BJH - volume 11, issue 6, october 2020
C. Tersteeg PhD, H. Deckmyn PhD
Blood platelets are playing a key role in maintaining the integrity of the vascular system or haemostasis, however they can become detrimental when activated at sites of e.g. atherosclerosis, potentially leading to thrombosis or occlusion with devastating effects. To prevent this, a number of antiplatelet agents is currently used in the clinic. However, all antiplatelet agents are accompanied with an increased risk of bleeding, and hence the search for better and safer compounds is ongoing. In this effort, a good understanding of the biochemistry of platelet activation is of primordial importance. In the present review, we intend to bring together the current knowledge on platelet behaviour in thrombosis and haemostasis in a coherent manner by subdividing the entire process into different steps: platelet adhesion, activation, amplification, aggregation, shape change and clot retraction, as well as inhibition of platelet activation and aggregation.
(BELG J HEMATOL 2020;11(6):240-5)
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L. De Smaele , M. Hofmans MD, PhD, T. Lammens PhD, A. Van Damme MD, PhD, J. van der Werff ten Bosch MD, PhD, A. Ferster MD, PhD, J. Verlooy MD, C. Chantrain , J. Philippé MD, PhD, N. Van Roy PhD, P. De Paepe MD, PhD, V. Labarque MD, PhD, B. De Moerloose MD, PhD
Childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukaemia (JMML) are very rare clonal stem cell disorders of early childhood. Paediatric MDS can be further subdivided in refractory cytopenia of childhood (RCC) and high grade MDS, in case of excess blasts. Given their rarity, little is known about the epidemiology of these diseases in Belgium. The aim of this study is to investigate the incidence, characteristics, treatment and prognosis of paediatric MDS and JMML in Belgium. Prospectively collected data of 56 Belgian patients with MDS and JMML were enrolled in the study, of which 41 (73%) with MDS, eleven with JMML (20%) and four (7%) with Noonan syndrome associated myeloproliferative disorder. The incidence rates of MDS and JMML in Belgium were 1.5 and 0.4 per million children per year respectively, with a median age of diagnosis of 9.3 years for RCC, 9.5 years for high grade MDS and 2.6 years for JMML. Monosomy 7 was the most common cytogenetic abnormality and could particularly be found in high grade MDS (33%) and JMML (45%). RCC treatment consisted of immunosuppressive therapy (IST) and haematopoietic stem cell transplantation (HSCT), but in high grade MDS and JMML only HSCT was a valid treatment option. Overall survival was significantly lower in high grade MDS (45.0%) compared to JMML (79.5%) and RCC (80.6%) (log-rank p-value = 0.038), whereas event-free survival (EFS) was comparably low in high grade MDS and JMML (46.7% and 58.4% respectively) due to a high cumulative incidence of relapse (CIR) of 33% and 29.9%, respectively. Outcome was best for RCC patients with highest EFS (76.3%; 57.1% if IST failure was considered as event) and lowest CIR (9.3%). This study highlights that paediatric MDS and JMML are very rare disorders with associated morbidity and mortality, especially in high grade MDS and JMML. Considering the high relapse risk in high grade MDS and JMML, new therapeutic options are required.
(BELG J HEMATOL 2020;11(6):233-9)
Read moreBJH - volume 11, issue 4, june 2020
B. Vandenhove PhD student, L. Canti PhD student, H. Schoemans MD, PhD, Y. Beguin MD, PhD, prof. F. Baron , E. Willems MD, PhD, C. Graux MD, PhD, T. Kerre MD, PhD, S. Servais MD, PhD
Acute graft-versus-host disease (aGVHD) remains a severe complication after allogeneic stem cell transplantation (alloHCT). It is a disregulated immune process, during which the immune cells of the donor attack the healthy tissues in the immunocompromised host. Over the past two decades, progress in understanding its pathophysiology have helped redefine aGVHD reactions and clinical presentations. Typically, the disease presents with serious inflammatory lesions mainly in the skin, gut and liver. Its severity is assessed by gathering clinical signs and dysfunctions of each organ. Despite standard prophylaxis regimens, aGVHD still occurs in approximately 30–60% of transplanted patients and remains a major cause of transplant-related morbidity and mortality. Hence, there is an urgent need for optimising preventive strategies. In this review, we give insights on how to make an accurate diagnosis and scoring assessment of aGVHD, propose a short overview of the current knowledge about its immunobiology and discuss the current and developing strategies for prevention.
