Acute leukemias

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

In particular, the following are checked:

• CBC: to check for anemia (decreased red blood cells), changes in white blood cells (which may be too low or too high), and decreased platelets;

• coagulation parameters: to identify any blood clotting problems(coagulopathy).

These data allow the physician to know immediately whether urgent supportive therapies, such as transfusions of blood, platelets, or plasma, are needed, which can be life-saving and stabilize the patient pending further investigation and specific treatment.

There are forms of acute leukemia that require the most rapid diagnosis and intervention. These include acute promyelocytic leukemia (APL): a rare disease that, in its early stages, carries a very high risk of severe, even potentially fatal, hemorrhage. The good news is that, if recognized and treated early, LAP is a potentially curable leukemia.

For this reason, it should be suspected and confirmed as quickly as possible in patients with altered blood counts and coagulation.

The specialist may request further follow-ups to evaluate:

• kidney and liver function, organs that are also critical for tolerance to treatment;

• the level of certain substances in the blood, such as lacticodehydrogenase (LDH) and uric acid, which give information about how quickly the disease develops and the possible involvement of other organs.

Even today, light microscope observation remains one of the main tools for diagnosing and classifying acute leukemias. The goal is to identify blasts, the immature cells typical of the disease, in the patient’s blood.

Cytomorphological examination (smear)

After a simple blood draw, a few drops are spread on a slide. The slide is stained with special reagents and then observed under a microscope.This allows the leukemic cells to be seen directly and their shape and size assessed.

Cytofluorimetric examination (immunophenotyping)

Analyze the proteins present on the surface of blasts. It uses specific antibodies that bind to these proteins and make them visible with specialized instruments. It helps determine the type of leukemia (lymphoblastic or myeloid) and provides crucial information for planning the most appropriate therapy.

In both cases of acute leukemia (AML and LAL), there are identifiable Different subtypes with different clinical features and prognosis, which should be taken into account in therapy planning. This requires a further investigation of bone marrow blood, with the aim of characterizing bone marrow blasts.

During the procedure, which is performed under local anesthesia, the doctor inserts a needle into the upper part of the buttocks with which he penetrates the pelvic bone and aspirates a small sample of blood; he also extracts a small bone fragment in the same way if bone marrow blood cannot be extracted (punctio sicca). The collected specimens are then sent to the pathology laboratory for appropriate analysis:

• cytomorphologic examination: as with peripheral blood, some drops are used to make a smear on a slide, which, after appropriate staining, is viewed under a microscope;
• cytofluorimetric examination: with immunophenotyping, the expression of certain antigenic proteins on blast cells is identified using monoclonal antibodies, premising an initial classification of acute leukemia into AML or LAL;
• cytogenetic examination: a laboratory method that studies alterations in the chromosomes of blastic cells, either by analysis of the global chromosome stock (karyotype) or more selective analyses such as FISH (fluorescent in situ hybridization), which allows identification of the presence of specific altered DNA sequences of chromosomes using fluorescent probes. The latter method is, for example, behind the rapid identification of the genetic lesion of LAP, as previously mentioned a subtype of AML with totally different prognosis and therapy, and of the Philadelphia chromosome, which is present mainly in some forms of LAL and, more rarely, in some forms of AML;
• molecular biology examinations: laboratory methods that can identify specific genetic alterations in the DNA or RNA of blast cells.

In acute leukemias, certain genetic and molecular alterations are associated with particular cell characteristics observed under the microscope or by immunophenotyping. This information is critical to, confirm the diagnosis, identify the specific subtype of leukemia, establish the prognosis and risk class, and choose the most effective and personalized therapy.

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

Why it is important to turn to specialized centers

Diagnosis and classification of acute leukemias require advanced methods and highly trained personnel.
Our institute has all the latest diagnostic technologies and an experienced team, and is recognized as a qualified center for integrated diagnostics of myeloid malignancies through the LabNet platform of GIMEMA (Gruppo Italiano Malattie Ematologiche dell’Adultores).

