BJH - volume 8, issue 7, december 2017
K. Saevels MD, Z.N. Berneman MD, PhD, S. Anguille MD, PhD
Paroxysmal nocturnal haemoglobinuria is a rare, acquired haematological disease that manifests with haemolytic anaemia, thrombosis and impaired bone marrow function. The absence of two glycosylphosphatidylinositol-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for haemolysis and other paroxysmal nocturnal haemoglobinuria manifestations. Patients may present with a variety of clinical manifestations, such as anaemia, thrombosis, kidney disease, smooth muscle dystonias, abdominal pain, dyspnoea, and extreme fatigue. Delayed recognition of this condition is common due to the variable clinical presentation. This delay in diagnosis confers an increased risk of mortality and morbidity. Therefore, the purpose of this review is to raise awareness about this potentially life-threatening disease among haematologists and to provide a guide to diagnosis and treatment.
(BELG J HEMATOL 2017;8(7):259–64)
Read moreBJH - volume 8, issue 7, december 2017
K.P.M. van Galen MD, MSc, E.P. Mauser-Bunschoten MD, PhD
Von Willebrand disease is the most common congenital bleeding disorder characterised by mucocutaneous bleeding. However, joint bleeds also occur in a significant proportion of patients with severe Von Willebrand disease. Until recently, joint bleeding did not get much attention in clinical research on Von Willebrand disease, despite the fact that recurrent joint bleeds may lead to arthropathy. Arthropathy in Von Willebrand disease has a negative impact on joint function, participation and quality-of-life. Risk factors are a low FVIII level and a history of more than five joint bleeds. Arthropathy in Von Willebrand disease can be measured using the Haemophilia Joint Health Score and the joint X-ray Pettersson score. The value of magnetic resonance imaging or ultrasound to detect early arthropathy in Von Willebrand disease remains to be determined. The Haemophilia Activities List questionnaire is feasible to quantify functional abilities in Von Willebrand disease. The most important measure to prevent arthropathy is to prevent joint bleeding. Clotting factor prophylaxis has proven very effective to do so. Since there is no general consensus to guide the use of prophylaxis in Von Willebrand disease, the decision on when and how to start prophylaxis is based on individual patient’s assessments by a haemophilia treatment centre. Future studies in Von Willebrand disease arthropathy could address the optimal timing and schedule of prophylaxis, optimal treatment of an acute joint bleed to prevent arthropathy, effectiveness of rehabilitation programs, orthopaedic surgery and the clinical use of measurement instruments. Prospective joint assessments and registration of joint bleeds in future population studies on severe Von Willebrand disease will be a good starting point.
(BELG J HEMATOL 2017;8(7):253–8)
Read moreBJH - volume 8, issue 6, october 2017
R. Willemze MD
Primary cutaneous B-cell lymphomas are a heterogeneous group of B-cell lymphomas that present in the skin without evidence of extracutaneous disease at the time of diagnosis. In recent classifications three main types of cutaneous B-cell lymphomas are recognised: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma and primary cutaneous large B-cell lymphoma, leg type. In this review, the main characteristics and practice guidelines for the management and treatment of these three types of cutaneous B-cell lymphomas are presented. Other types of B-cell lymphomas that can present with skin-limited disease, such as intravascular large B-cell lymphoma, B-lymphoblastic lymphoma and immunodeficiency-associated B-cell proliferations will shortly be discussed.
(BELG J HEMATOL 2017;8(6):213–21)
Read moreBJH - volume 8, issue 5, september 2017
F. Ghazavi PhD, T. Lammens PhD, P. Van Vlierberghe PhD, B. De Moerloose MD, PhD
Acute lymphoblastic leukaemia, a clinically and biologically heterogeneous disease, represents the most common malignant disease in childhood. Approximately 20–25% of B-cell precursor acute lymphoblastic leukaemia in childhood carry the cryptic chromosomal translocation t(12;21)(p13;q22). This translocation combines two transcription factors and essential regulators of normal haematopoiesis, ETV6 and RUNX1, into the fusion oncogene ETV6/RUNX1 (formerly known as TEL/AML1). Recent studies in various animal models have strengthened the view that ETV6/RUNX1-positive cells give rise to pre-leukemic clones with a differentiation block in the pro/pre-B stage of B-cell development that, after acquisition of additional mutations, may transform into full malignancy. Despite the favourable prognostic parameters of this B-cell precursor acute lymphoblastic leukaemia subgroup, relapse and resistance to chemotherapeutics do occur and increased knowledge of the molecular mechanisms underlying ETV6/RUNX1-driven leukaemia is essential to develop novel therapeutic strategies to selectively target ETV6/RUNX1-positive leukaemia. In this manuscript, an overview of the most recent genetic insights in ETV6/RUNX1-positive B-cell precursor acute lymphoblastic leukaemia is given.
