D. Dierickx MD, PhD

Diagnosis and treatment of thrombotic thrombocytopenic purpura

SUMMARY

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathic disorder (TMA) due to a severe deficiency of ADAMTS13 (A Disintegrin And Metalloprotease with Thrombo-Spondin type 1 repeats, member 13). The deficiency in ADAMTS13 can either be caused by mutations in ADAMTS13 (congenital TTP or Upshaw-Schulman syndrome, cTTP) or by anti-ADAMTS13 autoantibodies (immune-mediated TTP, iTTP). Diagnosis of TTP is challenging but crucial for the survival of the patient. TTP should be suspected when microangiopathic haemolytic anaemia and severe thrombocytopenia are observed. A severely decreased ADAMTS13 activity (activity <10%) should confirm the diagnosis of TTP. Standard treatment of TTP is plasma therapy (plasma exchange for iTTP, while plasma infusion for cTTP), but novel therapeutics like rituximab, caplacizumab and recombinant ADAMTS13 show promising results regarding the recovery and sustained remission of TTP patients. However, although major advances have been made in the management of TTP, TTP is a chronic disease and patients still relapse, careful and stringent patient follow-up is needed to improve the patients’ quality of life.

(BELG J HEMATOL 2020;11(6):253-60)

Oxaliplatin-induced immune mediated haemolytic anaemia, thrombocytopenia and renal failure

SUMMARY

Oxaliplatin-based chemotherapy is commonly used to treat colorectal cancer. After prolonged administration it can rarely lead to hypersensitivity reactions such as immune mediated haemolytic anaemia and thrombocytopenia. We present the case of a 50-year old patient admitted with acute onset of fever, dark urine and back pain during the ninth infusion of oxaliplatin. Two weeks before the current event he experienced similar though less severe symptoms. Laboratory signs were compatible with severe Coombs positive haemolytic anaemia, thrombocytopenia and acute kidney injury. Signs of haemolysis abated quickly, however, the patient developed anuria and required dialysis for thirty days. Immune mediated haemolytic anaemia is a rare but potentially life-threatening complication of prolonged oxaliplatin therapy, especially when kidney failure develops. A careful history and high index of suspicion may identify warning signs leading to increased vigilance and possible prevention of such events.

(BELG J HEMATOL 2020;11(3):128–32)

The role of immunotherapy in the treatment of classic Hodgkin lymphoma

SUMMARY

Classic Hodgkin lymphoma (cHL) is one of the most frequent lymphomas in the Western world. Its incidence has a bimodal distribution with the most important peak arising in the age group of children and adolescents and a second less prominent peak in the elderly. Until recently, therapeutic options consisted solely of chemotherapy and/or radiotherapy. Despite the achievement of relatively high cure rates with these regimens, long-term toxicity remains a great concern. Moreover, patients that relapse or are refractory to these treatments generally have a poor prognosis despite the fact that autologous or allogeneic stem cell transplantation are options in fit patients. In the last decade, increased understanding of the pathobiology of Hodgkin lymphoma has led to the identification of several molecular targets for new therapeutic agents. Several of these molecules (i.e. brentuximab vedotin, nivolumab and pembrolizumab) have already proven their benefit in clinical trials and were subsequently approved by the US Food and Drug administration (FDA) and the European Medicine Agency (EMA) as safe and efficacious therapies for relapsed or refractory (R/R) cHL. Further results of randomised controlled trials (RCTs) are awaited to determine if these therapies also have a place in first-line. In the meantime, several other novel agents – ranging from checkpoint inhibitors to antibody-based drugs and cellular therapies – are being tested in clinical and preclinical studies. In this review we present an overview of the most important types of immunotherapies that are currently being used in the treatment of cHL or who demonstrated promising therapeutic potential.

(BELG J HEMATOL 2019;10(8):320–5)

03 Renal allograft function following treatment of post-transplant lymphoproliferative disorder

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)

PP38 Autologous hematopoietic stem-cell transplantation in lymphoma – a single center experience