HEMATOTHESIS

BALT lymphomas: A retrospective analysis at the University Hospitals Leuven

SUMMARY

Bronchus-associated lymphoid tissue (BALT) lymphoma is a rare indolent non-Hodgkin lymphoma (NHL). It is a primary pulmonary marginal zone lymphoma originating from the BALT. Diagnosis is often delayed due to nonspecific symptoms, wide variability and low specificity of radiological patterns, and difficulties in getting representative biopsies.¹ There are several treatment options: active surveillance, local therapy (surgery or radiotherapy), or systemic therapy ((chemo)immunotherapy, immunomodulating, or targeted therapy). ^1–3 In this retrospective analysis, 30 patients diagnosed with primary BALT lymphoma were enrolled. The median time to diagnosis was six months (IQR 1.5 – 15.5 months). Median follow-up time was 67.3 months (IQR 30.6 – 106.1). Our review shows that the watch-and-wait approach is a valid option for a newly diagnosed BALT lymphoma, as we see no negative impact on outcome in our small case series. There is no evidence that postponing the start of systemic therapy holds a risk for transformation, which would mean an inferior outcome. Treatment must be guided primarily by symptomatology and not only by radiologic alterations.

(BELG J HEMATOL 2024;15(7):286–97)

Understanding hairy cell leukaemia after analysing the University Hospitals Leuven database retrospectively

SUMMARY

Hairy cell leukaemia (HCL) is a rare hematologic malignancy with high response rates after purine-analogue based therapy and an excellent long-term prognosis. We reviewed 104 HCL patients diagnosed between 1980 and 2022 at the University Hospitals Leuven to analyse long-term outcomes and complications. Median follow-up was twelve years. In total, 96 patients (92%) received a first-line treatment consisting of splenectomy (n=13), interferon-α (n=13) and cladribine (n=70). This last therapy resulted in the best response rates (overall response (OR) 99%, complete response (CR) 71%) and a long-lasting progression-free-survival (median PFS ten years). Forty-three percent of patients received multiple therapies for subsequent relapses. The median number of treatment lines was one. The median overall survival (OS) was 30.8 years with a 5-year and 10-year OS of approximately 98% and 91%. Although the prognosis of HCL patients is very good, infections and second malignancies are frequently observed. In this cohort, 55% of the patients had a major infection with an infection-related mortality of 3%. After diagnosis, 22% of the HCL patients developed one or more second malignancies, ranging from 1–3 per patient, with a 10-year cumulative risk of 14.5%.

(BELG J HEMATOL 2024;15(6):249–56)

Circulating cell-free DNA: A novel pathway to the genome of Hodgkin lymphoma

SUMMARY

The low abundance of Hodgkin/Reed-Sternberg (HRS) cells in lymph node biopsies in classical Hodgkin lymphoma (cHL) complicates the analysis of somatic genetic alterations in HRS cells. As circulating cell-free DNA (cfDNA) contains circulating tumour DNA (ctDNA) from HRS cells, we prospectively collected cfDNA from 177 patients with newly diagnosed, mostly early-stage cHL in a monocentric study at Leuven, Belgium (n=59) and the multicentric BREACH study by Lymphoma Study Association (n=118). To catalogue the patterns and frequencies of genomic copy number aberrations (CNAs), cfDNA was sequenced at low coverage (0.26×), and data were analysed with ichorCNA to yield read depth-based copy number profiles and estimated clonal fractions in cfDNA. At diagnosis, the cfDNA concentration, estimated clonal fraction, and ctDNA concentration were significantly higher in cHL cases than controls. More than 90% of patients exhibited CNAs in cfDNA. The most frequent gains encompassed 2p16 (69%), 5p14 (50%), 12q13 (50%), 9p24 (50%), 5q (44%), 17q (43%), 2q (41%). Losses mostly affected 13q (57%), 6q25–q27 (55%), 4q35 (50%), 11q23 (44%), 8p21 (43%). In addition, we identified loss of 3p13–p26 and of 12q21–q24 and gain of 15q21–q26 as novel recurrent CNAs in cHL. At diagnosis, ctDNA concentration was associated with advanced disease, male sex, extensive nodal disease, elevated erythrocyte sedimentation rate, metabolic tumour volume, and HRS cell burden. CNAs and ctDNA rapidly diminished upon treatment initiation, and persistence of CNAs was associated with increased probability of relapse. This study endorses the development of ctDNA as gateway to the HRS genome and substrate for early disease response evaluation.

