Articles

Highlights in chronic myeloid leukaemia

BJH - volume 12, issue 5, september 2021

G. Verhoef MD, PhD

SUMMARY

Chronic myeloid leukaemia (CML) received a lot of interest at EHA 2021. New ELN recommendations for CML management were presented, which highlighted the importance of risk stratification and cytogenetic analysis. The primary analysis of the phase II OPTIC study concluded that ponatinib showed dose-escalated efficacy in CML patients who were resistant to second-generation tyrosine kinase inhibitors (TKIs). Additionally, final analysis of the EURO-SKI trial revealed that TKI cessation might be appropriate in some CML patients. The Harmony Plus project shed light on the genetic heterogeneity of advanced CML. Finally, mutations in mitochondrial DNA were found to be associated with response to treatment with imatinib. The most important messages of these different presentations will be discussed in this article.

(BELG J HEMATOL 2021;12(5):225-7)

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

BJH - 2021, issue 2, march 2021

P. Beuselinck MD, Ir J. Van Ham , N. Boeckx MD, PhD, T. Devos MD, PhD, P. Vandenberghe MD, PhD, G. Verhoef MD, PhD

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)

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Highlights in chronic myeloid leukaemia

BJH - volume 11, issue 5, september 2020

G. Verhoef MD, PhD

SUMMARY

At the EHA annual meeting of 2020, interesting new data with regard to chronic myeloid leukaemia (CML) were presented. This report will briefly summarise the key messages from the main topics in the oral CML clinical session.

(BELG J HEMATOL 2020;11(5):222-5)

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Guidelines of the Belgian Hematological Society for newly diagnosed and relapsed follicular lymphoma anno 2019

BJH - volume 11, issue 2, march 2020

M. Clauwaert MD, V. Galle MD, M. Maerevoet MD, A. Janssens MD, PhD, K. Saevels MD, S. Snauwaert MD, PhD, C. Springael MD, PhD, V. Van Hende MD, G. Verhoef MD, PhD, F. Offner MD, PhD

SUMMARY

Follicular lymphoma is the most common low-grade non-Hodgkin lymphoma. Survival rates have been rising over time mainly due to advancing therapeutic strategies. As the last Belgian guidelines date from 2012, we present an update of the scientific evidence regarding diagnosis, staging, treatment and follow-up, and confront these to the Belgian reimbursement rules anno 2019. Follicular lymphoma grade 3B is classified as high-grade lymphoma and treated accordingly, and will not be discussed in this paper. Early stage disease can be treated with involved-field radiotherapy, which has curative potential. Advanced stage disease is virtually incurable, but many treatment options are available with good results. In first line, treatment is mostly based on chemotherapy combined with rituximab; the latter can be continued as maintenance therapy. In relapsed setting, introduction of the newer and more potent anti-CD20-antibody obinutuzumab, also in combination with chemotherapy, can lead to improved survival in high-risk patients. For older patients with comorbidities, rituximab monotherapy is the preferred option. In further lines, PI3K-inhibition with idelalisib and radioimmunotherapy are available. Finally, autologous or allogeneic stem cell transplantation remain an option in a small group of selected patients.

(BELG J HEMATOL 2020;11(2):67–74)

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The role of immunotherapy in the treatment of classic Hodgkin lymphoma

BJH - volume 10, issue 8, december 2019

A. Van Besien MD, G. Verhoef MD, PhD, D. Dierickx MD, PhD

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)

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

BJH - volume 10, issue 7, november 2019

T. Goos MD, G. Verhoef MD, PhD, T. Devos MD, PhD

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)

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BHS guidelines for the treatment of marginal zone lymphomas: 2018 update

BJH - volume 10, issue 4, june 2019

D. Bron MD, PhD, M. Maerevoet MD, E. Van den Neste MD, PhD, V. Delrieu MD, F. Offner MD, PhD, W. Schroyens MD, PhD, A. Van Hoof MD, PhD, G. Verhoef MD, PhD, J.B. Giot MD, J.P. Loly MD, A. Janssens MD, PhD, C. Bonnet MD, PhD

Marginal zone lymphomas (MZL) are a heterogeneous subtype of indolent B-non-Hodgkin lymphomas that includes distinct entities:

  • Extranodal mucosa-associated lymphoid tissue lymphoma arises in a variety of tissue but primarily in the stomach. They are usually localised and often associated with chronic antigenic stimulation by microbial pathogens. Eradication of the pathogen is a major part of the first-line therapy. The prognosis is excellent in early stages. In advanced stages, observation, anti-CD20 antibodies and/or cytostatic drugs are therapeutical approaches.
  • Nodal MZL is usually confined in lymph nodes, bone marrow and peripheral blood. The prognosis is somewhat worse in this entity. Current recommendations suggest that they should be managed as follicular lymphomas.
  • Splenic MZL is a unique entity involving the spleen, bone marrow and blood. Hepatitis infection should be eradicated before considering treatment. These lymphomas have an indolent behaviour, and only symptomatic patients should be treated by splenectomy and/or anti-CD20 antibodies.
  • Two novel entities are described, non-chronic lymphocytic leukaemia monoclonal B-cell lymphocytosis, probably closely related to splenic MZL lymphoma, and a less well-defined provisional entity involving primarily the spleen called splenic B-cell lymphoma/leukaemia, unclassifiable, including splenic diffuse red pulp lymphoma and hairy-cell leukaemia variant.

This review will discuss separately the diagnosis, work-up and treatment of extranodal mucosa-associated lymphoid tissue lymphoma, nodal MZL and splenic MZL. These guidelines include the recently published ESMO consensus conference on malignant lymphoma.1–3

(BELG J HEMATOL 2019;10(4):153–64)

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