BACKGROUND:Chemotherapy-induced thrombocytopenia (CIT) is a common complication of chemotherapy that is associated with bleeding, reduced relative dose intensity, and potentially worse outcomes. No widely available therapies are approved for CIT. METHODS:We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial involving patients with persistent CIT (platelet count, ≤85×109 per liter on trial day 1) who were receiving oxaliplatin-based multiagent cytotoxic chemotherapy for gastrointestinal cancers. Patients were randomly assigned in a 2:1 ratio to receive romiplostim or placebo for three chemotherapy cycles. The primary end point was the absence of CIT-induced modifications of the chemotherapy dose (reduction, delay, omission, or discontinuation) in both the second and third chemotherapy cycles. RESULTS:Of the 165 patients who underwent randomization (109 in the romiplostim group and 56 in the placebo group), 75% had colorectal cancer, 13% had gastroesophageal cancer, and 12% had pancreatic cancer; 72% of the patients in the romiplostim group and 61% of those in the placebo group had stage 4 disease. The percentage of patients with no CIT-induced modifications of the chemotherapy dose was 84% (92 of 109 patients) with romiplostim and 36% (20 of 56 patients) with placebo, which corresponded to an odds ratio of 10.16 (95% confidence interval [CI], 4.44 to 23.72; P<0.001) and a risk ratio of 2.77 (95% CI, 1.78 to 4.30; P<0.001). Adverse events of grade 3 or higher occurred in 37% of the patients who received romiplostim and in 22% of those who received placebo, which primarily reflected chemotherapy effects. Adverse events that were considered by the investigator to be related to romiplostim or placebo occurred in 12% of patients who received romiplostim and in 7% who received placebo, with the most frequent being nausea (2% in each group) and headache (2% in the romiplostim group); none were serious or led to death or discontinuation of romiplostim, placebo, or chemotherapy. Thromboembolic events occurred in 2% of patients who received romiplostim and in no patients who received placebo. CONCLUSIONS:In this phase 3, placebo-controlled trial, romiplostim was efficacious in treating CIT. (Funded by Amgen and the Biomedical Advanced Research and Development Authority; RECITE ClinicalTrials.gov number, NCT03362177.).

3580 Background: Chemotherapy-induced thrombocytopenia (CIT) is a frequent complication of chemotherapy. Persistent CIT (not adequately resolved by day 1 of the following cycle) may lead to reduction or delay in treatment. There are no FDA approved therapies for CIT. Aim: To evaluate the safety and efficacy of avatrombopag (AVA), an oral thrombopoietin receptor agonist, to treat persistent CIT and prevent its recurrence in GI cancer. Methods: ACT-GI (NCT05772546) was a multicenter, randomized, double-blind, placebo-controlled, investigator-initiated trial of GI cancer patients with persistent CIT (platelets [Plt] <85×10 9 /L on day 1 of a scheduled chemotherapy cycle). Patients were randomized 1:1 to AVA 40 mg daily or placebo and treated for two on-study phases. In the lead-in phase, patients were treated up to 2 weeks while chemotherapy was held. Patients proceeded to the on-cycle phase and resumed chemotherapy only if their Plt recovered to ≥100×10 9 /L. In the on-cycle phase, patients received a single full-dose chemotherapy cycle with continued study drug. The primary endpoint was successful correction of CIT and prevention of recurrence (achieving Plt ≥100×10 9 /L within the lead-in period AND prevention of CIT recurrence (Plt ≥100×10 9 /L) at end of the cycle). Results: Efficacy: ACT-GI was closed to enrollment by the DSMB, for overwhelming efficacy, at a prespecified interim analysis when 20 patients in each arm completed the double-blind period. 16 of 23 patients (70%; 95% CI 47% to 87%) in the AVA arm achieved the primary endpoint versus 4/24 patients (17%; 95% CI 5% to 37%) in the placebo arm (Z=3.67, P<0.001). 74% and 88% of patients had stage IV cancer in AVA and placebo arms, respectively. 44/47 patients completed study drug; 2 discontinuations were due to physician decision and 1 was due to an adverse event. Plt improvement to ≥100×10 9 /L during lead-in was achieved by 83% of patients in the AVA arm vs. 46% of patients in the placebo arm. The median (IQR) Plt at the end of the on-cycle treatment period was 157 (136-202) in the AVA arm vs 72 (68-134) in the placebo arm. In the AVA arm there were two clinically relevant bleeding events (intestinal stoma site bleed at Plt 105×10 9 /L and intracranial hemorrhage). No patient received platelet transfusion. Safety: AEs and serious AEs (SAEs) occurred in 74% and 13% of patients in the AVA arm and 46% and 0% of patients in the placebo arm, respectively. No SAEs were study drug-related. There were no treatment-related AEs leading to death or discontinuation of study drug. Conclusions: In this randomized, placebo-controlled trial, AVA demonstrated safety, tolerability, and efficacy in treatment and prevention of persistent CIT in GI cancers. These findings are promising for a common, serious condition that prevents delivery of full-dose, on-time cancer-directed therapy. Clinical trial information: NCT05772546 .

