Hematology of Perugia, an Italian excellence. Prof. Martelli: “It is often hard, but what we can give is beautiful”

Interview with Professor Maria Paola Martelli, acting director of Hematology at the Hospital Trust of Perugia. «Here we can welcome pain, give comfort and hope, provide professionalism and save lives. The effort is also rewarded by the smiles and infinite thanks of patients and their families».

It is the story of a patient suffering from an extremely aggressive acute leukemia (which can cause death within 48-72 hours) that Professor Maria Paola Martelli, acting director of Hematology at the Santa Maria della Misericordia Hospital Trust of Perugia, tells us, with a voice marked by emotion. A case that, after years, still moves her: «I apologize, this memory moves me.»
It all started ten years ago. The patient, a Jehovah’s Witness, refused the transfusions without which she could not have been treated and would not have survived. She made a difficult choice, putting her faith aside, to care for her daughter who was suffering from cancer, and she sought treatment. She recovered, but her daughter unfortunately did not make it. Ten years later, now in her eighties, she had a relapse. This time, however, she had no reason to go beyond her faith: her daughter was no longer there; so she refused to undergo blood transfusions. The professor and her collaborators did not give up and thanks to targeted therapies – available today compared to 10 years ago – they were able to treat her without subjecting her to transfusions. Today she continues to undergo her treatments, but she can consider herself cured.

Professoressa Maria Paola Martelli nel Centro Ricerche Emato-Oncologiche (CREO). Foto di Marco Giugliarelli

“In cases like this, courage and humanity are needed from many points of view. Everyone must be respected in their beliefs and in the way they decide to live their life. Knowing that there are innovative non-chemotherapy therapies that can be used in some conditions leads you to dare. You have to push to be able to reach recovery, if you believe in that therapy. This was a case that I will never forget: for how we managed it, for the strong unity of intent, for the result and for the emotional involvement. It was a great satisfaction especially from a human point of view. I admit that it is often hard but what we can give is beautiful, we can welcome the pain, give comfort and hope, give professionalism and save lives. The effort is also repaid by the smiles and infinite thanks of the patients and their families” says Professor Martelli.

The Hematology Department of Perugia is an Umbrian excellence, but not only: it collaborates with several Italian and foreign hospitals, and has obtained – for the second time – the global JACIE accreditation (Joint Accreditation Committee-ISCT & EBMT) to promote high quality standards in the field of hematopoietic stem cell transplantation and cellular therapies.
This certification gives the opportunity to implement transplants and innovative therapies, without which they could not be implemented. «In order to have this accreditation, all the procedures that concern the transplant – from the manipulation of the cells to the collection, from freezing to thawing, from transport from the laboratory to the department, to the hospitalization of the patient, up to the drafting of the medical record – must be written respecting the rigorous adherence to very specific rules and guidelines. It is a work carried out, with the collaboration of everyone, by the Transplant Program coordinated by Dr. Alessandra Carotti with the fundamental role of the Nursing Coordinator of the department. In short, it is a certification of the quality path at an international level, and, as with all quality paths, it requires deep experience and teamwork to maintain it. In our country, the transplant center is integrated with the department: this makes the structure, if you like, even more articulated and complex, but it represents a great advantage for the patient who – from diagnosis to treatment – is followed throughout the process at the same center in shared and coordinated paths” continues Martelli.

This department – which has 38 beds – is not only visited by Umbrians, but also by patients from other Italian regions or from abroad, in particular to be candidates for therapies and certain types of unique transplant procedures, which at the moment are only being implemented here.
In Hematology, many different pathologies are treated, from non-oncological forms, even very frequent ones, such as iron-deficiency anemia or vitamin deficiency, hemolytic anemia or autoimmune thrombocytopenia, to serious and even very aggressive hemato-oncological conditions that require immediate hospitalization, a timely diagnosis and therapy within three days. The timeliness of action, the high specialization in care and assistance and in diagnostics, for some serious pathologies, make the difference. In short, the cases that arise are varied and put the department’s healthcare forces into play, with an engaging commitment, not only from a medical point of view, but also human, both with the patient and with the family.
However, there is no shortage of difficulties. “It is difficult to find space for all the patients, many of them we follow in Day Hospital, but many need highly specialized hospitalizations in our departments. We could increase our catchment area also by coordinating with other facilities in the Umbrian territory; to date any hematological patient who needs hospitalization turns to us, which is why we are overloaded. It should be added that innovative treatments often require a prolonged period of assistance as the treatment options involve several steps. In this context, the Chianelli residence gives us a great help by hosting patients and their families, as a certified facility for outpatients, it has recently expanded and includes 50 apartments. The ideal is to “insert it into the network”! But that’s not enough. It is essential – with training, collaboration, sharing, support and adequate assistance – to ensure that all the territorial realities of Umbria are able to manage different types of patients, in the various phases of the disease, perhaps also using telemedicine. The projects to be developed are there and the vision as well. We just need to work through discussion and together” explains the professor.

