Haematologica最新文献

It has been proposed that low power, high frequency ultrasound can augment the ability of thrombolytic agents to dissolve clot in patients with venous thromboembolism. We created a bench model to examine what role and mechanism ultrasound may have in this process. Fibrin polymerization was analyzed through modified light-scattering experiments with the inclusion of catheter-mediated ultrasound application. We studied fibrin fiber diameters through scanning electron microscopy of ultrasound treated fibrin clots. Clot porosity was investigated using permeation tests, while fibrinolysis was analyzed through light-scattering experiments, and by changes in porosity of lysing clots under flow. Whilst application of ultrasound did not change initial fibrin polymerization, it did induce a reversible change in maximal turbidity of already formed fibrin clots. This change in turbidity was caused by a reduction in fibrin fiber diameter and was associated with an increase in clot porosity. These reversible structural changes were associated with a linear increase in fibrinolysis rates under static conditions, while an exponential increase in rates was observed under flow. The use of ultrasound augmentation of thrombolysis enhances clot dissolution through greater and more rapid fibrin degradation. This is due to conformational change created by the ultrasound in clot structure, a reversible phenomenon that may increase binding sites for lytic agent, and could potentially allow the use of lower doses and shorter infusion times of ultrasound-assisted thrombolytic to treat venous thromboembolism in vivo.

This study assessed the comparative efficacy of lisocabtagene maraleucel (liso-cel) in the open-label, phase II PILOT study (clinicaltrials.gov NCT03483103) versus conventional second-line (2L) chemotherapy regimens in the real world administered to patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who were not intended for hematopoietic stem cell transplantation (HSCT). The liso-cel-treated cohort (N=61) was based on patients who received liso-cel in the PILOT study. The conventional chemotherapy cohort included patients who met PILOT eligibility criteria and received conventional 2L chemotherapy in the real-world clinical setting (N=273). After using the trimmed stabilized inverse probability of treatment weighting method to balance cohorts according to baseline characteristics, there were statistically significant differences in all tested measures of efficacy. Compared with real-world conventional chemotherapy regimens, liso-cel demonstrated higher overall response rates (79.6% with liso-cel vs. 50.5% with conventional chemotherapy; relative risk [RR]: 1.6; P<0.0001) and complete response rates (53.1% vs. 24.0%; RR: 2.2; P<0.0001), longer median duration of response (12.1 vs. 4.3 months; hazard ratio [HR: 0.40; P=0.0001), longer median event-free survival (7.0 vs. 2.8 months; HR: 0.43; P<0.0001), longer median progression-free survival (7.0 vs. 2.9 months; HR: 0.46; P<0.0001), and longer median overall survival (not reached vs. 12.6 months; HR: 0.58; P=0.0256). Results from analyses applying various additional statistical approaches consistently favored outcomes with liso-cel over real-world conventional chemotherapy regimens. These results reinforce the efficacy of liso-cel as 2L therapy for patients with R/R LBCL who are not intended for HSCT.

This study aimed to demonstrate the clinical outcomes of granulocyte colony-stimulating factor (G-CSF)/antithymocyte globulin (ATG), posttransplantation cyclophosphamide (PTCy) and PTCy combined with low-dose ATG (PTCy with ATGlow)-based haploidentical transplantation protocols in patients with hematologic malignancies. The comparisons were conducted via propensity score matching (PSM) analysis to balance the basic characteristics among different groups and were based on the transplantation data reported to the Chinese Bone Marrow Transplantation Registry Group (CBMTRG) from January 2020 to December 2022. For each patient in the PTCy or PTCy with ATGlow group, patients (at a 1:2 ratio) from the G-CSF/ATG group were selected. In total, the PTCy group (N=122) was matched with the G-CSF/ATG group 1 (N=230), and the PTCy+ATGlow group (N=123) was matched with the G-CSF/ATG group 2 (N=226). Compared with those in the PTCy group, the incidences of 28- day neutrophil engraftment (P=0.005), 100-day platelet engraftment (P=0.002), median time to neutrophil engraftment (P<0.001) and platelet engraftment (P=0.011) were significantly greater in the G-CSF/ATG group. No significant differences were observed in acute graft-versus-host disease (aGVHD) incidence or relapse incidence. In addition, patients in the G-CSF/ ATG group had lower non-relapse mortality (NRM; P<0.001), better 3-year overall survival (OS; P<0.001) and leukemia-free survival (P<0.001) rates than those in the PTCy group. Similarly, the G-CSF/ATG group achieved lower NRM (P<0.001) and better 3-year leukemia-free survival (P=0.002) than the PTCy+ATGlow group. In conclusion, G-CSF/ATG-based haplo-HSCT may be a preferential choice for the Chinese population with hematologic malignancies. In the future, a randomized controlled study is needed for further confirmation.

