Myelodysplastic Neoplasms

Most patients with myelodysplastic neoplasms (MDS) present with abnormalities in their complete blood count. These may include anemia, neutropenia, thrombocytopenia, or a combination of two or all three cytopenias.

Before confirming a diagnosis of MDS, several blood tests are required to exclude other conditions that may cause similar abnormalities:

• Reticulocyte count, LDH, and bilirubin levels to exclude hemolysis
• Iron studies and assessment of vitamin B12 and folate levels to identify nutritional deficiencies
• Serum erythropoietin measurement and evaluation of transfusion history
• Peripheral blood smear for morphological assessment of blood cells
• Liver and kidney function tests, inflammatory markers, serum protein electrophoresis, and thyroid function tests to exclude other conditions associated with cytopenias, such as chronic liver disease, kidney failure, inflammatory disorders, or thyroid dysfunction
• Screening for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), parvovirus B19 (particularly in hypoplastic forms), and cytomegalovirus (CMV)
• Peripheral blood immunophenotyping, in selected cases, to identify clones associated with paroxysmal nocturnal hemoglobinuria (PNH)

These investigations help establish the diagnosis and exclude alternative causes of blood count abnormalities.

diagnosis of myelodysplastic neoplasms (MDS) requires both a bone marrow aspiration and a bone marrow biopsy.

These procedures are usually performed during the same session under local anesthesia, typically at the level of the posterior iliac crest of the pelvis. During the procedure, a sample of bone marrow blood is aspirated, and a small bone marrow tissue sample is collected for analysis.

Bone Marrow Aspiration

The bone marrow aspirate is used for several investigations:

• Morphological examination: a small amount of bone marrow blood is spread onto a slide, stained, and examined under a microscope. Morphological assessment remains a cornerstone of MDS diagnosis and classification. It allows the identification of abnormalities in blood-forming cells and the quantification of blasts, the immature precursors of blood cells.
• Flow cytometry immunophenotyping: used to identify abnormal cell populations, evaluate maturation abnormalities, and quantify blasts.
• Cytogenetic analysis: evaluates chromosomal abnormalities through techniques such as karyotyping and fluorescence in situ hybridization (FISH), which can detect specific genetic alterations with diagnostic, prognostic, and therapeutic relevance.
• Perls staining: used to identify and quantify ring sideroblasts, a feature that characterizes specific MDS subtypes and may influence treatment decisions.
• Molecular testing: assesses mutations in genes such as SF3B1, TP53, and IDH1. These analyses contribute to diagnosis, risk stratification, prognosis, and the selection of targeted therapies when appropriate.

Bone Marrow Biopsy

The bone marrow biopsy provides tissue for histological examination, allowing evaluation of:

• Bone marrow cellularity
• Morphological and structural abnormalities
• Blast percentage through immunohistochemical analysis
• Degree of bone marrow fibrosis

The Importance of Specialized Diagnostic Evaluation

Current international classifications recognize that specific cytogenetic and molecular abnormalities are often associated with distinct biological and morphological features and have important diagnostic, prognostic, and therapeutic implications.

For this reason, comprehensive laboratory evaluation is essential for all patients with newly diagnosed MDS and should be performed in highly specialized centers.

The Candiolo Cancer Institute offers access to advanced diagnostic technologies, specialized expertise, and collaboration with national reference laboratories to ensure a comprehensive and accurate diagnostic assessment.

The diagnostic workup may be complemented by laboratory and instrumental investigations, such as abdominal ultrasound or echocardiography, to evaluate any existing comorbidities and the patient’s overall health status.

For all patients who may be candidates for active treatment, it is important to assess general health, performance status, and the presence of other medical conditions in order to determine fitness for therapy and define the most appropriate treatment strategy.

For patients with reduced functional independence, the availability of family members or caregivers who can provide support during treatment should also be considered when planning care.

The diagnostic evaluation should allow classification of patients according to the criteria established in 2022 by the World Health Organization (WHO) and the International Consensus Classification (ICC). In addition, prognosis is assessed using internationally validated scoring systems, including the IPSS, IPSS-R, and IPSS-M, which help guide treatment decisions and risk stratification.

