REVIEW HEMATOLOGY

Detecting venous thromboembolism in COVID-19 patients: DUS & CT scanning

BJH - volume 13, issue 4, june 2022

C. Vandenbriele MD, PhD, D.A. Gorog MD, PhD

SUMMARY

COVID-19 is associated with pulmonary thromboembolism and deep venous thrombosis. Its prevalence increases in the intensive care unit and is especially high in patients on extracorporeal membrane oxygenation (ECMO). This literature review aimed to assess the usefulness of screening for peripheral venous thrombosis or pulmonary thrombosis in patients admitted with COVID-19. In the non-ICU setting, increased D-dimer levels from baseline indicate the need for Doppler ultrasound scan of the lower limbs. In the ICU setting, clinical features and D-dimer levels may not accurately reflect the occurrence of pulmonary thromboembolism. Therefore, it is necessary to increase vigilance for VTE, with a low threshold for Doppler ultrasound and CTPA in high-risk in-patient cohorts.

(BELG J HEMATOL 2022;13(4):145–8)

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Implementing cellular therapies in mantle cell lymphoma

BJH - volume 13, issue 3, may 2022

C. Gonzalez Arias MD, PhD, S. Iyengar MD, PhD

SUMMARY

The last decade has seen much needed progress in the development of novel therapies against Mantle cell lymphoma (MCL). The licensing of the Bruton’s tyrosine kinase inhibitor (BTKi) Ibrutinib for relapsed/refractory MCL was a significant therapeutic milestone in the management of this condition and represents a highly effective, novel oral therapy in a disease characterised by progressive development of chemo-resistance. However, patients invariably progress on Ibrutinib. Multiple studies have demonstrated limited efficacy of subsequent therapies and poor outcomes post-Ibrutinib. In addition, patients with MCL displaying high-risk features such as blastoid morphology and/or TP53 mutations, are now widely recognised as a subset that are particularly challenging to manage. Brexucabtagene-autoleucel (Brexu-Cel) is a novel chimeric antigen receptor (CAR) T-cell therapy that was recently approved for management of patients relapsing on Ibrutinib. This approval was based on the ZUMA-2 study, which demonstrated impressive activity of Brexu-Cel in relapsed/refractory MCL, including in patients with high-risk features. Brexu-Cel is however not without toxicity and is associated with a moderate incidence of severe cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS). Importantly these adverse events are both manageable and acceptable for a therapy that holds the promise of providing long-term remissions from MCL. This review examines CAR-T therapy in MCL including the implementation of Brexu-Cel therapy in the routine management of MCL, and discusses some of the other novel cellular therapy approaches currently being evaluated in this disease.

(BELG J HEMATOL 2022;13(3):108–115)

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FLT3 mutation in AML, which test for which patients?

BJH - volume 13, issue 2, march 2022

K. Rack PhD, L. Michaux MD, PhD

SUMMARY

Genetic analysis of acute myeloid leukaemia (AML) has identified multiple genetic markers of prognostic significance that can be used for risk stratification of patients at diagnosis. Of these, mutations of the FMS-like tyrosine kinase 3 receptor gene (FLT3) are one of the most important. FLT3 mutations are found in 30% of AML cases overall. They are present in different AML entities and across the cytogenetic subgroups, the most common being in AML patients with a normal karyotype. They are generally considered poor prognostic indicators although the prognostic impact is influenced by the type of FLT3 mutation as well as the co-existence of other mutations and cytogenetic background. FLT3 encodes a tyrosine kinase receptor that can be targeted by tyrosine kinase inhibitors and their introduction into treatment protocols has significantly improved the prognosis of these patients with a prior dismal outcome. Given the poor prognosis, and availability of targeted treatment, FLT3 testing is recommended for all new AML cases at diagnosis with the results available within 72 hours for determination of treatment strategies. This short turnaround time (TAT) is challenging for diagnostic laboratories and affects the method of testing. Herein, we review the current recommendations for FLT3 testing in AML, discuss the different available methods for FLT3 mutation testing, and highlight considerations for AML clinicians when faced with AML patients at diagnosis or at a relapsing stage.