PURPOSE:Chemotherapy-induced thrombocytopenia (CIT) is a challenging and common complication of cytotoxic chemotherapy in patients with GI cancers. There is no widely available approved treatment. Avatrombopag is a potent, second-generation oral thrombopoietin receptor agonist promising for CIT management. METHODS:We conducted a multicenter, randomized, double-blind, investigator-initiated US trial of avatrombopag or placebo (1:1) in GI cancer patients with persistent CIT (platelets ≤85 × 109/L on day 1 of a chemotherapy cycle despite adequate time to recover from the prior cycle). The primary end point was successful correction of CIT and prevention of recurrence (defined as recovery of platelets to ≥100 × 109/L, no chemotherapy dose modification/delay, and prevention of CIT recurrence [platelets ≥100 × 109/L] at end of the on-study cycle). RESULTS:The trial was closed to enrollment by the data and safety monitoring board at the planned interim analysis after meeting prespecified stopping criteria for efficacy. Sixteen of 23 patients (70% [95% CI, 47 to 87]) receiving avatrombopag achieved the primary end point versus 4/24 patients (17% [95% CI, 5 to 37]) receiving placebo (Z = 3.67, P < .001). The median (IQR) platelet count at the end of the on-cycle treatment period was 157 (136-202) × 109/L with avatrombopag versus 72 (68-134) × 109/L with placebo. Adverse events (AEs) and serious AEs occurred in 78% and 17% of patients receiving avatrombopag and 46% and 0% of patients receiving placebo, respectively. No serious AEs were study drug-related. There were no treatment-related AEs leading to death or discontinuation of study drug. CONCLUSION:In this randomized, placebo-controlled trial, avatrombopag was efficacious in the management of persistent CIT in patients with GI cancers. These findings are promising for a common, challenging oncologic complication that prevents delivery of full-dose, on-time, cancer-directed therapy.

Current guidelines recommend consideration of prophylactic anticoagulation in lymphoma, supported by the Khorana score, which assigns lymphoma 1 point for risk of developing venous thromboembolism (VTE). We hypothesized that different lymphoma types convey different risk of VTE. To better characterize VTE rates and predictive parameters, we assessed lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE) events in 879 lymphoma patients. VTE was found in 4.9%, with a higher incidence rate among patients with aggressive lymphoma (8.3%), compared with indolent lymphoma (1.9%) and Hodgkin lymphoma (0%). The International Prognostic Index (IPI) was a strong predictor of VTE. The Khorana score did not predict VTE within lymphoma but was and independent risk factor for mortality. VTE was also an independent risk factor for mortality. Our study confirms that lymphoma subtypes are associated with different VTE risks.

Introduction Prolonged thrombocytopenia (high-grade thrombocytopenia lasting more than 28 to 30 days after CAR T-cell therapy) affects approximately 22% to 54% of patients (Brudno JN, et al JAMA. 2024;332(22):1924–1935). This study analyzes predictors of prolonged thrombocytopenia following CAR-T therapy. Objectives 1. To determine predictive factors related to post CAR-T thrombocytopenia2. To identify malignant cellularity within the bone marrow pre CAR-T therapy as a predictor of post CAR-T thrombocytopenia3. To acknowledge thrombocytopenia post CAR-T is secondary to a hypoproductive process as demonstrated by low immature platelet fraction Methods 284 patients underwent CAR-T therapy at our institution from 2016 to 2025 (lymphoma or lymphocytic leukemia (N=257), myeloma (n=27)). We analyzed the immature platelet fraction (IPF) in 226 patients with lymphoma or lymphocytic leukemia. We also assessed the percentage of total and malignant cellularity within the latest pre-treatment bone marrow biopsy, available in 134 patients with lymphoma, lymphocytic leukemia, or myeloma. Results Prolonged thrombocytopenia (<25 × 10^9/L) was identified in 32% patients. Baseline thrombocytopenia and marrow infiltration with malignant cells were the two parameters that predicted prolonged thrombocytopenia at 30 days. At 30 days: patients with severe thrombocytopenia had mean baseline platelets of 85 × 10^9/L (95% CI 79-90) versus 166 × 10^9/L (95% CI 169-172) without severe thrombocytopenia. Overall bone marrow cellularity (pre-CAR-T) did not correlate with prolonged thrombocytopenia at 30 days. As cellularity reflects a mixture of hematopoietic and malignant cells, we assessed the predictive value of percent malignant cells within the bone marrow.Malignant cell infiltration in baseline bone marrow biopsy predicted prolonged thrombocytopenia (malignant involvement: <=5% malignant involvement, mean platelets 62.5 × 10^9/L (95% CI 55.3-69.6), 6-49% malignant involvement, mean platelets 71.2 × 10^9/L (95% CI 57.1-85.3), >=50% malignant involvement, mean platelets 41.2 × 10^9/L (95% CI 31.6-50.7).At day 30, the mean IPF was not significantly increased in the patients with severe thrombocytopenia (5.8% (CI 4.1-7.6)) compared to those without severe thrombocytopenia (4.6% (CI 3.4-5.8)). Conclusion We confirmed the high incidence of prolonged thrombocytopenia after CAR-T therapy. Malignant involvement of the bone marrow (>=50%) at baseline, and baseline thrombocytopenia, both predicted prolonged thrombocytopenia. The non-elevated IPF further supports the hypoproductive mechanism, as IPF is elevated in patients with increased peripheral destruction of platelets. (Goel G, et al, J Lab Physicians, 2021).As the two predictors of prolonged thrombocytopenia are available pre-treatment, these findings may identify a subgroup for whom thrombopoietic support may be studied.

