How to understand if and when a myelodysplasia will evolve into acute leukemia? The answer from a new genetic test – breaking latest news

There are about three thousand Italians, mostly over seventy, who discover that they have a myelodysplastic syndrome, also called myelodysplasia. A name that groups though a diverse group of rare blood disordersvery different from patient to patient, ranging from “indolent” conditions, i.e. slowly progressing that make no difference on the life expectancy of the person concerned, to cases progressing rapidly to acute myeloid leukaemia. How to distinguish from each other? What is the chance that a patient with myelodysplastic syndrome will develop leukemia? An answer, which is also fundamental for establishing the necessary treatments, comes from a study just published in the scientific journal Journal of Clinical Oncology
which he developed a new tool to significantly improve the ability to predict the risk of leukemic evolution on the basis of the genetic profile of the individual patient.

Various parameters to be measured to choose treatments

«Myelodysplastic syndromes are blood disorders caused by damage to bone marrow stem cells – explains Matthew Della Porta, head of the Leukemia and myelodysplasia Unit at IRCCS Humanitas in Milan and coordinator of the study —. The damaged stem cells fail to produce an adequate amount of functional blood cells and this leads to a shortage of white blood cells, red blood cells and/or platelets. Often in the initial stage there are no obvious symptoms and the disease is therefore diagnosed late, or accidentally thanks to blood tests done for other reasons. But if discovered in time, it can be counteracted (there are many new therapies available) and prevent it from evolving into leukemia ». The most relevant complications, especially in the initial stages of the disease, are anemia, thrombocytopenia and recurrent infections. Up until a few years ago, the treatment of patients was based almost exclusively on supportive therapy which aimed to mitigate the symptoms, especially related to anemia (present in almost all patients), while today more and more effective therapies have arrived which improve in important way the life of patients. The drugs to be administered are different and are prescribed on the basis of certain criteria that they take into consideration the specific subtype of syndrome that the person suffers fromhow it evolves, the reactions and the patient’s quality of life.

The study to evaluate the optimal therapeutic path of each patient

Haematologists usually decide which treatment strategies to propose to patients on the basis of a “clinical score” (IPSS-R), obtained on the basis of indicators such as the number of leukemia cells in the bone marrow, the levels of white and red blood cells and platelets in the blood (cytopenias), and abnormalities in the chromosomes of blood-forming cells (cytogenetic abnormalities). Also for the decision to execute a hematopoietic stem cell transplant (the only definitive cure, able to lead to recovery, but often too heavy to tolerate for the elderly) is normally taken considering the parameters of this score, which however does not contain information on the genomic profile of the syndrome. «It is an increasingly important aspect to evaluate the impact of the disease on the quality and life expectancy of each patient continues Della Porta. Thus he was born the study that led to the development of the “molecular score” (IPSS-M) which demonstrated, on 2,876 patients with myelodysplastic syndromes, of significantly improve the ability to predict the risk of leukemia evolution and life expectancy. It uses the molecular data of the disease detected in each patient with a test on 31 genes and it is especially useful in evaluating the optimal therapeutic path for each patient. Indeed the possibility of identifying on the basis of the molecular profile people at highest risk of disease progression allows for optimize the choice of treatments and the most appropriate moment in which to intervene, as well as identifying candidates for the hematopoietic stem cell transplantation and when”.

New technologies for a vast amount of data

The study coordinated by Matteo Della Porta was conducted in collaboration with Gastone Castellani of the University of Bologna, within the GenoMed4All European consortium, with the support of EuroBloodNET, the European reference network for rare hematological diseases, and the AIRC Foundation for cancer research. Molecular testing is not yet routine around the world due to cost and infrastructure required. “The development and application of innovative methods with which to analyze and integrate large amounts of clinical and genomic data have made it possible to shorten the time with which research results can be translated into a practical benefit for patients – he concludes Elisabetta Sauta, data scientist at Humanitas AI Center —. In fact, the technologies used help to define and improve prediction models useful for diagnosis and increasingly targeted therapeutic decisionstaking into account individual patient variability. It is important to underline that these results were also achieved thanks to the multidisciplinary collaboration between clinicians, researchers, data scientists and other European partners: a collaboration that has made it possible to respond to the specific clinical needs of such heterogeneous diseases”.