(BELG J HEMATOL 2017;8(5):179–84)
Read moreBJH - volume 8, issue 5, september 2017
D. Selleslag MD
Allogeneic stem cell transplantation can cure about 40% of patients with chronic lymphocytic leukaemia. The early transplant related mortality with reduced intensity conditioning is low, but the late non relapse mortality is around 20% due to the high incidence of chronic graft versus host disease. The graft versus leukaemia effect is crucial for cure of chronic lymphocytic leukaemia after allogeneic stem cell transplantation and can be obtained by immune interventions. The place of allogeneic stem cell transplantation needs to be redefined in the era of novel targeted treatments (BCR pathway inhibitors and BCL2 inhibitors). Taking into consideration the promising results of BCR pathway inhibitors in genetically high-risk chronic lymphocytic leukaemia (with 17p deletion/TP53 mutation or complex karyotype) and fludarabine resistant chronic lymphocytic leukaemia, the current recommendation is to proceed with allogeneic stem cell transplantation in chronic lymphocytic leukaemia patients failing a BCR pathway inhibitor. The question when to proceed with allogeneic stem cell transplantation in responding patients remains unanswered. In the absence of randomised or prospective observational studies comparing novel agents to allogeneic stem cell transplantation the decision should be individualised and depend on the estimated transplantation risks and the patient’s desires.
(BELG J HEMATOL 2017;8(5):185–91)
Read moreBJH - volume 8, issue 3, june 2017
T. Kerre MD, PhD
CAR T-cells have revolutionised the treatment of relapsed and refractory B-cell malignancies. Especially in B-ALL, exciting results have been published. This article reviews CAR T-cell design, the optimal T-cell product used, the lymphodepleting regimen preceding the adoptive therapy, successes and toxicities induced by CAR T-cells in clinical trials (especially B cell malignancies), and the future of CARs and their position in the quickly evolving field of targeted therapies and immunotherapy for haematological malignancies.
(BELG J HEMATOL 2017;8(3):94–101)
Read moreBJH - volume 8, issue 2, march 2017
H. Haguet , J. Douxfils PhD, PharmD, F. Mullier PhD, PharmD, C. Chatelain MD, C. Graux MD, PhD, J-M. Dogné PhD, PharmD
Tyrosine kinase inhibitors targeting BCR-ABL have been a real revolution in the treatment of chronic myeloid leukaemia, greatly improving surrogate outcomes and overall survival. However, new generation BCR-ABL tyrosine kinase inhibitors have recently been associated with occurrence of cardiovascular events. Indeed, during ponatinib clinical development, a high rate of patients with chronic myeloid leukaemia developed a vascular occlusive event. Retrospective analyses also demonstrated an increased incidence of similar events with nilotinib. Recently, a meta-analysis of randomised clinical trials confirmed this risk with nilotinib and ponatinib, but also identified dasatinib at higher risk of cardiovascular events than imatinib. Sub-analysis of this meta-analysis and retrospective studies indicated predominance of arterial events rather than venous. The number of patients treated with dasatinib and nilotinib has considerably increased since they have been approved in first-line indication for patients with chronic-phase chronic myeloid leukaemia. In this context, the evaluation of the benefit-risk profile of these treatments is important, and implementation of measures to minimise the onset of cardiovascular events are required. They should include the selection of patients treated with new generation tyrosine kinase inhibitors, the monitoring of cardiovascular events and risk factors during treatment, and if required, the treatment of cardiovascular comorbidities. The pathophysiology of these events is probably multifactorial. Numerous hypotheses have already been advanced and suggest a worsening of the metabolic syndrome, an increase of atherosclerosis development and an impact of new generation tyrosine kinase inhibitors on off-targets related to vascular function.
(BELG J HEMATOL 2017;8(2):45–52)
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