Most patients with lower-risk MDS present with anemia. Treatment is aimed at improving blood counts, reducing transfusion requirements, relieving symptoms, and maintaining quality of life.

Erythropoiesis-Stimulating Agents

The most commonly used first-line treatment is recombinant erythropoietin (EPO).

Erythropoietin is a naturally occurring hormone that stimulates the production of red blood cells. In patients with MDS, red blood cell production may be insufficient, and when endogenous EPO levels are not excessively elevated, a synthetic form can be administered by subcutaneous injection.

Treatment with recombinant EPO can increase hemoglobin levels or achieve transfusion independence in approximately 40-50% of patients, while also improving clinical outcomes in responders.

Luspatercept

For patients with MDS with ring sideroblasts or an SF3B1 mutation who are not suitable candidates for EPO therapy or who do not respond adequately, luspatercept may be used.

Luspatercept is a targeted therapy that promotes red blood cell maturation by modulating the TGF-β signaling pathway. It can improve anemia and reduce transfusion requirements in a substantial proportion of patients. The treatment is administered by subcutaneous injection every three weeks and is generally continued long term.

Recent clinical studies have also expanded the potential role of luspatercept in selected patients with lower-risk MDS requiring transfusions, including some patients without ring sideroblasts or an SF3B1 mutation.

Lenalidomide for MDS With del(5q)

Patients with MDS associated with deletion of chromosome 5q [del(5q)] who are not eligible for or do not respond to EPO therapy may benefit from lenalidomide.

Lenalidomide is an oral targeted therapy that selectively affects cells carrying the del(5q) abnormality. It can achieve transfusion independence in a large proportion of patients and may improve long-term outcomes.

Red Blood Cell Transfusions

When hemoglobin levels become significantly reduced, particularly below 8 g/dL, or below 10 g/dL in symptomatic patients or those with underlying cardiovascular disease, red blood cell transfusions may be required.

Transfusions can rapidly improve anemia-related symptoms, including fatigue, shortness of breath, and reduced physical capacity.

Iron Chelation Therapy

Patients who require repeated red blood cell transfusions over an extended period may develop iron overload, which can affect organs such as the heart, liver, and endocrine glands.

In these cases, iron chelation therapy may be prescribed to remove excess iron from the body. Oral agents, such as deferasirox, are commonly used for this purpose.

Treatment of Neutropenia

For patients with neutropenia associated with recurrent or severe infections, treatment with granulocyte colony-stimulating factor (G-CSF) may be considered to increase neutrophil production.

Treatment of Thrombocytopenia

Patients with severe thrombocytopenia may require platelet transfusions to reduce the risk of bleeding.

In addition, therapies that stimulate platelet production, known as thrombopoietin receptor agonists, are being investigated in selected patients.

Immunosuppressive Therapy

Selected patients with hypoplastic MDS, particularly younger individuals in good overall health and with specific clinical and biological characteristics, may benefit from immunosuppressive therapy.

These treatments act by reducing immune-mediated damage to bone marrow cells, allowing normal blood-forming cells to recover and improve blood counts.

Allogeneic Stem Cell Transplantation

Younger patients in good general condition who have persistent or severe cytopenias, do not respond adequately to conventional therapies, and have a significant risk of disease progression may be considered candidates for allogeneic stem cell transplantation.

This approach remains the only treatment with the potential to achieve long-term disease eradication in selected patients.

Patients with intermediate-risk or high-risk MDS have a greater likelihood of disease progression to acute myeloid leukemia (AML). For this reason, it is important to initiate appropriate treatment as early as possible.

The choice of therapy depends on several factors, including the biological characteristics of the disease, such as chromosomal abnormalities and genetic mutations, as well as the patient’s age, overall health, and comorbidities.