(BELG J HEMATOL 2020;11(4):159–173)
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M.G.M. Roemer PhD, B. Ylstra PhD, D. de Jong MD, PhD, M.E.D. Chamuleau MD, PhD
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. The addition of rituximab to the chemotherapy regimen (R-CHOP) has resulted in a significant improvement in survival of DLBCL patients. However, 30–40% of patients still have refractory disease or develop a recurrence. The effectiveness of treatment is limited by the considerable morphological, immunophenotypic, genetic and clinical heterogeneity of DLBCLs. Since 2000, increasing knowledge about the genetic landscape of DLBCL has led to the identification of various genetic prognostic factors, which are associated with poor prognosis following standard R-CHOP treatment, such as ABC genotype and MYC translocation. However, more recent large genomic studies have shown that the genetic landscape of DLBCL is far more complex than this. In this article, these new insights and the first results of prospective clinical studies based on genetic subtypes directed treatment choice will be discussed. This article aims to provide a basis for discussions on future implementation of the knowledge on the genetic complexity of DLBCL in next generation treatment.
(BELG J HEMATOL 2020;11(4):153–8)
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J. Versluis MD, PhD, J.J. Cornelissen MD, PhD
The majority of patients with acute myeloid leukaemia (AML) obtain a first complete remission (CR) with intensive induction chemotherapy. Despite post-remission treatment with allogeneic hematopoietic stem cell transplantation (alloSCT), the incidence of relapse remains considerable and depends on the risk of the AML. In addition, the assessment of the quality of CR with measurable residual disease (MRD) has become pivotal in the prognostication of AML patients. MRD may be detected with multiparametric flow cytometry and/or molecular methods including qPCR for specific mutations or next-generation sequencing. Patients with MRD have a high risk of short-term AML recurrence and may benefit from personalised application of post-remission treatment with alloSCT. The graft-versus-leukaemia effect of alloSCT appears to be virtually similar in both MRD positive and MRD negative patients suggesting that alloSCT could be applied not only based on the risk of the disease and quality of remission, but also on the risk of the treatment. Such a risk-adapted approach is recommended for the clinical assessment of all AML patients and should include AML risk, MRD status, and the risk for non-relapse mortality, preferably addressed by dedicated risk scores.
(BELG J HEMATOL 2020;11(4):147–52)
Read moreBJH - volume 11, issue 3, may 2020
L.C. Holthof MSc, T. Mutis MD, PhD
Over the past decades, immunotherapy has significantly improved the overall survival of multiple myeloma (MM) patients. In addition to immunomodulatory drugs and targeted antibodies that are currently standard of care, novel promising immunotherapeutic approaches, such as bispecific antibodies and chimeric antigen receptor-transduced T-cells (CAR T-cells) are being increasingly tested in clinical trials. Nonetheless, similar to what has been seen in chemotherapy, MM is also capable of developing resistance against immunotherapy. Direct and indirect interactions between MM and the MM bone marrow microenvironment (BM-ME) enable MM-cells to escape not only from chemotherapy but also from immunotherapy. This review will discuss how BM-ME enables MM-cells to evade the immune system and immunotherapy via immunosuppression and via induction of genuine resistance against cytotoxic mechanisms of immune killer cells.
(BELG J HEMATOL 2020;11(3):102–7)
Read moreBJH - volume 11, issue 3, may 2020
K. Maes MD, B. De Moerloose MD, PhD, M. Quaghebeur , J. De Munter , T. Kerre MD, PhD, I. Moors MD
Adolescents and young adults (AYAs), aged 15 to 39 years, with newly diagnosed acute myeloid leukaemia (AML) differ from both younger and older patients in terms of patient-specific as well as disease-specific factors. The improvement in outcome over time for this group is noticeably less than for their younger and older counterparts. Reasons for this are thought to be lack of standardisation of therapy, being treated with either adult or paediatric regimens, low trial participation and specific psychosocial factors. In this article, we review the distinct characteristics of AYA AML in order to address this issue and conclude that an AYA-specific approach and research are warranted to overcome stagnating outcome results.
(BELG J HEMATOL 2020;11(3):98–101)
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