Chemotherapy-induced thrombocytopenia (CIT) is a common complication of cancer therapy that may result in major bleeding events and reduction of chemotherapy relative dose intensity. While there remain no widely available licensed therapies to manage CIT, major studies-including global pivotal phase 3 clinical trials of the thrombopoietin receptor agonists (TPO-RAs) romiplostim and avatrombopag in CIT- have been completed, along with additional supporting evidence from other clinical trials and observational studies. Like patients with chemotherapy-induced neutropenia, not all patients with CIT require treatment-but for those who do, it can have a major impact on a patient's oncologic care and outcomes. Proper management of CIT requires an understanding of the two clinical subtypes of CIT (persistent and nadir), the limited role of platelet transfusions and antifibrinolytics, and when and how to appropriately use TPO-RA support. In this article, 4 patient cases of CIT are used to illustrate common and challenging scenarios occurring in clinical practice. Built on a framework of published studies and supported by extensive clinical experience, appropriate treatment strategies for CIT are described in detail, with emphasis on proper patient selection, dosing, titration, and monitoring for the use of TPO-RAs in CIT.

Background/Objectives: Intensive chemotherapy is the cornerstone of lymphoma treatment but often leads to severe chemotherapy-induced thrombocytopenia (sCIT), resulting in treatment delays, reduced dose intensity, and the need for transfusions. While granulocyte colony-stimulating factors (G-CSFs) are commonly used to manage neutropenia, the use of thrombopoietic growth factors has not been adequately studied. Methods: This phase I dose-finding study evaluated the use of weekly romiplostim as prophylaxis for recurrent sCIT in patients undergoing chemotherapy for lymphoma. Eligible patients were those treated with a 21-day chemotherapy cycle who previously experienced sCIT, thus serving as their own "controls". sCIT was defined as one of the following: (A) a platelet count (PLT) <50 × 109/L on day 1 of the subsequent cycle, leading to delay or dose reduction in chemotherapy, or (B) grade 4 thrombocytopenia (<25 × 109/L) and/or (C) platelet transfusion for bleeding. The primary endpoints were the incidence of sCIT and the rate of romiplostim-associated-adverse-events, with thromboembolic complications being an event of special interest. Results: Nine patients with sCIT requiring a PLT transfusion on the prior treatment cycle were treated across three dose schedules. The phase 2 recommended schedule was defined as a starting dose of 3-5 mcg/kg based on the baseline PLT count, with weekly adjustments for counts <150 × 109/L and >450 × 109/L. Romiplostim prevented recurrent grade 4 thrombocytopenia in 47% of the chemotherapy cycles and averted recurrent transfusion in 65% of cycles. Notably, low starting doses, as used in solid malignancies, were insufficient, leading to recurrent thrombocytopenia. Conclusions: Romiplostim was well-tolerated, with no thromboembolic events, and allowed most patients to complete their chemotherapy on schedule at full dose intensity.

Chemotherapy-induced thrombocytopenia (CIT) is a common toxicity in patients with cancer, leading to chemotherapy dose reductions and increased platelet transfusions. Although there are well-documented data using thrombopoietin receptor agonists (TPO-RA) in both adult CIT and pediatric immune thrombocytopenia, there is a paucity of data in pediatric CIT. This is a single institutional, retrospective study evaluating the use and safety of romiplostim in pediatric patients with solid tumors undergoing cancer treatment. Romiplostim was well tolerated and appeared to provide clinical benefit. This report advocates for further research using TPO-RA in pediatric patients being treated for cancer.

