Myelodysplastic neoplasms

Most patients present with an altered blood count. As mentioned above, there may be only anemia or neutropenia or plateletopenia, or two or all three cytopenias may coexist. Before confirming a diagnosis of myelodysplasia, it is necessary to conduct blood tests such as:

• reticulocytes, LDH, bilirubin to rule out a hemolytic process;
• Assessment of iron and vitamin (B12 and folate) balance to rule out deficiencies;
• Erythropoietin assay and transfusion history;
• Peripheral venous blood smear for morphological analysis;
• hepato-renal function tests, indices of inflammation, serum protein electrophoresis to exclude concomitant diseases that may give pictures of anemia/cytopenia (e.g., chronic hepatopathy, renal failure, chronic inflammatory states), thyroid function;
• Screening for HIV, HBV, HCV, parvovirus B19 (in the hypoplasmic forms), CMV;
• immunophenotype on peripheral blood to search for clones of paroxysmal nocturnal hemoglobinuria in selected cases.

To confirm a diagnosis of myelodysplasia, it is always necessary to To perform a bone marrow aspirate and an osteomedicular biopsy..

These examinations are usually performed concurrently, under local anesthesia, at the level of the postero-superior iliac crest of the pelvis (at the top of the buttock). In this procedure, bone marrow blood is aspirated and a small cylinder of bone is taken.

With the bone marrow aspirate, it is evaluated:

• morphological examination of the smear: a few drops of bone marrow blood are used to make a smear on a slide, which, after appropriate staining, is viewed under a microscope; observation under a light microscope still remains the fundamental method for the diagnosis and initial classification of myelodysplasias. This examination aims to identify morphological abnormalities of hematopoietic cells and quantify immature cells called blasts in circulating blood and marrow;
• immunophenotype in cytofluorimetry.: identifies abnormal cells, maturational changes, and quantifies blasts;
• cytogenetic examination: laboratory method that studies alterations in chromosomes, either by analysis of the global chromosome stock (karyotype) or more selective analysis such as FISH (fluorescent in situ hybridization), which allows identification of the presence of specific altered DNA sequences of chromosomes using fluorescent probes;
• Perls staining: for ring sideroblast counting (which identifies a subgroup of MDS and allows selection of targeted therapy);
• molecular biology tests: evaluate the presence of mutations in several genes (e.g., SF3B1, TP53, IDH1) and allow diagnostic framing, prognostic stratification, and can guide therapeutic choice (target therapies).

With bone biopsy, a specimen is obtained for histological examination, which evaluates:

• cellularity;
• Morphological and structural alterations;
• Blast count by immunohistochemistry;
• Assessment of the degree of spinal cord fibrosis.

According to international classifications and guidelines, specific cytogenetic and molecular abnormalities sometimes correlate with peculiar morphological aspects, and have diagnostic, prognostic, and therapeutic importance.

Therefore, these laboratory methods are essential in the evaluation of all patients with newly diagnosed MDS.

It follows that such diagnoses must be placed in highly specialized centers. The Candiolo Institute has all the most advanced diagnostic techniques and highly specialized staff, including networking with other national reference laboratories.

The investigations should be supplemented with biochemical and instrumental examinations (e.g., abdominal ultrasonography or echocardiogram) to evaluate any any comorbidities present.

In all patients who are candidates for active therapy, the general condition, performance status, and presence of other diseases should be evaluated in order to assess fitness and define the treatment program. In patients who are not fully autonomous, it is essential to consider the presence of someone who can help and assist the patient in choosing a treatment program.

The diagnostic procedures should allow the classification of patients according to the criteria formulated in 2022 by the international organizations WHO (World Health Organization) and ICC (International Consensus Classification), and according to the prognostic criteria assessed by the IPSS, IPSS-R and IPSS-M scores (see next paragraphs).

The majority of patients with MDS present with anemia. In low-risk patients, anemia therapy can make use of the transfusions of red blood cells and different drugs depending on the subtype of myelodysplasia.

The drug most commonly used as a first approach is theerythropoietin (EPO) recombinant. Erythropoietin is a hormone we produce to stimulate red blood cell production. In MDS this production may be insufficient, and if EPO levels are not too high a “synthetic” form can be administered subcutaneously. Recombinant EPO therapy leads to a increased hemoglobin levels or transfusion independence in 40-50% of patients, also improving survival in those who respond to therapy.

For patients with the form of MDS with ring sideroblasts or the SF3B1 mutation with unsatisfactory response or unsuitable for EPO therapy, luspatercept is indicated. Luspatercept is a “target therapy” that acts on red blood cell maturation via TGF-β binding by ameliorating anemia and reducing transfusion requirements in 30-40% of MDS-SF3B1/ ring sideroblast patients. It is administered subcutaneously every 3 weeks and is a chronic therapy.

Thanks to the results of a recent clinical trial, luspatercept will soon be available for patients with low-risk MDS who require transfusions and do not have the mutated SF3B1 form or ring sideroblasts.

Patients who have a particular abnormality of chromosomes, chromosome 5 deletion (MDS with del(5q)), and do not respond or are not eligible for EPO therapy may receive “target therapy” with lenalidomide. Lenalidomide is a chronic oral therapy that acts by driving the cells with the 5q deletion to death and leads to transfusion independence in up to 70% of patients with MDS of(5q), also improving their survival.

If the hemoglobin shows particularly low values, usually below 8g/dL, or below 10 g/dL if the patient is particularly symptomatic (presents with chest pain, difficulty breathing or conducting normal daily activities) or heart disease, red blood cell transfusions are performed, which allow the blood values to rise again, resulting in improvement of the symptoms complained of.

