Acute Leukemias

Blood tests are a critical first step in confirming suspicion of acute leukemia and, more importantly, in assessing whether the patient is in a condition that may rapidly become life-threatening.

In particular, the following are evaluated:

• Complete blood count (CBC): to assess anemia (reduced red blood cells), abnormalities in white blood cells (which may be either decreased or increased), and low platelet counts.
• Coagulation parameters: to detect any clotting abnormalities (coagulopathy).

These findings allow physicians to rapidly determine whether urgent supportive treatments are required, such as transfusions of red blood cells, platelets, or plasma. These interventions can be life-saving and help stabilize the patient while further diagnostic tests and specific treatment are arranged.

Some forms of acute leukemia require particularly urgent diagnosis and management. Among these is acute promyelocytic leukemia (APL), a rare subtype associated in its early stages with a very high risk of severe, potentially fatal hemorrhage. However, if recognized and treated promptly, APL is a potentially curable leukemia.

For this reason, it must be suspected and confirmed as quickly as possible in patients with abnormal blood counts and coagulation parameters.

The specialist may also request additional tests to evaluate:

• Kidney and liver function, which are essential for treatment tolerance
• Blood levels of substances such as lactate dehydrogenase (LDH) and uric acid, which provide information about disease activity and tumor burden, as well as possible involvement of other organs

Even today, light microscopy remains one of the main tools for the diagnosis and classification of acute leukemias. The primary objective is to identify blasts, the immature cells characteristic of the disease, in the patient’s blood.

Cytomorphological examination (blood smear)

After a simple blood draw, a small sample is spread onto a slide. The slide is then stained with special reagents and examined under a light microscope. This allows direct visualization of leukemic cells and assessment of their shape and size.

Flow cytometric examination (immunophenotyping)

This test analyzes the proteins expressed on the surface of blasts. It uses specific antibodies that bind to these proteins and makes them detectable through specialized instruments.

Immunophenotyping helps determine the type of leukemia (lymphoblastic or myeloid) and provides essential information for selecting the most appropriate treatment strategy.

In both forms of acute leukemia (AML and ALL), multiple subtypes can be identified, each with different clinical features and prognoses that must be considered when planning treatment. This requires a detailed examination of the bone marrow, with the aim of characterizing blasts.

The procedure is performed under local anesthesia. The physician inserts a needle into the upper posterior iliac crest, allowing access to the pelvic bone to aspirate a small sample of bone marrow. If aspiration is not possible (dry tap, or punctio sicca), a small core of bone marrow tissue is obtained.

The collected material is then sent to the pathology laboratory for analysis:

• Cytomorphological examination: as with peripheral blood, a smear is prepared on a slide, stained, and examined under a microscope to evaluate the morphology of blast cells.
• Flow cytometry (immunophenotyping): identifies the expression of specific surface antigens using monoclonal antibodies, enabling an initial classification of acute leukemia into AML or ALL.
• Cytogenetic analysis: studies chromosomal abnormalities in blast cells through karyotype analysis or targeted techniques such as FISH (fluorescence in situ hybridization), which detects specific DNA alterations using fluorescent probes. This approach allows rapid identification of key genetic lesions, such as those seen in acute promyelocytic leukemia (APL) or the Philadelphia chromosome, present mainly in some forms of ALL and more rarely in AML.
• Molecular biology tests: identify specific genetic alterations at the DNA or RNA level in blast cells.

In acute leukemias, specific genetic and molecular abnormalities are often associated with particular cellular features observed under the microscope or through immunophenotyping. This information is essential to confirm the diagnosis, identify the exact leukemia subtype, define prognosis and risk category, and select the most appropriate and personalized therapy.

Some of these alterations also represent targets for targeted therapies and are used to monitor minimal residual disease (MRD), meaning the presence of residual leukemic cells after treatment.

Acute leukemias are systemic diseases, as blasts, in addition to involving the bone marrow and blood, can circulate and infiltrate other organs and tissues, including lymph nodes, spleen, liver, testes, and the central nervous system.

When blasts cross the blood-brain barrier (BBB), the natural protective barrier of the brain and spinal cord, they may enter the cerebrospinal fluid (CSF) that surrounds and nourishes the nervous system, leading to leukemic meningosis.

Assessment of Nervous System Involvement

The presence of leukemia in the central nervous system is evaluated through a lumbar puncture (spinal tap), performed under local anesthesia:

• A needle is inserted into the space between two lumbar vertebrae to collect a small sample of cerebrospinal fluid (CSF)
• The CSF is then analyzed using:
  • Cytological examination, to detect abnormal cells under the microscope
  • Immunophenotyping, to identify surface proteins characteristic of blast cells

This assessment is essential to guide the most appropriate and targeted therapeutic strategy and to ensure adequate protection of the central nervous system during treatment.

