, her lab results showed thrombocytopenia), anemia; renal insufficiency; and elevated troponin, prothrombin time, and D-dimer levels. Because of the hemoptysis and thrombocytopenia, she initially received platelet transfusion and oxygen. She was found to have deep vein thrombosis of the lower extremity and started a referral to interventional radiology for inferior vena cava (IVC) filter placement. However, further review and consultation of the Benign Hematology service, discussion about the timing of decreased platelet count shortly after CVC placement and heparin administration, and the presence of thrombosis, suggested a high pre-test probability of HIT. Anticoagulation with argatroban was initiated, and IVC filter insertion was canceled. Further workup confirmed HIT diagnosis and saddle pulmonary embolism. During the patient's hospitalization, her platelets continued to improve and reached baseline upon discharge. She was transitioned to fondaparinux at the time of discharge. A few weeks later, she had successful stem cell transplantation. Emergency physicians treating patients with thrombocytopenia receiving heparin, even in small amounts, should consider the possibility of HIT and be familiar with its management.

Concomitant Deep Vein Thrombosis in Cancer Patients with Unsuspected Pulmonary Embolism.

Incidental venous thromboembolism (VTE) is common in cancer patients and identifying factors associated with these events can improve the management plan. We studied the characteristics of concomitant deep vein thrombosis (C-DVT) in cancer patients presenting with unsuspected pulmonary embolism (PE) and the association of C-DVT with VTE recurrence and survival outcomes. Patients presenting to our emergency department with confirmed unsuspected/incidental PE between 1 January 2006 and 1 January 2016, were identified. Radiologic reports were reviewed to confirm the presence or absence of C-DVT. Logistic regression analyses and cox regression modeling were used to determine the effect of C-DVT on VTE recurrence and survival outcomes. Of 904 eligible patients, 189 (20.9%) had C-DVT. Patients with C-DVT had twice the odds of developing VTE recurrence (odds ratio 2.07, 95% confidence interval 1.21-3.48, p = 0.007). The mortality rates among C-DVT were significantly higher than in patients without. C-DVT was associated with reduced overall survival in patients with unsuspected PE (hazard ratio 1.33, 95% confidence interval 1.09-1.63, p = 0.005). In conclusion, C-DVT in cancer patients who present with unsuspected PE is common and is associated with an increased risk of VTE recurrence and poor short- and long-term survival. Identifying other venous thrombi in cancer patients presenting with unsuspected PE is recommended and can guide the management plan. For patients with isolated incidental subsegmental pulmonary embolism and concomitant deep vein thrombosis, initiating anticoagulants if no contraindications exist is recommended.

Association between abnormal lipid profile and inflammation and progression of myelodysplastic syndrome to acute leukemia.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with a small risk of developing hematologic malignancies and a higher risk of cardiovascular diseases (CVD). We asked whether the reverse correlation exists and cardiometabolic risk factors have an impact on the progression of myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML). We investigated the association between abnormal lipid profiles and inflammation in MDS, which shares many genetic mutations with CHIP, and the risk of developing acute leukemia. We examined the medical records of 11071 MDS patients. Among them, 5422 had at least one lipid profile or C-reactive protein (CRP) measurement. In univariate and multivariate analyses, elevated triglyceride and high-sensitive C-reactive protein (HS-CRP) were significantly associated with a diagnosis of acute leukemia in MDS patients. Next, we examined these associations in patients with available MDS prognostic scores (International Prognostic Scoring System, IPSS, or its revised version IPSS/R) (n = 2786 patients). We found that the statistical association between CRP and the progression of MDS to leukemia was independent of other variables in the scoring system. MDS patients with elevated CRP in both the high-risk and low-risk groups had a higher risk of progression to AML than those with a lower CRP. We speculate that inflammation might be a common denominator in developing hematologic malignancies and CVD in patients with clonal hematopoiesis.

Thrombotic Thrombocytopenic Purpura Triggered by Acute Myeloid Leukemia: A Case Report.

