Anticoagulation and Antiplatelet Regimen in Cardiac Transplant. Clinical Characteristics, Outcomes, and Blood Product Transfusion.

BACKGROUND: We aimed to evaluate the characteristics, clinical outcomes, and blood product transfusion (BPT) rates of patients undergoing cardiac transplant (CT) while receiving uninterrupted anticoagulation and antiplatelet therapy. METHODS: A retrospective, single-center, and observational study of adult patients who underwent CT was performed. Patients were classified into four groups: (1) patients without anticoagulation or antiplatelet therapy (control), (2) patients on antiplatelet therapy (AP), (3) patients on vitamin K antagonists (AVKs), and (4) patients on dabigatran (dabigatran). The primary endpoints were reoperation due to bleeding and perioperative BPT rates (packed red blood cells (PRBC), fresh frozen plasma, platelets). Secondary outcomes assessed included morbidity and mortality-related events. RESULTS: Of the 55 patients included, 6 (11%) received no therapy (control), 8 (15%) received antiplatelet therapy, 15 (27%) were on AVKs, and 26 (47%) were on dabigatran. There were no significant differences in the need for reoperation or other secondary morbidity-associated events. During surgery patients on dabigatran showed lower transfusion rates of PRBC (control 100%, AP 100%, AVKs 73%, dabigatran 50%, p = 0.011) and platelets (control 100%, AP 100%, AVKs 100%, dabigatran 69%, p = 0.019). The total intraoperative number of BPT was also the lowest in the dabigatran group (control 5.5 units, AP 5 units, AVKs 6 units, dabigatran 3 units; p = 0.038); receiving significantly less PRBC (control 2.5 units, AP 3 units, AVKs 2 units, dabigatran 0.5 units; p = 0.011). A Poisson multivariate analysis showed that only treatment on dabigatran reduces PRBC requirements during surgery, with an expected reduction of 64.5% (95% CI: 32.4%-81.4%). CONCLUSIONS: In patients listed for CT requiring anticoagulation due to nonvalvular atrial fibrillation, the use of dabigatran and its reversal with idarucizumab significantly reduces intraoperative BPT demand.

Impact of SCHOLAR-1 Criteria on Chimeric Antigen Receptor T Cell Therapy Efficacy in Aggressive B Lymphoma: A Real-World GELTAMO/GETH Study.

In the pre-chimeric antigen receptor T cell (CAR-T) therapy era, the SCHOLAR-1 study identified a group of patients with refractory aggressive B cell lymphoma (ABCL) with particularly poor prognoses. We recently published our real-world data from Spain, focused on this SCHOLAR-1 refractory group, and compared patients who underwent CAR-T therapy with the previous standard of care. In this study, we found that the efficacy of CAR-T therapy in refractory patients, in terms of progression-free survival (PFS) and overall survival (OS), was superior to that of the treatments available in the pre-CAR-T era. The main objective of these new analyses was to analyze treatment efficacy in terms of response rates and survival for patients with ABCL with or without the SCHOLAR-1 criteria. In addition, we analyzed the prognostic impact of each SCHOLAR-1 criterion independently. Our study aimed to assess the prognostic impact of SCHOLAR-1 criteria on ABCL patients treated with CAR-T therapy in Spain. This multicenter, retrospective, observational study. We included all adult patients treated with commercially available CAR-T cell products and diagnosed with ABCL different from primary mediastinal large B cell lymphoma between February 2019 and July 2022. Patients meeting any SCHOLAR-1 criteria (progressive disease as the best response to any line of therapy, stable disease as the best response to ≥4 cycles of first-line therapy or ≥2 cycles of later-line therapy, or relapse at <12 months after autologous stem cell transplantation [auto-SCT]) in the line of treatment before CAR-T therapy (SCHOLAR-1 group) were compared with those not meeting any of these criteria (non-SCHOLAR-1 group). To analyze the prognostic impact of individual SCHOLAR-1 criteria, all the patients who met any of the SCHOLAR-1 criteria at any time were included to assess whether these criteria have the same prognostic impact in the CAR-T era. In addition, patients were grouped according to whether they were refractory to the first line of treatment, refractory to the last line of treatment, or relapsed early after auto-SCT. The PFS and OS were calculated from the time of appearance of the SCHOLAR-1 refractoriness criteria. Of 329 patients treated with CAR-T (169 with axi-cel and 160 with tisa-cel), 52 were in the non-SCHOLAR-1 group and 277 were in the SCHOLAR-1 group. We found significantly better outcomes in the non-SCHOLAR-1 patients compared with the SCHOLAR-1 patients (median PFS of 12.2 and 3.3 months, respectively; P = .009). In addition, axi-cel showed better results in terms of efficacy than tisa-cel for both the non-SCHOLAR-1 group (hazard ratio [HR] for PFS, 2.7 [95% confidence interval (CI), 1.1 to 6.7; P = .028]; HR for OS, 7.1 [95% CI, 1.5 to 34.6; P = .015]) and SCHOLAR-1 group (HR for PFS, 1.8 [95% CI, 1.3 to 2.5; P < .001]; HR for OS, 1.8 [95% CI, 1.2 to 2.6; P = .002]), but also significantly more toxicity. Finally, separately analyzing the prognostic impact of each SCHOLAR-1 criterion revealed that refractoriness to the last line of treatment was the variable with the most significant impact on survival. In conclusion, SCHOLAR-1 refractoriness criteria notably influence the efficacy of CAR-T therapy. In our experience, axi-cel showed better efficacy than tisa-cel for both SCHOLAR-1 and non-SCHOLAR-1 patients. Refractoriness to the last line of treatment was the variable with the most significant impact on survival in the CAR-T therapy era.

