V. Labarque MD, PhD

Sickle cell disease: A neglected haemoglobinopathy disorder with a huge global burden

SUMMARY

There are more than 1000 genetically determined variants of haemoglobin (Hb). Although most are harmless, some can have detrimental effect. Sickle cell disease (SCD) is the most common heritable genetic disease in the world, which affects not just the patients’ health, but also the psychological well-being of their loved ones. The SCD mutation occurs in the beta-globin gene of an adult Hb resulting in a sickle shaped Hb (HbS) which has a poor solubility and can easily polymerize during deoxygenation, leading to haemolysis and vaso-occlusion, the main hallmarks of the disease. These hallmarks are associated with both acute and chronic complications. Despite the advancement in the medical care of individuals with SCD, patients are experiencing substantial chronic dysfunctions, nevertheless several, especially genetic, modifying factors modulate patients’ outcome. This review explores the genetic basis, epidemiology, global burden, pathophysiology, complications, modifiers, and management of sickle cell disease.

(BELG J HEMATOL 2023;14(2):41–58)

New and emergent treatment options in sickle cell disease

SUMMARY

Sickle cell disease (SCD) is one of the most frequently inherited diseases but it no longer only affects children. More and more patients survive well into adulthood. They experience repeated acute complications and inevitably develop chronic organ damage. For years, hydroxyurea and chronic transfusions were the only disease-modifying options in the treatment of SCD patients. Thanks to a better understanding of the pathophysiology, new components have been and are now being tested. Three of these are already used in clinical practice, namely L-glutamine, crizanlizumab and voxelotor. On the other hand, progress has also been made in the field of haematopoietic stem cell transplantation, through the introduction of alternative donors as well as the use of less toxic conditioning regimens. Finally, hopeful results are being achieved in the first studies of gene therapy in patients with SCD but it has yet to be proven that genetically manipulated stem cells maintain the long-term repopulation potential.

(BELG J HEMATOL 2021;12(7):290–5)

Sickle cell disease for the adult hematologist

In recent years we have witnessed a growing interest in the treatment of patients with sickle cell disease (SCD). Advances in general medical care, early diagnosis and comprehensive treatment have led to substantial improvements in the life expectancy of individuals with SCD in high-income countries. During her lecture at the 2021 annual meeting of the BHS, Prof. Veerle Labarque gave an overview on the current treatment landscape for adult SCD patients.

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

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)

Highlights in red blood cell disorders

Summary

In the field of red blood cell disorders, ASH 2019 mainly focused on sickle cell disease (SCD). Current disease-modifying therapeutic options for SCD consist of hydroxyurea and chronic transfusions but none of them can fully prevent complications and both have their drawbacks. A haematopoietic stem cell transplantation is the only curative option to date. Yet, frequently a compatible donor is missing. ASH 2019 featured several abstracts on optimising disease-modifying therapies as well as curative options, such as gene therapy. A selection of abstracts is discussed below.

(BELG J HEMATOL 2020;11(1):21–6)

BHS clinical guidelines on the management of acute complications in sickle cell disease

With the increasing prevalence of sickle cell disease patients in Western countries, it is of importance to improve awareness among medical doctors of its complications. To reduce long-term morbidity and mortality, the prompt recognition and treatment of acute complications is important. The existing clinical guideline ‘Follow-up and treatment of patients with sickle cell disease hospitalised for Vaso Occlusive Crisis or infection’, published in 2012 by the Belgian Haematological Society, was revisited to better suit the practical needs of first-line practitioners.

(BELG J HEMATOL 2019;10(4):165–8)

O09 VISUALIZING DENSE GRANULE FORMATION IN MEGAKARYOCYTES USING ADVANCED MICROSCOPY AND ITS APPLICATION FOR HERMANSKY-PUDLAK SYNDROME