12007 Background: CIT is a common consequence of antineoplastic regimens for gastrointestinal (GI) cancers, occurring in >60% of colorectal cancer patients receiving multiagent chemotherapy. CIT can lead to chemotherapy dose reduction, delay, omission, and discontinuation, potentially worsening outcomes. There are no widely available licensed therapies for this unmet need. Aim: To evaluate the safety and efficacy of the thrombopoietin receptor agonist romiplostim (ROMI) in patients with GI cancers to limit chemotherapy dose modifications from CIT. Methods: This was a phase 3, placebo (PBO)-controlled RCT of patients receiving oxaliplatin-based multiagent regimens for GI cancers with persistent CIT, ie platelets (Plt) ≤85×10 9 /L on day 1 of a scheduled chemotherapy cycle (NCT03362177). Patients from 55 sites in 14 countries were randomized 2:1 to ROMI or PBO for 3 chemotherapy cycles, stratified by baseline Plt (< or ≥50×10 9 /L) and cancer type. Study drug started at 2 μg/kg subcutaneous weekly, adjusted weekly by 1 μg/kg up to 10 μg/kg to target Plt ≥100×10 9 /L in 12 weeks (≤4 weeks at 10 μg/kg). Chemotherapy started when Plt ≥100×10 9 /L (Plt response) or after week 4 per investigator. The primary endpoint was no CIT-induced dose modification of any myelosuppressive agent in either the second or third chemotherapy cycle per independent adjudication committee. Results: Patients (N=165; 109 ROMI, 56 PBO) had colorectal (75%), gastroesophageal (13%), or pancreatic (12%) cancer; 60% were male, 90% White, 4% Black, and 24% Hispanic, with mean (SD) age of 61.4 (11.1) years. Baseline median (range) Plt was 69 (8–85)×10 9 /L; 11% had Plt <50×10 9 /L. Stage IV disease rates were ROMI 65%, PBO 55%. Most (75%) patients completed study drug; 3% discontinued due to adverse events (AEs). The primary endpoint was achieved in 92/109 (84%) patients receiving ROMI vs 20/56 (36%) receiving PBO (odds ratio 10.2; 95% CI 4.6-22.5; P<0.001). Median (range) Plt nadirs were ROMI 87 (14–167)×10 9 /L, PBO 58 (22–95)×10 9 /L; P=0.005. For those with Plt responses (ROMI 97%, PBO 77%), median (95% CI) time to first Plt response was ROMI 1.1 (not estimable) weeks, PBO 2.1 (1.1-3.0) weeks; P<0.001. Treatment-related (TR) AE rates were ROMI: 12%, PBO: 7%, most frequently nausea (2%, 2%) and headache (2%, 0%). TR serious AEs and TRAEs leading to death or discontinuation of study drug or chemotherapy were not observed in either arm. Conclusions: In this first global phase 3 RCT of ROMI vs PBO for CIT, ROMI was well tolerated and efficacious in the treatment and prevention of CIT in GI cancers. These results are potentially practice-changing for a common serious condition encountered routinely in clinical practice worldwide that prevents delivery of on-time, full-dose anticancer therapy. Final results from long-term follow-up will be presented. Clinical trial information: NCT03362177 .

Venous thromboembolism (VTE) is a frequent complication in patients with lung cancer, but the risk factors and incidence in different lung cancer subtypes have not been fully characterized. Despite multiple studies supporting the use of VTE prophylaxis in patients with cancer at increased risk of VTE based on the Khorana score (KS), routine use of VTE prophylaxis is uncommon in clinical practice. This study further characterizes the risk factors and incidence of VTE in patients with lung cancer at a university cancer center. Furthermore, we assessed the association of KS and its individual components with overall survival in this same group of patients. Using natural language processing and human review to detect thrombotic events in the electronic medical record, a 12-month incidence of 10.1% was identified in the 632 patients with lung cancer analyzed. Significant risk factors included age <60 years and white blood cell (WBC) count ≥11 × 109/L, but KS itself was not significantly associated with VTE. The median overall survival was 12 months with VTE. The KS, age ≥60 years, stage III to IV, WBC count ≥11 × 109/L, hemoglobin <10 g/dL, body mass index, surgery, and VTE were identified as significant predictors of death. These findings warrant further validation, because the KS and 2 of its individual components in this study of lung cancer were significantly associated with reduced overall survival.

