REVIEW HEMATOLOGY

Micro-organisms and coagulation

The coagulation system is rarely left alone. Microorganisms, both harmless and harmful, can affect the function of the system, which can have clinical consequences of variable severity. The second State of the art session, entitled “microorganisms as an environmental factor”, chaired by prof. Simon De Meyer and dr. Muriel Sprynger featured several presentations on the interactions between these small lifeforms and thrombosis and haemostasis.

Cell of origin in diffuse large B-cell lymphoma: the way to targeted therapy?

SUMMARY

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma type worldwide, but the treatment still remains challenging because only 60–70% of the patients can be cured with the standard immunochemotherapy (rituximab, cyclophosphamide-doxorubicin-vincristine-prednisone) scheme. In the last twenty years, several molecular-genetic studies showed that DLBCL comprises at least two distinct molecular subtypes: the activated B-cell-like and the germinal centre B-cell-like subtype. The two groups have different genetic mutation landscapes and outcomes following treatment, with the ABC subtype having the worst prognosis. Gene expression profiling seems to be the gold standard method to subdivide DLBCL into ABC and GCB subtypes, but it is difficult to include this technology in clinical practice because it relies on fresh frozen tissue and microarray technology. To facilitate the DLBCL classification in daily clinical practice, other technologies have been developed allowing analysis of formalin-fixed paraffine embedded tissue biopsies. The unique genetic and epigenetic features of both DLBCL subtypes make targeted therapy a promising approach in the future.

(BELG J HEMATOL 2018;9(6):206–13)

A Belgian consensus protocol for autologous haematopoietic stem cell transplantation in multiple sclerosis

SUMMARY

Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous haematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality and increasing patient awareness have led to rising inquiry by our patients about this treatment option. With the aim of a standardised protocol and data registration, a Belgian working party on stem cell therapy in multiple sclerosis was established. In this paper, we report the consensus protocol of this working party on autologous haematopoietic stem cell transplantation in multiple sclerosis.

(BELG J HEMATOL 2018;9(5):167–74)

Recent advances in haemophilia treatment

SUMMARY

In the past few years, several new treatment options for haemophilia A and B have emerged. Formerly, replacement therapy comprised plasma-derived and recombinant factor VIII and IX concentrates containing human- and animal-derived components associated with a potential risk of contamination with infectious agents. Further optimisation of the manufacturing procedures virtually eliminated these hazards. Nowadays, the major drawbacks of the standard plasma-derived and recombinant factor VIII and IX products are their relatively short half-life. To overcome these limitations, different therapeutic approaches were developed. Novel extended half-life rFVIII and rFIX concentrates allow a reduction of the injection frequency and improve the efficacy of therapy and the quality of life of haemophilia patients. Besides the prophylactic treatment options, important progress has been made in gene therapy. Currently, the major complication of the treatment with FVIII or FIX concentrates is the development of inhibitor antibodies. In these cases, bypassing agents allow treating or preventing bleedings. However, the currently available bypassing agents have a short half-life, which limit their use for prophylactic treatment. Accordingly, several new therapies are now being developed to treat patients with inhibitors, including rFVIIa with extended half-life, recombinant porcine FVIII and bispecific antibodies bridging FVIII and FIX.

(BELG J HEMATOL 2018;9(5):175–81)

Iron overload in haematopoietic stem cell transplantation children and relation to organ damage and survival

SUMMARY

Adult patients with high serum ferritin have an increased risk of organ toxicity and iron chelation before stem cell transplant might be an option. We report our experience in 58 paediatric patients (excluding patients with haemoglobinopathy and hyper-transfused patients) undergoing allogeneic stem cell transplant between 2007 and 2012. Serum ferritin pre-transplant was highly variable (mean: 932 µg/L) and related to a number of PRC transfusions. Eighteen of 58 patients had ferritin level >1000 µg/L before transplant. Eight patients suffered from transplant-related mortality. We found no correlation between transplant-related mortality and pre-transplant serum ferritin (p=0.67). Seven patients developed veno-occlusive disease, reversible in all cases. We did not find a correlation between serum ferritin and veno-occlusive disease, graft-versus-host disease or relapse. The evolution of ferritin post-transplant shows a spontaneous lowering of ferritin in the first two years after haematopoietic stem cell transplantation to normal range. An association between serum ferritin and elevated AST/ALT at 12 and 24 months was noted and follow-up concerning possible liver damage in patients with a persistently high serum ferritin is recommended. This study concludes that high serum ferritin has no influence on transplant-related mortality in children, chronically poly-transfused patients excluded. Although chelation is already used in paediatric HSCT, there is insufficient, current evidence to do so.

(BELG J HEMATOL 2018;9(5):182–7)

Management of severe aplastic anaemia

SUMMARY

Aplastic anaemia is a rare condition characterised by pancytopenia and bone marrow hypocellularity and caused by the immune-mediated destruction of the haematopoietic precursors. The early complications are related to cytopaenias with infections being the major cause of morbi-mortality. The main long-term issue is clonal evolution to myelodysplastic syndrome or acute leukaemia. The diagnosis relies on exclusion of other causes of pancytopenia and characteristic pathologic findings. Severity is stratified according to peripheral blood counts. Nowadays, the survival of treated patients reaches 80–90%. The treatment of the severe form of aplastic anaemia consists on haematopoietic stem cell transplantation in eligible patients and immunosuppressive therapy in non-transplant candidates. Supportive therapy is an option in frail and/or elderly patients. Here, we define and briefly review the pathogenesis of aplastic anaemia. We propose a diagnostic and therapeutic strategy based on existing literature and experts’ recommendations. We finally report three cases illustrating particular clinical associations with pregnancy, hepatitis and paroxysmal nocturnal haemoglobinuria.

(BELG J HEMATOL 2018;9(3):76–85)

The diagnosis and treatment of lower risk myelodysplastic syndromes in the year 2018: update of the MDS guidelines

SUMMARY

The field of myelodysplastic syndromes has entered the molecular era. New diagnostic tools such as next-generation sequencing are rapidly entering clinical practice and will change the way we diagnose and manage patients with a myelodysplastic syndrome, especially patients considered lower risk by standard diagnostic tools. The treatment of lower risk patients has not changed much since the publication of the BHS recommendations in 2013. However, important trials in lower risk patients have recently been published and will be reviewed here. Finally, the recommendations from an international expert panel for allogeneic transplantation have been published. The key points of this paper will also be discussed as well as results of recently published trials.

(BELG J HEMATOL 2018;9(2):48–56)