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Acute Lymphoblastic Leukemia (ALL) Relapse in Children and Teens

What is Relapsed ALL?

Most children with acute lymphoblastic leukemia (ALL) are cured on current first-line therapy plans. But in 15-20 percent of cases in the United States — about 600 children — ALL comes back. When cancer returns, it is called relapse or recurrence.

Diagnosis

As in newly diagnosed ALL, patients will undergo a medical history/physical exam, blood tests, bone marrow aspirate/ biopsy, lumbar puncture, and chest X-ray.

Treatment

Relapsed childhood ALL can be a challenge to treat. Patients may require aggressive chemotherapy to attempt to achieve remission.

Medicines may include dexamethasone, vincristine, clofarabine, cyclophosphamide, etoposide, pegaspargase, methotrexate, mercaptopurine, cytarabine, mitoxantrone, teniposide, or vinblastine. Patients with T-cell ALL may receive nelarabine.

Patients with relapsed leukemia may be candidates for hematopoietic cell transplant (also called bone marrow transplant or stem cell transplant.)

The treatment plan may include new treatment approaches such as immunotherapy or targeted therapy.

Immunotherapy approaches may include CAR T-cells (tisagenlecleucel), blinatumomab, inotuzumab ozogamicin, or natural killer cell infusion and interleukin-2. Targeted drugs may include tyrosine kinase inhibitors, proteasome inhibitors, mTOR inhibitors, and HDAC inhibitors. Several of these therapies are quickly moving to first-line therapy for high-risk cases and patients with ALL that is refractory (resistant to treatment).

Aggressive treatments may cause severe side effects and an increased chance of serious infections. Palliative care specialists may be involved from the beginning to assist with the management of side effects and provide additional support for patients and families. Infectious diseases specialists may be involved to work with parents to prevent infections and to treat infections if they occur.

To determine the treatment approach and prognosis, doctors consider:

  • Site of relapse
  • Length of first complete remission
  • Specific type of relapsed ALL

Site of relapse

Bone Marrow

  • Chemotherapy with or without targeted therapy 
  • Hematopoietic cell transplant in high-risk cases

Central Nervous System

  • Systemic chemotherapy and intrathecal chemotherapy with radiation therapy to the brain and spine for relapses confined to the central nervous system (CNS).
  • Transplant for early CNS relapses if leukemia is also detected in the bone marrow (combined relapse)

Testicular (males only)

Length of the first complete remission

A case of ALL that relapses on therapy or less than 6 months after completion of first-line therapy has a poorer prognosis than ALL that returns more than 6 months after completion of first-line therapy.

Type of ALL

In general, B-cell ALL has a better treatment outlook than T-cell ALL.

In addition, the care team may also look at treatment response and minimal residual disease during certain points of treatment. Minimal residual disease (MRD) predicts a poorer treatment outlook because children with detectable MRD are more likely to relapse than those in MRD-negative remission.

Infections in Patients with Relapsed ALL

The risk of life-threatening infections increases dramatically during relapse for a number of reasons.

  • Intense chemotherapy can deplete the bone marrow. It may not be able to make white blood cells to fight infections.
  • Because patients have already been exposed to a number of antibiotics, there is a chance antibiotic-resistant bacteria have already colonized in the body. This means they could be on the skin or in the body but are not causing signs or symptoms of infection.
  • Skin breakdown, such as sores, make patients more vulnerable to infections. Patients and families should immediately report any signs and symptoms of skin breakdown, such as pain, redness, or bleeding. Children are particularly likely to develop sores in the perianal area (near the anus) and the mouth.

About half of children with relapsed ALL will develop a life-threatening infection. Prevention of infection can save children from developing a serious illness. Also, children who are candidates for transplant must be free of infections to have one.

Ways to Help Prevent Infections

Patients may be instructed to wear a mask over their nose and mouth to prevent infections.

Skin care is important. The body’s skin is an important defense against infections. When the skin breaks down, such as when a sore occurs, the body is more vulnerable to infections. Patients and families are encouraged to follow the care team’s instructions regarding good oral (inside the mouth) care and perianal (near the anus) care.

Antibiotic or antifungal medicines are often used to prevent infection in patients undergoing treatment for relapsed leukemia. These medicines can prevent many infections if taken regularly.

Families are encouraged to follow the care team’s directions in caring for the patient’s venous access catheter. It is a common site of infection. 

People around the patient should wash or sanitize their hands often. Patients should not be around people who are sick.

Common Side Effects

Pain, nausea, constipation, shortness of breath, itching, anxiety, and depression can be common side effects of treatment. 

To treat side effects, doctors may prescribe medications. Other treatment approaches such as integrative (complementary) medicine can be effective. 

Families are encouraged to engage with specialists for support including palliative care clinicians, psychologists, social workers, music therapists, chaplains, and child life specialists.

Prognosis

Currently 30-50% of patients survive after their first relapse. Some children may relapse more than once. Each time a patient relapses the chance of cure decreases.

Questions to Ask About Treatment Options

  • What are our treatment options?
  • What are the possible side effects of each treatment option?
  • What can be done to manage side effects so my child will feel as good as possible?
  • Will my child need to be in the hospital for this treatment or will it be delivered on an outpatient basis?
  • Where is the treatment available? Is it close to home or will we have to travel?


Reviewed: December 2018