The innovative use of arsenic trioxide (Ato) in tablets orally, and no longer intravenously, the improvement of therapeutic regimes for the treatment of elderly patients, up to new discoveries on the complications of the disease and post-treatment. These are some of the main topics that Italian and international hematologists discussed during the eighth International Symposium on Acute Promyelocytic Leukemia (APL) in Rome on 10, 11 and 12 April. At the center of the meeting were the latest challenges to overcome in the treatment of patients suffering from Lap as well as to commemorate Professor Francesco Lo Coco, who passed away in 2019, who with his research changed the history of Lap, also known as fulminant leukemia.
At the opening of the proceedings, the haematologists – reports a note – discussed in particular the optimization of therapeutic regimens without chemotherapy and the prevention of long-term relapses. Maria Teresa Voso, full professor of Hematology at the University Hospital of Rome Tor Vergata, among the scientific coordinators of the event, presented the data from the vast Apl Harmony database which highlights factors such as advanced age and high risk (according to classification currently in use) as associated with lower patient survival. The combination of all-trans retinoic acid (Atra) and Ato without chemotherapy has proven to be the best therapeutic option for the so-called “standard” risk groups, with high long-term survival rates and a reduced probability of relapse compared to other regimens therapeutic.
Significant updates have also been dedicated to the treatment of important complications of Lap. The results of recent studies presented during the symposium suggest that leukemic stem cells could play a significant role in the genesis of coagulopathy, a typical complication in which patients present with potentially lethal abnormal bleeding at the onset. It has been observed – the note details – that a specific subgroup of these leukemic cells could be responsible for the regulation of coagulation, thus suggesting the existence of new potential therapeutic targets and the development of more effective strategies to manage this complication.
Voso and Marco Vignetti, president of the Gimema Foundation, reviewed the present and future of Lap. “Franco Mandelli was the first Italian hematologist to learn to recognize this strange form of leukemia, learning in Paris from the discoverer of the disease, the hematologist Jean Bernard – said Vignetti – Mandelli's research was completed by Lo Coco, thanks also to his great organizational skills, as well as those of a valid researcher and laboratory technician”.
Yesterday, however, was dedicated to updating the new therapies being tested. Harry J Iland, professor of medicine at the University of Sydney, Australia, and medical specialist at Royal Prince Alfred Hospital, presented the results of a relevant study on the use of oral arsenic. Standard Ato-based therapy – we read in the note – requires prolonged infusions of two hours. This procedure, although effective, has an impact on the use of hospital resources and patient comfort. Oral Ato could thus represent an advantageous alternative from an economic point of view and perhaps also in terms of safety, but its availability for clinical use is currently limited mainly to China and Hong Kong.
Iland's study focused on the availability of a new oral formulation of Ato, developed as part of standard consolidation therapy for the treatment of Lap. The research confirmed the bioequivalence between oral and intravenous administration, which could open new perspectives in the management of the disease. In parallel, other researchers, such as Hongming Zhu of the Shanghai Institute of Hematology, are exploring the possibility of chemotherapy-free post-induction therapy for Lap patients, regardless of risk classification. This is a post-remission treatment completely free of chemotherapy – it emerged from the symposium – that includes oral maintenance therapy. A new perspective that could lead to significant benefits for a greater number of patients.
Today the work concluded with the Gimema national meeting during which the researchers updated doctors and researchers in hematology from all over Italy on the ongoing research activities, studies and projects carried out by the 9 working parties which embrace the majority of hematological pathologies, both of a neoplastic and non-neoplastic nature, and address more “transversal” topics such as quality of life and infectious complications, which, as is known, are very frequent in patients undergoing therapies such as marrow transplants.
Currently, there are more than 50 ongoing studies promoted by the Gimema Foundation – concludes the note – and see the active participation of almost all the Italian hematology centers – spread throughout the national territory – which belong to the Gimema network. Also important on this day was the session dedicated to laboratory activities both for the healthcare part (LabNet Network) and for the translational research part.
The three days of events were held thanks to the support of Ail – Italian Association against Leukemia, lymphoma and myeloma, Ail Rome, Ail Bari, European hematology association (Eha), the University of Tor Vergata; with the non-conditioning contribution of Abbvie, Amgen, Novartis, Astellas, AstraZeneca, Bristol Myers Squibb, Roche, Incyte, Jazz Pharmaceuticals, Servier Italia and with the patronage of the Italian Society of Hematology (Sie) and the Italian Society of Experimental Hematology (Sies ).
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