This ensures that each patient receives a comprehensive and individualized evaluation, which is essential to begin the most appropriate therapy immediately.

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

When blasts cross the blood-brain barrier (BEE)-the natural barrier that protects the brain and spinal cord-they can enter the cephaloroachid fluid (CSF), which surrounds and nourishes nerve cells, causing what is called leukemic meningosis.

How to test for leukemia in the nervous system

A CSF examination by spinal tap (lumbar puncture) is performed to confirm the localization of leukemia to the nervous system. The procedure is done under local anesthesia:

• the doctor inserts a needle into the space between two lumbar vertebrae to take a small CSF sample;

• the fluid is then analyzed by cytological (observation of cells under a microscope) and immunophenotypic (study of proteins on the surface of blasts) examination to confirm the presence of leukemic cells.

This assessment is critical for choosing the most appropriate and targeted therapy and protecting the nervous system during treatment.

Rarely, acute leukemia may manifest as a mass outside the bone marrow (extramedullary localization).

In LAL (acute lymphoblastic leukemia), blasts can infiltrate the lymphatic tissues of various organs.

In AML (acute myeloid leukemia), this “solid” form is called myeloid sarcoma.

To assess involvement of other organs of the immune system (liver, spleen, lymph nodes) or other tissues, the following tests may be useful:

• Abdominal ultrasound: radiation-free, ultrasound-based radiological examination. It allows detection of any enlarged spleen (splenomegaly), liver (hepatomegaly) or deep lymph nodes. It is performed on an empty stomach at Radiodiagnostics;
• Testicular ultrasound: indicated in male patients with LAL, it is used to check whether blasts have crossed the blood-testicular barrier, localizing in the testes;
• CT (computed axial tomography) scan: a radiological examination that reconstructs three-dimensional images of tissues and organs. Total body CT scan (skull, neck, chest, abdomen, and pelvis) allows checking for lymph nodes or tumor masses. It involves the injection of an intravenous contrast agent;
• PET (positron emission tomography) scan: a rarer test in acute leukemias, it highlights tumor cells based on their abnormal metabolism using a glucose-based contrast agent. Useful especially in some subtypes of LAL.

Assessment of cardiac function

Some drugs used in acute leukemia therapy may affect the heart.
For this reason, it is important to perform a cardiologic examination andechocardiogram, to check for any problems and plan therapy in the safest way possible for the patient.

In acute leukemias, physicians assess the presence of internationally recognized prognostic factors. These factors help predict the likelihood of response to therapy and survival.

Factors considered include:

• Extent of the disease: for example, whether there are extramedullary masses or involvement of the nervous system;

• Cytogenetic and molecular data: genetic alterations in leukemic cells;

• Dynamic hematological parameters: assessment of initial response to therapy.

Based on these elements, patients are placed in risk classes: standard, intermediate or high.

This classification allows the physician to understand how aggressive the disease is and to choose the most suitable and personalized treatment for each patient.

The term chemotherapy refers to the drugs that eliminate cancer cells Taking advantage of their faster reproduction rate than healthy ones. Because it interferes with the replication mechanisms of cells, chemotherapy also damages the body’s healthy cells, causing side effects that fortunately often disappear once the treatment is over and are in any case well controlled with appropriate supportive therapies, such as irritation of the mucous membranes of the digestive tract (mucositis).

Patients under the age of 65 years, without major other health problems, are considered “fit,” that is, suitable for an intensive chemotherapy. In most cases, chemotherapy is administered by intravenous injection. For this reason, it is often necessary to place a cannula into a large vein (such as the subclavian vein or jugular vein), called a Central Venous Catheter (CVC). The duration of each administration, which is carried out on an inpatient or day hospital basis depending on the scheme used involving the combination of various drugs, can vary from minutes to hours.

