Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

Despite an 85 to 90 percent cure rate after first treatment for children, adolescents and young adults with acute lymphoblastic leukemia (ALL), 10 to 15 percent of patients with pediatric ALL will experience relapse. ALL relapse can happen months or years following remission. Some patients are never able to achieve remission because their cancer does not respond to treatment, called refractory leukemia.

Getting the news that ALL has relapsed or hasn’t responded to treatment is incredibly stressful. At this point it’s important to understand all of your options for treating relapsed or refractory ALL.

Our approach to relapsed/refractory leukemia

The Relapsed/Refractory Leukemia and Lymphoma Program at Children’s Hospital of Philadelphia (CHOP) is led by oncologists who are internationally recognized for their expertise in pediatric leukemias. Our team draws on the most current and comprehensive knowledge of pediatric leukemia to make critical decisions about your child’s care plan.

The experts at CHOP will leave no stone unturned in caring for children, adolescents and young adults with relapsed/refractory ALL. We will perform cutting-edge comprehensive molecular diagnostic testing on the leukemia cells using assays (tests) developed at CHOP to identify the therapy that will be most targeted to her/his leukemia. The results of these tests are discussed in a weekly multi-disciplinary team meeting of:

  • over a dozen oncologists focused on leukemia treatment
  • pathologists
  • cancer genetics experts
  • other team members 

This discussion will ensure that we are considering every possible treatment option. Our expertise in targeted therapy starts at the scientific discovery of genes and pathways that are mutated/altered in leukemia and continues through clinical trials, which test the effectiveness of the latest drug discoveries in children, adolescents and young adults.

Our relapsed/refractory leukemia team also offers unmatched expertise in the use of cellular therapies — like blood and marrow transplant, CAR T-cell therapy and immunotherapy — to treat children with relapsed blood cancers.

Arranging for evaluation at CHOP

Our dedicated Intake Specialists will make the process of getting an evaluation for relapsed or refractory ALL as easy as possible. We encourage you to reach out to an Intake Specialist for guidance through this process.

Contact our Intake Specialists:  267-426-0762 or

If needed, we will connect you to our Oncology Social Work Services team oncology insurance specialists to help get you here as easily as possible. The Cancer Center's financial liaison might also be a helpful resource.  

We know the logistics of traveling to seek medical care for your child can be daunting. We are here to help with anything from how to get here to where to stay in Philadelphia while your child is receiving therapy.

In many cases funding is available to help support travel and accommodations in Philadelphia.

Treatment options for relapsed ALL

Our team of relapsed leukemia experts will customize a course of treatment based on all available information, and may consider clinical trials testing novel chemotherapy and immunotherapy options not used in the initial treatment, as well as blood and marrow transplant.

Treatment for relapsed or refractory ALL is typically more intensive than the treatment used following initial diagnosis. The goal is the same: to eliminate the leukemia and keep it from returning while protecting against side effects, such as infection, and addressing the symptoms of low blood counts.

The course of treatment for relapsed or refractory ALL will depend on:

  • The type of ALL (B-cell or T-cell)
  • Where in the body the relapse has occurred (bone marrow, spinal fluid, testicles, or elsewhere)
  • How much time has passed between the initial diagnosis and detection of relapse
  • The results of the extensive genetic and molecular profiling leukemia cells that we perform here at CHOP
  • Prior therapy received (chemotherapy and/or radiation therapy and/or blood and marrow transplant)

If your child’s ALL has relapsed for the first time, the CHOP team will sometimes recommend relapse chemotherapy regimens available for this situation. In some cases, we will recommend chemotherapy combined with radiation therapy, or chemotherapy followed by blood and marrow transplantation or CAR T-cell therapy.

Treatment options for multiply relapsed ALL

For ALL that has relapsed multiple times, our team will customize a course of treatment based on history and prior treatment. We may consider chemotherapy, immunotherapy, or another therapy that is targeted to abnormalities identified in the leukemia cells.

Treatment options for refractory ALL

For leukemia that did not respond to the most recent treatment attempt, our team will try to attack the disease in a different way. Our goal is to use alternative therapies to attain remission and then to employ blood and marrow transplant and/or CAR T-cell therapy to optimize chances for cure.

