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)

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)

Systemic mastocytosis: Overview of recent updates and novel therapies

SUMMARY

Systemic Mastocytosis (SM) is a rare, clinically heterogeneous haematological disorder. Over 90% of patients carry a mutation in the receptor tyrosine kinase KIT (i.e. KIT D816V) resulting in the clonal expansion of neoplastic mast cells (MCs) impacting multiple organs and leading to variable clinical presentations ranging from skin-limited disease to more aggressive variants associated with multi-organ dysfunction and reduced survival. Furthermore, the quality of life can be impaired by excess mediator release from neoplastic mast cells resulting in a significant symptom burden. Based on the above, there have been increasing efforts to develop novel, targeted therapies in order to improve quality of life while also affecting survival outcomes. This review will give an overview of the diagnostic work-up for SM patients as well as therapeutic management, including updates from recent clinical trials.

(BELG J HEMATOL 2024;15(6):216–24)

Germline predisposition in the context of acute myeloid leukaemia: A single-centre descriptive study of current practice and review of the literature

SUMMARY

The awareness of potential germline predisposition in patients with acute myeloid leukaemia (AML) has increased in the years since NGS testing with large gene panels became standard of care. Yet, it must be noted that still little is known regarding incidences in the Belgian population and specific guidelines for clinical practice are lacking. This narrative review attempts to provide an overview of the most common germline variants in the context of AML, optimal diagnostic approaches, and the impact on the patient and family. In a retrospective study of a cohort of 241 AML-patients, we describe the current situation at Ghent University Hospital. Using the available NGS panels, we identified twelve patients with germline pathogenic variants: 5.0% of the total cohort, 34.3% of the patients that were referred for germline testing. It must be realized that the NGS panels expanded during the study period, and probably will expand further in the future: the amount of germline pathogenic variants will likely be higher. This demonstrates the importance of awareness for underlying germline predisposition, and the implications for the patient, their family, as well as during donor search in case of allogenic stem cell transplantation.

(BELG J HEMATOL 2024;15(4):135–46)