New Markers Discovered in Chronic Lymphatic Leukaemia

A study identified markers in chronic lymphatic leukaemia associated with the risk of Richter syndrome, or progression of leukaemia into an aggressive lymphoma.

Chronic lymphatic leukaemia: Discovering markers leading to its development into aggressive lymphoma

New research published in the journal Haematologica identified the main markers associated with the risk of developing Richter's syndrome and, by integrating the data, the research team succeeded in developing a prognostic score for Richter's syndrome. With this tool at the time of diagnosis of chronic lymphatic leukaemia, it will be possible to identify the risk of developing Richter syndrome 10 years later (3% in low risk, 31% in high risk).

Chronic lymphatic leukaemia is a rare cancer but still the most frequent type of leukaemia affecting Western populations. It is characterised by a wide clinical variability. Some patients will never need treatment and have a very good survival, while others unfortunately suffer from a disease that requires numerous treatments and have a poorer chance of survival.

“Patients can develop various complications including autoimmune diseases, second neoplasms and Richter's syndrome,” explains Dr Andrea Visentin, researcher at the Department of Medicine of the University of Padua and first author of the study. The latter is the least common but most serious complication of this type of leukaemia, as the median survival of these patients is less than one year.

A number of markers are responsible for this heterogeneity. These include abnormalities, namely deletion or mutation of the TP53 gene, the mutation status of the genes for the variable portion of immunoglobulin heavy-chains (IGHV), and the presence of at least three chromosome alterations (complex karyotype). The haematology group in Padua, of which I am a member, has been working on this for more than 10 years and has actively contributed to scientific progress.”

Examining the largest group of patients treated with ibrutinib

In a second newly published study in the prestigious American Journal of Hematology, researchers from the Padua haematology department published another very important study.

“The treatment of chronic lymphatic leukaemia has radically changed over the last 10 years. Today, almost no one is treated with chemotherapy any more, except for very few selected cases,” explains Livio Trentin, Professor of Haematology at the University of Padua and Director of the UOC of Haematology at the University Hospital of Padua. “Today, nearly all patients receive targeted biological drugs such as BTK and BCL2 protein inhibitors. Given the high cost of these drugs, it is crucial to understand exactly how best to use them and how to manage possible side effects. This is why our team joined forces with researchers from 15 other institutes throughout Italy. Our goal was to examine the largest group of patients with chronic lymphatic leukaemia with TP53 abnormalities who were treated with ibrutinib. We succeeded in analysing not only the drug's efficacy but also its side effects.”

“Until now, clinical trials have included a maximum of 20-30 patients with an unfavourable prognostic change," Visentin continues. “With this large national study group, we were able to collect data from 100 patients treated first-line with ibrutinib. This resulted in important news with practical implications for our daily work.”

Scientific collaboration is key

Prof. Trentin concludes: “These studies are the result of a fundamental networking activity that we are developing with the Istituto Oncologico Veneto (IOV), the haematology units in Veneto thanks to the Rete Ematologica Veneta (REV), as well as other Italian haematology centres thanks to AIL-GIMEMA and European centres. The importance of these studies also lies in the social aspect because they were carried out thanks to the support of the voluntary association Ricerca per Crede nella vita (RCV), an association created by Franca Boschello, a patient I followed with my team for 16 years. Unfortunately, she passed away in 2020 due to a complication of this disease.”

Visentin A, Bonaldi L, Rigolin GM, Mauro FR, Martines A, Frezzato F, Pravato S, Gargarella LR, Bardi MA, Cavallari M, Volta E, Cavazzini F, Nanni M, Facco M, Piazza F, Guarini A, Foà R, Semenzato G, Cuneo A, Trentin L. The complex karyotype landscape in chronic lymphocytic leukemia allows the refinement of the risk of Richter syndrome transformation. Haematologica. 2022 Apr 1;107(4):868-876. doi: 10.3324/haematol.2021.278304. PMID: 34092056; PMCID: PMC8968897.