BJH - volume 15, issue 6, october 2024
P. Sriskandarajah MD, MRCP, FRCPath, PhD, D.H. Radia MD, MRCP, FRCPath
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)
Read moreBJH - volume 15, issue 4, june 2024
S. Le Roy MD, R. de Putter MD, L. Vandepitte PharmD, K. Vandepoele PhD, K. Claes BM, PhD, T. Kerre MD, PhD, I. Moors MD
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)
Read moreBJH - volume 15, issue 3, may 2024
A. Janssens MD, PhD, C. Lambert MD, PhD
Chemotherapy-induced thrombocytopenia (CIT) is a common complication of cancer treatment that poses a severe clinical burden to patients with solid or haematologic malignancies. As this thrombocytopenia can present a barrier to continue chemotherapy at full dose and on schedule, it can hamper the patient’s long-term oncologic outcomes. Despite the clinical challenges related to CIT, there are currently no available agents approved by the FDA or EMA for the treatment or prevention of CIT. However, treatment with thrombopoietin receptor agonists (TPO-RAs) may increase platelet counts and benefit the safe administration of full-dose chemotherapy without dose delays. This not only reduces the patient’s bleeding risks, but also benefits the long-term oncologic outcomes. To date, most evidence for the use of TPO-RAs in the setting of CIT come from trials with romiplostim.
(BELG J HEMATOL 2024;15(3):94–102)
Read moreBJH - volume 15, issue 2, march 2024
A-M. Hulshof PhD, T. van de Berg MD, H. Spronk PhD, H. ten Cate MD, PhD, B. van Bussel MD, PhD, Y. Henskens PhD
This manuscript evaluates the application of global assays of haemostasis in mechanically ventilated COVID-19 patients. The results presented here originate from the serial rotational thromboelastometry (ROTEM) and thrombin generation measurements in the Maastricht Intensive Care COVID (MaastrICCht) cohort. Routine and tissue plasminogen activated (tPA) ROTEM were able to characterise the complex haemostatic abnormalities in this population over time and deceased COVID-19 patients demonstrate further deterioration of the observed hypercoagulability and hypofibrinolysis. Furthermore, thrombin generation assays suggest a limited in vivo heparin anticoagulant effect; whereas routine laboratory assays (anti-Xa) generally fell within the heparin-therapeutic range. In summary, global assays of haemostasis may be suitable to quantify the heparin anticoagulant effect and to characterise complex haemostatic pathologies in an ICU setting. However, more research focused on the prognostic value and application in non-COVID ICU patients is required prior to clinical implementation.
(BELG J HEMATOL 2024;15(2):43–8)
Read moreBJH - volume 15, issue 2, march 2024
A.G.H. Niezink MD, R.W.M. van der Maazen MD, PhD, B.D.P. Ta MSc, H. Vos-Westerman MD, C.P.M. Janus MD, L.A. Daniels MD, PhD
Chimeric antigen receptor T-cell (CAR T-cell) therapy is available in the Netherlands as a third-line treatment option in patients with large B-cell lymphoma. Bridging is often required during the waiting period between leukapheresis and CAR T-cell infusion. Radiotherapy is an increasingly applied bridging strategy, which is well tolerated by patients and also safe and effective. The most commonly used radiation schedule is 20 Gy in five fractions. In addition to bridging, radiotherapy can also be used as consolidation or salvage treatment after CAR T-cell therapy. Involving a radiation oncologist in a timely manner for patients who are going to be treated with CAR T-cell therapy is of benefit.
(BELG J HEMATOL 2024;15(2):37–42)
Read moreBJH - volume 14, issue 8, december 2023
A.S. van Velzen MD, PhD, B.F. Goemans MD, PhD, A.B. Versluys MD, PhD
In 15–20% of children with acute myeloid leukaemia (AML), a mutation in the FMS-like tyrosine kinase 3 (FLT3) protein is present. This is usually an internal tandem duplication (FLT3-ITD), an activating mutation that ensures cell survival and proliferation. A FLT3-ITD mutation is associated with a lower chance of survival and is an indication for allogeneic stem cell transplantation (SCT) in children with AML. Since the risk of relapse after allogeneic SCT can be up to 40%, additional treatment after allogeneic SCT is also being investigated. In recent decades, several targeted therapies have been developed for patients with AML, including several generations of FLT3 inhibitors (tyrosine kinase inhibitors). The effect of these inhibitors has already been demonstrated in adult patients with AML; however, the role of FLT3 inhibitors in children with AML with an FLT3-ITD mutation is not yet fully understood. In this article, we discuss the role of FLT3 inhibitors after allogeneic stem cell transplantation for children with AML.
(BELG J HEMATOL 2023;14(8):331–5)
Read moreBJH - volume 14, issue 8, december 2023
S. Vandelanotte MSc, B. Calcoen MD, C. Tersteeg PhD, K. VanHoorelbeke PhD, S.F. De Meyer PhD
von Willebrand disease (VWD) is the most common inherited bleeding disorder, caused by mutations in the von Willebrand factor (VWF) gene. These mutations can affect the biosynthesis, secretion, function or clearance of VWF. As a result, quantitative or qualitative abnormalities of VWF lead to the bleeding phenotype found in VWD patients. Current management of VWD aims at correcting the bleeding phenotype via the use of supportive therapy, stimulating the release of endogenous VWF reserves and implementation of replacement strategies. Despite current treatment options, VWD patients experience a substantial negative impact on their overall health-related quality-of-life (HRQoL). Development of long-term approaches to manage VWD would not only avoid the current limitations of short-term therapies but could also significantly ameliorate the HRQoL of VWD patients. Gene therapy for VWD offers the potential of a long-term, if not lifelong, correction of VWF deficiency. During the last two decades, gene therapy for VWD has been studied via different strategies. The aim of this review is to give an overview of the different strategies and improvements that were investigated to develop a gene therapy for VWD.
(BELG J HEMATOL 2023;14(8):326–30)
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