In the case of red blood cell transfusions that last for months, excess iron (which can cause problems in vital organs such as the heart, liver and endocrine glands) will also need to be removed with drugs called ferrochelating agents, also available in oral formulations, such as deferasirox.

In case of deficiency of white blood cellsneutrophils associated with infectious events, one can use growth factors aimed at increasing white blood cells (G-CSF).

In case of severe plateletopenia one can perform platelet transfusions; drugs that stimulate platelet production by mimicking the action of thrombopoietin hormone (thrombopoietin-mimetic) are also currently being studied.

Some patients who are not too old and in good general condition who have an underpopulated marrow (MDS – hypoplastic) and certain clinical and biological features may make use of immunosuppressants. These therapies act on the immune system with the aim of preventing the destruction of bone marrow hematopoietic cells and allowing bone marrow stem cells to grow, resulting in improved blood counts.

Younger patients in good general condition with persistent cytopenias who do not respond to conventional therapies and who present a potential risk to life may be considered candidates for allogeneic hematopoietic stem cell transplantation

In cases of intermediate-high risk MDS, there is a greater likelihood that the disease will evolve into acute myeloid leukemia. For this reason, it is important to start targeted therapy early.

The choice of therapy depends on the characteristics of the disease, such as chromosomal alterations and genetic mutations, age, and comorbidities of the patient, and may include:

• hypomethylating agents(5-azacytidine): act by reversing a biological process called hypermethylation, which prevents some genes important for controlling cell growth from functioning properly in dysplastic cells. Azacitidine is administered subcutaneously and can improve blood counts, reduce the need for transfusion, and the proportion of blast cells in a significant proportion of patients . Therapeutic response to azacitidine is generally observed after a minimum period of 6 months of treatment. Therapy should be continued as long as clinical benefit is maintained or until allogeneic stem cell transplantation in patients eligible for this procedure;
• chemotherapy similar to that used in acute leukemia: especially in young patients or those who are candidates for allogeneic stem cell transplantation, the physician may choose intensive chemotherapy aimed at rapidly eliminating abnormal bone marrow cells. This treatment requires hospitalization in isolation.

Studies are also underway on combinations of azacitidine with new drugs that act on specific cellular targets (e.g., BCL2 or IDH1) with the goal of further improving the efficacy of therapies.

All cancer treatments involve side effects that impact the patient’s quality of life more or less severely. Treatments for myelodysplasias also involve major side effects, both physical and psychological, that change the way people cope with daily life.

At the Candiolo Institute, attention to the patient’s quality of life remains a priority throughout the entire course of treatment: the physicians and nurses of the multidisciplinary team are available to provide the patient with all the support needed to manage the various side effects, particularly through nutritional counseling, psychological support and pain therapy.

The cancer patient is a person with complex needs that requires multidisciplinary support not only for the cancer disease, but also for all related issues.

At the Candiolo Institute, patients who need or require it have access to specialists in different areas to receive nutritional support, physical therapy, pain therapy and management of other associated conditions.

To ensure timely and direct support and receive timely answers to concerns and questions, a dedicated helpline is in place at the Candiolo Institute for all patients.

From Monday to Friday, from 8 a.m. to 5 p.m., you can contact the secretariat of the oncology day hospital at 011.993.3775, reporting the need for urgent consultation.

The patient will be quickly put in touch with his or her medical specialist, to receive clear answers and immediate support.

The impact of cancer in a person’s life also affects the psychological sphere: in fact, falling ill with cancer is always a traumatic event that affects all dimensions of the person and can generate anxiety, fear, anger, depression.

In our institute, alongside cutting-edge therapies, the treatment and care pathway always includes a qualified psycho-oncological support that helps the patient cope positively not only with treatment but also with the delicate phase of physical and psychological recovery.

It is also possible to participate in psychological support groups to engage with other people who have gone through or are going through the same experience.

We also collaborate with patient associations that can offer additional tools in disease management.

The Social Service Department of the Candiolo Institute conducts information and orientation interviews to patients and their families on how to access services in the area and how to obtain welfare and social security benefits provided by law (disability, benefits for aids and prostheses, work leave, etc.).

The service operates on Wednesdays and Fridays from 9 a.m. to 1 p.m. (phone: 011 9933059).

Due to the high number of cases treated each year, the Candiolo Institute is a national reference for taking care of esophageal cancer. Our experience enables us to deal with even the most complex situations, always with a personalized approach built on the clinical and personal profile of each patient.

Establishing the treatment plan always starts with an accurate and timely diagnosis. Patients have access to state-of-the-art imaging technologies that allow accurate assessment of the extent of the disease.

In addition, the Institute offers advanced and sophisticated laboratory investigations, including molecular and genomic analyses, which are critical for identifying biological features of cancer and guiding therapeutic decisions.

As an IRCCS, the Candiolo Institute combines clinical practice with a strong vocation for scientific research. Patients can be evaluated for inclusion in active clinical trials, which provide a real opportunity to access innovative therapies not yet available in standard practice. Collaboration between care and research is a distinctive value that translates into concrete opportunities for the patient.

The Interdisciplinary Care Group takes care of the person at every stage: from diagnosis to treatment to follow-up, with attention to nutritional support, psychological health, and reintegration into daily life. The organization of checkups, examinations and treatment is designed to ensure continuity and serenity, always valuing the human dimension of care.