Over the past 20 years the percentage of patients with lymphoma who obtains and maintains complete remission (CR) has increased significantly. In children and in children aged between 2 and 20 years, the chances of complete recovery are greater than 70%, while for the indolent forms have not yet been achieved these results.

 

The treatment regimen to use depends on many factors such as type and grade of NHL, the extent of disease, and various prognostic factors.
Treatments used include chemotherapy, radiation therapy, new biological therapies, in some cases, practice the stem cell transplant, and surgery is indicated only in certain circumstances but not for therapeutic purposes.
The goal of treatment is to achieve complete remission (CR).

What might be the response to treatment?

The first-line therapy is the first in which the patient undergoes, the answer may be:

 

1. Complete Remission:
total disappearance of all signs of illness does not mean that the disease is cured, but at that moment there is no apparent disease.
If this state is maintained long term then we speak of healing and this possibility is greater the further away from the time of diagnosis. The disease can recur, so it is important to monitor the patient over time.
2. Healing:
talk about it after a few years after the end of therapy, high-grade forms are more easily treatable forms of low grade, which tend to recur even years later.
3. Partial Remission:
This term is used to indicate that there has been a response but has not achieved the complete disappearance of the disease, that there is residual disease (less than 50% of the initial disease).
4. Refractory disease:
resistant treatment
5. Progression of disease
despite treatment the disease progresses.

Other factors that may affect the success of therapy in addition to the histological type of NHL and the degree are:

• • age: patients aged <60 years have a better prognosis because better tolerate more aggressive treatment, the younger then have a body more healthy and efficient.
• • Performance status (PS): indicates the general conditions and the status of self-sufficiency of the patient, is expressed on a scale from 0 to 4 where 4 indicates a terminal condition. Clearly the prognosis is worse if the PS is high.
• • LDH: high levels of this enzyme correlate with more aggressive disease.
• • extranodal disease: the involvement of other organs such as bone marrow, central nervous system, skin, internal organs, worsens the prognosis.
• • Stage of disease stages I and II show a localized NHL that has a better prognosis, III and IV indicate advanced disease that has a less good prognosis.
• We must clarify the concept of good prognosis, saying that the formulation of a prognosis based on information collected from hundreds or thousands of patients who have suffered the same disease, who received similar treatment and who have obtained a certain type of response, but no patient alike, and the statistics made on large numbers does not always apply to everyone.
• In the treatment of other malignancies such as NHL, we can distinguish between standard therapies, which are those commonly used, and experiments that are being studied.

Chemotherapy

These chemotherapeutic drugs are used that can lead to death of tumor cells by acting on several crucial points of the cell and in various stages of its development cycle, unfortunately these drugs are not selective and thus also causes damage to healthy cells (toxicity ).
Currently, treatment protocols involving the use of more drugs (chemotherapy) to exploit different mechanisms of action by various substances and then to attack the lymphoma cells on multiple fronts (synergies), and also this also allows use of lower doses and then to reduce a bit 'toxicity. Di solito una sola dose di farmaco non è sufficiente per uccidere tutte le cellule tumorali, per questo è necessario somministrare più dosi ad intervalli di tempo prestabiliti in base alle caratteristiche dei farmaci impiegati: si parla così, di cicli di chemioterapia. The division into cycles is useful for achieving greater effectiveness for preventing tumor cell resistance to drugs, to reduce the toxic effects and to allow the body to recover between cycles and the other.
The treatment protocols in place are the result of studies and national and international cooperation with a documented experience in the care of pediatric lymphomas.

 

It 'very important to respect the dosages and methods of treatment provided by the treatment protocols.
When we speak of "dose intensity (maximum dose) is the maximum dose of medication that the body can endure the side effects acceptable, it was shown that this approach is effective in many cancers and also in aggressive lymphomas; reducing the dose intensity was observed to reduce both the possibility of care for long-term survival, it is important that patients know that reducing the dosage of medicines to reduce side effects in the short term, it can be harmful in the long term, some side effects are unpleasant but bearable, others can be serious but predictable and tractable: it is very important so that treatment protocols are not modified at all possible.

The mode of administration of chemotherapy are injected intravenously, which is the most frequent, by intramuscular injection, by mouth. If you plan an intravenous treatment for long periods, your doctor may suggest the insertion of a temporary or permanent venous catheter to administer drugs and other therapy in a more convenient, painless and not to damage the peripheral veins that can be seriously damaged by chemotherapy.
There are several types of central venous catheter, the most common type is called a Hickman-Broviac, and consists of two tubes that are inserted through the chest wall in a large vein: about 20-30 cm of tube remaining outside. The advantage of positioning the catheter is being able to perform the blood sampling and chemotherapy without subjecting children to continue bites. The disadvantage is the possibility of infection and thrombosis.

