From immunotherapy, the new therapeutic pillar, to allogeneic hematopoietic stem cell transplantation

Xavier Poiré, Nicole Straetmans, Sarah Bailly, Marie-Christiane Vekemans Published in the journal : February 2020 Category : Hematology/Oncology

In this article focused on innovations in onco-hematology are highlighted the successes of immunotherapy, as well as current challenges of allogeneic hematopoietic stem cell transplantation.

The treatment of hematological malignancies has traditionally been dominated by chemotherapy or radiotherapy. The discovery of the cytogenetic and molecular bases of these diseases has paved the way for targeted therapies; more recently, the field of immunotherapy has emerged with the development of CAR-Ts, BiTEs, immunoconjugates, and checkpoint inhibitors. These innovations have enabled us to better understand the complex interactions between a patient's immune system and potential tumor cells. However, the idea of exploiting the patient's immune system in an attempt to control his disease is not a recent concept, since allogeneic haematopoietic stem cell transplantation is based on the principle of using graft’s T lymphocytes to eliminate the recipient's tumor cells.

To date, allogeneic hematopoietic stem cell transplantation remains a mainstay of therapeutic weapons in hematology. Moreover, there is a great deal of research being done to improve outcomes. In order to reduce the risk of relapse without increasing toxicity, conditioning regimens with reduced toxicity are becoming a new standard. Graft-versus-host disease would be better prevented by administering post-transplant cyclophosphamide. Finally, numerous post-transplant relapses are the consequence of immune escape. A better understanding of their mechanisms likely opens the way to new therapeutic strategies.

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Side effects of multiple myeloma treatments

Sarah Bailly, Sarah Amat, Catherine Percy, Thomas Gérard, Laurane Lallemand, Aline Munting, Marie-Christiane Vekemans Published in the journal : January 2020 Category : Hematology/Oncology

The prolonged use of new drugs such as proteasome inhibitors, immunomodulators, and monoclonal antibodies in the treatment of multiple myeloma is associated with adverse side effects that represent a daily challenge for physicians. We propose a series of recommendations based on clinical cases.

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Hypereosinophilic syndrome: description of three clinical cases and literature review

Léa Schmitz(1), Christian Michaux(2), Laurent Plawny(3) Published in the journal : November 2018 Category : Hematology/Oncology

Hypereosinophilic syndrome (HES) is characterized by hypereosinophilia associated with subsequent damage of one or more target organs. HES has various causes, that can be divided into primary (clonal involvement of the myeloid lineage), secondary (polyclonal by interleukin-5 production), and idiopathic. Thanks to technological advances, particularly in genetics, six clinical-biological variants could be defined, thus leading to the emergence of targeted therapies. Imatinib, a tyrosine kinase inhibitor, is used in myeloproliferative HES (M-HES), while other variants are treated in first line by corticosteroids. The development of new agents, such as IL-5 inhibitors (mepolizumab), has allowed sparing corticosteroids and thus avoiding their adverse effects, thereby improving the patients’ quality of life.

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Hematologic abnormalities as a manifestation of a defect of intracellular cobalamin metabolism – report of five cases

Elise Osterheld(1), Lutz Bindl(1), Wolfgang Boehm(1), Leon Bofferding(1), Jean Bottu(1), Christine Geron(1), Sandra Heck(1), Charlotte Pierron(1), Moritz Vogel(1), Linda De Meirleir(2), Geert Martens(2), Luc Regal(2), Emmanuel Scalais(1) Published in the journal : November 2018 Category : Hematology/Oncology

Intracellular cobalamin (IC) and its two coenzymes, adenosylcobalamin and methylcobalamin, are necessary for the homeostasis of methylmalonic acid and homocysteine (Hcy). Defects of intracellular cobalamin metabolism are responsible for isolated methylmalonic aciduria (MMA), isolated increased Hcy, or both. MMA occurs when adenosylcobalamin, a cofactor of methylmalonic-CoA mutase, is low, thereby causing elevated MMA and decreased succinyl-CoA. A lack of methylcobalamin, a cofactor for methionine synthase, impairs the transformation of Hcy into methionine, thus leading to increased Hcy and low methionine levels.

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Anticoagulant therapy of lower-extremity deep vein thrombosis in 2018

Cédric Hermans Published in the journal : June 2018 Category : Hematology/Oncology

For most patients with lower-extremity deep vein thrombosis (DVT), direct oral anticoagulants (DOAs) can replace safely and effectively vitamin K antagonists (VKAs), with multiple benefits. Some DOAs can be started immediately upon diagnosis, without any previous treatment with low-molecular-weight heparin (LMWH). In some settings and patients, initial LMWH therapy should, however, be favored. Though their use should not be trivialized and precautions are necessary, DOAs facilitate the management of the 3-month anticoagulation that is required in most DVT patients. DOAs, at full or reduced dose, are probably most beneficial in patients requiring prolonged or long-term anticoagulation. This article reviews the current management of DVT using DOAs and summarizes the main criteria for identifying candidates to prolonged or long-term anticoagulation.