Results of haploidentical transplant in patients with donor-specific antibodies: a survey on behalf of the Spanish Group of Hematopoietic Transplant and Cell Therapy.

Background: Donor-specific antibodies (DSAs) are IgG allo-antibodies against mismatched donor HLA molecules and can cause graft failure (GF) in the setting of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Our aim was to report the experience of the Spanish Group of Hematopoietic Transplant (GETH-TC) in DSA-positive patients who had undergone haplo-HSCT. Methods: We conducted a survey of patients who underwent haplo-HSCT in GETH-TC centers between 2012 and 2021. Data were collected on the DSA assay used, monitoring strategy, complement fixation, criteria for desensitization, desensitization strategies and transplant outcomes. Results: Fifteen centers from the GETH-TC responded to the survey. During the study period, 1,454 patients underwent haplo-HSCT. Seventy of the transplants were performed in 69 DSA-positive patients, all of whom lacked a suitable alternative donor; 61 (88%) patients were female (90% with prior pregnancies). All patients received post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis. Regarding baseline DSA intensity, 46 (67%) patients presented mean fluorescence intensity (MFI) >5,000, including 21 (30%) with MFI >10,000 and three (4%) with MFI >20,000. Six patients did not receive desensitization treatment, four of them with MFI <5,000. Of 63 patients receiving desensitization treatment, 48 (76%) were tested after desensitization therapy, and a reduction in intensity was confirmed in 45 (71%). Three patients (5%) experienced an increase in MFI after desensitization, two of whom experienced primary GF. Cumulative incidence of neutrophil engraftment at day 28 was 74% in a median of 18 days (IQR, 15─20); six patients died before engraftment due to toxicity or infection and eight patients had primary GF despite desensitization in seven of them. After a median follow-up of 30 months, two-year overall and event-free survival were 46.5% and 39%, respectively. The two-year cumulative incidence of relapse was 16% and non-relapse mortality (NRM) was 43%. Infection was the most frequent cause of NRM, followed by endothelial toxicity. Multivariate analysis identified baseline MFI >20,000 as an independent risk factor for survival and an increase in titers after infusion as an independent risk factor for GF. Conclusions: Haplo-HSCT is feasible in DSA-positive patients, with high rates of engraftment after desensitization guided by DSA intensity. Baseline MFI >20,000 and increased intensity after infusion are risk factors for survival and GF.

Best Treatment Option for Patients With Refractory Aggressive B-Cell Lymphoma in the CAR-T Cell Era: Real-World Evidence From GELTAMO/GETH Spanish Groups.

Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4-6 months, p ≤ 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44-0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31-0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria.