REVIEW HEMATOLOGY

Prime-time for lncRNA signatures in acute myeloid leukaemia?

SUMMARY

Long non-coding RNA (lncRNA) signatures have emerged as important prognostic biomarkers in acute myeloid leukaemia (AML), stratifying patients into high-risk and low-risk groups and thus providing valuable insights for personalised treatment strategies. The development of these signatures often involves comprehensive bioinformatics analyses, employing various statistical methods to ensure robustness and accuracy. Nevertheless, many reports are flawed by the presence of specific biases and/or incompleteness. Here we performed a comprehensive review of recently identified prognostic lncRNA signatures in AML, including our own report on a 69-lncRNA signature predicting relapse-free survival in paediatric acute myeloid leukaemia. Next to their predictive impact, we provide insights into their strengths and shortcomings.

(BELG J HEMATOL 2025;16(2):54–64)

Restoring the delicate coagulation balance in haemophilia

SUMMARY

Thrombophilia is very prevalent in the general population. In patients with haemophilia, it leads to an attenuation of their bleeding phenotype. Rebalancing agents work in similar fashion by targeting the natural anticoagulants, which enhances thrombin generation, and restores the balance of coagulation. The most important targets are antithrombin, tissue factor pathway inhibitor (TFPI) and activated protein C with its cofactor protein S. Antithrombin levels can be lowered by the short interfering RNA fitusiran via subcutaneous injection, which results in more thrombin generation and clot formation. Its efficacy was demonstrated in patients with haemophilia A and B, with and without inhibitors. The other clinically advanced drugs are concizumab and marstacimab, which both inhibit TFPI, thereby relieving the suppression of the extrinsic pathway, and reducing the bleeding rate in patients with haemophilia. Initially, several thrombotic events were observed in patients using fitusiran and concizumab, but these could be managed by using an adapted dosing strategy. Finally, several compounds target either activated protein C or protein S. The development of SerpinPC, inhibiting protein C, was recently halted, but other drugs continue to be under clinical development and show promising results. In short, rebalancing agents are effective in selected patients with haemophilia, and they could potentially even open new possibilities to treat many hitherto neglected rare bleeding disorders.

(BELG J HEMATOL 2025;16(3):111–7)

Non-myeloablative haploidentical haematopoietic stem cell transplantation for adult patients with sickle cell disease: Current status and future perspectives

SUMMARY

Allogeneic haematopoietic stem cell transplantation is a curative therapy for patients with sickle cell disease. The introduction of non-myeloablative conditioning regimens has made this treatment accessible to adult patients with sickle cell disease. Due to the limited availability of HLA-identical related donors and poor outcomes of matched unrelated donor transplantations, research of the past years has focused on developing new conditioning regimens to improve the outcomes of haploidentical transplantations. This overview article discusses the findings of a recently published phase II study on non-myeloablative haploidentical haematopoietic stem cell transplantation in patients with sickle cell disease. Additionally, the article discusses the effects of transplantation on sickle cell disease-related complications and future perspectives.

(BELG J HEMATOL 2025;16(3):118–24)

Approach to febrile neutropenia in Belgian hospitals

SUMMARY

Background: Febrile neutropenia (FN) is an important complication in high-risk haematological patients, occurring in 80–90% of cases. While rapid initiation of broad-spectrum antibiotics has improved FN-related mortality, the optimal duration of treatment remains controversial. Prolonged use of antibiotics not only leads to resistance and toxicity but also to increased mortality and GVHD in allogeneic stem cell transplantation recipients due to disruption of the microbiome. Different guidelines provide different recommendations, leading to inconsistent practice and the ECIL guidelines are not widely implemented.

Methods: A national survey was conducted in Belgium to assess current practices for the management of FN in high-risk haematological patients. The electronic survey, consisting of 40 questions, was distributed to haematology centres via the newsletter of the Belgian Society of Haematology in January 2023. Responses from seventeen large haematology centres, including university hospitals, were analysed.