Side Effects

The chemotherapy drugs are designed to destroy cancer cells, but also have various side effects. The combination of multiple drugs increases the effectiveness of treatment but can not eliminate the inevitable side effects.
Chemotherapy in fact acts on all cells that are actively replicating in the body. In addition to cancer cells, healthy cells that are actively replicating and that used more often affected by chemotherapy are the cells of the bone, the hair follicles, gastrointestinal tract and the reproductive system. As a result, the most common side effects include infection, anemia, bleeding, hair loss, mucositis, difficulty swallowing, nausea, vomiting, constipation or diarrhea, sterility.

Blood cells

Every cell in the blood has a specific function. Red blood cells carry oxygen, white blood cells are important in preventing infection, platelets prevent and block any bleeding. During the treatment the red cells, white and platelets are continuously monitored.
Anemia is established when hemoglobin levels fall. An important part of red blood cells is precisely the hemoglobin that carries oxygen to tissues. When hemoglobin is low, the level of oxygen in the tissues decreases and the body begins to have difficulty in performing normal activities. The symptoms of anemia are paleness, weakness, fatigue, headache, irritability.

 

White blood cells are of different types. There are neutrophils that we defend against infections caused by bacteria. When neutrophils are below levels 1000/mmc the patient is considered neutropenic. In the course of neutropenia is important to notify your doctor immediately when they appear the following symptoms: fever> 38 ° C, chills and sweating, coughing and shortness of breath.
During the period that is carried out mainly in the course of chemotherapy and neutropenia is useful to take some precautions: measuring the temperature frequently, avoid crowded and closed environments, avoid eating uncooked foods that may contain bacteria such as fresh vegetables, fruits not peeled, sweets.

 

Platelets have an important haemostatic function. The normal level of platelets across 150000/mmc and 400000/mmc. When platelet levels fall below the 40000/mmc increases the risk of bleeding. The most frequent symptoms of thrombocytopenia are: the presence of bruises and petechiae on the skin, bleeding from the nose and gums, blood in the urine.
In the course of thrombocytopenia is good to use certain rules of behavior: brush your teeth gently with a soft toothbrush, avoid the consumption of drugs such as aspirin or other anti-inflammatory drugs, avoid activity or exercise that can cause injuries, do not use clothing too tight, always protect from possible trauma feet and legs with stockings and shoes.

Hair Loss

Hair loss is an inevitable effect of chemotherapy and radiotherapy.
The cells responsible for hair growth in actively replicating cells are affected by the action of chemotherapeutic drugs. The speed with which hair loss occurs varies from person to person and depends on the type and dosage of chemotherapy used, usually begins 2-3 weeks after the first cycle of therapy and interesting addition to the hair even the hair on the face, arms and legs, pubic and eyebrows. Regrowth occurs in all patients about four months after the last cycle of chemotherapy. In many cases the color of the hair may temporarily be different but the weather returns to normal.

Mucositis

Mucositis can be a side effect of chemotherapy or radiotherapy and is caused by destruction of cells that produce saliva. The temporary loss of these cells and the reduction of white blood cells susceptible to infections that worsen the picture of mucositis.
Prevention of mucositis of the mouth is to do frequent washing with solutions containing sodium bicarbonate, disinfectants and antifungal. It 'is also helpful to prefer soft non-irritating foods and easily chewable.

Nausea and vomiting

Nausea and vomiting are common side effects of chemotherapy. However the effects are temporary and easily respond to treatment. Are commercially available several types of antiemetic drugs to be administered before chemotherapy.

Constipation

Constipation is caused by a small amount of liquid and a reduced motility in the intestine. Some chemotherapy drugs can help to determine constipation because they act on the nervous structures of the intestine and reduce the contractility of the colon. It 'good to increase fluid intake during the administration of chemotherapy and possibly involve the treatment of mild laxatives.

What other inspections are needed?

Can be requested a study of the heart with electrical and echocardiogram and lung function to assess the functionality of these organs before starting therapy.

Diarrhea

Diarrhea can have many causes: chemotherapy, radiation, infection, hypersensitivity to certain foods, emotional disturbances. During an episode of diarrhea foods shipped very quickly in the intestines before the body can absorb enough vitamins, minerals and water. This can cause dehydration and increase the risk of infection. E 'recommended, when this event occurs, maintain good hydration, preferring beverages containing minerals, such as tea, and take small but frequent meals.

