BJH - volume 11, issue 6, october 2020
L. De Smaele , M. Hofmans MD, 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 more
BJH - volume 11, issue 6, october 2020
B. Depreter PhD, PharmD, B. De Moerloose MD, PhD, J. Philippé MD, PhD, T. Lammens PhD
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)Read more
BJH - volume 11, issue 3, may 2020
R. Callens MD, B. De Moerloose MD, PhD, T. Kerre MD, PhD, M. Quaghebeur , J. De Munter , I. Moors MD
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)Read more
BJH - 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)Read more
BJH - volume 11, issue 2, march 2020
M. Hofmans MD, T. Lammens PhD, B. De Moerloose MD, PhD
Juvenile myelomonocytic leukaemia is a heterogeneous disease caused by constitutional activation of the Ras signal transduction pathway. The clinical course of the disease is variable and non-specific. In the majority of patients prompt hematopoietic stem cell transplantation is necessary for long-term survival, whereas in a minority the disease will resolve without treatment. In more than 90% of the patients, mutations in one or more of the following genes can be found (somatic NRAS, KRAS and PTPN11, germline NF1 and CBL). However, these canonical mutations are insufficient to explain the phenotypic heterogeneity of this disease. More recently, secondary mutations, non-coding RNA expression, and genomic DNA methylation have led to a better understanding of the pathobiology of the disease, and shown to play a role in the classification and prognostication of this rare disease. In addition, this novel information has been crucial for novel drug development and introduction of novel patient-tailored therapies, which are currently being tested in vitro or in vivo in clinical trials.
(BELG J HEMATOL 2020;11(2):49–55)
BJH - volume 10, issue 7, november 2019
M. Verstraeten MD, C. Verbeke MD, B. De Moerloose MD, PhD
We describe a 7-month-old girl with severe neutropenia born to a mother treated for ulcerative colitis with infliximab until the 24th week of pregnancy. Despite the recommendation of using Tumour Necrosis Factor inhibitors (TNFi) only in the first and second trimester of pregnancy, significant levels of TNFi in offspring are possible. Hence, drug-induced neutropenia should be considered in the differential diagnosis of infants with severe neutropenia if these were exposed to TNFi in utero. Moreover, additional information is given on the risk of infection and dysfunctional immune development in these new-borns.
(BELG J HEMATOL 2019;10(7):285–9)Read more
BJH - volume 9, issue 2, march 2018
B. De Moerloose MD, PhD, E. Nauwynck MD, K. Arts MD, L. Willems MD, PhD, V. Labarque MD, PhD, T. Lammens PhD, A. Uyttebroeck MD, PhD
Infant leukaemia is a rare disease but the 3rd most frequent malignancy in this age group. Both acute lymphoblastic leukaemia and acute myeloid leukaemia in the first year of life have particular clinical and biological characteristics such as B-cell phenotype with co-expression of myeloid markers in acute lymphoblastic leukaemia, FAB M5 or M7 in acute myeloid leukaemia, the presence of extramedullary symptoms and a high frequency of KMT2A rearrangements. Survival rates for infant acute leukaemia are worse than for older children. In this study, the characteristics and outcome of 50 infants with acute lymphoblastic leukaemia and acute myeloid leukaemia treated at the University Hospitals of Ghent and Leuven between 1989 and 2015 were studied and correlated with literature data. With event-free survival and overall survival rates of 44% and 52% for the entire cohort, the outcome of these patients was comparable to those in published clinical trials. In general, the event-free survival and overall survival was superior in acute myeloid leukaemia compared to acute lymphoblastic leukaemia infants and not influenced by age (< or ≥6 months), white blood cell count at diagnosis or presence of a KMT2A rearrangement. For future trials in infant leukaemia, the high number of early deaths, toxic deaths and relapses remain the most challenging problems.
(BELG J HEMATOL 2018;9(2):57–63.)Read more