Results: Prophylactic measures such as germ-free diets and fluoroquinolone use were common, with 13/17 centres implementing germ-free diets and 11/17 centres using fluoroquinolone prophylaxis. Empirical broad-spectrum antibiotic treatment (EBAT) was initiated as monotherapy in 15/17 centres, predominantly with piperacillin-tazobactam (8/17) or third-/fourth-generation cephalosporins (7/17). Escalation to broader-spectrum antibiotics was common when FN persisted, with 9/17 centres using this approach. De-escalation practices varied, with 12/17 centres de-escalating if the patient showed improvement despite a severe initial presentation. Withdrawal of EBAT before neutrophil recovery occurred in 15/17 centres in stable, afebrile patients.

Discussion: The survey revealed partial compliance with the ECIL guidelines, with variations in escalation and de-escalation practices. While most centres followed recommended empirical treatments, de-escalation and early cessation remain difficult. The findings highlight the need for further research to optimise antibiotic use, reduce associated risks and reduce healthcare costs.

Conclusions: Although Belgian centres show better adherence to ECIL guidelines compared to other regions, challenges remain in de-escalation and early cessation of EBAT. A multicentre randomised controlled trial is needed to establish the safety of shorter EBAT durations and to improve antimicrobial stewardship.

(BELG J HEMATOL 2024;15(8):307–12)

Gene therapy for beta thalassemia and sickle cell disease in Europe and the United States

SUMMARY

Following the lead of the United States (US) Food and Drug Administration (FDA), the European Medicines Agency (EMA) approved gene-editing therapy with exagamglogene autotemcel in early 2024 for the treatment of patients with transfusion-dependent β-thalassemia or severe sickle cell disease. A year earlier, the FDA granted marketing authorisation for gene therapy with lovotibeglogene autotemcel in patients with severe sickle cell disease. This article describes the results of the clinical trials on the basis of which these new treatments were authorised for marketing.

(BELG J HEMATOL 2024;15(8):313–4)

Teclistamab also effective in patients with relapsed or refractory multiple myeloma who previously received anti-BCMA therapy

SUMMARY

Teclistamab is registered as a monotherapy in patients with relapsed or refractory multiple myeloma after previous ‘triple-class’ therapy. Recently, results from the MajesTEC-1 trial showed that teclistamab was safe and effective not only in patients who received ‘triple-class’ therapy in the past, but also for those who received both ‘triple-class’ therapy and BCMA-targeted therapy.

(BELG J HEMATOL 2024;15(8):315–7)

Precision medicine in relapsed and refractory paediatric haematological malignancies and the role of an International Tumour Board

SUMMARY

Despite improvements in the outcome of newly diagnosed paediatric haematological malignancies, the prognosis of refractory and high-risk relapsed patients remains poor, and their treatment is challenging. The increased use of molecular and functional profiling technologies and the growing number of targeted therapies provide opportunities to alter the treatment landscape of these patients and offer the potential to improve patient outcomes. However, this approach comes with many challenges. First, there is a need for accessibility to the analysis and interpretation of sequencing technologies. Second, the prioritisation of targetable events and matching treatments needs to be established. Third, there is a need to facilitate access to early-phase clinical trials. Recently, the international Leukaemia/Lymphoma Target Board (iLTB, NCT05270096, ITCC107) was initiated by the Prinses Máxima Centre and developed in collaboration with the international community to address these barriers. The iLTB provides a forum for an international panel of experts to advise the treating physicians on the best possible treatment options for their patients diagnosed with relapsed or refractory haematological malignancies, for which there is no standard treatment option. In addition, the iLTB aims to facilitate enrolment in clinical trials and collect structured real-world data on patients treated with compassionate use programs. The purpose of this article is to discuss the current challenges in relapsed and refractory haematological malignancies and to introduce the use of international tumour boards to help physicians when confronted with difficult cases.

(BELG J HEMATOL 2024;15(7):263–8)