BJH - volume 8, issue 5, september 2017
D. Selleslag MD
Allogeneic stem cell transplantation can cure about 40% of patients with chronic lymphocytic leukaemia. The early transplant related mortality with reduced intensity conditioning is low, but the late non relapse mortality is around 20% due to the high incidence of chronic graft versus host disease. The graft versus leukaemia effect is crucial for cure of chronic lymphocytic leukaemia after allogeneic stem cell transplantation and can be obtained by immune interventions. The place of allogeneic stem cell transplantation needs to be redefined in the era of novel targeted treatments (BCR pathway inhibitors and BCL2 inhibitors). Taking into consideration the promising results of BCR pathway inhibitors in genetically high-risk chronic lymphocytic leukaemia (with 17p deletion/TP53 mutation or complex karyotype) and fludarabine resistant chronic lymphocytic leukaemia, the current recommendation is to proceed with allogeneic stem cell transplantation in chronic lymphocytic leukaemia patients failing a BCR pathway inhibitor. The question when to proceed with allogeneic stem cell transplantation in responding patients remains unanswered. In the absence of randomised or prospective observational studies comparing novel agents to allogeneic stem cell transplantation the decision should be individualised and depend on the estimated transplantation risks and the patient’s desires.
(BELG J HEMATOL 2017;8(5):185–91)
Read moreBJH - volume 8, issue 3, june 2017
T. Kerre MD, PhD
CAR T-cells have revolutionised the treatment of relapsed and refractory B-cell malignancies. Especially in B-ALL, exciting results have been published. This article reviews CAR T-cell design, the optimal T-cell product used, the lymphodepleting regimen preceding the adoptive therapy, successes and toxicities induced by CAR T-cells in clinical trials (especially B cell malignancies), and the future of CARs and their position in the quickly evolving field of targeted therapies and immunotherapy for haematological malignancies.
(BELG J HEMATOL 2017;8(3):94–101)
Read moreBJH - 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
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, 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)
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