The course of treatment for refractory ALL will depend on:

  • The type of ALL (B-cell or T-cell)
  • Location in the body where the leukemia is persistent
  • The results of the extensive genetic and molecular profiling leukemia cells that we perform here at CHOP
  • Prior therapy received

Types of treatments used to treat relapsed/refractory ALL

  • New or different chemotherapy drugs, or new combinations of chemotherapy drugs. These may be given by mouth, in the vein, in the muscle or under the skin. Intrathecal chemotherapy may be used, injecting medications into the fluid-filled space surrounding the spinal cord.
  • Targeted therapy / Precision cancer medicine. Once a mutated pathway (a group of proteins that have been abnormally activated) in your leukemia is identified, we will try to match new targeted drugs that attack that pathway.
  • Immunotherapy. Therapies that attack the leukemia using the body’s own immune system or by attaching poisonous drugs directly to the leukemia cells.
  • CAR T-cell therapy, a new approach to cancer treatment in which immune cells called T-cells are taken from a patient's own blood. These cells are then genetically modified to express a protein which will recognize and bind to a target on the leukemia cells such as the protein CD19, which is found on cancerous B cells. This form of CAR T-cell therapy was developed through a collaboration of Children’s Hospital of Philadelphia and the Hospital of the University of Pennsylvania, and was approved by the FDA for use in children with relapsed B-cell ALL in 2017. At CHOP, we have treated hundreds of children with CAR T-cell therapy, more than any other center in the world. We are researching new protein targets on all types of leukemia.
  • Blood and marrow transplantation, which involves
    • collection of healthy stem cells from a donor without cancer (allogeneic transplant)
    • administration of high doses of chemotherapy and possibly radiation therapy to kill any remaining leukemia cells
    • infusion of the healthy stem cells through an intravenous line to produce normal blood-forming cells.
  • Radiation therapy, using high-energy waves such as X-rays to kill or shrink cancer cells.
  • Proton therapy, specialized radiation therapy which can focus radiation to defined areas such as “clumps” of leukemia and avoid radiation exposure to nearby organs. 

Comprehensive care of the relapsed/refractory leukemia patient

Children, adolescents and young adults receiving cancer therapy can get sick, sometimes very quickly. At CHOP, we have every clinical and non-clinical resource you might possibly need. We know this is a stressful time and every one of our patients has an assigned social worker to help them navigate relapse.

Nationally recognized pediatric specialists are available 24 hours a day, 7 days a week to help provide care to our patients with leukemia. Top physicians specializing in pediatric infections, kidney and liver complications, neurology or other areas will see you every day if needed and collaborate actively with your oncology team. Our patients never have to be transferred to another hospital to get care from a specialist outside of oncology.

In the case of critical illness, CHOP offers an internationally renowned Pediatric Intensive Care Unit (PICU) containing over 60 beds, which is driving new discoveries in caring for critically ill children, adolescents and young adults.

Dedicated pediatric pharmacists, nutritionists, child life specialists and social workers participate on daily inpatient rounds. Radiologists who are trained in reviewing scans on children, adolescents and young adults are available around the clock. Your oncology team has access to all the latest cancer imaging equipment including the newest PET/MRI scanners.

Clinical trials for relapsed/refractory ALL

The Cancer Center at CHOP is one of the largest treatment centers in the world providing care to children, adolescents and young adults with cancer. This provides our patients with access to many newer therapies that are not available at other cancer centers.

When appropriate, our team may recommend a clinical trial to treat relapsed or refractory ALL. We offer many experimental options for treatment of relapsed and refractory ALL. Some trials are unique to our Cancer Center, evolving from research done at CHOP or through our many collaborators. We are a Children's Oncology Group (COG) Phase I / II institution and a member of the Therapeutic Advances in Childhood Leukemia (TACL) consortium. This permits us to have multiple relapse/refractory leukemia trials open at any time; one of which may be a perfect fit for you.

Next Steps
Existing Patients or Family Members
New Patients, Referrals and 2nd Opinions
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Your Philadelphia Campus Visit

Planning a trip to CHOP? Find information about visiting hours, where to park, where to stay, how to prepare your child for a visit and more.


Relapsed Leukemia or Lymphoma Evaluation

Our leukemia and lymphoma relapse experts will talk with you about whether the Cancer Center at CHOP is a good fit for your child and your family.

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