(BELG J HEMATOL 2023;14(4):183–5)

Outpatient management of patients with acute myeloid leukaemia during intensive consolidation chemotherapy: A feasibility study

SUMMARY

Introduction: Fit patients with acute myeloid leukaemia (AML) are treated with intensive therapy. This consists of an induction (intensive chemotherapy) and a consolidation (intensive chemotherapy and/or stem cell transplantation). Because of the risk of complications during these different cycles, patients are followed up in-hospital in most Belgian centres. However, the consolidation course is considered tolerable and could possibly be followed up on an outpatient basis, which may also have a financial and psychological benefit.

Objective: To identify patients for whom an outpatient approach is medically justified. To this end, prognostic factors predicting the development of neutropenic fever, intensive care unit (ICU) admission and chemotherapy-related mortality (day 30 mortality) were investigated.

Methods: Retrospective analysis of all patients aged sixteen years and older with a new diagnosis of AML who underwent at least one consolidation course at the Ghent University Hospital during the period February 2016 to November 2020.

Results: One hundred and fifty-five cycles of consolidation chemotherapy were listed in 83 patients. The average duration of hospitalisation was 22.4 days. At least one episode of neutropenic fever occurred in 52 courses (33.5%). The occurrence of neutropenic fever in the previous cycle of chemotherapy was significantly associated with a higher risk of developing neutropenic fever in the subsequent cycle (p = 0.04). In a multivariate analysis, this parameters were associated with neutropenic fever with an odds ratio of 1.9 (0.90–4.01) (p = 0.09). Given the rare occurrence of an ICU admission (n = 3) and early mortality (n = 1), it was not meaningful to perform statistical analysis on this.

Conclusion: Outpatient follow-up of a consolidation chemotherapy cycle for AML is feasible. Prospective follow-up research is needed to confirm this and to investigate the economical and psychological impact.

(BELG J HEMATOL 2023;14(3):139–44)

Anaemia and its association with asymptomatic malaria, iron and zinc deficiencies, and Ferroportin Q248H mutation in children aged under five years in South Kivu, Democratic Republic of Congo

SUMMARY

Anaemia is a public health problem affecting one quarter of the global population with significant health consequences as well as an adverse impact on social and economic development. In malaria endemic areas, Plasmodium infection remains the major cause of anaemia. The ferroportin Q248H mutation has been described to protect red blood cells against oxidative stress and malaria infection. The objective of this study was to describe the main mechanisms causing anaemia and the role of ferroportin Q248H mutation in relation with anaemia and malaria in childhood in a Bantu population living in the volcanic region of South Kivu. 1088 healthy children aged under five years were randomly selected in the health zone of Miti Murhesa in South Kivu/Democratic Republic of Congo. Almost 40% of children under five years were anaemic, submicroscopic Plasmodium infection was as high as 22.3%. The prevalence of ferroportin Q248H mutation was 11.4%. No difference was observed in the frequencies of malaria or anaemia between ferroportin mutated compared to ferroportin wild type children. The prevalence of iron deficiency was found to be high (49.1%) when free erythrocyte protoporphyrin (FEP) was used to assess iron status. We found zinc deficiency in 17.6% of children. The prevalence of anaemia in South Kivu remains high, children with low parasitemia detected by loop mediated-isothermal amplification assay (LAMP) but not by microscopy showed a significantly increased prevalence of anaemia. Ferritin, an acute phase protein of infection is less suited to assess iron status in endemic areas of Plasmodium infection.

(BELG J HEMATOL 2022;13(7):281–3)

Genetic drivers of peripheral T-cell lymphomagenesis

SUMMARY

Peripheral T-cell lymphomas represent an unmet medical need. The paucity of biological studies impedes the development of new treatment strategies. In this doctoral thesis, I leveraged next-generation sequencing technologies to identify new gene fusions in peripheral T-cell lymphomas. These insights were used to engineer cell systems and mouse models, which closely resemble human peripheral T-cell lymphomas. These models are valuable tools to understand the biology of peripheral T-cell lymphomas and provide a rational for new treatment regimens.

(BELG J HEMATOL 2022;13(6):253–5)

TCR-based T cell immunotherapy for AML: Multidimensional aids in optimising treatment and patient identification

SUMMARY

Acute myeloid leukaemia (AML) has a dismal outcome, as demonstrated by a 5-year overall survival rate of only 26%. Although a complete remission can be achieved in approximately 50% of the patients with classical chemotherapy, the chances of relapse are high. Current treatment options for relapsed or refractory AML only offer a bridge to allogeneic haematopoietic stem cell transplantation since no other curative option exists. In primary refractory patients, and patients at high risk for relapse, harnessing the power of the immune system with immunotherapy might provide a new treatment option. In this dissertation, we approached AML immunotherapy from two sides: the optimisation of TCR-based immunotherapy for AML, and of the identification of patients eligible for this type of treatment.

(BELG J HEMATOL 2022;13(4):165–7)