REVIEW HEMATOLOGY

The role of myeloid-derived suppressor cells in haematology: hype or reality?

BJH - 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

Summary

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)

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Onco-haematology geriatry: impact of cognitive disorders

BJH - volume 7, issue 5, october 2016

S. Dubruille PhD, Y. Libert PhD, D. Razavi MD, PhD, D. Bron MD, PhD

Summary

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)

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Targeted next generation sequencing in myeloid neoplasms

BJH - volume 7, issue 3, june 2016

B. Maes MD, PhD, F. Nollet PhD, MSc

Summary

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)

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Challenges and pitfalls of next generation sequencing in molecular haematology

BJH - volume 7, issue 2, april 2016

F. Nollet PhD, MSc, B. Maes MD, PhD

Summary

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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Acute myeloid leukaemia in first relapse

BJH - volume 6, issue 5, december 2015

D.A. Breems MD, PhD, B. Löwenberg MD, PhD

Summary

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)

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Epidemiological data on sickle cell disease in Belgium

BJH - 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

summary

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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Use of multiparameter flow cytometry in multiple myeloma and other plasma cell neoplasms

BJH - volume 6, issue 2, may 2015

M. Oyaert MSc, M. Delforge MD, PhD, N. Boeckx MD, PhD

Summary

Flow cytometric immunophenotyping is recommended for diagnosis, classification and monitoring of disease in monoclonal gammopathies. Furthermore, it is a useful diagnostic tool for clinical practice and has various applications, such as its ability to distinguish between normal, reactive and malignant plasma cells, to evaluate the risk of progression from monoclonal gammopathy of undetermined significance to plasma cell myeloma, to provide prognostic information, to evaluate the presence of minimal residual disease and to identify new therapeutic targets. The incorporation of novel therapies in the management of patients diagnosed with plasma cell neoplasms has increased depth and frequency of response, as well as prolonged progression free and overall survival. Along with these improvements in therapeutic strategies, definition of responses to treatment has evolved over time. It was therefore necessary to develop reproducible and sensitive assays for detection and monitoring of minimal residual disease and to define its prognostic value in predicting progression free and overall survival, to allow for consolidation and maintenance therapeutic strategies and to evaluate the efficacy of novel therapies.

(BELG J HEMATOL 2015;6(2):46–53)

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