REVIEW HEMATOLOGY

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)

State of the Art I: Thrombosis

The first state of the art session of the 2018 annual BSTH meeting focused on thrombosis. While Dr. Anna Falanga (Hopsital Papa Giovanni XXIII, Bergamo, Italy) and Dr. Cihan Ay (Medical university of Vienna, Austria) specifically addressed the close relationship between thrombosis and cancer, Dr. Walter Ageno (Ospedale di Circolo, Varese, Italy) discussed the practicalities of managing splanchnic (SVT) and cerebral vein thrombosis (CVT).

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)