Chemotherapy is received “in cycles”: each cycle can be administered over one or more days and is followed by a few weeks of rest. The number of cycles depends on the type of acute leukemia and, of course, the response to the drugs, which can vary greatly from patient to patient and according to the disease subtype.

Following chemotherapy, white blood cell, platelet, and red blood cell counts drop to very low levels (aplasia phase) before normal cells begin to regrow, putting the patient at risk of even severe infections and bleeding, conditions that often necessitate supportive therapies and hospitalization of the patient.

These are drugs capable of blocking specific molecular alterations that underlie the growth of some types of acute leukemias (FLT3 gene mutations and BCL-2 gene alterations in some forms of AML, etc.). These drugs are administered orally, and are usually taken continuously. These include Midostaurin, Gilteritinib, Venetoclax, Glasdegib, etc.

The eventual use of such “biologic” drugs, either in combination with standard chemotherapy or as a substitute for chemotherapy, depends on the subtype of the acute leukemia and proper risk classification of the patient. These therapeutic strategies have reported benefits in terms of response and survival, and lead to optimal treatment choices, such as the use of trans-retinoic acid (ATRA) and arsenic trioxide (ATO) in LAP, which spares the use of chemotherapy altogether while still being able to cure the disease.

Finally, in some forms of LAL characterized by the Philadelphia chromosome(an alteration that promotes the formation of the tumor protein BCRABL) tyrosine kinase inhibitors (such as Imatinib, Dasatinib, etc.) are used in addition to the steroid alone, allowing complete remission to be achieved in the vast majority of cases and minimizing the severe toxic effects of chemotherapy.

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

Monoclonal antibodies act like our body’s natural antibodies: they bind to specific receptors on leukemia cells, stimulating the immune system to eliminate them. Some examples include:

• Gemtuzumab ozogamicin, which binds to the CD33 antigen in AML,

• Inotuzumab ozogamicin, which binds to the CD22 antigen in B-cell LALs.

Some antibodies, called bispecific, have a dual function: they bind to blasts and simultaneously activate the patient’s T lymphocytes to attack the leukemic cells. One example is Blinatumomab, which binds CD19 of blasts to CD3 of T lymphocytes, promoting the selective destruction of cancer cells.

Monoclonal antibodies can be given alone or together with chemotherapy, increasing the effectiveness of treatment.

Finally, in particularly aggressive or resistant forms of B-cell LAL, CAR T cells may be used. These are T lymphocytes taken from the patient, modified in the laboratory to recognize the CD19 antigen on leukemia cells and then reinfused so as to selectively attack them. This therapy is reserved for selected patients, generally up to 25 years of age, and requires special attention for possible serious side effects.

In elderly patients (older than 65-70 years) or very frail due to other concomitant diseases (defined from a general point of view in oncology by the term “unfit”), or in patients with very unfavorable genetic alterations indicative of poor response to conventional chemotherapy, conservative therapymay be considered , with the goal of temporary disease control to avoid potentially fatal toxic effects.

This treatment is based on agents called hypomethylating agents (such as 5-azacytidine and decitabine), which act by intervening in an epigenetic (i.e., associated with a change in DNA function without genetic variation) biological process called hypermethylation. Through this phenomenon, the function of certain genes important for controlling cell evolution in a tumor-like direction (oncosopressor genes) is deactivated in blastic cells. Because it is not genetic, however, this variation is reversible, thus representing a potential therapeutic target. Such drugs function as inhibitors of the enzyme that determines DNA methylation, thereby restoring antitumor activity in cells.

With these therapies it is possible to achieve not only an appreciable proportion of complete remission, but also a stabilization and an improvement of the disease (CBC values and transfusion need). This avoids worsening the frailty of such patients, and exposing them to risky therapies that would not lead to improved life expectancy.

