BJH - volume 8, issue 2, march 2017
H. Haguet , J. Douxfils PhD, PharmD, F. Mullier PhD, PharmD, C. Chatelain MD, C. Graux MD, PhD, J-M. Dogné PhD, PharmD
Tyrosine kinase inhibitors targeting BCR-ABL have been a real revolution in the treatment of chronic myeloid leukaemia, greatly improving surrogate outcomes and overall survival. However, new generation BCR-ABL tyrosine kinase inhibitors have recently been associated with occurrence of cardiovascular events. Indeed, during ponatinib clinical development, a high rate of patients with chronic myeloid leukaemia developed a vascular occlusive event. Retrospective analyses also demonstrated an increased incidence of similar events with nilotinib. Recently, a meta-analysis of randomised clinical trials confirmed this risk with nilotinib and ponatinib, but also identified dasatinib at higher risk of cardiovascular events than imatinib. Sub-analysis of this meta-analysis and retrospective studies indicated predominance of arterial events rather than venous. The number of patients treated with dasatinib and nilotinib has considerably increased since they have been approved in first-line indication for patients with chronic-phase chronic myeloid leukaemia. In this context, the evaluation of the benefit-risk profile of these treatments is important, and implementation of measures to minimise the onset of cardiovascular events are required. They should include the selection of patients treated with new generation tyrosine kinase inhibitors, the monitoring of cardiovascular events and risk factors during treatment, and if required, the treatment of cardiovascular comorbidities. The pathophysiology of these events is probably multifactorial. Numerous hypotheses have already been advanced and suggest a worsening of the metabolic syndrome, an increase of atherosclerosis development and an impact of new generation tyrosine kinase inhibitors on off-targets related to vascular function.
(BELG J HEMATOL 2017;8(2):45–52)
Read moreBJH - volume 7, issue 6, december 2016
M. Beckers MD, PhD, D. Dierickx MD, PhD, T. Devos MD, PhD, S. Fevery MD, PhD, B. Sprangers MD, PhD
One of the hallmarks of failure of elimination of malignant cells by activated T-cells is the immunosuppressive environment of the tumour. Myeloid-derived suppressor cells contribute to this immunosuppressive environment by inhibition of the adaptive and innate immune system. In this article we describe the current knowledge of the role of myeloid-derived suppressor cells in the progression of haematological malignancies.
(BELG J HEMATOL 2016;7(6):213–6)
Read moreBJH - volume 7, issue 5, october 2016
S. Dubruille PhD, Y. Libert PhD, D. Razavi MD, PhD, D. Bron MD, PhD
A Comprehensive Geriatric Assessment is recommended to detect vulnerable cancer patients for whom chemotherapy may lead to severe impairment on functionality, quality of life, or survival. Although Comprehensive Geriatric Assessment is useful for better management of older patients with unsuspected problems, little is known about the reliability of the Comprehensive Geriatric Assessment to optimise the therapeutic approach in a specific patient with a malignant haemopathy. Particularly, the prognostic value of cognitive impairment in clinically fit older patients with haematological malignancies admitted to receive chemotherapy, are poorly investigated. This article investigated this question and tries to explain links between cognitive impairment and poor overall survival. Finally, this article tries to propose supportive interventions to reduce morbidity and mortality in older cancer patients with cognitive impairment.
(BELG J HEMATOL 2016;7(5):180–3)
Read moreBJH - volume 7, issue 3, june 2016
B. Maes MD, PhD, F. Nollet PhD, MSc
For most haematological disease entities whole genome and/or exome sequencing efforts identified a core set of recurrently mutated genes. Multiplex DNA mutation screening proves to be highly applicable for myeloid malignancies, since mutations in many genes, e.g. FLT3, NPM1, CEBPA, KIT, DNMT3A, IDH1, IDH2, TET2, ASXL1, RUNX1, SF3B1, SRSF2, U2AF1, ZRSR2, TP53, STAG2, SMC1A, SMC3, RAD21, PHF6, RAS, EZH2, ETV6, JAK2, MPL, CALR, SETBP1, CSF3R, are described to be significantly associated with diagnosis, disease subtyping, prognostication, and/or for tailoring therapy. Obviously, their analysis is no longer feasible using conventional, single gene molecular diagnostic techniques, urging the use of a multi-gene ‘pan-myeloid’ Next Generation Sequencing panel.