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Diagnosis and management of Richter's syndrome in 2017

Hélène Vellemans, Stéphane Lepretre Published in the journal : June 2018 Category : Hematology/Oncology

Richter’s syndrome is a rare syndrome characterized by the development of aggressive lymphomas in patients with concomitant chronic lymphocytic leukemia. Known for several years, this syndrome is still very heterogeneous and represents a real clinical challenge, given its aggressive nature and very limited prognosis. In the era of targeted therapies and due to the increasingly-thorough characterization of the genetic abnormalities of this condition, there is an unmet need for new molecules in order to better manage patients suffering from this syndrome. This article is a brief literature review as regards diagnosis and management of Richter's syndrome in 2017.

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Mehdi Bsilat ¹, Daniel Leonard ², Sandy Van Nieuwenhove ³, Catherine Lambert ⁴ Published in the journal : September 2017 Category : Hematology/Oncology

We here present a case of diverticulitis complicated by a pylephlebitis of the portal and superior mesenteric vein, requiring treatment with heparin and antibiotics. The patient subsequently developed a splenic vein thrombosis and suffering bowels. A large resection of the small bowel was performed, with subsequent ileostomy and parenteral nutrition. Following anticoagulation therapy initiation, a thrombocytopenia was observed, and the patient was found to have developed heparin-induced thrombocytopenia (HIT), as evidenced by high levels of anti-heparin/PF4 antibodies. Furthermore, he had a contributory family history of thrombophilia, and molecular tests confirmed that he was carrying a thrombophilic G20210A factor II mutation. To our knowledge, this is the first case report of a bowel ischemia in a context of pylephlebitis treated with heparin, leading to another rare thrombophilic syndrome: heparin-induced thrombocytopenia and thrombophilia (HITT).

This article illustrates how a rare complication of a common disease and its treatment can aggravate the primary condition. We discussed the pylephlebitis and the HITT as the explanation for such a rare consequence on the bowel in the context of inherited thrombophilia.

Key Words

Pylephlebitis, heparin-induced thrombocytopenia, surgery, bowel ischemia, prothrombin mutation

Note: Full text in english

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Innovations in Hematology

Marie-Christiane Vekemans Published in the journal : February 2017 Category : Hematology/Oncology

The development of proteasome inhibitor (PI) and immunomodulatory drugs (IMiDs) have considerably changed the treatment paradigm of multiple myeloma (MM), while significantly improving survival. Nevertheless, many patients exhibit disease relapse and develop drug resistance. The better understanding of disease biology will likely influence our approach to myeloma treatment, resulting in the advent of newer drug classes, such as monoclonal antibodies and adoptive cellular therapies. There is much hope that MM will soon become a chronic illness with sustained complete response in a significant number of patients. 

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Edoxaban (Lixiana®): a new factor Xa-inhibiting oral anticoagulant for patients with atrial fibrillation or venous thromboembolic disease

C. Hermans Published in the journal : November 2016 Category : Hematology/Oncology

Edoxaban (Lixiana®) is a novel factor Xa-inhibiting oral anticoagulant that has recently been validated both for the treatment of venous thromboembolism (VTE) and for the prevention of arterial thrombotic events associated with non-valvular atrial fibrillation (NVAF). This article aims at reviewing the results of the two large studies (HOKUSAI-VTE and ENGAGE-AF) that validated this new anticoagulant in these two indications.

These clinical studies clearly demonstrated the efficacy and tolerability of this new oral anticoagulant in both indications as compared to conventional anticoagulants. They especially established the role of a standard dose of 60 mg edoxaban administered once daily and demonstrated the value and effectiveness of a dose reduction to 30 mg daily in some patients at risk of accumulation. This article also summarizes the main properties of edoxaban, which should establish itself as a promising anticoagulant for patients with VTE or NVAF.

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“Translating clinical trials into daily practice” by an international expert, Professor Giancarlo Agnelli

C. Lambert Published in the journal : September 2015 Category : Hematology/Oncology

Due to the development and approval of new oral anticoagulants (NOACs), the treatment of venous thromboembolic disease (VTE) has changed dramatically over the last years. Our therapeutic habits are evolving, thus raising new issues, especially regarding the use of NOACs in daily practice. The first part of this paper reviews major clinical trials that have led to the approval of NOACs for VTE treatment. In the second part, the international expert Giancarlo Agnelli shares his experiences and recommendations regarding the use of NOACs in VTE.

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