Along with specific therapy for acute leukemia, supportive therapy, which can have life-saving effects, is essential. This includes:

• Transfusions of blood and blood components (red blood cells, platelets, plasma) to prevent bleeding problems or cardiovascular complications;

• hematopoietic growth factors to improve blood values and reduce the risk of anemia or infection;

• Adequate hydration to prevent tumor lysis syndrome, which is related to the release of toxic substances from blasts;

• Antimicrobial drugs (antibiotics, antifungals, antivirals) to prevent or treat infections due to immunodepression;

• Parenteral nutrition, if needed in case of weight loss or reduced caloric intake due to mucositis;

• Pain relief therapy to relieve bone pain or discomfort in the digestive tract caused by the disease or treatments.

This supportive therapy is essential to keep the patient stable, reduce risk, and improve tolerance to leukemia-specific therapies.

Good-prognosis acute leukemias, which respond well to drug therapy, usually do not require hematopoietic stem cell (HSC) transplantation. Transplantation is considered only if, during treatment, the disease reappears(relapse) or if the response to treatment is incomplete or absent (refractory disease).

Allogeneic HSC transplantation, in which stem cells come from a matched donor (familial or unrelated), is an effective strategy to improve long-term survival in patients with intermediate- or high-risk acute leukemia, or in relapsed or refractory cases. These healthy cells replenish the bone marrow and help the immune system eliminate any remaining leukemia cells. Before transplantation, a good preliminary response to drug therapies must be obtained to increase the likelihood of success and reduce risks.

In summary, transplantation is used as a consolidation therapy to strengthen care in the most at-risk patients, providing them with the best chance of stable remission and long-term survival.

After the treatment cycles, it is crucial to check how the leukemia has responded to the therapy. This is done bybone marrow aspirate, which allows us to determine whether the disease is in complete or partial remission or whether it persists(nonresponse).

During this examination, it is also possible to detect any recurrences by monitoring Minimal Residual Disease (MMR), a very sensitive analysis that detects residual leukemia cells before the disease becomes clinically evident.

The results are discussed by the Interdisciplinary Group, which decides whether the treatment can be considered completed or whether it needs to be modified or continued, thus ensuring the best chance of controlling the disease.

All cancer treatments involve side effectsthat impact the patient’s quality of life more or less severely. Treatments for acute leukemia 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 impact of cancer in a person’s life also affects the psychological sphere: falling ill with cancer is in fact always a traumatic event that affects all dimensions of the person and can generate anxiety, fear, anger, depression.

At the Candiolo 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 support groups psychological to compare with other people who have gone through or are going through the same experience.

To ensure timely and direct support and receive timely answers to concerns and questions, a dedicated support service 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 cancer patient is a person with complex needs who requires multidisciplinary support not only for the cancer disease but also for all related issues.

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

The Social Service Department of the Candiolo Institute conducts information and orientation interviews for 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).

With the conclusion of the course of treatment, the follow-up period begins during which, through a series of examinations and visits, the side effects of the therapies performed and their effectiveness are monitored and the patient’s functional recovery is assessed.

Follow-up examinations are especially important to intercept any recurrences early so that appropriate therapy can be intervened. For the patient, they are also a valuable opportunity for dialogue with their medical specialist.

The follow-up course is planned with different timing and modalities depending on the type of acute leukemia, the therapy performed and the response obtained, and the patient’s own characteristics.

For patients undergoing stem cell transplantation, initially outpatient monitoring occurs very closely, weekly or several times a week depending on the treatment, type of protocol, and expected or ongoing complications.

Generally, checks become less frequent as time passes.

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.

When indicated, surgery is performed with minimally invasive techniques (laparoscopic or thoracoscopic), which reduce operative trauma, promote faster recovery, and improve postoperative quality of life. Every treatment choice is defined within the GIC, ensuring a consistent and integrated approach.

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 represent a real chance 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, visits and treatment is designed to ensure continuity and serenity, always valuing the human dimension of care.