REVIEW HEMATOLOGY

Retrospective analysis of the incidence and characteristics of paediatric myelodysplastic syndrome and juvenile myelomonocytic leukaemia in Belgium

BJH - volume 11, issue 6, october 2020

A. Ferster MD, PhD, A. Van Damme MD, PhD, B. De Moerloose MD, PhD, C. Chantrain , J. Philippé MD, PhD, J. van der Werff ten Bosch MD, PhD, J. Verlooy MD, L. De Smaele , M. Hofmans MD, N. Van Roy PhD, P. De Paepe MD, PhD, T. Lammens PhD, V. Labarque MD, PhD

SUMMARY

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)

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The biochemistry of platelet function regulation

BJH - volume 11, issue 6, october 2020

C. Tersteeg PhD, H. Deckmyn PhD

SUMMARY

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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Leukaemic stem cells in AML: where are we now? An update on recent findings and detection

BJH - volume 11, issue 6, october 2020

B. De Moerloose MD, PhD, B. Depreter PhD, PharmD, J. Philippé MD, PhD, T. Lammens PhD

SUMMARY

Ample evidence was provided these past decades that leukaemic stem cells (LSC) play a role in the outcome of adult and paediatric acute myeloid leukaemia (AML) patients. Although it is generally accepted that the CD34+/ CD38- compartment is most LSC-enriched, novel data have emerged illustrating a distinct biology between CD34+ and CD34- AML. In this review, we discuss the main LSC phenotypes in CD34+ and CD34- AML , as they are of utmost importance for the development of broadly applicable LSC-targeted strategies. The leukaemia-initiating capacity of these cells upon xenografting is still considered to be the gold standard for LSC detection. However, more feasible techniques have been researched to allow the implementation of LSC measurements into clinical practice. Here, we summarise the current state-of-the-art methodologies using flow cytometry and molecular detection, and emphasise their relevance in terms of prognosis and targeted drug therapy.

(BELG J HEMATOL 2020;11(6):246-52)

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Clinical implications of measurable residual disease in patients with AML

BJH - volume 11, issue 4, june 2020

J. Versluis MD, PhD, J.J. Cornelissen MD, PhD

SUMMARY

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)

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The genetic landscape of diffuse large B-cell lymphoma

BJH - volume 11, issue 4, june 2020

B. Ylstra PhD, D. de Jong MD, PhD, M.E.D. Chamuleau MD, PhD, M.G.M. Roemer PhD

SUMMARY

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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Acute graft-versus-host disease: diagnosis, pathophysiology and prevention

BJH - volume 11, issue 4, june 2020

B. Vandenhove PhD student, C. Graux MD, PhD, E. Willems MD, PhD, F. Baron MD, PhD, H. Schoemans MD, PhD, L. Canti PhD student, S. Servais MD, PhD, T. Kerre MD, PhD, Y. Beguin MD, PhD

SUMMARY

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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Big Children or Small Adults? Leukaemia Treatment in Adolescence and Young Adulthood

BJH - volume 11, issue 3, may 2020

B. De Moerloose MD, PhD, I. Moors MD, J. De Munter , M. Quaghebeur , R. Callens MD, T. Kerre MD, PhD

SUMMARY

The outcome of adolescents and young adults (AYAs) with acute lymphoblastic leukaemia (ALL) has improved dramatically over the last decades by using paediatric and paediatric-inspired protocols in this age group. The outcome of different paediatric, paediatric-inspired and adult-based regimens are compared in this review. Despite pre-existing fear among clinicians to use these high-intensity paediatric regimens in AYAs, toxicities seem manageable, with treatment-related mortality comparable to that seen with adult protocols. In paediatric protocols, the use of allogeneic stem cell transplantation is restricted to certain high-risk groups and prophylactic cranial irradiation is omitted. In recent years, evaluation of minimal residual disease is increasingly used as prognostic marker and as a tool to guide therapy. In Philadelphia-positive ALL, the use of tyrosine-kinase inhibitors has completely changed prognosis and therapeutic decisions.

(BELG J HEMATOL 2020;11(3):88–97)

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