e23053 Background: Aggressive cancer is associated with an increased rate of thrombosis. In addition to body mass index (BMI), the Khorana score has identified several hematologic parameters associated with an increased risk of thrombosis. In this study, we assessed the relationship of these parameters with overall survival. Methods: Using data from our tumor registry, we selected patients with aggressive lymphomas (AL), glioblastoma multiforme (GBM), metastatic prostate (MP), metastatic lung (ML), and metastatic colorectal (MCRC) cancer from 2018 to 2023. Laboratory data were extracted from our electronic medical record, with a timeframe of 90 days before and 30 days after first contact, but prior to initiating treatment. We analyzed the relationship of hemoglobin (Hgb), white blood cell (WBC) count, platelet (Plt) count, and body mass index (BMI), with overall survival (OS). Each cancer type was analyzed as a separate group and multivariable analysis was controlled by sex and age at diagnosis. Dichotomizing the variables from categories of the Khorana score, we evaluated the relationship of such variables and OS using Kaplan-Meier Analysis and Cox Proportional Hazards Models. Patients were censored at two years of follow-up. Data analysis was done using R (version 4.3). Results: Of 2,362 patients, 55% were male, and median age was 63 years. (Cancer types: 622 ML, 604 AL, 453 GBM, 281 MCRC, 203 MP, and 199 MB). An initial, pre-treatment Hgb < 10 g/dL was associated with a shorter OS in patients with ML, MCRC, MP, and AL patients. Plt ≥350 x 109/L was associated with a shorter OS in ML and MCRC patients. WBC > 11 x 109/L was associated with a shorter OS in ML, AL, and MCRC, and a BMI ≥35 was associated with a shorter OS only in GBM patients (Table). Conclusions: While not in all cancer types, the hematologic parameters of the Khorana score that predict thrombosis correlate with a reduced overall survival. This effect was significant for different parameters in different cancers. The increased hazard ratio is beyond that which would be expected from thrombosis-related mortality. Our study is limited to data from our single institution and the retrospective nature of the study. [Table: see text]

Thrombocytopenia is a common adverse effect of chemotherapy. The development of chemotherapy-induced thrombocytopenia (CIT) is influenced by cancer type and therapy, occurring in approximately one-third of patients with a solid tumor diagnosis and half of all patients with a hematologic malignancy. CIT may complicate the administration of chemotherapy, leading to therapeutic delays or dose reductions. This guidance document, presented by the International Society on Thrombosis and Haemostasis (ISTH) Subcommittee on Hemostasis and Malignancy, provides a comprehensive summary of the evidence and offers direction on the use of thrombopoietin receptor agonists (TPO-RAs) in various settings of CIT, including solid tumors, acute myeloid leukemia, stem cell transplant, and lymphoma. Studies have shown that TPO-RAs can improve platelet counts in CIT, but the clinical benefits of TPO-RA in terms of reducing bleeding, limiting platelet transfusion, avoiding chemotherapy delay, or dose reduction are uncertain. Further research is needed to optimize the selection of appropriate indications and study design to manage thrombocytopenia following chemotherapy.

Background: Patients with aggressive cancer (metastatic solid tumor (mST) or aggressive lymphoma (AL)) are at an increased risk of both thrombosis and death. The Khorana Score (KS) predicts cancer-associated thrombosis using hematologic parameters and the body mass index (BMI). In this study, we assessed the relationship of routine hemogram (complete blood count, CBC) parameters, ABO blood type and BMI with overall survival in patients with aggressive lymphoma and metastatic solid tumors. Methods: Utilizing the electronic medical record (EMR) and tumor registry from the University of Miami/Sylvester Comprehensive Cancer Center, patients were identified and data extracted, from 2018 to 2023. We analyzed patients with metastatic lung (ML), metastatic colorectal (MC) and metastatic prostate (MP) cancer, and aggressive lymphoma (AL). Prostate cancer tends to be more indolent, while ML and MC are more aggressive. This study was approved by the Institutional Review Board. Baseline demographics, CBC, and BMI were extracted from the EMR prior to initial treatment. We analyzed the association of hemoglobin (Hgb), white blood cell count (WBC), platelet count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), mean corpuscular volume (MCV), ABO blood group, and BMI with overall survival (OS), measured in days from cancer diagnosis. mST and AL were analyzed separately. Continuous variables were divided into quintiles (Q1-Q5) and analyzed using ANOVA to determine association with OS. ABO blood type was stratified into type O and non-type O and analyzed using t test. Data analysis was performed using R (version 4.3). Results: Of 1709 patients, 1105 (64%) had mST (621 ML, 281 MC, 203 MP), and 604 (36%) had AL. 59% were male, and the mean age at diagnosis was 62 years. For mST patients, pre-treatment Hgb levels, WBC, platelet counts, ANC, and ALC were significantly associated with OS. The effect was parallel to the known thrombosis effect of the KS, i.e. lower Hgb, higher WBC, and higher platelet count were associated with reduced OS. Higher ANC and lower ALC were associated with reduced OS. Both low BMI (16-25) and elevated BMI (30-54) were associated with reduced OS, compared with Q3, BMI 25-27. MCV and ABO blood group were not associated with OS. None of these relationships were observed in AL. The relationships of hematologic parameters and OS in mST tended to be continuous across the quintiles, even within normal, or minimally abnormal values. As one example, from minimal anemia at baseline (Q2, Hgb 10.7-12.2 gm/dL) to normal (Q5, 14.3-17.5), OS increased from 425 to 622 days, a 46% increase, p<0.001. Similarly, from baseline WBC of 6.2-7.7 X 10^9/L (Q2) to WBC 9.4-12.0 (Q4), OS decreased by 34% (640 to 420 days) (p<0.001). To assess if these associations simply reflected differences in baseline parameters with different cancer types, we analyzed the three ST categories separately. In ML, the relationship of Hgb, WBC, ANC, ALC with OS maintained significance, while platelet count showed a similar, but not significant trend. In MC, the relationship of WBC, platelets, ANC with OS were significant. In MC, the effect of anemia could not be meaningfully assessed as >80% of the patients were anemic at baseline. In MP, none of the relationship of CBC parameters with OS were significant. Conclusions: Several baseline hematology parameters significantly correlate with OS in solid tumor patients. In addition to the parameters of the KS, associated with thrombosis, we also assessed ANC, ALC, MCV, and ABO. Subgroup analysis, by cancer type, indicated that the relationships were not significant in MP or AL, however, in those cancer types there was no conflicting trends. The magnitude of the survival effects was much larger than one would expect from a possible contribution of cancer associated thrombosis. The adverse association with elevated WBC, ANC, and platelet counts argue against a possible adverse impact on ability to administer treatments. We hypothesize that the differences of hematologic values may reflect levels of cytokines or other markers of inflammation. The absence of correlation of MCV with OS, despite the adverse association of anemia, suggests the effect is due to anemia of chronic inflammation and not iron deficiency. Our study is limited by its single institution data and retrospective nature. Ultimately, one will need to confirm these findings and determine the mechanism(s) of the associations.