Rarely, acute leukemia may present with a mass outside the bone marrow (extramedullary disease).

In ALL (acute lymphoblastic leukemia), blasts may infiltrate the lymphoid tissues of various organs.

In AML (acute myeloid leukemia), this solid form is known as myeloid sarcoma.

To assess possible involvement of other organs of the immune system (such as liver, spleen, and lymph nodes) or other tissues, the following examinations may be useful:

1. Abdominal ultrasound: a radiation-free imaging technique based on ultrasound waves. It can detect splenomegaly, hepatomegaly, or enlarged deep lymph nodes. It is performed on an empty stomach in the radiology department.
2. Testicular ultrasound: indicated in male patients with ALL, used to evaluate possible infiltration of the testes due to crossing of the blood-testis barrier by blasts.
3. CT (computed tomography) scan: a radiological technique that produces three-dimensional images of organs and tissues. A total-body CT scan (head, neck, chest, abdomen, and pelvis) can identify lymph node enlargement or tumor masses. It requires intravenous contrast administration.
4. PET (positron emission tomography) scan: less commonly used in acute leukemias, it detects tumor activity based on increased glucose metabolism using a radiolabeled tracer. It may be useful in selected subtypes of ALL.

Assessment of Cardiac Function

Some drugs used in the treatment of acute leukemia may affect the heart. For this reason, a cardiological evaluation and echocardiogram are essential to assess cardiac function and ensure that therapy is planned in the safest possible way for the patient.

In acute leukemias, clinicians assess a series of internationally recognized prognostic factors. These factors help estimate the likelihood of response to treatment and overall survival.

The main elements considered include:

• Extent of disease: for example, the presence of extramedullary masses or involvement of the central nervous system
• Cytogenetic and molecular data: genetic abnormalities identified in leukemic cells
• Dynamic hematologic parameters: evaluation of the initial response to therapy

Based on these variables, patients are stratified into risk categories: standard, intermediate, or high risk.

This classification allows clinicians to assess the aggressiveness of the disease and to select the most appropriate and individualized treatment strategy for each patient.

These are drugs capable of blocking specific molecular alterations that drive the growth of certain types of acute leukemias, such as FLT3 gene mutations and BCL-2 alterations in some forms of AML.

These medications are administered orally and are usually taken on a continuous basis. Examples include Midostaurin, Gilteritinib, Venetoclax, and Glasdegib.

The use of these “biologic” therapies, either in combination with standard chemotherapy or as a substitute for it, depends on the subtype of acute leukemia and the patient’s risk classification. These strategies have demonstrated benefits in terms of response rates and survival, and can lead to highly specific treatment approaches, such as the use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in APL, allowing in some cases the disease to be cured without conventional chemotherapy.

Finally, in some forms of ALL characterized by the Philadelphia chromosome, which leads to the formation of the oncogenic protein BCR-ABL, tyrosine kinase inhibitors such as Imatinib and Dasatinib are used, often in combination with steroids alone. This approach allows complete remission in the majority of cases while significantly reducing the toxic effects associated with standard chemotherapy.

Immunotherapy uses drugs that restore the immune system’s ability to recognize and destroy cancer cells. In patients with acute leukemia, these agents are mainly monoclonal antibodies.

Monoclonal antibodies act similarly to the body’s natural antibodies, binding to specific receptors on leukemia cells and promoting their elimination by the immune system. Examples include:

• Gemtuzumab ozogamicin, which targets the CD33 antigen in AML
• Inotuzumab ozogamicin, which targets the CD22 antigen in B-cell ALL

Some antibodies, known as bispecific antibodies, have a dual mechanism of action: they bind to leukemia blasts and simultaneously activate the patient’s T lymphocytes, enabling them to attack cancer cells. An example is Blinatumomab, which binds CD19 on blasts and CD3 on T cells, promoting selective destruction of leukemic cells.

Monoclonal antibodies may be used alone or in combination with chemotherapy, increasing treatment effectiveness.

Finally, in particularly aggressive or treatment-resistant forms of B-cell ALL, CAR T-cell therapy may be used. This involves collecting the patient’s T lymphocytes, genetically modifying them in the laboratory to recognize the CD19 antigen on leukemia cells, and reinfusing them to selectively attack the tumor. This therapy is reserved for selected patients, generally up to 25 years of age, and requires careful monitoring due to the risk of serious side effects.