Acute myeloid leukemia (AML) is mainly a disease of the elderly: however, knowledge about the outcomes of treatment of core-binding factor (CBF) AML in an older population is limited. We retrospectively collected data on 229 patients with CBF-AML followed long-term in the last two decades. The 5-year overall survival was 44.2% (95% confidence interval [95% CI]: 39.9-47.5) and the 5-year event-free survival was 32.9% (95% CI: 25.5-40.1). In a subgroup of patients ≥70 years old who completed intensive therapy (induction + ≥3 courses of consolidation including autologous stem cell transplantation: 10 patients) the median event-free survival was 11.8 months (95% CI: 9.4-15.2) and overall survival was 40.0% (95% CI: 36.4- 44.1) at 5 years. In univariate analysis, age ≥70 years (hazard ratio [HR]=1.78, 95% CI: 1.15-2.54, P=0.008), failure to achieve remission following induction (HR=8.96, 95% CI: 5.5-13.8; P<0.0001), no consolidation therapy (HR=0.75, 95% CI: 0.47-1.84, P=0.04) and fewer than three cycles of consolidation (HR=1.48, 95% CI: 0.75-3.2; P=0.0004) predicted poorer event-free survival. Our study shows that intensive therapy, in selected older CBF-AML patients, leads to longer survival. Achieving a complete remission seems to be the most important first step and at least three cycles of consolidation, an important second one. The analysis suggests that these patients should not be excluded from studies with intensive therapies.

This multicenter, open-label, phase Ib study (ACE-LY-106) assessed the safety and efficacy of acalabrutinib, bendamustine, and rituximab (ABR) in treatment-naïve (TN) and relapsed or refractory (R/R) mantle cell lymphoma (MCL). Patients received acalabrutinib from cycle 1 until disease progression or treatment discontinuation, bendamustine on days 1 and 2 of each cycle for up to 6 cycles, and rituximab on day 1 of each cycle for 6 cycles, continuing every other cycle from cycle 8 for 12 additional doses (TN cohort). Eighteen patients enrolled in the TN cohort and 20 in the R/R cohort. Median duration of exposure to acalabrutinib was 34.0 and 14.6 months in the TN and R/R cohorts, respectively. No new safety risks were identified, and most adverse events (AE) were grades 1 or 2. Thirteen patients from the TN cohort (72.2%) and 17 patients from the R/R cohort (85.0%) reported grade 3-4 AE, most commonly neutropenia (TN: 38.9%; R/R: 50.0%). AE leading to death were pneumonitis (N=1, TN cohort), COVID-19, and cerebrospinal meningitis (N=1 each, R/R cohort). Overall response was 94.4% and 85.0% in the TN and R/R cohorts, respectively; complete response rates were 77.8% and 70.0%, respectively. After a median follow-up of 47.6 months, median progression-free survival (PFS) and overall survival (OS) were not reached in the TN cohort. After a median follow-up of 20.4 months, median PFS was 28.6 months and OS was not reached in the R/R cohort. Results indicate that ABR was safe and efficacious, supporting further study in patients with TN MCL.

Realgar-Indigo naturalis formula (RIF) is an oral form of arsenic that is effective against acute promyelocytic leukemia (APL). This multicenter, randomized, controlled trial compared the efficacy of all-trans retinoic acid (ATRA) plus RIF with ATRA plus arsenic trioxide (ATO) in a simplified regimen for non-high-risk APL. Following induction therapy with ATRA and ATO, participants were randomly assigned to receive either ATRA plus ATO or ATRA plus RIF both in a 2-week on 2-week off schedule for consolidation therapy. Once achieving molecular complete remission, the regimen was administered for a total of six cycles. All of 108 eligible patients achieved hematological complete remission after induction therapy. The median follow-up time was 29 months. The primary endpoint of 2-year disease-free survival was 97% in the ATRA-RIF arm and 98% in the ATRA-ATO arm, respectively (the ATRA-RIF arm was found to be non-inferior to the ATRA-ATO arm, [P<0.01], with a percentage difference of -1% [95% confidence interval: -4.8 to 6.9]). No deaths have been observed. Most adverse events were moderate. This study confirms the non-inferiority of RIF to ATO for non-high-risk APL, while also offering a more favorable regimen schedule for post-remission therapy (clinicaltrials gov. identifier: NCT02899169).