(BELG J HEMATOL 2022;13(2):59–64)

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Acute promyelocytic leukaemia (APL) in the elderly patient

BJH - volume 12, issue 8, december 2021

A. Salaroli MD, C. Spilleboudt MD, P. Lewalle MD, PhD, S. Wittnebel MD, PhD

SUMMARY

The prognosis of acute promyelocytic leukaemia has passed from nearly desperate to highly curative over the last 40 years due to better understanding of the biology of the disease, the introduction of anthracyclines, all-trans-retinoic acid (ATRA), arsenic trioxide (ATO) and the implementation of better supportive care during the treatment. If this also holds true for older patients will be discussed in this review.

(BELG J HEMATOL 2021;12(8):332–7)

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New and emergent treatment options in sickle cell disease

BJH - volume 12, issue 7, november 2021

V. Labarque MD, PhD

SUMMARY

Sickle cell disease (SCD) is one of the most frequently inherited diseases but it no longer only affects children. More and more patients survive well into adulthood. They experience repeated acute complications and inevitably develop chronic organ damage. For years, hydroxyurea and chronic transfusions were the only disease-modifying options in the treatment of SCD patients. Thanks to a better understanding of the pathophysiology, new components have been and are now being tested. Three of these are already used in clinical practice, namely L-glutamine, crizanlizumab and voxelotor. On the other hand, progress has also been made in the field of haematopoietic stem cell transplantation, through the introduction of alternative donors as well as the use of less toxic conditioning regimens. Finally, hopeful results are being achieved in the first studies of gene therapy in patients with SCD but it has yet to be proven that genetically manipulated stem cells maintain the long-term repopulation potential.

(BELG J HEMATOL 2021;12(7):290–5)

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Current developments and hurdles in CAR-T cell therapy for acute myeloid leukaemia

BJH - volume 12, issue 6, october 2021

A. Uyttebroeck MD, PhD, B. De Moerloose MD, PhD, L. Van Camp MD, T. Lammens PhD

SUMMARY

Despite huge progress in the past decades, the overall survival (OS) of patients with acute myeloid leukaemia (AML) remains poor. The treatment options run low for those refractory or intolerant to first and second line treatment or in case of relapse. The need for alternative treatment is great and imperative to further improve the OS of these patients. The success of CAR-T19 therapy for the treatment of B cell acute lymphoblastic leukaemia has demonstrated the feasibility of delivering these therapies, and success in further improving survival rates. Among others, the fundamental biological factor limiting the applicability of CAR-T immuno-therapy in the treatment of AML includes the lack of a leukaemia-specific antigen, or an antigen shared by leukaemia blasts and haematopoietic stem and progenitor cells whose sustained depletion could be clinically tolerated. In this review, we describe the most recent developments, clinical results and challenges in CAR-T cell therapy for AML.

(BELG J HEMATOL 2021;12(6):244-50)

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Paraprotein-related peripheral neuropathy

BJH - volume 12, issue 6, october 2021

A. Kentos MD, PhD, M. Delforge MD, PhD, N. Mavroudakis MD, PhD

SUMMARY

Monoclonal gammopathy of undetermined significance (MGUS) is quite frequent in the general population. The association between MGUS and peripheral neuropathy (PN) was described in various studies demonstrating a higher than expected prevalence of PN in patients with MGUS. The demonstration of causality remains a diagnostic challenge as a coincidental association may also occur. Specific diagnostic criteria are available for only a few disorders: DADS, POEMS, amyloidosis, cryoglobulinemia. Data to guide management are quite limited. We present a short review of the literature and emphasise the need of a close collaboration between haematologists and neurologists for an optimal management.

(BELG J HEMATOL 2021;12(6):251-7)

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