Background: Cancer and major abdominopelvic surgeries pose significant thrombosis risks, making cancer-related surgery highly susceptible to venous thromboembolism (VTE) despite prophylaxis. Without post-operative thromboprophylaxis (TPX), VTE risk can reach 29% in the weeks following major surgeries. National Comprehensive Cancer Network (NCCN) guidelines recommend anticoagulation for up to 4 weeks after such surgeries, primarily using low molecular weight heparin (LMWH) for 28 days postoperatively. This study aimed to determine VTE rates linked to various gynecologic cancer-related surgeries and explore TPX utilization in a large cancer-center cohort. Additionally, we sought to further understand the necessity for post-discharge TPX in this setting. Methods: Patients (pts) diagnosed with gynecologic cancer between January 1st, 2012, through September 15th, 2022, at our institution were identified through our tumor registry. Using an in-house automated text search tool from our electronic medical record (Epic®), combined with natural language processing review, venous thromboembolism (VTE) events were identified, with secondary adjudication by the study leader (GAS). VTE was defined as either lower extremity deep vein thrombosis (DVT), or pulmonary embolism (PE) diagnosed from the day of surgery until 90 days after the first day of surgery. Logistic regression was performed on binary outcomes for the presence of VTE and TPX use at discharge. Kaplan-Meier curves and Cox regression were used for overall survival analysis. Results: 801 pts who underwent gynecologic cancer-related surgeries were identified. Patient demographics and surgery types are described in Table 1. VTE occurred in 1.9% (n=15) of the overall population but was unequally distributed. The number of VTE in those undergoing minimally invasive surgery (MIS), vulvovaginal surgery, and biopsies collectively was low (0.57%, n=3), even when considering that only 11.1% of those pts received TPX at discharge. VTE was more commonly diagnosed in patients who underwent open surgery (4.3%, n=12), with 5 pts (1.8%) diagnosed before discharge and 7 pts (2.5%) after discharge. In multivariable logistic regression analysis, during the full study period, open procedures were associated with a higher risk of thrombosis, (relative risk 7.5, p < 0.001) and higher use of post-discharge TBX (RR 4.55, p < 0.001). Notably, only 50% (139 of 279) of pts who underwent open surgery received TPX at the time of discharge. Within the open surgery cohort, the rate of post-discharge VTE correlated with the use of post-discharge TPX. Of pts on TPX, 0.7% (n=1) were diagnosed with VTE compared to 4.3% (n=6) of pts who did not receive TPX (RR=0.17, p= 0.12). There was no difference in overall survival in pts who received TPX and those who did not after open surgery up to 36 months after the surgery. Conclusions: Our findings suggest a tiered risk of post-operative VTE after gynecologic cancer surgery, with a clinically relevant risk observed only in women undergoing open surgery. Our gynecologic oncology practice already reflects this, as post-operative TPX is not routinely prescribed for lower-risk procedures. In patients who underwent open surgery, TPX at discharge showed a trend towards a protective effect, although this result did not reach statistical significance, probably due to sample size, it supports the need for a targeted prospective study. If this trend towards benefit holds in a prospective study, the number needed to treat to avoid one clinically detected post-operative VTE would be 28 pts. The relatively high fraction of post-op VTE events during the inpatient hospital stay also supports efforts for early TPX, as has been done with a prophylactic dose of pre-operative unfractionated heparin or LMWH in other high-risk cancer surgery settings (Selby et al, J Am Coll Surg. 2016). The limitations of this study include being conducted at a single institution, retrospective and non-randomized.