(BELG J HEMATOL 2016; 7(3):98–102)
Read moreBJH - volume 7, issue 2, april 2016
F. Nollet PhD, MSc, B. Maes MD, PhD
In the past few years the cost of next generation sequencing decreased substantially and the technology has significantly matured, allowing for its introduction into clinical practice. For most haematological disease entities whole genome and/or exome sequencing efforts identified a core set of recurrently mutated genes. Several of these genes are expected to be included in the upcoming revision of the 2008 edition of the World Health Organisation classification of haematological malignancies. Next generation sequencing technology allows transforming current single gene mutation analysis into multiplexed mutational profiling. Next generation ‘deep’ sequencing is a promising new tool to monitor minimal disease burden and to detect mutations within malignant subclones. With current platforms point mutations can be detected with a sensitivity of 1–5% mutant DNA. For indel mutations or clonal IG/TCR rearrangements sensitivity in the range of 10−5 can be reached. In this review we will highlight the opportunities and challenges of the introduction of next generation sequencing technology into a setting where it will contribute significantly to individual patient cancer management.
(BELG J HEMATOL 2016;7(2):63–8)
Read moreBJH - volume 6, issue 5, december 2015
D.A. Breems MD, PhD, B. Löwenberg MD, PhD
Relapse is the most prevalent cause of treatment failure and death in patients with acute myeloid leukaemia. Because only a minority of patients who experience relapse will derive durable benefit from current reinduction and salvage therapy, prognostic factors and predictive models have been developed. Achievement of a second complete remission and the application of salvage allogeneic stem cell transplantation represent crucial objectives for reaching long-term disease-free survival and improving the prognosis of patients with acute myeloid leukaemia in first relapse. Combination chemotherapy schedules that include high-dose cytarabine are frequently used in therapeutic efforts of attaining a second complete remission. In relapsed acute myeloid leukaemia with poor risk genetic features or those with early relapse after previous exposure to high-dose cytarabine, investigational drugs may be the preferred choice. The search for improved treatment with novel agents in clinical trials represents an active area of research.
(BELG J HEMATOL 2015;6(5):182–7)
Read moreBJH - volume 6, issue 4, october 2015
O. Ketelslegers MD, F. Eyskens MD, PhD, F. Boemer PhD, V. Bours MD, PhD, J-M. Minon MD, PhD, B. Gulbis MD, PhD
Although neonatal screening for sickle cell disease is one of the best tools for reducing mortality during infancy and early childhood, it is not part of the approved neonatal screening programme in Belgium. As epidemiological data on sickle cell disease are still incomplete in Belgium, we planned to screen the samples of newborns available in the biggest reference centre for approved neonatal screening in Flanders. From July to December 2013, a total of 18,989 newborns from 36 Flemish maternity wards were systematically screened, representing about 60% of the total number of births in Flanders. For the same period, results of the neonatal screening that is routinely performed for sickle cell disease in three other Belgian centres were collected. Overall, 39,599 newborns were screened, representing about two-thirds of Belgian births for this period. With an incidence of sickle cell disease and sickle cell trait of 1/2,329 and 1/77, respectively, sickle cell disease is the most frequently inherited disease observed in the population tested; the highest incidences were registered in urban areas. In addition, screening techniques identified 122 other clinically significant haemoglobin (Hb) variant carriers (83 for HbC, twenty for HbE, thirteen for HbD-Punjab, and six for HbO-Arab) and two HbC diseases. Carriers of clinically significant Hb variants were observed in almost all the maternity wards included in the study, showing a wide dispersal of populations at risk. These epidemiological data remind us of the warnings and recommendations from the World Health Organization, urging policy-makers to consider the most appropriate strategy to prevent and treat patients with sickle cell disease in Belgium.
(BELG J HEMATOL 2015;6(4): 135–41)
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