In elderly patients (generally over 65 to 70 years of age) or in those who are clinically frail due to comorbidities (often defined in oncology as “unfit”), as well as in patients with unfavorable genetic abnormalities associated with poor response to conventional chemotherapy, a less intensive therapeutic approach may be considered. The goal is disease control while avoiding potentially severe treatment-related toxicity.

This strategy is based on hypomethylating agents, such as 5-azacytidine and decitabine, which act on an epigenetic process known as DNA hypermethylation. This mechanism can silence genes that are important for regulating normal cellular behavior, including tumor suppressor genes, thereby contributing to malignant transformation. Because these changes do not involve alterations in the DNA sequence, they are potentially reversible and therefore represent a therapeutic target.

These drugs inhibit the enzymes responsible for DNA methylation, thereby helping to restore normal gene activity and reactivate antitumor mechanisms within the cells.

With these therapies, it is possible to achieve a meaningful proportion of complete remissions, as well as disease stabilization and improvement in blood count values and reduced transfusion requirements. This approach helps avoid further clinical deterioration in fragile patients and limits exposure to intensive therapies that would not provide a survival benefit.

Alongside specific treatment for acute leukemia, supportive therapy plays an essential role and can be life-saving.

It includes:

• Transfusions of blood components (red blood cells, platelets, and plasma) to prevent bleeding complications and cardiovascular instability
• Hematopoietic growth factors to improve blood counts and reduce the risk of anemia and infections
• Adequate hydration to prevent tumor lysis syndrome, which results from the rapid release of toxic substances from destroyed blasts
• Antimicrobial therapy (antibiotics, antifungals, antivirals) to prevent or treat infections due to immunosuppression
• Parenteral nutrition, when necessary, in cases of weight loss or reduced oral intake due to mucositis
• Pain management therapy to relieve bone pain or gastrointestinal discomfort caused by the disease or its treatment

This supportive care is essential to maintain clinical stability, reduce complications, and improve tolerance to leukemia-specific therapies.

Acute leukemias with a favorable prognosis that respond well to drug therapy usually do not require hematopoietic stem cell (HSC) transplantation. This procedure is generally considered only in cases of relapse during treatment, or when there is an incomplete response or resistance to therapy (refractory disease).

Allogeneic HSC transplantation, in which stem cells are obtained from a compatible donor (related or unrelated), is an effective strategy to improve long-term survival in patients with intermediate- or high-risk acute leukemia, as well as in relapsed or refractory cases. The transplanted cells restore normal bone marrow function and support the immune system in eliminating any residual leukemia cells. Before transplantation, achieving a good response to initial drug therapy is essential to increase the likelihood of success and reduce treatment-related risks.

In summary, transplantation is used as a consolidation therapy in selected high-risk patients, offering the best chance of achieving stable remission and long-term survival.

After completing treatment cycles, it is essential to evaluate the leukemia’s response to therapy. This is performed through bone marrow aspiration, which determines whether the disease is in complete remission, partial remission, or still present (non-response).

During this assessment, it is also possible to detect early signs of relapse by monitoring minimal residual disease (MRD), a highly sensitive method that identifies residual leukemia cells before the disease becomes clinically apparent.

The results are reviewed by the Interdisciplinary Team, which decides whether treatment can be considered complete or whether it should be modified or continued, ensuring the best possible disease control.

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.

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.

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.

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.

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.

After completion of treatment, a follow-up period begins. During this phase, a series of clinical examinations and medical visits are performed to monitor the effectiveness of therapy, assess treatment-related side effects, and evaluate the patient’s functional recovery.

Follow-up visits are particularly important for the early detection of relapse, allowing timely intervention with appropriate treatment. They also provide an important opportunity for discussion between the patient and the medical specialist.

The follow-up schedule is tailored according to the type of acute leukemia, the treatments received, the response to therapy, and the patient’s individual characteristics.

For patients who have undergone stem cell transplantation, follow-up is initially very close, often requiring weekly or more frequent outpatient monitoring, depending on the treatment protocol and the presence of complications.

In general, follow-up visits become progressively less frequent over time.

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.

When appropriate, surgeries are performed using minimally invasive, laparoscopic or robotic techniques. These approaches involve the use of camera-equipped instruments introduced into the abdomen through small incisions, thus reducing surgical trauma. Benefits to the patient include shorter hospital stay times, faster recovery, and lower risk of complications compared with traditional open surgery.

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.