REVIEW HEMATOLOGY

Causes, diagnosis and management of congenital or acquired neutropaenia

Neutropaenia is a common incidental finding on routine blood studies. This manuscript will focus on the possible causes, challenging differential diagnosis and appropriate management of neutropaenia. Different mechanisms may explain a decreased production, impaired development or increased destruction of neutrophilic granulocytes. We distinguish between congenital and acquired causes. The former includes benign ethnic neutropaenia, severe congenital neutropaenia and cyclic neutropaenia. For the latter, infections, drugs, auto-immune reactions, nutritional deficiencies as well as haematological malignancies are all possible reasons of neutropaenia. The risk of infection in those with non-chemotherapy-induced neutropaenia mainly depends on the bone marrow reserve. Asymptomatic patients with mild or moderate neutropaenia can be observed with serial blood counts at increasing intervals. Infections should always be treated according to the severity of neutropaenia. Therapy with growth factors, drug discontinuation and immunosuppressive therapy can be considered depending on the underlying cause.

(BELG J HEMATOL 2019;10(3):103–12)

Clinical and biologic correlates of frailty in older patients with malignant hemopathies

Frailty assessment in older patients with malignant hemopathies is very useful in order to improve care and treatment options. However, some lacks of data exist regarding the unsuspected frail population in presumed ‘clinically fit’ patients who should not benefit from chemotherapy. In this article, we review current data regarding prognostic factors and frailty scoring in older patients with malignant hemopathies. Prospective trials are needed to build a new frailty scoring to assess the unsuspected frail population in ‘clinically fit’ patients including specifically assessment of cognitive impairment.

(BELG J HEMATOL 2019;10(2):65–8)

Diffuse large B-cell lymphoma refractory to R-CHOP

SUMMARY

Rituximab with cyclophosphamide, adriamycin, vincristine and prednisone (R-CHOP) is the standard treatment for diffuse large B-cell lymphoma and is able to cure 50–60% of the patients. However, patients resistant to or in early relapse after R-CHOP have a very poor prognosis with a median overall survival of only six months, and very few patients have a long survival. Double-hit lymphoma (rearrangement MYC and BCL2) has a major risk of refractoriness, and more intense chemotherapy than R-CHOP is recommended. Early PET-CT could identify resistance to conventional chemotherapy. Intensification with autologous or allogeneic stem cell transplantation is recommended in case of a response to salvage regimen. New agents are expected and chimeric antigen receptor T-cell therapy is a very promising approach.

(BELG J HEMATOL 2018;9(7):249–53)

Extracorporeal photochemotherapy for graft-versus-host disease: Where we are now and where we are going!

SUMMARY

Graft-versus-host disease remains the leading cause of morbidity, non-relapse mortality and treatment failure after allogeneic haematopoietic stem cell transplantation. So far, steroids are the first line treatment, but around 40% of patients become steroid-resistant or fail to respond at a safe dose. Patients who fail to respond to the initial therapy have a dismal prognosis, and no standard treatment is well established for them to date. Treatments that modulate the immune system rather than directly suppressing its function, although not dampening a potential graft-versus-malignancy effect, would therefore be highly desirable, and extracorporeal photopheresis appeared as being a good candidate to fill in these criteria. Multiple reports of treatments in both paediatric and adult patients with graft-versus-host disease have been published, and the overall favourable profile compared with other available immunosuppressive therapies continues to make extracorporeal photopheresis appealing despite all of the unknowns. In this article, we review the use of extracorporeal photopheresis for the treatment of graft-versus-host disease, including technical aspects, mechanism of action, safety profile and clinical efficacy data.

(BELG J HEMATOL 2018;9(7):254–65)

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)

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)

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)