Relapsed/ Refractory Acute Lymphoblastic Leukemia (ALL)

What is relapsed/ refractory ALL? 

Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow. The overall cure rate for ALL in children is about 90% in the United States. But in some cases, it does not go away or comes back after treatment.

Relapsed acute lymphoblastic leukemia is ALL that comes back after treatment. This is called a relapse or recurrence. It can happen months or years later.

Refractory acute lymphoblastic leukemia is ALL that does not respond to treatment and does not go away despite treatment.

Relapsed or refractory leukemia happens in 15–20% of childhood ALL patients in the United States.

Treatment for relapsed or refractory leukemia is often more intensive than for newly diagnosed ALL. Treatment may include:

• Chemotherapy
• Radiation therapy
• Stem cell (bone marrow) transplant
• Immunotherapy
• Targeted therapy
• A combination of treatment

For some patients, treatment may be offered as part of a clinical trial.

Symptoms of relapsed/ refractory ALL

Signs and symptoms of relapsed or refractory ALL include:

• Fatigue
  
• Pain in the bones or joints
• Fever
• Frequent infections
• Easy bruising and bleeding that is hard to stop
• Tiny, flat, dark-red skin spots (petechiae)
• Lumps in the neck, underarm, stomach, or groin
• Pain or fullness below the rib cage
• Paleness
• Loss of appetite
• Shortness of breath
• Enlarged liver
• Enlarged spleen

Diagnosis of relapsed/ refractory ALL

Doctors diagnose relapsed ALL with:

• Medical history and physical exam
• Complete blood count test
  
• Bone marrow aspirate or biopsy
• Lumbar puncture
• Chest x-ray
• Ultrasound of testicles if there is a concern of relapse in that area

Treatment of relapsed/ refractory ALL

Relapsed or refractory childhood ALL can be a challenge to treat. Treatment may include chemotherapy, radiation therapy, stem cell (bone marrow) transplant, immunotherapy, targeted therapy, or a combination of treatments. A clinical trial may be an option.

Chemotherapy used to treat ALL

Patients with relapsed or refractory ALL may need high doses of chemotherapy.

Medicines may include:

• Dexamethasone
• Vincristine
• Pegaspargase
• Mitoxantrone
• Doxorubicin
• Cyclophosphamide
• Etoposide
• Methotrexate
• Mercaptopurine
• Cytarabine

Patients with T-cell ALL may receive nelarabine or bortezomib.

Other treatments

Other treatment options include:

• Stem cell (bone marrow) transplant
• Immunotherapy
• Targeted therapy

The treatment plan will be based on several factors. Doctors consider:

• Where leukemia cells are found
• Length of the first complete remission
• Specific type of ALL

Site of ALL relapse

Your child’s treatment plan may be different depending on where leukemia cells are found, such as the bone marrow, spinal fluid, or testicles. 

Bone marrow

• Chemotherapy with or without targeted therapy 
• Stem cell (bone marrow) transplant in high-risk cases
• CAR T–cell therapy in some high-risk cases

Central nervous system (brain and spinal cord)

• Chemotherapy and intrathecal chemotherapy with radiation therapy to the brain and spine for relapses only in those areas.
• Transplant for early brain and spinal cord relapse if leukemia is found in the bone marrow

Testicular (males only)

• Chemotherapy and radiation therapy

Length of the first complete remission

ALL that returns more than 6 months after the end of treatment has a better treatment outlook than ALL that comes back sooner.

The care team may also look at treatment response and minimal residual disease (MRD). MRD means a small number of cells remain during or after treatment. It predicts a poorer prognosis because patients are more likely to relapse again.

Type of ALL

There are 2 types of ALL: B–cell ALL and T–cell ALL. Overall, B–cell ALL has a better treatment outlook than T–cell ALL.

Prognosis of relapsed/ refractory ALL

About 30–50% of patients survive after their first relapse. Some children may relapse more than once. Each time the chance of cure decreases. Survival rates are only estimates. Your child’s doctor is the best source of information on your child’s case.

Support for patients with relapsed/ refractory ALL

A diagnosis of relapsed or refractory leukemia is challenging for patients and families. Intense treatments may cause severe side effects and increase your child’s risk of infections.
Good communication with the care team can help patients and family caregivers know what to expect and take an active role in the treatment decisions.

Supportive care

A team of health care providers can support emotional, social, and spiritual needs of patients and families. Your care team may include:

• Palliative care clinicians
• Psychologists
• Social workers
• Music therapists
• Chaplains
• Child life specialists

Help for side effects

Early palliative care can help with pain and other side effects. Common side effects include:

• Pain
• Nausea
• Constipation
• Shortness of breath
• Itching
• Anxiety
• Depression

Doctors may prescribe medications to help with side effects. Other treatments may include integrative (complementary) medicine.

Ways to prevent infection

About half of children with relapsed or refractory ALL will develop life-threatening infections. Reasons infection may occur include:

• Intense chemotherapy can damage bone marrow. The bone marrow may not be able to make white blood cells to fight infections.
• A patient may already have bacteria on or in their body that can resist antibiotics. Signs or symptoms of infection from these bacteria may not occur right away.
• The body’s skin is a defense against infections. Patients are more likely to have infections if they have skin breakdown, such as sores.

Follow infection prevention guidelines to reduce your child’s risk of illness. Take steps to prevent infection:

• Wash your hands or use alcohol-based hand sanitizer often. Tell others to do the same.
• Avoid people who are sick, and make sure that people around your child are vaccinated against infectious diseases such as flu and COVID-19.
• Have your child wear a face mask as instructed by your care team.
• Follow skin care guidelines and watch for skin breakdown.
• Care for your child’s central line as instructed by your care team. It is a common site of infection.
• Follow instructions for good oral (inside the mouth) care and perianal (near the anus) care.
• Use antibiotic or antifungal medicines as recommended by your care team to prevent infections.

Questions to ask the care team

• What are our treatment options?
• What are the possible side effects of each treatment?
• What can be done to manage side effects?
• Will my child need to be in the hospital for treatment?
• Where is the treatment available? Is it close to home or will we have to travel?