Frequency of and finding risk factors for thromboembolism and major bleeding in patients with myelodysplastic syndrome undergoing allogeneic transplantation

Abstract

Abstract INTRO: The myelodysplastic syndromes (MDS) are a heterogenous group of neoplasms with dysregulation of hematopoiesis, increasing risk for thromboembolic events (TEE) and bleeding. Allogeneic stem cell transplantation (allo-SCT) is the only curative option, but also increases risk for TEE and bleeding. Factors predisposing MDS patients to these events are unclear, particularly in the setting of allo-SCT. Here, we describe the incidence of TEE and bleeding in MDS patients undergoing allo-SCT and evaluate effect sizes of patient and disease characteristics in these complications. METHODS: We identified all MDS patients who underwent allo-SCT at Loyola University Medical Center (LUMC) between 1/1/2013 to 1/1/2023. Data was collected retrospectively from electronic medical records. All arterial and venous TEE were included. Major bleeding was defined using International Society for Thrombosis and Hemostasis criteria (PMID: 32767653). Descriptive statistics were computed and summarized, and 95% confidence intervals were estimated around variables of interest. RESULTS: Eighty-one patients received allo-SCT for MDS at LUMC. Mean age at diagnosis was 60 (+/-13), 56 (69%) were male and 73 (91%) were white. Common phenotypes were MDS with low blasts (35.8%), MDS with increased (5-9%) blasts-1 (23.5%), and MDS with increased (10-19%) blasts-2 (18.5%). Twenty-one (26%) patients had a total of 25 TEE. Fourteen (56%) were venous and 11 (44%) were arterial. Nine (36%) were before and 16 (64%) were after allo-SCT. Median platelet count at TEE was 130 (62 - 168). Three were on anticoagulation (AC), 5 were on antiplatelet therapy (APT), and 1 was on both – 43% at time of TEE. One was on lenalidomide and 3 were on azacitidine. Mean age at MDS diagnosis was 58 (+/-14) with mean BMI 31 (+/-7.5). Fifteen (71%) were male and 19 (90%) were white. Eleven (52%) had very-high/high-risk disease by IPSS-R, 5 (24%) were intermediate risk, and 5 (24%) were low/very-low risk. Eleven (52%) had very-poor/poor cytogenetic profiles; 3 (14%) were intermediate and 7 (33%) were good/very-good. A numerically higher proportion of patients with very-poor/poor cytogenetics had TEE: 52% (95% CI 29.8-70.3) vs. 28% (95% CI 16.8-42.4). Age, sex, race, BMI, MDS subtype, IPSS-R, comorbid conditions (cardiovascular, pulmonary, gastrointestinal, renal), aGVHD, cGVHD and tobacco use did not demonstrate a clear effect in development of TEE. Survival at the end of the study was not clearly different: 7 (33%, 95% CI 14.6–57.0) with TEE vs 30 (56%, 95% CI 41.4–69.1) without. Eighteen patients (22%) had a total of 22 major bleeds: gastrointestinal (12), nasopharyngeal (4), intracranial (2), retroperitoneal (2), pulmonary (1), and urethral (1). Five (23%) were before and 17 (77%) were after allo-SCT. Median platelet count at bleeding event was low: 22.5 (10 - 47). Two were on AC and 0 were on APT – 11%. Four were on decitabine, 1 was on lenalidomide, and 1 was on azacitidine. Mean age at MDS diagnosis was 61 (+/-8) with mean BMI 28 (+/-6). Twelve (67%) were male and 16 (89%) were white. Ten (56%) had very high/high-risk disease by IPSS-R, 6 (33%) were intermediate risk, and 2 (17%) were low/very low risk. Ten (56%) had very-poor/poor cytogenetic profiles; 3 (17%) were intermediate and 5 (28%) were good/very-good. A numerically higher proportion of patients with very-poor/poor cytogenetics had bleeding: 56% (95% CI 30.8-78.5) vs. 34% (95% CI 22.3-47.0). A lower proportion of patients with bleeding had pulmonary comorbidities (6% (95% CI 0.14-27.3) vs. 39% (95% CI 26.6-51.9)), and cGVHD, (6% (95% CI 0.14-27.3) vs. 43% (95% CI 30.5-56.0)); significance of this is not clear. Age, sex, race, BMI, MDS subtype, IPSS-R, other comorbid conditions (cardiovascular, gastrointestinal, renal), aGVHD, and tobacco use did not demonstrate clear effect in occurrence of bleeding. Survival was decreased in those with bleeding: 3 (17%, 95% CI 3.5-41.4) with bleeding were alive vs 34 (54%, 95% CI 30.5-56.0) without at the end of the study period. CONCLUSION: Rates of TEE and bleed in MDS patients undergoing allo-SCT were similar and common at 26% and 22%, respectively. Bleeding, but not TEE, seemed to impact survival in line with one other report (Gergi et al. Blood 2024). Here, we evaluated effect sizes of many MDS-related characteristics, finding some numeric differences. This sets the basis for a larger multi-center database being planned to bring more clarity to this understudied disease.