I. Moors MD

Germline predisposition in the context of acute myeloid leukaemia: A single-centre descriptive study of current practice and review of the literature

SUMMARY

The awareness of potential germline predisposition in patients with acute myeloid leukaemia (AML) has increased in the years since NGS testing with large gene panels became standard of care. Yet, it must be noted that still little is known regarding incidences in the Belgian population and specific guidelines for clinical practice are lacking. This narrative review attempts to provide an overview of the most common germline variants in the context of AML, optimal diagnostic approaches, and the impact on the patient and family. In a retrospective study of a cohort of 241 AML-patients, we describe the current situation at Ghent University Hospital. Using the available NGS panels, we identified twelve patients with germline pathogenic variants: 5.0% of the total cohort, 34.3% of the patients that were referred for germline testing. It must be realized that the NGS panels expanded during the study period, and probably will expand further in the future: the amount of germline pathogenic variants will likely be higher. This demonstrates the importance of awareness for underlying germline predisposition, and the implications for the patient, their family, as well as during donor search in case of allogenic stem cell transplantation.

(BELG J HEMATOL 2024;15(4):135–46)

Highlights from the 18^th biannual symposium Acute Leukaemias (ISALXVIII)

SUMMARY

Leading topics at the international symposium Acute Leukaemias (ISALXVIII) in 2023 were: the new classifications for acute leukaemia, interpretation of clonal haematopoiesis (CHIP), advancing insights of venetoclax-azacitidine (VEN-AZA) administration and associated supportive care, the position of new treatment options in fit and unfit patients, the renewed role of maintenance, and first steps in bringing immunotherapy to the acute myeloid leukaemia (AML) population.

(BELG J HEMATOL 2023;14(4):186–91)

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)

Venetoclax-Azacitidine, the new standard of care for AML patients unfit for intensive treatment: A guide for clinical practice

SUMMARY

Acute myeloid leukaemia is an aggressive form of bone marrow cancer with poor prognosis, especially in elderly, unfit patients. The VIALE-A study showed an impressive improvement in complete remission rate and overall survival with the addition of venetoclax, a BCL-2 inhibitor, to azacitidine. This combination therapy is now reimbursed in Belgium for newly diagnosed adult AML patients who are considered unfit for intensive chemotherapy based on age and/or comorbidities. In this article, we provide recommendations on the use of this new combination, as well as on prophylaxis and management of specific side effects.

(BELG J HEMATOL 2023;14(2):59–66)

A multicentric observational study on the management of hyperleukocytic acute myeloid leukaemia in Belgium

SUMMARY

INTRODUCTION

In hyperleukocytic acute myeloid leukaemia (AML) the risk of leukostasis is high due to the rapid increase in WBC count and the size of the myeloid blasts. It is associated with poor prognosis due to an increased risk of early death and relapse. Immediate initiation of cytoreductive treatment is essential to improve outcome, but evidence to prefer hydroxyurea, leukapheresis, intensive chemotherapy (IC) or a combination treatment, is lacking. Therefore, we decided to investigate the current approach of hyperleukocytic AML in Belgium.

METHODS

A brief questionnaire on the management of hyperleukocytic AML was sent to all Belgian centres currently treating AML with IC and was replied by ten centres. Four centres agreed to a more detailed retrospective analysis. All newly diagnosed AML patients presenting with hyperleukocytosis between January 2013 and April 2019 were included. Patient and disease characteristics were collected, as well as treatment choice and outcome parameters.

RESULTS

We included 121 patients with a median WBC count of 116,360/µL. Mortality at day 21 was 20% and overall mortality was 64% at a median follow-up of six months. Twenty percent received leukapheresis, which was started within 24 hours. There was no difference in age distribution, treatment intensity or time to start IC between patients receiving leukapheresis or not. Although the leukapheresis group had a more severe presentation with a higher median WBC and blast count and a worse performance status, there was no difference in response to therapy, early or long-term mortality. In a multivariate analysis, age at diagnosis and treatment modality (IC vs non-IC) were the only independent parameters that significantly affected early death.

CONCLUSION

Evidence on optimal treatment options in hyperleukocytic AML is lacking. We could not demonstrate any added value of leukapheresis. To improve the prognosis of this dramatic presentation, national or even European databases should be used to document and learn from the outcome of current practice.

(BELG J HEMATOL 2020;11(7):325-34)

Therapy-related myeloid neoplasms: epidemiology, pathogenesis and therapeutic options

SUMMARY

Therapy-related myeloid neoplasms are increasingly seen in our daily practice, as a consequence of increased long-term cancer survivorship and an aging population. Typically, there is an overrepresentation of high-risk cytogenetics and TP53 mutations. In recent years, there have been new insights in the pathogenesis of these neoplasms, especially with regard to the role of CHIP (clonal haematopoiesis of indeterminate potential) in patients receiving cytotoxic therapy for a malignant or non-malignant disorder. Unfortunately, prognosis seems worse in comparison to de novo AML, despite intensive induction and consolidation with allogeneic stem cell transplantation, with a high frequency of treatment-related toxicity and relapse. However, there is hope for the future with the emergence of novel therapies that could be of special interest in the context of these poor-risk leukaemias.

(BELG J HEMATOL 2020;11(6):261-7)

Big Children or Small Adults? Acute Myeloid Leukaemia (AML) Treatment in Adolescence and Young Adulthood

SUMMARY

Adolescents and young adults (AYAs), aged 15 to 39 years, with newly diagnosed acute myeloid leukaemia (AML) differ from both younger and older patients in terms of patient-specific as well as disease-specific factors. The improvement in outcome over time for this group is noticeably less than for their younger and older counterparts. Reasons for this are thought to be lack of standardisation of therapy, being treated with either adult or paediatric regimens, low trial participation and specific psychosocial factors. In this article, we review the distinct characteristics of AYA AML in order to address this issue and conclude that an AYA-specific approach and research are warranted to overcome stagnating outcome results.

(BELG J HEMATOL 2020;11(3):98–101)