Abstract Chemotherapy‐induced thrombocytopenia (CIT) is a common challenge of cancer therapy and can lead to chemotherapy dose reduction, delay, and/or discontinuation, affecting relative dose intensity, and possibly adversely impacting cancer care. Besides changing anticancer regimens, standard management of CIT has been limited to platelet transfusions and supportive care. Use of the thrombopoietin receptor agonist romiplostim, already approved for use in immune thrombocytopenia, has shown promising signs of efficacy in CIT. In a phase 2 prospective randomized study of solid tumor patients with platelet counts <100 × 109/L for ≥4 weeks due to CIT, weekly romiplostim corrected the platelet count to >100 × 109/L in 93% (14/15) of patients within 3 weeks versus 12.5% (1/8) of untreated patients (p < 0.001). Including patients treated with romiplostim in an additional single‐arm cohort, 85% (44/52) of all romiplostim‐treated patients responded with platelet count correction within 3 weeks. Several retrospective studies of CIT have also shown responses to weekly romiplostim, with the largest study finding that poor response to romiplostim was predicted by tumor invasion of the bone marrow (odds ratio, 0.029; 95% CI: 0.0046–0.18; p < 0.001), prior pelvic irradiation (odds ratio, 0.078; 95% CI: 0.0062–0.98; p = 0.048), and prior temozolomide treatment (odds ratio 0.24; 95% CI: 0.061–0.96; p = 0.043). Elsewhere, lower baseline TPO levels were predictive of romiplostim response (p = 0.036). No new safety signals have emerged from romiplostim CIT studies. Recent treatment guidelines, including those from the National Comprehensive Cancer Network, now support consideration of romiplostim use in CIT. Data are expected from two ongoing phase 3 romiplostim CIT trials.

Introduction: According to the World Health Organization, 25% of pregnancy related deaths were due to severe bleeding occurring in the postpartum period (Khan et al. 2006). Women with inherited bleeding disorders are known to have an increased risk of bleeding complications during delivery (Leebek et al. 2020; Peyvandi et al. 2011). There is a scarcity of published data on obstetric related outcomes in women with congenital bleeding disorders in the US, and even less information on minority ethnic subgroups. Herein we provide bleeding outcomes for a cohort of patients with inherited bleeding disorders, a majority of whom were Hispanic, compared to their age-matched control counterparts. Methods: 44 patients with bleeding disorders (52 deliveries) were identified at the University of Miami and Jackson Memorial Hospitals. Inclusion criteria included reproductive-age women pregnant from 2012-2024 with a clinician diagnosis of an inherited bleeding disorder (Von Willebrand Disease (VWD), or carrier of hemophilia A or B, or other factor deficiency. Patients were identified through pregnancy and bleeding disorder ICD codes, hematology consult notes, and identification by treating provider. Age-matched controls (n=104) were defined as any delivery by a pregnant woman without a history of bleeding disorder and identified using pregnancy ICD codes. All methods were approved by our institution's IRB. Analysis was performed using unpaired t-testing. Results: Of the 52 bleeding disorder deliveries, 36 had clinical diagnosis of VWD (11 with unspecified type, 12 with type 1, 2 with type 2 unspecified, 7 with type 2A, 1 with type 2B, 3 with type 2M), 7 were hemophilia A carriers, 6 hemophilia C /factor XI deficiency carriers, 1 factor VII deficiency carrier, 1 factor XIII deficiency carrier, and 1 platelet storage pool disorder. 104 age-matched controls deliveries were identified, with a 2:1 ratio per bleeding disorder delivery, 3 years within delivery of their counterparts. Of the 52 deliveries in the bleeding disorder group, 31 (59.6%) were Hispanic. Of the control group, 63 (60.6%) were Hispanic. In the bleeding disorder group of 52 deliveries, 24 (46.2%) were cesarean sections and 28 (53.8%) were vaginal deliveries. In the control group of 104 deliveries, 46 (44.2%) were cesarean sections and 58 (55.8%) were vaginal deliveries. Average initial hemoglobin (Hgb) for the bleeding disorder group was 11.8 +/- 1.0 g/dL and for the control group was 11.5 +/- 1.4 g/dL. The average Hgb drop (pre vs post-delivery) for the bleeding disorder group was 1.575 +/- 0.95 g/dL and the average Hgb drop for the control group was 1.26 +/- 0.90 g/dL (p = 0.046). Average EBL for the bleeding disorder group was 557.9 +/- 417.7 g/dL and for the control group was 483.85 +/- 296.2 g/dL, which was not statistically significant (p = 0.203). Subgroup analysis of VWD, hemophilias, and factor deficiencies showed only VWD had a significant Hgb drop, with an average of 1.69 +/- 1.00 g/dL (p = 0.025). EBL difference was unremarkable (p = 0.203). Of note, there was no significant difference in Hgb drop in factor deficiency carriers. Subgroup analysis of cesarean section in the bleeding disorder subjects showed a significant Hgb drop of 1.82 +/- 0.99 g/dL compared to 1.34 +/- 0.87 g/dL in controls who underwent cesarean section (p=0.040). EBL difference was similar, (p = 0.152). In subgroup analysis of Hispanic bleeding disorder subjects compared to non-Hispanic bleeding disorder subjects there was no significant difference in Hgb drop or EBL between the groups. Conclusions: Our bleeding disorder cohort consists of a majority of Hispanic patients. Subjects with VWD had objectively more blood loss with a larger Hgb drop than their age-match control counterparts. In addition, cesarean section had a more significant Hgb drop in bleeding disorder subjects than controls. EBL did not correlate with the more objective drop in Hgb and is not likely to be reliable. Underestimation of blood loss could have poor implications for management of bleeding and risk of further hemorrhage. It is important for clinicians to be aware of the risk of underestimation of bleeding in patients with inherited bleeding disorders, and further assess with corresponding clinical signs and lab values.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.Venous thromboembolism occurs frequently in patients with cancer and is the second leading cause of death, after the cancer itself. There is a well-established consensus of the need for anticoagulation in patients with a proximal deep vein thrombosis or pulmonary embolism. But with improved imaging technology and widescale use of contrast imaging for cancer staging, many incidental pulmonary emboli are detected in patients with cancer. Furthermore, many isolated distal deep vein thromboses and subsegmental pulmonary emboli are identified. There have been questions if these small or asymptomatic thromboses require anticoagulation management similar to more proximal or symptomatic thromboses. In this Oncology Grand Rounds, we will review the existing evidence for these situations. We will also review management strategies for cancer-associated thrombosis, reflecting the evolving drugs and evidence over the past 20 years.

