BJH - volume 11, issue 6, october 2020
B. Depreter PhD, PharmD, B. De Moerloose MD, PhD, J. Philippé MD, PhD, T. Lammens PhD
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 moreBJH - volume 11, issue 4, june 2020
J. Versluis MD, PhD, J.J. Cornelissen MD, PhD
The majority of patients with acute myeloid leukaemia (AML) obtain a first complete remission (CR) with intensive induction chemotherapy. Despite post-remission treatment with allogeneic hematopoietic stem cell transplantation (alloSCT), the incidence of relapse remains considerable and depends on the risk of the AML. In addition, the assessment of the quality of CR with measurable residual disease (MRD) has become pivotal in the prognostication of AML patients. MRD may be detected with multiparametric flow cytometry and/or molecular methods including qPCR for specific mutations or next-generation sequencing. Patients with MRD have a high risk of short-term AML recurrence and may benefit from personalised application of post-remission treatment with alloSCT. The graft-versus-leukaemia effect of alloSCT appears to be virtually similar in both MRD positive and MRD negative patients suggesting that alloSCT could be applied not only based on the risk of the disease and quality of remission, but also on the risk of the treatment. Such a risk-adapted approach is recommended for the clinical assessment of all AML patients and should include AML risk, MRD status, and the risk for non-relapse mortality, preferably addressed by dedicated risk scores.
(BELG J HEMATOL 2020;11(4):147–52)
Read moreBJH - volume 11, issue 4, june 2020
M.G.M. Roemer PhD, B. Ylstra PhD, D. de Jong MD, PhD, M.E.D. Chamuleau MD, PhD
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. The addition of rituximab to the chemotherapy regimen (R-CHOP) has resulted in a significant improvement in survival of DLBCL patients. However, 30–40% of patients still have refractory disease or develop a recurrence. The effectiveness of treatment is limited by the considerable morphological, immunophenotypic, genetic and clinical heterogeneity of DLBCLs. Since 2000, increasing knowledge about the genetic landscape of DLBCL has led to the identification of various genetic prognostic factors, which are associated with poor prognosis following standard R-CHOP treatment, such as ABC genotype and MYC translocation. However, more recent large genomic studies have shown that the genetic landscape of DLBCL is far more complex than this. In this article, these new insights and the first results of prospective clinical studies based on genetic subtypes directed treatment choice will be discussed. This article aims to provide a basis for discussions on future implementation of the knowledge on the genetic complexity of DLBCL in next generation treatment.
(BELG J HEMATOL 2020;11(4):153–8)
Read moreBJH - volume 11, issue 4, june 2020
B. Vandenhove PhD student, L. Canti PhD student, H. Schoemans MD, PhD, Y. Beguin MD, PhD, prof. F. Baron , E. Willems MD, PhD, C. Graux MD, PhD, T. Kerre MD, PhD, S. Servais MD, PhD
Acute graft-versus-host disease (aGVHD) remains a severe complication after allogeneic stem cell transplantation (alloHCT). It is a disregulated immune process, during which the immune cells of the donor attack the healthy tissues in the immunocompromised host. Over the past two decades, progress in understanding its pathophysiology have helped redefine aGVHD reactions and clinical presentations. Typically, the disease presents with serious inflammatory lesions mainly in the skin, gut and liver. Its severity is assessed by gathering clinical signs and dysfunctions of each organ. Despite standard prophylaxis regimens, aGVHD still occurs in approximately 30–60% of transplanted patients and remains a major cause of transplant-related morbidity and mortality. Hence, there is an urgent need for optimising preventive strategies. In this review, we give insights on how to make an accurate diagnosis and scoring assessment of aGVHD, propose a short overview of the current knowledge about its immunobiology and discuss the current and developing strategies for prevention.
(BELG J HEMATOL 2020;11(4):159–173)
Read moreBJH - 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
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 moreBJH - volume 11, issue 3, may 2020
K. Maes MD, B. De Moerloose MD, PhD, M. Quaghebeur , J. De Munter , T. Kerre MD, PhD, I. Moors MD
Adolescents and young adults (AYAs), aged 15 to 39 years, with newly diagnosed acute myeloid leukaemia (AML) differ from both younger and older patients in terms of patient-specific as well as disease-specific factors. The improvement in outcome over time for this group is noticeably less than for their younger and older counterparts. Reasons for this are thought to be lack of standardisation of therapy, being treated with either adult or paediatric regimens, low trial participation and specific psychosocial factors. In this article, we review the distinct characteristics of AYA AML in order to address this issue and conclude that an AYA-specific approach and research are warranted to overcome stagnating outcome results.
(BELG J HEMATOL 2020;11(3):98–101)
Read moreBJH - volume 11, issue 3, may 2020
L.C. Holthof MSc, T. Mutis MD, PhD
Over the past decades, immunotherapy has significantly improved the overall survival of multiple myeloma (MM) patients. In addition to immunomodulatory drugs and targeted antibodies that are currently standard of care, novel promising immunotherapeutic approaches, such as bispecific antibodies and chimeric antigen receptor-transduced T-cells (CAR T-cells) are being increasingly tested in clinical trials. Nonetheless, similar to what has been seen in chemotherapy, MM is also capable of developing resistance against immunotherapy. Direct and indirect interactions between MM and the MM bone marrow microenvironment (BM-ME) enable MM-cells to escape not only from chemotherapy but also from immunotherapy. This review will discuss how BM-ME enables MM-cells to evade the immune system and immunotherapy via immunosuppression and via induction of genuine resistance against cytotoxic mechanisms of immune killer cells.
(BELG J HEMATOL 2020;11(3):102–7)
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