The participation of transplant centres in research studies that request detailed follow-up data on included patients can be challenging due to the amount of time centre Data Managers have to complete additional requests. The Research Data Manager (RDM) Pilot Project was designed to support Anthony Nolan's longitudinal Patient/Donor project and provide real-world evidence of the benefit of additional and dedicated data management resources in transplant centres.
For Anthony Nolan to continue advancing the field of donor selection, up-to-date and accurate follow-up data is needed. This 12-month pilot project aimed to demonstrate how on-the-ground support could improve access to outcome data.
Following RDM placements at two participating centres, we reviewed the data quality and quantity collected, thus ensuring the methods used remain effective and are likely to result in successful and continuous data improvement. The cohort covered a broad timespan and included historical patient records, posing challenges in availability of prior data and long-term follow-up of discharged patients.
Following the placements, over 400 patients now have the most up-to-date and complete patient clinical outcome data available within the EBMT/BSBMTCT registry database for any group to study, reducing the burden on these centres to complete research data requests for these individuals.
The authors have confirmed clinical trial registration is not needed for this submission
Andexanet alfa, a Gla-domainless mutant factor Xa (GDXa), reverses oral FXa inhibitors but can cause severe heparin resistance during cardiopulmonary bypass (CPB). Antithrombin (AT) supplementation may mitigate this effect, though dosing evidence is limited.
We evaluated in vitro the effectiveness of combined heparin and AT in restoring heparin responsiveness after andexanet exposure. Whole blood and platelet-poor plasma from surgical patients on CPB were spiked with andexanet at target concentrations of 2.9 and 4 µM, respectively. Heparin responsiveness was assessed using kaolin-activated clotting time (ACT), ellagic acid-activated thromboelastometry (INTEM), and thrombin generation (TG) assays. Heparin alone or with AT (0.8–3.1 µM in whole blood; 1.1–4.4 µM in plasma) simulated clinical AT dosing (25–100 U/kg).
Andexanet shortened ACT by 68% versus native on-CPB blood. Heparin alone or low-dose AT failed to restore ACT, while high-dose AT with heparin prolonged ACT to > 400 s. INTEM showed a 102% increase in clotting time with moderate-dose AT, with modest α-angle and MCF reductions (≤ 16%). In plasma, high-dose AT plus heparin increased TG lag time ∼5-fold, with thrombin peak and velocity reduced by 86%.
High-dose AT with heparin mitigates andexanet-induced heparin resistance in vitro, though residual TG and clot formation suggest ongoing thrombotic risk, warranting further study.
The authors have confirmed clinical trial registration is not needed for this submission
Large B-cell lymphomas (LBCLs) are a common subtype of non-Hodgkin lymphomas. CD19 chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized LBCL treatment, with high remission rates but also significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Venous thromboembolism (VTE) in CAR-T therapy patients is understudied.
This study aims to determine the incidence and characteristics of acute VTE in LBCL patients treated with CAR-T therapy and identify baseline clinical features associated with VTE. Methods: We retrospectively reviewed 172 adult LBCL patients treated with CAR-T therapy from January 2018 to November 2019 at MD Anderson Cancer Center. Data on demographics, clinical characteristics, and adverse events were collected. VTE events within 6 months post-CAR-T therapy were confirmed by diagnostic imaging. Statistical analyses included univariate analyses and cumulative incidence functions.
The cohort was predominantly male (70%), with a median age of 59 years and advanced-stage disease (76.16%). The 6-month incidence of VTE was 7.6%, primarily involving upper extremity events related to central venous catheters. Significant associations were found between VTE and disease histology (p = 0.033) and high-grade ICANS (p = 0.013). PMBCL patients had a higher VTE incidence (30%) compared to DLBCL and TFL. Most VTE events occurred within the first month post-CAR-T therapy.
LBCL patients receiving CAR-T therapy have a significant risk of VTE, particularly within the first month and among those with PMBCL and high-grade ICANS. This highlights the need to study the role of venous thromboprophylaxis in this context.
Real-world data on teclistamab in relapsed or refractory multiple myeloma (R/R MM), particularly in elderly patients, remain limited.
We analysed efficacy and safety outcomes in patients ≥ 75 years from the French RetrosTECtive cohort. Among 303 patients, 90 were aged ≥ 75 years and compared with 213 younger patients.
Elderly patients had fewer high-risk cytogenetic abnormalities and a longer disease history. Remarkably, teclistamab appeared more effective in this population, with 74% achieving at least a very good partial response, compared with 62% of younger patients. Median progression-free survival was 15.1 months in the elderly cohort versus 12.4 months in younger patients.
This improved efficacy did not come at the cost of increased toxicity: adverse event rates were comparable, although older patients more frequently received prophylactic measures. These findings support teclistamab as a safe and effective therapeutic option for geriatric patients with R/R MM.
The authors have confirmed clinical trial registration is not needed for this submission.
Acute myeloid leukemia (AML) with plasmacytoid dendritic cell differentiation (pDC-AML) is a newly described subtype of leukemia with features resembling blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Herein, we present a case of pDC-AML in which bone marrow findings were best classified as AML, whereas cutaneous manifestations by morphology and immunophenotype were highly suggestive of a pDC neoplasm.
A high-dose cytarabine with anthracycline backbone and venetoclax was administered based on efficacy in AML and BPDCN, respectively. The patient achieved complete remission as well as resolution of FDG-avid activity by PET-CT imaging.
This report highlights that clinical correlation with immunophenotype and molecular testing is important in distinguishing these unique entities to guide appropriate diagnosis and management.
Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM) and a primary cause of disability in affected patients. Its pathogenesis is driven by an imbalance in bone remodeling, largely attributed to the overexpression of C-C motif chemokine ligand 3 (CCL3). While both bortezomib and statins have been reported to inhibit CCL3, their combined effect on promoting osteogenesis in MBD remains unexplored. This study aimed to investigate the therapeutic potential and underlying mechanism of rosuvastatin in combination with bortezomib for MBD.
Bone marrow samples from MBD patients were analyzed to correlate CCL3 levels with bone turnover markers. Human myeloma cell lines (IM9, XG-1) were treated with bortezomib and/or rosuvastatin. Cell viability was assessed by CCK-8 assay, and CCL3 expression was measured by ELISA and Western blot. A NOD/SCID mouse model of MBD was established to evaluate the in vivo effects on tumor growth, CCL3 secretion (by immunohistochemistry), and bone remodeling (by ALP and TRAP double staining).
CCL3 levels were significantly elevated in MBD patients and positively correlated with the severity of bone destruction. The combination of bortezomib and rosuvastatin synergistically inhibited CCL3 secretion in vitro and in vivo more effectively than either monotherapy. Consequently, the combination treatment significantly enhanced osteoblast activity, suppressed osteoclast formation, and improved survival in the murine model.
The combination of rosuvastatin and bortezomib exerts a synergistic effect by inhibiting CCL3, thereby rebalancing bone remodeling and promoting osteogenesis. This strategy represents a promising novel therapeutic approach for mitigating MBD.
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