Radiotherapy

Radiation therapy is used in energy X-rays to kill cancer cells and eliminate the tumor, this is a local therapy that works only on the tumor cells of the treated area, by type of cancer, radiation therapy can be used alone or in combination with chemotherapy.
Field of irradiation is the term used to describe the body part to be radiated, since the extension of lymphoma is not always defined precisely, the radiation is confined to the lymph nodes and the areas closely adjacent fields of irradiation are determined on a case case basis, depending on the type and extent of the disease.
Areas that are commonly irradiated are: the mantle (the region of the neck, chest and supraclavicular), the upper abdomen (para aortic lymph nodes and spleen), the pelvis and inguinal lymph nodes. In some cases it may be necessary to irradiate all fields.
To prepare the patient to radiation therapy is necessary to identify radiologically the area to display and draw the contours on the skin so that every time it is the right area. The normal tissues surrounding the area to be irradiated will be shielded with protective lead. The patient is exposed to radiation in daily sessions of a few minutes, because the total required dose is achieved gradually in a few weeks.


Side effects of radiotherapy

Radiotherapy is not painful and the patient is not radioactive, the most common side effects are: l 'fatigue that can last a few weeks after the end of treatment, decreased appetite and sense of taste, throat irritation especially if radiated area of the neck, dry mucous membranes of the mouth to reduce the production of saliva (it is advisable to take light food, small quantities, excluding those irritating introducing liquids such as fruit juices, lemon), reactions such as redness of the skin Accompanied by discomfort, itching and edema. These changes usually disappear a few weeks after discontinuation of therapy, the skin may look sunburned and eventually peeled. It 'important during radiotherapy, do not expose to the sun irradiated areas to avoid dangerous burns.
Nausea may occur after the first treatment especially in patients who are irradiated to the abdomen, some patients may experience nausea if they have not eaten in the hours before radiotherapy especially sugary foods, fatty or spicy. If nausea is a problem we can use antiemetics.
Hair loss or hair may occur in irradiated areas.

Biological therapies

The biological therapy (including immunotherapy) is a treatment that uses the defense capabilities of that sick body to treat cancer or to minimize side effects caused by treatments.
These therapies may act directly or restore the natural defenses against disease, for example, these treatments include monoclonal antibodies, radio immunotherapy, interferon, vaccines, angiogenesis inhibitors, therapies and pro apoptotic gene therapy.

Monoclonal antibodies (MAbs)

Are similar to a guided missile that reaches its target. When an outside agent comes in contact with the body's immune system produces different antibodies (polyclonal) directed against specific molecules called antigens expressed on the surface of the invader.
Antibodies are produced by plasma cells that are more mature B lymphocyte line in the body, each plasma cell is responsible for the production of an antibody, therefore, that antibody. Each monoclonal antibody specifically acting against a specific antigen. Using new techniques is now possible to produce large quantities of monoclonal antibodies that are directed against a single antigen, expressed on the cell surface.
Various therapeutic strategies involving the use of MAbs are under study.

• - MAbs that react with specific types of tumor cells by inducing the patient's immune response against the tumor.
• - MAbs as carriers of drugs, toxins or radioisotopes bringing them into contact with the cancer cell to destroy.
• - MAbs that are used prior to an autologous transplant to destroy residual cancer cells.

Rituximab was the first monoclonal antibody for use in the treatment of many aggressive lymphomas. Rituximab is active against the CD20 antigen on the surface of most B lymphocytes and is able to eliminate both the lymphoma cells that normal B cells. It is thought that the lymphoma cells are attacked by the immune system in response to the binding of cells with MAb.
Since younger normal lymphocytes do not have the CD20 antigen, are not affected by MAb. B cells are regenerated after treatment from these so-called stem cells.

The radioimmunotherapy

Monoclonal antibodies (MAbs) are directed against a specific antigen expressed on tumor cells, there are some MAbs which is tied a radioactive molecule that will act directly on cancer cells. The antibody radioimmunotherapy lies in attacking such radioactive isotopes: iodine 131 and yttrium 90 (the second) these antibodies are used to treat low-grade B NHL or transformation, resistant to standard therapies. Many studies are underway that aim to broaden the applications and to synthesize new ones.

