Drug therapy for childhood Hodgkin's lymphomaMedical editor Alexander Fosså MD
Oslo University Hospital
Children up to 18 years with Hodgkin's lymphoma are treated as in the German protocol GPOH-HD-95. This is the protocol resulting from an international collaborative study where Norway was also a participant. This protocol, including its most recent changes, is currently the standard treatment for childhood Hodgkin's lymphoma in Norway. The treatment takes place at regional hospitals only, or under their supervision.
The treatment consists of chemotherapy for all patients, and radiation therapy for most after finishing chemotherapy. It is therefore very important to have a close cooperation between the pediatric oncologist and oncologist/radiation therapist from the start of treatment. The patients are stratified into therapy groups according to stage. Therapy group 1 includes the early stages. Therapy group 2 includes the intermediary stages and therapy group 3 includes the advanced stages.
|Therapy groups according to GPOH-HD-95
||I A/B and II A
||IEA/B, IIEA, II B or III A
||IIEB, IIIEA/B, III B or IV A/B
Treatment consists of 2-6 regimens with acronyms OPPA, OEPA and COPP. All of the regimens last for 15 days and are repeated every 4 weeks. In the GPOH-HD-95 protocol, girls receive OPPA for the first two courses regardless of therapy group. Recently, OEPA has also been given to girls for fertility reasons. Boys also receive OEPA since it is shown to cause lower rates of infertility in men. The patients in therapy group 1 only receive 2 courses. In therapy groups 2 and 3, COPP is also given 2 and 4 times, respectively.
Patients in therapy group 1 in complete radiological remission after 2 OPPA/OEPA courses do not have radiation therapy. Radiation therapy is given if there is remaining tumor. Patients in therapy groups 2 and 3 will have radiation therapy regardless after completing 4 and 6 courses. Radiation therapy is given mainly to the tumor area (involved field). The amount of irradiation is normally 20 Gy (1.8 Gy x 11), but for areas with less than 75% reduction of original tumor volume, it is recommended to give 30 Gy. For areas with less than 75% reduction and remaining tumor over 100 ml in volume, it is recommended to give 35 Gy. There are more detailed specifications in the protocol for radiation therapy, for example, with primary infiltration in the mediastinum, lungs, bone marrow, or skeleton, which must be assessed carefully.
Since 2008, the EuroNet-PHL-C1 protocol is the recommended treatment in Norway. Participation in this study is also recommended.
The treatment plan for patients with Hodgkin's lymphoma is available in an interactive flow chart. This serves as an overview of the treatment for the different patient groups.
Click to open the flow chart:
For large tumor masses, tumor lysis syndrome is a threat at the beginning of the first course of chemotherapy. Early initiation of hydration, forced diuresis, and treatment with allopurinol or rasburicase, may be necessary (prophylaxis for tumor lysis). The extent of necessary monitoring of tumor lysis prophylaxis or manifest signs of tumor lysis syndrome (fluid balance, blood tests, urine pH) must be assessed in these cases. Serious tumor lysis syndrome is less likely for Hodgkin's lymphoma than most other childhood lymphomas.
Symptoms must be monitored in cases of large mediastinal tumors with risk of restricting central airways or causing superior vena cava syndrome.
It may be necessary to measure organ function of susceptible organs:
- Heart (echocardiography, MUGA)
- Kidneys (glomular filtration rate, GFR)
- Lungs (lung function testing)
The patient should have a central vein catheter or VAP installed under general anesthesia.
The child and parents/guardian should be informed of the disease, treatment, and side effects.
With the permission of the parents/guardian, the child's school/preschool should be informed of the diagnosis and what the treatment involves. Written information should be sent out. If the child attends school, a nurse will visit the school to inform the child's classmates about the disease and its treatment.
- Parents/guardians will receive help in writing an informative letter to family and friends.
- The hospital teacher/ preschool teacher contacts the child and family and informs about hospital schooling.
- The child will be offered a customized wig/scarf/hat and a wig maker will come to the hospital with samples.
- Boys over 12 years who have reached sexual maturity are offered the possibility of sperm banking.
- In cases where radiation to the small pelvis is necessary, ovarian tissue freezing or ovaropexi should be considered. Chemotherapy alone as given in the GPOH-HD-95 protocol does not currently qualify for freezing of ovarian tissue.
- All chemotherapy and radiation therapy are potentially teratogenic. Pregnancy testing should be assessed before starting chemotherapy. Also, the need and extent of information given for contraception in teenagers should be assessed.