BACKGROUND Acute myeloid leukemia (AML) is a myeloid progenitor malignancy characterized by clonal expansion of immature blasts. Complications of AML can result from disease-related or treatment-related complications and commonly include bleeding and disseminated intravascular coagulation. Thrombotic thrombocytopenic purpura (TTP) is a microangiopathy syndrome characterized by a mechanical hemolytic anemia and a consumptive thrombocytopenia resulting in end-organ damage from thrombotic occlusion of small vessels. CASE REPORT We describe a case of TTP at our institution that developed after diagnosis of AML, an exceedingly rare phenomenon with only one such documented case in the current literature. We were advised to see this patient after development of renal failure and encephalopathy. Suspicion for TTP was initially low, as our patient had a low pre-test probability of TTP by the PLASMIC score. Our patient was treated for disseminated intravascular coagulopathy, without response. Plasma exchange pheresis (PLEX) was eventually begun 3 days after presentation upon result of ADAMTS13 activity at 10%, with presence of inhibitor. ADAMTS13 activity levels were used to guide continuation of PLEX, given our patient's persistent pancytopenia. CONCLUSIONS Our case demonstrates the challenges of identifying and managing TTP in patients with concomitant hematologic malignancies. ADAMTS13 activity levels should be collected in patients presenting with evidence of hemolytic anemia, even if the pre-test probability of TTP is low.

Complexity and clinical significance of drug-drug interactions (DDIs) in oncology: challenging issues in the care of patients regarding cancer-associated thrombosis (CAT).

Cancer patients have an increased risk of developing venous thromboembolic events. Anticoagulation management includes prophylactic or therapeutic doses of low molecular weight heparins (LMWHs) or direct oral anticoagulants (DOACs). However, the management of thrombosis in patients with cancer is complex due to various individual and disease-related factors, including drug-drug interactions (DDIs). Furthermore, DDIs may impact both, cancer and venous thrombosis, treatment effectiveness and safety; their relevance is highlighted by the advances in cancer therapeutics. Given that these new oncology drugs are extensively used, more attention should be given to monitoring potential DDIs to minimize risks. Recognition of DDIs is of utmost importance in an era of rapid developments in cancer treatments and introduction of novel treatments and protocols. When managing cancer-associated thrombosis (CAT), the concomitant use of a DOAC and a moderate or strong modulator (inhibitor or inducer) of CYP3A4 or a P-glycoprotein (P-gp) is most likely to be associated with significant DDIs. Therefore, LMWHs remain the first-line option for the long-term management of CAT under these circumstances and physicians must consider utilizing LMWHs as first line. This review describes the risk of DDIs and their potential impact and outcomes in patients with cancer associated thrombosis (CAT) receiving anticoagulation.

Spectrum of Immune Checkpoint Inhibitor Anemias: Results From a Single Center, Early-Phase Clinical Trials Case Series Experience.

Immune checkpoint inhibitor anemias (ICI-A) are a rare entity which can be potentially life-threatening without prompt identification. The goal of the study is to characterize the presentation, evaluation, and outcomes of ICI therapy in early phase clinical trial setting to guide future research and to develop standardized care guidelines. Retrospective chart review of 333 patients who participated in early phase clinical trials at the University of Texas MD Anderson Cancer Center revealed four cases with ICI-A between 2016 and 2020. We identified a spectrum of four cases which included ICI-related autoimmune hemolytic anemias, hemophagocytic lymphohistiocytosis and thrombotic microangiopathy as a result of combinatory investigational therapies involving ICI. Patient presentation, evaluation, bone marrow pathology, interventions, and clinical course were reviewed. The median time to onset of hematological immune-related adverse events (heme-irAEs) in this retrospective series was 3.5 weeks (2 - 6 weeks). One patient had pre-existing untreated chronic lymphocytic leukemia. Glucocorticoids are an effective first-line treatment in most patients although most patients were not rechallenged but successfully had complete recovery and pursued further non-immunotherapy-based therapies. Cognizance of ICI-A in clinical trial setting is paramount to early recognition of heme-irAEs. Further research is needed to identify and stratify risk factors during clinical trial enrollment and optimal management strategies for immune-mediated hematologic toxicities.

Characterization of coagulopathy and outcomes in cancer patients with severe COVID -19 illness: Longitudinal changes in hospitalized cancer patients.