Interferon

Interferon alpha (IFNa) is a protein normally produced by the body that acts against cancer cells, is artificially synthesized for therapeutic use. It destroys cancer cells either directly or through the immune system, some studies have shown that administration of IFNa in combination with chemotherapy can improve the response in patients with low grade NHL, and many recommend its use as maintenance therapy following chemotherapy, many studies have Demonstrated The Effectiveness of 'IFNa in Prolonging remission duration but limited effectiveness in terms of prolongation of IFNa and survival.
One of the most common side effects of flu-like syndrome: fever, weakness, drowsiness, muscular-skeletal pain; intake before bedtime combined with good hydration and intake of NSAIDs reduces these effects. IFNa may also sometimes leads to severe depressive syndrome, others more rare effects include anorexia, and thyroid dysfunction.

Vaccines

Still not a standard treatment but are being studied. Stimulate the patient's immune system against disease. Preliminary studies have shown that an antineoplastic effect in patients with residual disease or in remission. It is still too early to draw conclusions.

Therapies "antisense"

Are drugs that should induce the arrest of protein production that in many cases are cancer-specific, so that cancer cells can not survive. Therapies are directed against specific cancers including NHL.
These drugs may be less toxic than others because spare healthy cells. Are being tested various protocols.

Gene therapy and therapy antiangiogenesi

Treatments are being studied. The development of new blood vessels is called angiogenesis, many tumors stimulate angiogenesis resulting in development of new blood vessels and thus allow the growth of the tumor. Drugs antiangiogenesi prevent the development of new blood vessels and destroy the system of abnormal vessels supplying the tumor, thus limiting the growth of the same.
Gene therapy aims to change the gene structure of tumor cells so that they are recognized and eliminated by the immune system, or is intended to make the cells more sensitive to treatment.
Both treatment strategies could be used in combination with chemotherapy. It is however still experimental therapies.

Long-term effects and relapses

Many patients respond well to treatment and survive in good health for many years but unfortunately there are some problems that arise late, for example patients who received radiation therapy to the neck may develop hypothyroidism.
Possible long-term infertility and early menopause, this risk depends on the type of treatment and dose received, is more common to occur in women over 30 years, while 80% of women with less than 30 years resumed menstrual function. In men, infertility may be temporary or permanent, before starting therapy can man and woman cryopreserved semen, ova.
Patients treated for NHL may be at high risk of developing a second type of cancer such as leukemia, melanoma, or otherwise.
Other issues affecting the lungs and heart, in fact there is an increased risk of developing diseases borne by these organs because of the toxicity of chemotherapy.

 

Patients receiving radiation therapy are at increased risk of developing cancer in the irradiated in the next 20 years, excessive sun exposure in these areas may induce the development of skin cancers, the greater the risk of developing breast cancer in women who have undergone irradiation to the chest.

Treatment for repeat offenders.

The reappearance of the NHL after the RC is called relapse and the type of NHL and the time between remission and relapse influence the choice of treatment. Rescue therapies often lead to a second remission or cure, and include other chemotherapy regimens, monoclonal antibodies, stem cell transplantation.

Marrow transplant or stem cells

Bone marrow contains immature cells called stem cells that give rise to the three cellular elements that are in the blood: red cells, white cells and platelets. In some cases, high doses of chemotherapy or radiation needed to destroy the lymphoma cells leads to a failure of normal bone marrow cells to regenerate blood cells, the transplantation of bone marrow or stem cells is needed to replenish the normal bone.
Transplants are divided into two categories according to the sources of stem cells:

• • Allogeneic transplants: the cells are taken from a compatible donor can be a relative (brother, sister) or unfamiliar (to register).
• • Autologous transplantation: in this case the patient receives healthy stem cells taken from himself after chemotherapy and with appropriate stimulation.

Stem cells are taken from bone marrow, peripheral blood with appropriate equipment, and from umbilical cord. The transplantation of stem cells has a greater chance of success in patients in complete remission than in those in partial remission or full relapse.

 

The stem cell transplant is a highly sophisticated and potentially dangerous procedure in which the bone marrow of the patient, and possibly all residual lymphoma cells are destroyed by a prior intensive therapy with high doses and the subsequent action of immunologically active cells of the donor against cells of the recipient. The bone marrow is destroyed and then replaced with the cells of the donor (allograft), or with those of the same receiver taken in remission (autograft).

 

Until the new marrow begins to function, patients depend entirely supportive care to counteract the anemia, bleeding, and infection. In allogeneic transplant patients are at risk of a crisis of rejection, which is a potentially fatal immune reaction in which the donor marrow rejects the tissues of the receiver.
In the case of successful treatment, the marrow transplant creates a new population of healthy cells.