Innovative therapies

Hematology covers a wide range of patients with extremely complex pathologies. Nowadays, the innovative therapies available concern both the oncological and non-oncological fields. However, this type of treatment is mostly aimed at acute leukemia, lymphomas, and myelomas. Precision therapy is the cutting edge of therapies: it aims to exclusively target diseased cells, avoiding healthy or vital cells (such as cardiac cells). However, the basis is always standard therapies – such as chemotherapy for acute leukemia or some forms of lymphoma – which still represent the starting point and give concrete healing results in many cases. For many pathologies, precision therapy is combined with standard therapy, while in some cases it can intervene immediately.

Innovative therapies can be pharmacological: new molecules designed in the laboratory and created to target a very specific genetic alteration. These drugs inhibit the oncogenic protein that caused the development of the tumor and the growth of diseased cells, thus leading to the reduction of the pathology. They are often drugs that are administered orally and their variety makes them act in different types of pathologies. «Fundamental – for a targeted intervention – is the framing of the disease in its most specific case (for example: it is not enough to identify an acute leukemia, you need to know which genetic alterations it has and which can be hit with a precision drug). This type of therapy can often be implemented immediately, which is why the diagnosis must be timely. This is guaranteed by the Integrated Diagnostics Laboratory divided into eight functional units and coordinated by Dr. Roberta La Starza; thanks to them, the pathology is framed and the target to aim for is defined to identify the most specific treatment, which sometimes must begin in a very short time (even 5 days). This requires rapid and coordinated action between clinicians and laboratory hematologists. The precise characterization of the disease can, for example, also tell us in advance whether or not that patient will need a transplant: this is extremely important information for establishing his treatment path and the possible involvement of family members or registry donors” explains the professor. Both the clinical center and the Hematology laboratories are – since 2021 – also AIFA certified for Phase 1 Clinical Trials, which guarantees patients with various pathologies access to new drugs and therefore to new treatment opportunities otherwise unavailable.

La prof. Martelli con alcuni ricercatori del CREO

Another type of innovative therapies are cellular ones, that is, cells (and not drugs) capable of specifically attacking diseased cells: an example are CAR-T. They are taken from the diseased subject, modified in the laboratory and grafted to be directed – in substitution of the immune system that has failed to block the tumor – towards the diseased cells. But there are not only CAR-T. In transplantation, specific lymphocytes – called regulatory T cells – for example, are used to protect the patient from a possible attack of the transplant towards the recipient, what is called graft-versus-host disease (GVHD): they intervene by blocking GVHD but not the ability of the immune cells to react against the disease. This is a protocol designed and implemented for the first time right here in Perugia. Cellular therapies are certainly extremely complex therapies that see the fundamental role and coordinated work of the clinical team and the Laboratory of Cellular Manipulation and Therapies, coordinated by Professor Antonio Pierini in our center and the Immuno-Transfusion Service directed by Dr. Mauro Marchesi.

«Transplants are also the subject of cutting-edge research at an international level and require multidisciplinary work. Specifically, in collaboration with the US center City of Hope Cancer Center (in California) and the Oncology Radiotherapy directed by Professor Cynthia Aristei, an innovative protocol has been developed that involves the use of a non-standard radiotherapy with an advanced machine (helical tomotherapy) capable – after careful planning – of precisely adapting the type of radiation to the patient’s bone structure, following his physical conformation. In this way the rays are directed only at the areas of the bone marrow or lymph nodes, sparing the attack on healthy and vital organs such as the heart, liver and intestine and reducing toxicity enough to be able to use this type of treatment even on older people. I would like to conclude by saying that hematological diseases are often curable, but for some more serious pathologies there is still a lot to do: research is very important, which we – both as a university structure affiliated with the Department of Medicine and Surgery and as a structure of the Hospital Trust of Perugia – promote and on which we focus with the support of public and private entities. Research has changed the history of many diseases, we have seen it firsthand. In the last 25 years there have been extraordinary changes, I have witnessed a crazy evolution that has materialized only thanks to study, research and their integration with the clinic.” concludes Martelli.

Translation made by an automatic tool