Over 70, with ‘phantom’ symptoms and other health problems such as tumors or cardiovascular diseases that make them particularly fragile. This is the identikit of the patient with a myelodysplastic syndrome as it emerges from the first national census conducted on over 6,000 patients in 70 centers located throughout the country by the Italian Association of Myelodysplastic Syndrome Patients (AIPaSIM) together with the Italian Myelodysplastic Syndromes Foundation ( Fisim) has decided to create and publish an important update of the Pathology Register. A picture that has brought out the need to personalize the therapy more and more through the sequencing of the DNA of each patient and innovative therapies capable of targeting specific molecular alterations.
The register of myelodysplasia
The Pathology Register was created by Fisim in 2011. With the new census, 288 new cases of myelodysplastic syndrome were entered, compared with a retrospective series (2011-2018) of 6,309 patients. “For too long, myelodysplastic syndromes have not been adequately perceived not only with respect to their spread, but above all with regard to the socio-health impact that they actually generate on patients and on society more generally”, he explains Paolo Pasini, President of AIPaSiM. “This first register, which will be updated annually, created with the contribution of Fisim, allows us as an Association to collect the most important information to support the patient community and draw the attention of institutions and the health system for a better diagnostic care path “. Among the data that emerged from the census, there is that relating to the age of patients which has increased over time and is currently 77 years old. Furthermore, in 2/3 of cases other chronic diseases such as cardiovascular diseases or tumors are already present and the arrival of myelodysplasia means breaking the balance of care for these patients.
The stage of diagnosis
Myelodysplastic syndromes are complex blood disorders, classified as rare diseases, which mainly affect people in old age and manifest themselves through anemia, decreased white blood cells and thrombocytopenia. They have an incidence of about 3,000 new cases per year, even if in some cases the patients do not receive a correct diagnostic classification and for this reason they do not start the therapeutic path in a timely manner. In fact, the Registry shows that, at the time of diagnosis, about 70% of cases are diagnosed at an early stage of the disease, while in about 30% of cases the disease is already advanced. “Currently it is possible to make an accurate diagnosis and a correct assessment of prognosis through blood tests, marrow aspiration followed by a biopsy and cytogenetic tests that are used to determine which chromosome modification has occurred” he declares Matteo Della Porta, head of the Leukemia Unit – IRCCS Humanitas Research Hospital, Milan and President of the AIPaSiM Scientific Committee.
The mapping of the genome
From a diagnostic point of view, in recent years, there has been a revolution thanks to the study of the genome. “Today, through DNA sequencing with new generation technologies – continues Della Porta – it is possible to produce a specific mapping, for each patient, of the molecular defects of the disease. Another very important thing is that this technology has recently been included in the LEA (Essential Levels of Assistance) as a diagnostic test relevant to people with myelodysplastic syndrome and this will allow from now on to develop targeted diagnosis, therapy and health care pathways. “.
Therapies and transplantation
Myelodysplasias are extremely heterogeneous pathologies: they range from patients who have the same life expectancy as the general population of the same age, to cases that, on the other hand, have a very rapid evolution into acute leukemia within a few months. The therapy changes according to the level of risk, i.e. the severity of the disease. “Over the past 10-15 years, the survival and quality of life of high-risk patients has increased, moving from transfusion to more targeted drugs such as azacitidine – he explains Valeria Santini, Head of the MSD Unit, AOU Careggi, University of Florence, and President of the FISiM Scientific Committee. But often the improvements have only temporary improvements and this happens in about 60% of patients. To date, stem cell transplantation is the only cure that can erase the disease in most cases, but only 4% of patients can access it ”. Unfortunately, even from the census data, it emerges that there are still few patients who have access to transplantation also due to their advanced age which makes them more fragile and therefore less suitable for the risks of this type of intervention.
Innovate with experimentation
Thanks to the latest scientific discoveries, it is possible to identify both from a clinical point of view and from a biomolecular point of view, an adequate therapeutic choice, “targeted” for that particular patient. “Experimental studies with innovative drugs – continues Santini – allow patients to be able to use, without any risk, drugs which, as they undergo clinical trials, will only be available in one or two years. Patients are followed with great attention within the experimental protocols, all obviously approved and controlled, even if to date in Italy the percentage of patients participating in clinical trials is only 3%.
Recently, new drugs have been approved such as the very recent inhibitor of the TGF-beta signaling pathway for the treatment of anemia in low-risk myelodysplasia, or, now a few years ago, hypomethylating drugs that reduce the risk of evolution into leukemia in high risks. The latter have contributed to revolutionizing the therapeutic approach to the patient with myelodysplasia. “These are innovative therapies capable of targeting specific molecular alterations that have been shown to significantly increase patients’ response and, in some cases, their survival, with long response durations – says Santini.
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