- The child and parents should be instructed on oral hygiene.
- The child should not have immunizations during treatment.
All children receive trimethoprim-sulfa during the entire treatment to prevent pneumocystic jirovecii pneumonia.
Before each course, the following is taken:
- Blood tests. Total white count with neutrophil and thrombocytes should be increasing at the start of each course.
- Blood pressure and pulse
- Urine dipstick
- Weight and height
- Secure intravenous access
- Proper hydration
- Children using diapers should be changed every 2 hours to prevent sore skin.
- Proper antiemetic treatment
- Patients taking procarbazine orally may have difficulties ingesting the capsules. These can be opened and given on a spoon with jam/juice or stomach tube. It must be done as hygienically as possible.
- Etoposide can, in rare cases, cause anaphylactic shock. Drugs for treating anaphylaxis should be with the child during the entire course. The child does not need permanent monitoring by a nurse, but should not be left alone during the etoposide infusion.
- Intravenous hydration and use of mesna is given as hemorrhagic cystitis prophylaxis on days with cyclophosphamide.
- Patients taking procarbazine orally may have difficulties ingesting the capsules. These can be opened and given on a spoon with jam/juice or stomach tube. It must be done as hygienically as possible. Procarbazine also requires a restricted diet.
The child is often followed-up by their local hospital during block treatments. Due to declining blood values after treatments, regular blood tests are taken. Transfusions and treatment for infections are also necessary.
The treatment causes many side effects therefore, it is very important to have cooperation among the parents, the local hospital, and regional hospital.
The parents/guardian must observe the child at home and should contact the hospital immediately if the child develops symptoms of:
- Infection (fever over 38.5°C from one measurement or two of 38.0°C with one hour interval). Since prednisolone is a fever-reducer and is taken for 15 days after each course of chemotherapy, a lower temperature may also be of significance if there is suspicion of infection. Also, symptoms of infection other than fever may be masked during prednisolone treatment. Particular caution must be taken if the patient is simultaneously neutropenic, taking prednisolone, and has a mild temperature increase or other symptom of infection.
- Poor appetite
Common side effects
Nutritional problems occur in varying degrees in patients undergoing this treatment. This is due to nausea, vomiting, mucositis, dry mouth, pain, constipation, and sensory changes. Many will need tube-feeding to meet their nutritional needs. Steroids can lead to an increase in appetite and good nutritional guidance is important.
Vincristine can cause neuromuscular manifestations. Pain often starts with sensory disturbances and paresthesia. Neural pain and delayed serious motor disturbances can occur with continued treatment. The neuromuscular side effects are muscle atrophy, loss of deep tendon reflexes, bone pain, jaw pain, and tracheal pain. Vincristine can also lead to drooping eyelids (ptosis). Side effects usually resolve after cessation of the drug but may remain longer in some patients.
Mucositis, in the mouth and other mucosa occurs when blood values are at the lowest. The degree of soreness is individual. Sore mucosa in the mouth is not only an entrance for bacteria but it can also be painful. Prophylactic oral hygiene is practiced during the entire treatment.
For sore rectal mucosa, lubrication is necessary. A remedy is to use soft toilet paper with peanut oil for lubrication after each toilet visit. Bathing in green soap is also soothing. Do not take temperatures rectally, or give suppositories or enemas, etc. during chemotherapy to avoid the risk of bleeding and infections.
Vincristine can lead to constipation which is treated prophylactically with laxatives.
The nausea will diminish 1-2 days after finishing a course of chemotherapy depending on the drug. Parents will receive a prescription for anti-nausea medication.
Because of large steroid doses, the child is susceptible to gastritis. The child should be treated prophylactically with H2 blockers or proton pump inhibitors.
Change in appearance
Change in self-image
The treatment is usually a major burden for the child both physically and psychologically. This can change the way the child thinks of himself/herself.
Change of mood
Use of steroids makes the child susceptible to significant changes in mood. This may be a great burden for both the child and the rest of the family.
Treatment usually leads to isolation from local community. The child may not be included in normal play. Finding a balance between protecting the child from infection and allowing him/her to live a normal life is difficult, since the child is susceptible to infection during the entire treatment period. The child should avoid crowds such as shopping centers and public transportation. Ten to fourteen days after finishing a course of chemotherapy, the blood values are at their lowest. This is when the child is most susceptible to infection.
If the child feels well and does not have a white blood cell count that is too low, he/she may go to school. Otherwise, the child receives home-schooling. Younger children should not go to preschool during treatment, or during the first months after treatment is over.