10563 Background: Sickle cell disease (SCD) is the most common inherited blood disorder in the United States and is caused by a mutation of β-globin ( HBB-Mt). The risk of developing solid malignancies in this population remains controversial, with research showing increased rates of some solid tumors (colon, kidney, and thyroid) and decreased rates of others (breast and male genitourinary). We report the prevalence of HBB mutations across a cohort of solid tumors and clinical outcomes between HBB-Wild type (-Wt) v Mutant (-Mt) tumors. Methods: Non-small cell lung cancer (NSCLC, N = 3307), breast (BC, N = 1960), colorectal (CRC, N = 2161), prostate (N = 899), and gynecologic cancers (N = 2,805) in persons of African descentwere tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing of DNA (whole exome) and RNA (whole transcriptome). Her2/Neu (+: ≥3+ and >10%) and HR (ER or PR+: ≥1+ and ≥1%) expression was tested by immunohistochemistry. Tumors were assessed for single nucleotide variations (SNVs) and insertions/deletions (indels) in HBB associated with a sickle cell phenotype. Mutation prevalence for all other genes was calculated for pathogenic SNVs/indels. Differentially regulated pathways were assessed by gene set enrichment analysis (GSEA). Fisher’s Exact/χ2 tests were applied as appropriate with p-values adjusted for multiple comparisons ( p < .05). Real-world overall survival (OS) and ethnicity data was obtained from insurance claims and log-rank estimates were calculated for molecularly defined subpopulations. Results: Amongst persons of African descent, uterine sarcoma had the highest prevalence of HBB-Mt (17.1%, 43/251) followed by uterine serous carcinoma (9.1, 70/768) and endometrial carcinoma (7.8, 55/708). Tumors with the highest absolute number of HBB-Mt tumors were NSCLC (7.0, 230/3307), CRC (8.1, 176/2161) and BC (6.7, 131/1960). In CRC, there was no significant difference in the prevalence of right-sided tumors between HBB-Wt v Mt (42% v 51, p = .06), nor in the prevalence of HBB-Mt by consensus molecular subtype ( p = .34). No significant enrichment of HBB-Mt across BC subtypes was observed (HR- HER2-: 7.8%, HR-HER2+: 9.7, HR+/HER2-:5.8, HR+/HER2+: 8.1, p = .34). No difference in the prevalence of pathogenic alterations was observed between HBB-Mt vs -Wt across NSCLC, CRC, and BC ( p > .05). HBB-Mt NSCLC were significantly enriched (GSEA) for genes related interferon /, inflammatory response and IL6/JAK/STAT3. No significant difference in OS was observed in CRC (median survival HBB-Wt: 957 days v -Mt: 1034, p = .43), NSCLC (-Wt: 591 v -Mt: 648, p = .59) or BC (-Wt: 924 v -Mt: 922, p = .61). Conclusions: No significant differences in the genomic landscape nor in OS of HBB-Mt vs HBB-Wt NSCLC, CRC or BC were observed. NSCLC HBB-Mt was enriched with inflammatory response genes. Future work should focus on potential role HBB-Mt plays in NSCLC.