Treatments

Chemotherapy

Chemotherapy refers to treatment with drugs used to control the rapid growth of cancer cells and prevent their replication. Typically, multiple drugs are given together to improve effectiveness and balance their different toxicities.

Treatment is usually administered in repeated cycles, with intervals between each cycle (commonly referred to as “combination chemotherapy cycles”). Chemotherapy is most often given intravenously, although some drugs are taken orally and, in certain types of lymphoma, may be administered intrathecally (into the cerebrospinal fluid via lumbar puncture).

For repeated intravenous treatments, a central venous catheter (CVC) may be placed and kept in position for several months.

Chemotherapy drugs are not entirely selective and can also affect healthy cells, particularly those in the bone marrow that produce red blood cells, white blood cells, and platelets.

Common side effects include:

• anemia
• reduced white blood cells (increased risk of infections)
• low platelet counts (increased risk of bleeding)
• damage to mucosal tissues (mouth, stomach, genital areas)
• hair loss

In recent years, outcomes in lymphoma have improved thanks to the combination of chemotherapy with monoclonal antibodies and the development of new drugs that act more selectively on lymphoma cells or enhance the immune system’s ability to attack them.

Monoclonal antibodies

Monoclonal antibodies are laboratory-produced proteins designed to bind selectively to molecules on the surface of lymphoma cells, such as CD20 (common in B-cell lymphomas) or CD30 (found in Hodgkin lymphoma and some T-cell lymphomas)

These antibodies target substances that are relatively specific to lymphoma cells. Once bound, they may:

• directly damage the cancer cell
• help the immune system recognize and destroy it

Some antibodies act on their own, while others deliver toxins or radioactive substances directly into the cancer cell.

They can be used alone or in combination with chemotherapy, depending on the type of lymphoma, and are administered intravenously.

They are generally well tolerated and can be given either in outpatient or inpatient settings. Infusions may vary in duration and are often preceded by medications (such as paracetamol, antihistamines, or corticosteroids) to prevent allergic-like reactions.

Targeted therapies

A new generation of drugs—known as targeted therapies—has been developed. Unlike traditional chemotherapy, these drugs do not act on all rapidly dividing cells but specifically block key biological processes that cancer cells depend on.

These treatments are more selective, although not completely exclusive to cancer cells. Each drug is typically used for specific lymphoma subtypes, either alone or in combination with standard therapies.

Side effects vary depending on the specific drug.

Immunotherapy

Immunotherapy is a highly innovative treatment developed in recent years.

Cancer cells differ from normal cells, so the immune system can recognize and attack them. However, tumor cells can evade detection by “masking” themselves or changing over time, making natural immune defenses insufficient.

Immunotherapy works by activating and strengthening the patient’s immune system, enabling it to better recognize and destroy cancer cells.

Currently, immunotherapy is used in certain types of lymphoma and can be effective even in patients who have not responded to previous treatments. Many new immunotherapy drugs are under development.

Main types include:

Immune checkpoint inhibitors 
These drugs block inhibitory signals (checkpoints) that normally reduce immune activity, thereby reactivating the immune response against cancer cells.

CAR T-cell therapy 
This is an advanced, personalized treatment. A patient’s T lymphocytes (a type of white blood cell) are collected and genetically modified in the laboratory to recognize and attack cancer cells through a specific receptor (called CAR, Chimeric Antigen Receptor).
These engineered cells are then reinfused into the patient, where they actively target and destroy tumor cells.

Radiotherapy

Radiotherapy is an important treatment option for lymphoma. It may be used alone or in combination with systemic treatments (such as chemotherapy or chemo-immunotherapy), depending on the type and stage of the disease.

It is a localized, painless treatment that targets specific areas of the body where lymphoma is present.

Radiation is delivered by advanced machines called linear accelerators. It damages or destroys cancer cells in the treated area. The radiation dose is measured in Gray (Gy).

Thanks to technological advances, modern radiotherapy is highly precise, minimizing damage to surround healthy tissues. Over time, both radiation doses and treated volumes have been reduced, lowering the risk of long-term side effects.

Supportive pharmacological treatments

Side effects vary depending on the type of therapy and the individual patient. Although they can be unpleasant, they are often temporary and manageable. It is important to inform your doctor about any symptoms.

