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)

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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)

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Effectiveness of a recombinant coagulation Factor IX–albumin fusion protein, rIX-FP, in haemophilia B patients: Results of a non-interventional study in Belgium

BJH - volume 12, issue 5, september 2021

C. Hermans MD, PhD, K. Peerlinck MD, PhD, A. Gadisseur MD, PhD, P. Quoc MD, V. Mondelaers MD, P. Maes MD, C. Van Geet MD, PhD

SUMMARY

The aim of this non-interventional, observational study conducted in haemophilia B patients in Belgium was to collect real-world data to confirm the efficacy and safety of rIX-FP established in pivotal clinical trials.

(BELG J HEMATOL 2021;12(5):203-6)

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PEG-asparaginase in the treatment of childhood acute lymphoblastic leukaemia

BJH - volume 4, issue 4, december 2013

V. Mondelaers MD, T. Bauters PharmD, PhD, B. De Moerloose MD, PhD, Y Benoit MD, PhD

Summary

Asparaginase is an essential compound of combination chemotherapy in acute lymphoblastic leukaemia in children and adults. Essentially, three preparations of asparaginase are used in childhood acute lymphoblastic leukaemia: native Escherichia coli asparaginase, Erwinia chrysanthemi asparaginase and PEG-asparaginase. Although PEG-asparaginase seems to have some advantages over the other asparaginase preparations, its clinical use in Europe is limited to second-line therapy after allergic reactions to native asparaginase. This is in contrast to the United States, where PEG-asparaginase has been approved as first-line treatment of children with acute lymphoblastic leukaemia. This report describes the properties, clinical benefits and side effects of PEG-asparaginase.

(BELG J HEMATOL 2013;4(4): 138–143)

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Cost-minimisation analysis of PEG-L-Asparaginase versus native L-Asparaginase for the treatment of children with acute lymphoblastic leukaemia in Belgium

BJH - volume 4, issue 4, december 2013

T. Bauters PharmD, PhD, V. Mondelaers MD, B. De Moerloose MD, PhD, H. Robays PharmD, Y Benoit MD, PhD

Summary

PEG-L-Asparaginase (Oncaspar®) is a major compound of antineoplastic combination therapy for reinduction in acute lymphoblastic leukaemia in children and adults with known hypersensitivity. In the United States, it has been approved for many years as first-line treatment of children with acute lymphoblastic leukaemia. Its clinical benefits have been extensively described. In this report, a cost-minimisation analysis comparing the direct cost of PEG-L-asparaginase with that of native E. coli and Erwinia L-asparaginase treatment is described.

(BELG J HEMATOL 2013; 4(4): 144–147)

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Musculoskeletal manifestations in children with acute lymphoblastic leukaemia

BJH - volume 3, issue 1, march 2012

H. Mulder , N. Herregods , V. Mondelaers MD, Y Benoit MD, PhD, B. De Moerloose MD, PhD

Summary

Acute lymphoblastic leukaemia (ALL) is the most common kind of childhood malignancy. Although the vast majority of patients are presented with medullary signs and symptoms such as an abnormal blood count, about one third will initially be presented with musculo-skeletal complaints (with or without radiological abnormalities) as the only apparent abnormality. These skeletal manifestations in ALL are not pathognomonic and may mimic several orthopaedic conditions, such as juvenile rheumatoid arthritis, osteomyelitis, septic arthritis and transient synovitis. This may therefore contribute to a delay in diagnosis, resulting in higher morbidity and mortality rates. However, musculoskeletal manifestations in leukaemia are usually associated with a precursor-B-ALL and have a good prognosis.

The purpose of this review is to highlight the diagnostic pitfalls in this type of ALL. ALL should always be considered as a differential diagnosis in any child with unexplained or persistent bone pain and a bone marrow examination is highly recommended when steroid therapy is being considered.

(BELG J HEMATOL 2012;3:3–11)

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