British Journal of Haematology最新文献

In newly diagnosed (ND) adults with immune thrombocytopenia, standard first-line treatment (steroids ± IVIG) effectively raises platelet counts and mitigates bleeding or the risk thereof. In difficult-to-treat patients who fail first-line treatment, combination therapy may be appropriate; however, first- and second-line treatments could be combined at diagnosis to further improve initial platelet count and sustained off-treatment response in ND patients following the hypothesis that autoimmune responses are more malleable at diagnosis than later. Three randomised controlled trials (2 dexamethasone (dex) vs. dexamethasone + rituximab (ritux), 1 mycophenolate mofetil (MMF) + steroids vs. steroids alone) and six single-arm trials (dex + ritux ± ciclosporin and dex + TPO-RA ± ritux) were analysed to determine the effects of combining these therapies. Across the studies, initial and short-term responses were robust (50%-84%) with responses past 1 year ranging from 47% to 77%. While short-term responses were promising, many studies lacked a longer follow-up past 1-1.5 years. The amount of ND patients who would have entered sustained response off therapy long term with no treatment/steroids only, as well as with combination therapy, is thus unknown and remains to be investigated.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors are predisposed to silent cerebral infarctions (SCI) defined as radiological evidence of brain ischaemia without focal symptoms. This study examined risk factors associated with SCI burden in iTTP survivors during remission. We included the first 39 iTTP survivors enrolled in the prospective neurological sequelae of TTP (NeST) study. Participants underwent brain magnetic resonance imaging during clinical remission. SCI burden was quantified using the modified age-related white matter changes (ARWMC) score. Multivariate linear regression models identified the predictors of SCI burden. Of 39 participants, 20 (51.3%) had SCI. On univariate analysis, higher SCI burden was associated with older age, elevated level of peak serum creatinine and peak lactate dehydrogenase (LDH) during the index iTTP episode, comorbidities including diabetes mellitus, prior stroke, coronary artery disease (CAD) and family history of cerebrovascular disease. In the multivariate model, higher SCI burden was significantly associated with older age (p < 0.001), diabetes mellitus (p = 0.007), prior stroke (p = 0.01), CAD (p = 0.02) and elevated peak LDH (p = 0.046). Total days of thrombocytopenia (surrogate for 'days with active iTTP') were not associated with SCI burden. Both modifiable and non-modifiable factors contribute to SCI in iTTP survivors. Targeted management of cardiovascular comorbidities during remission may reduce long-term neurological sequelae. Validation in larger cohorts is needed.

Bone marrow (BM) involvement in B-cell non-Hodgkin lymphoma (B-NHL) is associated with poor prognosis, as the BM microenvironment provides a protective niche that promotes therapeutic resistance. We developed a simplified, automated and high-throughput 3D BM co-culture model that faithfully reproduces key tumour-stroma interactions. In our system, BM stromal cells (BMSCs) decreased lymphoma cell sensitivity to Phosphatidylinositol 3-kinase (PI3K) and BTK inhibitors. Moreover, we show that our 3D platform enables the mechanistic studies of microenvironment-mediated drug resistance and has the potential to be developed into a tool for personalized therapeutic strategies for B-NHL.

Young adults (YAs) undergoing allogeneic haematopoietic stem cell transplantation (HSCT) represent a unique population with distinct medical and psychosocial needs. Optimizing graft-versus-host disease (GvHD) prophylaxis in this population remains critical to improving outcomes. We performed a retrospective analysis of YAs undergoing unrelated donor HSCT using a contemporary Center for International Blood and Marrow Transplant Research (CIBMTR) dataset. GvHD-free, relapse-free survival (GRFS) at 24 months was evaluated across three GvHD prophylaxis strategies: Group A (post-transplant cyclophosphamide [PTCy] + calcineurin inhibitor [CNI] + mycophenolate mofetil [MMF]), Group B (CNI + methotrexate [MTX]/MMF), and Group C (CNI + MTX/MMF + anti-thymocyte globulin [ATG]). A propensity score-matched (PSM) analysis was conducted to adjust for baseline differences. A total of 1387 YA patients were included. In the total cohort, 24-month GRFS was 58.9% (confidence intervals [95% CI], 53-64) in Group A, 32.2% (95% CI, 29-36) in Group B and 44.2% (95% CI, 39-49) in Group C (p < 0.001). On multivariable analysis (MVA), both Group A (hazard ratio [HR] = 0.44; 95% CI, 0.35-0.54) and Group C (HR = 0.79; 95% CI, 0.70-0.90) showed improved GRFS compared to Group B. In the propensity score-matched cohort, GRFS at 24 months remained higher in the PTCy group (58.2%, 95% CI, 52-64) versus the CNI-MTX/MMF ± ATG group (32.9%, 95% CI, 27-39; p < 0.001), with PTCy independently associated with improved GRFS (HR = 0.48; 95% CI, 0.40-0.60; p < 0.001). PTCy-based prophylaxis also reduced non-relapse mortality (NRM), with no significant differences in relapse or overall survival (OS) between groups. In this large, retrospective analysis, PTCy was associated with significantly improved GRFS and reduced NRM in YAs undergoing unrelated donor HSCT. These findings support the use of PTCy-based regimens in this population and warrant prospective evaluation.