British Journal of Haematology最新文献

Evidence suggests that iron deficiency may reduce sickle cell disease (SCD) complications by decreasing sickle haemoglobin polymerization through reduced red cell haemoglobin concentration. The aim is to investigate the effects of iron deficiency in SCD patients. We reviewed clinical and laboratory data from 512 patients (408 HbSS, 104 HbSC) at King's College Hospital (2008-2020). Outpatient data were collected from patients with no blood transfusions or hydroxyurea (hydroxycarbamide) use in the prior 90 days. Patients were categorized as hypoferritinaemic (<45 μg/L), normoferritinaemic (45-800 μg/L) or hyperferritinaemic (>800 μg/L) and analysed for laboratory markers and clinical complications. In HbSC patients, hypoferritinaemia was associated with significantly fewer hospital admissions and inpatient days per year compared to normoferritinaemia. Although this was not seen in HbSS patients, hypoferritinaemia correlates with lower haemolysis and inflammation markers, with no differences in total haemoglobin or erythropoietin in both groups. In HbSS patients, haemoglobin F was significantly lower in hypoferritinaemic compared to normoferritinaemic patients. Iron deficiency may reduce inflammation and haemolysis in both HbSS and HbSC, with clinical benefits demonstrable in HbSC. Low ferritin levels were not associated with increased anaemia, suggesting improved red cell survival. Iron-restricted erythropoiesis may benefit SCD patients in certain circumstances.

Myelodysplastic syndromes (MDS) are heterogeneous stem cell disorders with a 30%-40% risk of transformation to acute myeloid leukaemia (AML). This study characterised the genetic and clinicopathological features of 437 newly diagnosed MDS patients. A predictive model for AML transformation was developed, which identified the bone marrow blast percentage, KRAS, STAG2 and TP53 mutations as significant predictors of disease progression. Novel prognostic models for overall survival (OS) and progression-free survival (PFS) were established and validated. The OS model incorporated age, sex and mutations in TP53, NF1, SRSF2, CSF3R, ETV6, CEBPA, BCOR, TET2, JAK2 and SF3B1. The PFS model incorporated age, sex, bone marrow blast percentage and mutations in STAT3, TP53, NF1, CEBPA, ETV6, CALR, DNMT3A, IDH2, GATA2, BCOR, JAK2, TET2 and SF3B1. These models stratify patients into favourable, intermediate-1, intermediate-2 and adverse risk groups, demonstrating superior risk stratification compared to the Revised/Molecular International Prognostic Scoring System (IPSS-R/M). This work provides the first genomic characterisation of a diagnosed MDS cohort in China and establishes the first risk prediction model for MDS-to-AML transformation, alongside novel prognostic models for OS and PFS. These tools offer improved prognostic prediction and potential guidance for therapeutic strategies in Chinese patients with MDS.

B-cell acute lymphoblastic leukaemia (B-ALL) in adolescents and adults remains challenging due to high relapse rates and suboptimal outcomes. Although minimal residual disease (MRD) and cytogenetic risk classification are independent prognostic indicators for B-ALL in adolescents and adults, their combined utility remains under explored. This retrospective study analysed 609 adolescent and adult patients with B-ALL to evaluate the integrated prognostic value of MRD at end of induction (MRD1) and after first consolidation (MRD2), combined with cytogenetic risk stratification (standard risk [SR] vs. poor risk [PR]). Although cytogenetic risk alone was not an independent prognostic factor, MRD positivity at either time point significantly predicted inferior 5-year RFS and OS in PR patients. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) improved outcomes overall; however, PR patients with MRD2 positivity remained at high risk of relapse post-transplant. Multivariate analysis identified MRD1 and MRD2 as independent predictors of both relapse (RFS HR = 2.048) and mortality (OS HR = 1.979) in PR patients (all p < 0.01). These results demonstrate that combining MRD assessment with cytogenetic risk improves risk stratification, precisely identifying poor-risk patients with persistent MRD who may benefit from treatment intensification, including novel strategies post-transplant.

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.