Treatment options may include:

• Hypomethylating Agents (Azacitidine): Azacitidine acts by reversing abnormal DNA methylation patterns that can interfere with the normal regulation of genes involved in cell growth and differentiation. Administered by subcutaneous injection, it can improve blood counts, reduce transfusion requirements, and decrease the proportion of blast cells in many patients. Clinical benefit is usually observed after several treatment cycles, and therapy is generally continued as long as it remains effective or until allogeneic stem cell transplantation is performed in eligible patients.
• Intensive Chemotherapy: In selected patients, particularly younger individuals or those eligible for allogeneic stem cell transplantation, intensive chemotherapy regimens similar to those used for acute myeloid leukemia may be considered. The goal is to rapidly reduce the number of abnormal bone marrow cells. This treatment typically requires hospitalization in a specialized unit.
• Targeted Therapies and Combination Approaches: Ongoing research is evaluating combinations of azacitidine with targeted therapies directed against specific molecular pathways, including BCL2 and IDH1. These strategies aim to improve treatment outcomes and expand therapeutic options for patients with higher-risk disease.

All cancer treatments are associated with side effects that can affect the patient’s quality of life to varying degrees. Treatments for acute leukemia may also cause significant physical and psychological effects, which can impact daily functioning and overall well-being.

At the Canciolo Cancer Institute, attention to the patient’s quality of life remains a priority throughout the entire treatment pathway. The physicians and nurses of the Multidisciplinary Team provide ongoing support to help manage side effects, including nutritional counseling, psychological support, and pain management therapy.

Cancer patients often have complex needs that extend beyond the treatment of the disease itself and require comprehensive, multidisciplinary care.

At the Candiolo Cancer Institute, patients who need additional support have access to specialists from a range of disciplines, ensuring personalized management of cancer-related symptoms and associated conditions. Services may include nutritional counseling, physical rehabilitation, pain management, and support for other medical needs that may arise during the course of treatment and recovery.

The goal is to improve quality of life, promote overall well-being, and provide comprehensive care tailored to each patient’s individual needs.

To ensure timely support and provide prompt answers to questions or concerns, the Candiolo Cancer Institute offers a dedicated assistance service for all patients.

From Monday through Friday, between 8:00 a.m. and 5:00 p.m., patients can contact the Oncology Day Hospital Secretariat at +39 011 993 3775 to request an urgent consultation.

Patients are promptly connected with their specialist physician, ensuring rapid access to expert advice, clear information, and immediate support when needed.

The impact of cancer also extends to the psychological sphere. A cancer diagnosis is often a traumatic event that affects all aspects of a person’s life and may generate anxiety, fear, anger, and depression.

At the Canciolo Cancer Institute, alongside advanced medical therapies, the care pathway always includes specialized psycho-oncological support, helping patients cope not only with treatment but also with the delicate phases of physical and psychological recovery.

Patients may also participate in psychological support groups, where they can share experiences with others who are facing or have faced a similar condition.

The Social Work Service at the Candiolo Cancer Institute provides information, guidance, and support to patients and their families regarding access to community services and the welfare and social security benefits available under current legislation.

During dedicated consultations, social workers assist with matters such as disability recognition, access to aids and prosthetic devices, employment-related benefits and leave, and other social support services.

The service is available on Wednesdays and Fridays from 9:00 a.m. to 1:00 p.m. and can be contacted at +39 011 993 3059.

Thanks to the large number of cases treated each year, the Candiolo Cancer Institute is a national reference center for the care of this disease. This extensive experience allows us to manage even the most complex cases, always using a personalized approach, tailored to the clinical and individual profile of each patient.

Establishing a treatment plan always begins with an accurate and timely diagnosis. Patients have access to state-of-the-art imaging technologies, such as ultrasound, contrast-enhanced CT, MRI, and cholangio-RM, which are critical for accurately assessing the extent of the tumor.

Advanced laboratory tests, including molecular analyses, are also available to help define biological features of the disease and guide treatment choices.

As an IRCCS (Scientific Institute for Research, Hospitalization, and Healthcare), the Candiolo Cancer Institute combines clinical care with a strong focus on scientific research. Patients can be considered for participation in active clinical trials, offering access to innovative therapies not yet available in standard practice. This integration of care and research is a distinctive strength that translates into tangible benefits for patients.

The Interdisciplinary Care Group (GIC or MDT) supports the patient at every stage: from diagnosis, through treatment, to follow-up. Special attention is paid to nutritional support, psychological health and reintegration into daily life. The organization of checkups, examinations, and treatment is designed to ensure continuity, serenity, and a humane, caring approach to each patient’s needs.