Common supportive treatments include:

• Antiemetic drugs: prevent and control nausea and vomiting
• Erythropoietin: stimulates red blood cell production to treat anemia
• Granulocyte growth factors: increase white blood cell production, reducing infection risk
• Anti-infective prophylaxis: antiviral, antibacterial, or antifungal drugs used in high-risk situations

Complementary (non-conventional) support

There are currently no effective “alternative” therapies that can cure cancer. However, some complementary approaches may help relieve treatment-related side effects.

It is essential to inform your doctor about any products used, including natural remedies, as they may interfere with ongoing treatments or cause adverse effects.

Hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation is a procedure that may be used in the treatment of lymphomas, particularly in cases of relapse or lack of response to first-line therapy.

The procedure involves high-dose chemotherapy (conditioning), followed by the reinfusion (similar to a blood transfusion) of hematopoietic stem cells previously collected from the bone marrow (bone marrow transplant) or, more commonly, from the blood (peripheral stem cell transplant).

A transplant is defined as:

• Autologous (autologous transplant) when the cells come from the patient
• Allogeneic (allogeneic transplant) when the donor is another person (a sibling or a compatible unrelated donor)

In lymphoma, autologous transplantation is more commonly used, while allogeneic transplantation is reserved for selected cases, usually after failure of an autologous transplant.

Autologous Transplantation

Peripheral stem cells are usually collected from the bloodstream after stimulation with granulocyte growth factors.

During this stimulation phase, patients may occasionally experience bone pain or mild fever; these are common effects but should be reported to the medical team.

The collection procedure, called apheresis, is typically performed on an outpatient basis. Blood is drawn from a vein in the arm or from a venous catheter and processed through a machine that separates and collects only the stem cells. These cells are then frozen and later reinfused into the patient when needed.

After reinfusion, there is a period (typically 10–15 days) during which the stem cells return to the bone marrow, proliferate, and restore normal blood cell production.

During this phase, known as aplasia, immune defenses are reduced, and transfusions of red blood cells or platelets may be required.
A common side effect of high-dose therapy is inflammation of the mouth and/or intestinal lining (mucositis), which may occur during the period of low white blood cell counts.

Allogeneic Transplantation

Allogeneic hematopoietic stem cell transplantation involves reinfusing stem cells from a healthy donor after a conditioning regimen consisting of high-dose chemotherapy and/or radiotherapy.

Preparation for transplant also includes immunosuppressive therapy:

• before transplant, to prevent rejection
• after transplant, to prevent or control graft-versus-host reactions

Unlike autologous transplantation, allogeneic transplantation also has an immunological effect. The donor’s immune system can recognize and eliminate residual cancer cells in the recipient. This beneficial mechanism is known as the graft-versus-lymphoma effect.

The main complication of allogeneic transplantation is an immune reaction called graft-versus-host disease (GVHD), in which donor lymphocytes attack the patient’s healthy tissues.

Allogeneic transplantation also leads to a loss of immunological memory, including:

• reduced antibody levels (IgG, IgA, IgM), sometimes requiring immunoglobulin replacement
• loss or reduction of vaccine-induced immunity (vaccinations must be repeated after transplant)
• reduction in T lymphocytes (CD4), which are monitored to guide discontinuation of anti-infective prophylaxis

After Allogeneic Transplantation

Immediately after transplantation, low white blood cell counts increase the risk of infections.

Recovery of white blood cells and platelets usually takes between 10 days and 3 weeks after stem cell reinfusion.

During this period, the immune system is severely weakened, and hospitalization is typically required to prevent or promptly treat infections with antibiotics. Hospital stays for allogeneic transplantation generally last at least four weeks, followed by additional time for overall recovery.

Immunosuppression may persist for a long time, especially if graft-versus-host disease develops. Additional hospitalizations may be necessary to manage complications or recurrent infections. This phase varies from patient to patient and may last several months.

Post-Transplant Care and Precautions

Due to temporary immune system impairment, certain precautions are necessary:

Monitor symptoms carefully 
Report promptly any signs such as fever, cough, shortness of breath, diarrhea, constipation, skin redness, or weight changes.

Maintain strict hygiene 

• wear a mask when appropriate
• avoid crowded places
• avoid contact with pets (due to risk of infections from scratches, bites, saliva, or feces)
• avoid sun exposure
• do not share towels
• if possible, use a dedicated bathroom at home
• practice protected sexual activity
• keep the home clean using disinfectant products
• frequent handwashing is essential, especially during the first 6 months and during any period of immunosuppression

Follow dietary recommendations carefully 
Strictly adhere to dietary guidelines provided at discharge, including lists of permitted and prohibited foods. In case of doubt, consult the transplant center team during follow-up visits.