There is a lack of data focused on the specific coagulopathic derangements in COVID-19 versus non-COVID-19 acutely ill cancer patients. Our objective was to characterize features of coagulopathy in cancer patients with active COVID-19 illness who required hospitalization at MD Anderson in the Texas Medical Center and to correlate those features with thrombotic complications, critical illness, and mortality within the first 30 days after hospital admission for COVID-19 illness. COVID-19 and non-COVID-19 hospitalized cancer patients, with at least five consecutive measures of PT, PTT, d-dimer, and CBC during the same period, were matched 1:1 to perform a retrospective analysis. We reviewed complete blood cell counts with differential, PT, PTT, fibrinogen, D-Dimer, serum ferritin, IL-6, CRP, and peripheral blood smears. Clinical outcomes were thrombosis, mechanical ventilation, critical illness, and death. Compared with matched hospitalized cancer patients without COVID-19, we found elevated neutrophil and lower lymphocyte counts in those with critical illness ( p =  0.00) or death ( p =  0.00); only neutrophils correlated with thrombosis. COVID-19 cancer patients with a platelet count decline during the hospital stay had more frequent critical illness ( p =  0.00) and fatal outcomes ( p =  0.00). Of the inflammatory markers, interleukin-6 showed consistently higher levels in the COVID-19 patients with poor outcomes. The findings of unique platelet changes and coagulopathy during severe COVID-19 illness in the cancer population are of interest to explore disease mechanisms and future risk stratification strategies to help with the management of cancer patients with COVID-19.

External validation of the HIGH-2-LOW model: A predictive score for venous thromboembolism after allogeneic transplant.

In patients undergoing hematopoietic cell transplantation (HCT), venous thromboembolism (VTE) remains a serious complication that lacks validated risk assessment models (RAMs) to guide thromboprophylaxis. To address this dilemma, we performed a temporal and external validation study of the recently derived HIGH-2-LOW RAM. We selected adult patients undergoing allogeneic HCT from Fred Hutchinson Cancer Research Center (FHCRC) and MD Anderson Cancer Center (MDACC). Patients who died, received anticoagulation, or did not engraft platelets by day 30 were excluded. Primary outcomes were defined as overall VTE and pulmonary embolism ± lower-extremity deep venous thromboembolism (PE/LE-DVT) by day 180. Covariates were weighted according to the original model, except that grade 2-4 GVHD was substituted for grade 3-4. Discrimination and calibration were assessed. A total of 765 patients from FHCRC and 954 patients from MDACC were included. Incident VTE by day 180 was 5.1% at FHCRC and 6.8% at MDACC. The HIGH-2-LOW score had a c-statistic of 0.67 (0.59-0.75) for VTE and 0.75 (0.64-0.81) for PE/LE-DVT at FHCRC and 0.62 (0.55-0.70) for VTE and 0.70 (0.56-0.83) for PE/LE-DVT at MDACC. Twenty-five percent and 23% of patients were classified as high risk (2+ points) in the two cohorts, respectively. High versus low-risk was associated with odds ratio (OR) of 2.80 (1.46-5.38) for VTE and 4.21 (1.82-9.77) for PE/LE-DVT at FHCRC and OR of 3.54 (2.12-5.91) for VTE and 6.82 (2.30-20.16) for PE-LE-DVT at MDACC. The HIGH-2-LOW RAM identified allogeneic HCT recipients at high risk for VTE in both validation cohorts. It can improve evidence-based decision-making for thromboprophylaxis post-transplant.

Potential limitations of diagnostic standard codes to distinguish polycythemia vera and secondary erythrocytosis.

Red cell overproduction is seen in polycythemia vera (PV), a bone marrow myeloproliferative neoplasm characterized by trilinear cell proliferation (WBC, platelets), as well as in secondary erythrocytosis (SE), a group of heterogeneous disorders characterized by elevated EPO gene transcription. We aimed to verify the concordance of the International Classification of Diseases (ICD) code-based diagnosis of "polycythemia" or "erythrocytosis" with the true clinical diagnosis of these conditions. We retrospectively reviewed the electronic medical records (January 1, 2005, to December 31, 2016) of adult patients with ICD codes of polycythemia and/or erythrocytosis who had testing done for the presence of the JAK2V617F mutation. We verified the accuracy of the ICD code-based diagnoses by meticulous chart review and established whether these patients fulfilled the criteria by the evaluating physician for PV or SE and according to the World Health Organization 2016 diagnostic guidelines. The reliability of ICD coding was calculated using Cohen's kappa. We identified and chart reviewed a total of 578 patient records. Remarkably, 11% of the patients had concurrent diagnosis codes for PV and SE and were unable to be classified appropriately without individual chart review. The ICD code-based diagnostic system led to misidentification in an important fraction of cases. This represents a problem for the detection of PV or SE cases by ICD-based registries and their derived studies. Research based exclusively on ICD codes could have a potential impact on patient care and public health, and limitations must be weighed when research findings are conveyed.