T. Devos MD, PhD

Ravulizumab for paroxysmal nocturnal haemoglobinuria

SUMMARY

Paroxysmal nocturnal haemoglobinuria (PNH) is characterised by the deficiency of glycosylphosphatidylinositol (GPI) anchored proteins, such as CD55 and CD59, on hematopoietic cells resulting in uncontrolled complement activation and haemolysis. Ravulizumab is a new monoclonal antibody with high affinity for complement factor C5 and hereby inhibits complement activation. Due to its significant longer half-life time compared to eculizumab, another C5 targeting complement inhibitor, ravulizumab, is administered intravenously once every eight weeks. Since November 2023, ravulizumab is reimbursed in Belgium for patients with haemolysis and showing clinical symptoms of high disease burden, as well as for clinically stable patients who are treated with eculizumab for at least six months.

(BELG J HEMATOL 2024;15(8):318–24)

Advanced systemic mastocytosis: An uncommon cause of chronic diarrhoea and weight loss

SUMMARY

Introduction: Advanced systemic mastocytosis is a rare myeloproliferative disorder of mast cells, damaging the function of various organs and tissues. The diagnosis can be challenging due to its protean manifestations and rareness. Treatment options have improved over the last years. Currently, avapritinib, a novel tyrosine kinase inhibitor with activity against p.D816V mutated KIT, is under investigation.

Case: We report a case of a 64-year old man with chronic diarrhoea, fatigue, weight loss and ascites with hepatomegaly, developing an upper gastro-intestinal bleeding with multiple duodenal ulcers. Diagnostic work-up revealed hepatosplenomegaly and portal hypertension, a vertebral compression fracture and multiple ¹⁸F-FDG avid supra- and infradiaphragmatic lymph nodes and bone marrow. Based on the 2016 WHO criteria of systemic mastocytosis, and a concomitant chronic myelomonocytic leukaemia, the diagnosis of an aggressive systemic mastocytosis with an associated haematological neoplasm was made. The patient was consecutively treated with midostaurin, cladribine and avapritinib, the latter inducing a complete biochemical and molecular response.

Conclusion: This case illustrates the challenging clinical presentation of systemic mastocytosis. A deep response to avapritinib was observed despite prior use of midostaurin and cladribine, underlining its promise in advanced systemic mastocytosis.

(BELG J HEMATOL 2022;13(2):84–91)

Management of polycythemia vera: Recommendations from the BHS MPN subcommittee anno 2021

SUMMARY

Polycythemia vera (PV) is classified by the World Health Organization (WHO) under the BCR-ABL-negative myeloproliferative neoplasms (MPNs) and is characterised by clonal proliferation of myeloid cells, which leads primarily to an increased red blood cell mass. Bone marrow morphology remains the cornerstone of diagnosis. Patients can present with thrombosis, microcirculatory symptoms, haemorrhage, splenomegaly, pruritus and other symptoms that reduce their quality of life and they are at risk of transformation to secondary myelofibrosis (MF) or acute myeloid leukaemia (AML). The main goal of therapy in PV is to minimise the thrombotic risk. To achieve this goal PV patients are being treated with low-dose aspirin and phlebotomies to reach a target haematocrit below 45%. In addition, high-risk patients are being treated with cytoreductive agents. Over the last years, new insights in the pathophysiology, diagnosis and prognosis of polycythemia vera were acquired and novel therapeutic options are available. In this paper we give an update on PV and provide diagnostic and therapeutic recommendations, taking into account the Belgian situation.

(BELG J HEMATOL 2021;12(6):258-74)

Tyrosine kinase inhibitor discontinuation in patients with chronic myelogenous leukaemia: A retrospective study and review of the literature

ABSTRACT

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia (CML). TKIs can be successfully discontinued in some CML patients who have achieved a stable deep molecular response.

OBJECTIVE: The purpose of this article is twofold. On the one hand, this review provides an overview of current use and discontinuation of TKIs in patients with CML. On the other hand, we retrospectively investigated the use and possible discontinuation of TKIs in a specific patient population with CML at the University Hospital of Leuven.

METHODS: A literature search was carried out in May 2019 to identify all relevant articles. Articles were searched on PubMed, Embase, Web of Science and Cochrane Library. Additionally, the articles found in the reference list were used.

RESULTS: This review included ten articles (two on imatinib, four on dasatinib, four on nilotinib), with 970 patients. Treatment free remission (TFR) ratio varied from 41–68% after one year. One study published the results of TFR after three years. In UZ Leuven, the TFR ratio was 60% after 106 weeks.

CONCLUSION: Tyrosine kinase inhibitor (TKI) therapy can be safely terminated in selected patient groups. About half of the patients retain the molecular remission after discontinuation of TKI therapy.

(BELG J HEMATOL 2020;12(2):52-8)

Highlights in CML and MPN

SUMMARY

A huge amount of promising and novel data were presented during the virtual ASH 2020 congress. In this paper, I first will focus on the most interesting clinical CML abstracts, then I will present some highlights of the MPN presentations.

(BELG J HEMATOL 2021;12(1):4-7)

P.36 Phase 2, open-label, multicenter study to evaluate the efficacy and safety of pemigatinib in patients with myeloid/lymphoid neoplasms with fibroblast growth factor receptor 1 (FGFR1) rearrangement (FIGHT-203)

A single-center retrospective study of patients with systemic mastocytosis at University Hospital Leuven

SUMMARY

Systemic mastocytosis is a rare heterogeneous disorder characterised by abnormal proliferation of mast cells. It can be divided in subtypes with different phenotypes and prognoses. This article is a retrospective descriptive study of 37 patients with systemic mastocytosis according to the WHO criteria of 2008 at UZ Leuven. Twenty-eight patients had indolent systemic mastocytosis (75.7%), four smouldering systemic mastocytosis (10.8%), three aggressive systemic mastocytosis (8.1%) and two systemic mastocytosis with associated haematological neoplasia (5.4%). In one out of five patients, the diagnosis was made based on at least three minor criteria. The sensitivity of CD25 expression was 100%. In 75.7% a KITD816V mutation was detected. The value of serum tryptase was associated with the subtype of systemic mastocytosis. Seventy-eight percent had cutaneous lesions. Forty-eight percent experienced at least one anaphylactic reaction. Osteoporosis was reported in 24.6%. Eighty-nine percent and 64.9% of patients were treated with respectively H1 and H2 antihistamines. Cytoreductive treatment was administered to nine patients (24.3%). Three patients received as first-line treatment midostaurine, three imatinib, one cladribine, one nilotinib and one masitinib. This study reflects the heterogeneity of this condition and emphasises the importance of a multidisciplinary approach in a specialised center for early diagnosis and treatment of disease-associated manifestations.

(BELG J HEMATOL 2019;10(7):265–76)