Articles

Practice guidelines for the therapeutic drug monitoring of asparaginase in acute lymphoblastic leukaemia

BJH - volume 13, issue 6, october 2022

V. Mondelaers MD, T. Lammens PhD, M. de Jong , L. Deneweth , K. Vandemeulebroecke , B. De Moerloose MD, PhD

SUMMARY

Asparaginase is an essential therapeutic in the treatment of acute lymphoblastic leukaemia (ALL) in children and adults. Currently, there are three asparaginase products in clinical use: native Escherichia coli asparaginase, Erwinia chrysanthemi asparaginase and PEG-asparaginase. One of the important side effects is the occurrence of hypersensitivity reactions, such as clinical allergy or silent inactivation that can lead to inactivation of asparaginase with a negative impact on the outcome of the patient. Therapeutic drug monitoring (TDM) has proven to be a valuable tool to monitor asparaginase activity and detect decreased or absent activity at an early stage. Therefore, many contemporary paediatric ALL protocols include TDM of asparaginase as standard of care. In this report, the background of asparaginase hypersensitivity and silent inactivation is described and a practical flowchart regarding the use and TDM of PEG- and Erwinia asparaginase for patients with ALL is introduced.

(BELG J HEMATOL 2022;13(6):236–42)

Read more

Myeloid lineage switching as escape mechanism to chimeric antigen receptor T-cell therapy in precursor B-ALL with ZNF384-TCF3 fusion: A case report

BJH - volume 13, issue 3, may 2022

C. De Crem MD, M. Hofmans MD, PhD, M. de Ville de Goyet MD, PhD, V. Mondelaers MD, B. Brichard MD, PhD, B. De Moerloose MD, PhD

SUMMARY

Acute leukaemia with ZNF384-TCF3 fusion is considered high risk in contemporary frontline treatment protocols and will be treated by Hematopoietic Stem Cell Transplantation (HSCT) or Chimeric Antigen Receptor T-cell (CART) treatment in first complete remission. Although current cytogenetic and molecular work-up of newly diagnosed paediatric acute lymphoblastic leukaemia (ALL) includes the identification of the TCF3-ZNF384 fusion, this case underscores the importance of including this information in the choice of bridging therapy and the timing of CART treatment, as the high cytokine levels during high grade Cytokine Release Syndrome (CRS) might drive ALL cells to lineage switching.

(BELG J HEMATOL 2022;13(3):128–32)

Read more

Current developments and hurdles in CAR-T cell therapy for acute myeloid leukaemia

BJH - volume 12, issue 6, october 2021

L. Van Camp MD, T. Lammens PhD, A. Uyttebroeck MD, PhD, B. De Moerloose MD, PhD

SUMMARY

Despite huge progress in the past decades, the overall survival (OS) of patients with acute myeloid leukaemia (AML) remains poor. The treatment options run low for those refractory or intolerant to first and second line treatment or in case of relapse. The need for alternative treatment is great and imperative to further improve the OS of these patients. The success of CAR-T19 therapy for the treatment of B cell acute lymphoblastic leukaemia has demonstrated the feasibility of delivering these therapies, and success in further improving survival rates. Among others, the fundamental biological factor limiting the applicability of CAR-T immuno-therapy in the treatment of AML includes the lack of a leukaemia-specific antigen, or an antigen shared by leukaemia blasts and haematopoietic stem and progenitor cells whose sustained depletion could be clinically tolerated. In this review, we describe the most recent developments, clinical results and challenges in CAR-T cell therapy for AML.

(BELG J HEMATOL 2021;12(6):244-50)

Read more

Novel therapeutic targets in juvenile myelomonocytic leukaemia: Are noncoding RNAs valuable treatment options?

BJH - volume 12, issue 4, june 2021

M. Hofmans MD, PhD, T. Lammens PhD, J. Philippé MD, PhD, B. De Moerloose MD, PhD

SUMMARY

Juvenile myelomonocytic leukaemia is a rare and aggressive clonal disease of early childhood for which hematopoietic stem cell transplantation remains the only curative option, albeit with a high relapse rate and many associated toxicities. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have recently been implicated in a variety of biological processes, including haematopoiesis and receive much research attention as they possess features interesting for treatment, such as tissue specificity, low overall expression and easy targetability with RNAi or gene editing technology. Within this dissertation, we aimed at deciphering the lncRNA and circRNA transcriptome of JMML and use this knowledge to develop novel treatments.

(BELG J HEMATOL 2021;12(4):173-6)

Read more

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

BJH - volume 11, issue 6, october 2020

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

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)

Read more

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

BJH - volume 11, issue 6, october 2020

B. Depreter PhD, PharmD, B. De Moerloose MD, PhD, 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)

Read more

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

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

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)

Read more
X