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Drug therapy for childhood B-cell lymphoma

Medical editor Ingebjørg Storm-Mathisen MD
Pediatric Oncologist
Oslo University Hospital


For children up to 18 years with non-Hodgkins B-cell lymphoma, treatment is according to the European protocol BFM 04. The treatment takes place at regional hospitals only.

Treatment consists of 2-7 blocks with abbreviations A, AA, AAZ, B, BB, BBZ and CC. All of the blocks last for 5 days, except for the blocks given to children with B-cell lymphoma with primary CNS infiltration, which last for 6 days. A minimum of 16 days should pass between blocks.  

Risk groups

There are 4 risk groups. The risk groups are determined based on stage, LD values, extent of tumor resection, and CNS infiltration. Children with primary CNS infiltration and children with primary mediastinal B-cell lymphoma are excluded from the risk group categories and are treated on their respective protocols.

Children in risk groups 3 and 4 receive higher doses of methotrexate with a longer infusion time. This leads to more intense side effects and longer periods of neutropenia than risk groups 1 and 2. Immune suppression and severe mucositis is a significant problem for B-cell lymphoma treatment and can lead to a prolongation of treatment (8).

Cytoreductive preliminary phase

Children with B-cell lymphoma are often very ill at the time of the diagnosis. It is crucial to start treatment as soon as possible, even if the diagnosis is unclear. It is especially important to intiate treatment if the child presents with thoracic infiltration or spinal cord compression. Treatment should start with a cytoreductive preliminary phase lasting for 5 days. By starting with the preliminary phase, the chance of tumor lysis syndrome is reduced.

Risk group 1 does not have preliminary phase treatment.


  • B-cell lymphoma


  • Cure the disease

Treatment plan

The treatment plan for patients with B-cell lymphoma is available in an interactive flow chart. This is a function giving overview of treatment for the different patient groups.

Click to open the flow chart:

Overview of the treatment blocks

Preliminary phase

The preliminary phase consists of:

  • Dexamethasone orally 3x daily for days 1-5
  • Cyclophosphamide intravenously days 1-2
  • Methotrexate/cytarabine/prednisolone intrathecally under general anesthesia day 1

A/AA/AAZ cycle

The block consists of:

  • Dexamethasone orally 3x daily for days 1-5, day 1-6 in the AAZ blocks
  • Vincristine intravenously day 1 (vincristine is not given to risk group 1)
  • Cytarabine intravenously twice daily days 4 and 5
  • Etoposide intravenously days 4 and 5
  • Methotrexate intravenously day 1 (the number 4 and 24 in the course nomenclature indicates that the methotrexate is given over 4 or 24 hours)
    • Calcium folinate is given 42, 48, and 54 hours after starting methotrexate
  • Ifosfamide intravenously day 1-5
  • Methotrexate/cytarabine/prednisolone intrathecally under general anesthesia day 2 in A block, days 2 and 5 in AA blocks, days 2,4, and 6 in AAZ1 block, and day 2 and 6 in AAZ2 block  

B/BB/BBZ cycle

The block consists of:

  • Dexamethasone orally 3x daily on days 1-5, days 1-6 in the BBZ blocks 
  • Vincristine intravenously day 1 (vincristine is not given to risk group 1)
  • Doxorubicin intravenously days 4-5
  • Methotrexate intravenously day 1 (the numbers 4 and 24 in the course nomenclature indicates that the methotrexate is given over 4 or 24 hours) 
    • Calsium folinate is given 42, 48, and 54 hours after starting methotrexate
  • Cyclophosphamide intravenously daily days 1-5
  • Methotrexate/cytarabine/prednisolone intrathecally under general anesthesia day 2 and 5 in BB block, days 2, 4, and 6 in BBZ1 block, and day 2 and 6 in BBZ2 block   

CC cycle

The block consists of:

  • Dexamethasone orally 3x daily days 1-5
  • Vindesine intravenously day 1
  • Cytarabine intravenously 2x daily days 1 and 2 
  • Etoposide intravenously 2x daily on daysl 3 and 4 and once on day 5  
  • Methotrexate/cytarabine/prednisolone intrathecally under general anesthesia day 5 



  • A peripheral venous catheter is installed and hydration started (prophylaxis for tumor lysis syndrome)  
  • Susceptible organs must be tested:
    • Heart (Echocardiogram or MUGA)
    • Kidneys (Glomular filtration rate, GFR)
  • A central vein catheter is placed 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 sperm banking.  
  • The child and parents should be instructed on oral hygiene.
  • The child should not have immunizations during treatment.

The first course of drug therapy starts regardless of blood values.

All children receive trimethoprim-sulfa during the entire treatment to prevent pneumocystic jirovecii pneumonia and is started after the first block. Trimethoprim-sulfa should be stopped 3 days before methotrexate is taken to avoid interaction with methotrexate metabolism. 

Before each course, the following is taken:

  • Blood tests. Blood values should be increasing at the start of each course.
  • Blood pressure and pulse rate 
  • Temperature
  • Urine dipstick 
  • Weight and height 



The treatment can vary from 1 month up to about 7 months.

  • Proper hydration.
  • Fluid calculation should be performed during the entire block.
  • Children using diapers should be changed every 2 hours to prevent sore skin.
  • Proper antiemetic treatment.

When methotrexate/cytarabine/prednisolone are given intrathecally, the child is given general anesthesia.


  • Urine pH should be > 7 before starting methotrexate and during the entire course
  • Blood tests are taken to measure the concentration of methotrexate in the blood and calcium folinate is given intravenously 


  • Can cause reversible bleeding conjunctivitis which is prevented or reduced using eyedrops containing corticosteroids 
  • Cytarabine can also cause high fever which is treated with fever-reducing medication. This is an indication for starting antibiotics, but the child's clinical status must be monitored closely. 


  • May cause hemorrhagic cystitis and mesna is given prophylactically. 


  • Etoposide can, in rare cases, cause anaphylactic shock.
  • Treatment for anaphylaxis should be at bedside during the entire infusion. The child does not need permanent monitoring by a nurse, but should not be left alone during the etoposide infusion.  



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. 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 infections 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 increase in temperature or other symptoms of infection.   
  • Poor appetite
  • Constipation
  • Pain
  • Lethargy

Common side effects


Nutritional problems occur quite commonly 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 disappear after cessation of the drug but may persist 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 lubricatiion 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 and 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

  • Hair loss starts 7-14 days after initiation of chemotherapy. The hair will usually fall out in tufts.

  • The child will likely be Cushingoid from taking steroids.

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.


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