A. Uyttebroeck MD, PhD

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

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)

Retrospective study of infant leukaemia in the University Hospitals of Leuven and Ghent

SUMMARY

Infant leukaemia is a rare disease but the 3^rd most frequent malignancy in this age group. Both acute lymphoblastic leukaemia and acute myeloid leukaemia in the first year of life have particular clinical and biological characteristics such as B-cell phenotype with co-expression of myeloid markers in acute lymphoblastic leukaemia, FAB M5 or M7 in acute myeloid leukaemia, the presence of extramedullary symptoms and a high frequency of KMT2A rearrangements. Survival rates for infant acute leukaemia are worse than for older children. In this study, the characteristics and outcome of 50 infants with acute lymphoblastic leukaemia and acute myeloid leukaemia treated at the University Hospitals of Ghent and Leuven between 1989 and 2015 were studied and correlated with literature data. With event-free survival and overall survival rates of 44% and 52% for the entire cohort, the outcome of these patients was comparable to those in published clinical trials. In general, the event-free survival and overall survival was superior in acute myeloid leukaemia compared to acute lymphoblastic leukaemia infants and not influenced by age (< or ≥6 months), white blood cell count at diagnosis or presence of a KMT2A rearrangement. For future trials in infant leukaemia, the high number of early deaths, toxic deaths and relapses remain the most challenging problems.

(BELG J HEMATOL 2018;9(2):57–63.)

P06 Targeted single cell sequencing unravels the heterogeneity of human T-cell acute lymphoblastic leukemia samples

O.6 Non-invasive Detection of Genomic Imbalances in Hodgkin/Reed-Sternberg Cells in Early and Advanced Stage Hodgkin Lymphoma by Sequencing of Circulating Cell-free DNA

Minimal residual disease quantification by PCR in childhood acute lymphoblastic leukaemia

Summary

In Belgium approximately 70 children are diagnosed with acute lymphoblastic leukaemia annually. For these children, the monitoring of minimal residual disease has an important prognostic value. The level of minimal residual disease during the first three months of therapy is used to recognise subgroups that differ substantially in outcome. Two techniques are used for minimal residual disease monitoring: the Genescan method and the allele specific oligonucleotide polymerase chain reaction. The Genescan method is a less sensitive method (10⁻³) but is fast and less expensive. The allele specific oligonucleotide polymerase chain reaction requires more time and budget but has a sensitivity of 10⁻⁴–10⁻⁵. Both techniques have proven their value in minimal residual disease monitoring in childhood acute lymphoblastic leukaemia.

(BELG J HEMATOL 2014;5(3):81–8)

P2.09 Impact of minimal residual disease monitoring on therapy in Belgian childhood acute lymphoblastic leukaemia

O.1 Exome sequencing identifies mutation of the ribosome in T-ALL