Treatments for recurrent or refractory childhood ALL

Recurrent (relapsed) childhood acute lymphoblastic leukemia (ALL) means the cancer has come back after treatment and first remission. Primary refractory disease means the cancer was resistant to or didn’t respond to the first treatment and didn’t go into remission.

Recurrent childhood ALL may be described as medullary, which means there are leukemia cells (blasts) in the bone marrow. It may also be described as extramedullary, which means leukemia cells are outside of the bone marrow. Recurrent childhood ALL may come back in other parts of the body, such as the central nervous system (CNS). It may also come back in the testicles in boys.

Treatment and prognosis for recurrent or refractory childhood ALL depend on:

  • the treatment that the child received before
  • whether leukemia cells have come back in the bone marrow or outside of the bone marrow or both
  • how much time has passed since treatment (the more time that has passed between treatment and recurrence, the better the prognosis)
  • the subtype of ALL
  • chromosome and gene abnormalities in the leukemia cells

Treatment for recurrent childhood ALL usually includes giving induction chemotherapy again (called reinduction therapy). It is followed by consolidation and maintenance therapy. CNS therapy is used for ALL that comes back in the brain or spinal fluid. More aggressive treatments, such as a stem cell transplant, may be used for high-risk cases. Radiation therapy may be used when ALL comes back outside of the bone marrow. Targeted therapy can be used in some cases.

There is no standard treatment for refractory childhood ALL.

Reinduction chemotherapy

Drugs that may be used during reinduction chemotherapy for recurrent childhood ALL include:

  • vincristine (Oncovin)
  • pegaspargase (Oncaspar), asparaginase (Kidrolase) or asparaginase erwinia (Erwinase)
  • crisantaspase recombinant (Rylaze), if your child has an allergy or sensitivity to pegaspargase or asparaginase
  • doxorubicin (Adriamycin)
  • daunorubicin (Cerubidine, daunomycin)
  • cyclophosphamide (Procytox)
  • cytarabine (Cytosar)
  • etoposide (Vepesid, VP-16)
  • teniposide (Vumon)
  • prednisone
  • dexamethasone (Decadron, Dexasone)
  • mitoxantrone

CNS therapy is given when ALL comes back in the brain or spinal cord. CNS therapy is given as intrathecal chemotherapy, where drugs are given directly into the cerebrospinal fluid (CSF) around the spinal cord.

Find out more about chemotherapy for childhood leukemia.

Stem cell transplant

A stem cell transplant may sometimes be used to treat childhood ALL that comes back during treatment or soon after treatment is complete. It may also be used when T-cell ALL comes back. A stem cell transplant may also be used when ALL comes back after a second course of chemotherapy.

Doctors are more likely to suggest a stem cell transplant if the child has a brother or sister who is a good match for donation.

Find out more about stem cell transplants for childhood leukemia.

Targeted therapy

Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells and limit harm to normal cells.

Children that have recurrent or refractory precursor B-cell ALL without the Philadelphia chromosome may be given blinatumomab (Blincyto). It is given through a needle in a vein (called intravenous infusion).

Find out more about targeted therapy for childhood leukemia.


Immunotherapy helps strengthen or restore the immune system’s ability to fight cancer. CAR T-cell therapy is a type of immunotherapy that takes millions of T cells from a child with cancer. In the lab, they are changed so that they have chimeric antigen receptors (CARs) on their surface. These receptors recognize a specific antigen (protein) found on the leukemia cells. The T cells are then given back to the child where they multiply, attack and destroy the leukemia cells.

Tisagenlecleucel (Kymriah) is a CAR T-cell therapy used to treat children with B-cell ALL that has not responded to other treatment or has come back after a stem cell transplant or other treatments. It may also be used to treat young adults with B-cell ALL who are unable to have a stem cell transplant.

Find out more about immunotherapy for childhood leukemia.

Radiation therapy

Recurrent childhood ALL may be described as extramedullary, which means that leukemia cells are found in a part of the body, such as the CNS or testicles, but they are not found in the bone marrow. In addition to intensive chemotherapy, children with extramedullary recurrent ALL may be treated with radiation therapy to the affected area if it was not treated with radiation before.

Find out more about radiation therapy for childhood leukemia.

Clinical trials

Children with cancer may be treated in a clinical trial. Clinical trials look at new ways to prevent, find and treat cancer. Find out more about clinical trials.

Expert review and references

  • American Cancer Society. Childhood leukemia. Atlanta, GA: American Cancer Society; 2012.
  • Leukemia. B.C. Children's Hospital Oncology/Hematology/BMT Program. B.C. Children's Hospital. Vancouver, B.C.: B. C. Children's Hospital; 2003.
  • Drugs and Health Products, Health Canada. Regulatory Decision Summary: Blincyto. 2017:
  • Jazz Pharmaceuticals Canada Inc. Product Monograph: Rylaze.
  • Health Canada. Regulatory Decision Summary - Kymriah (B-cell ALL). Health Canada; 2018:
  • Kanwar, V. S. et al . Pediatric acute lymphoblastic leukemia. WebMD LLC; 2012.
  • Acute lymphoblastic leukaemia (ALL) in children. Macmillan Cancer Support. Macmillan Cancer Support. London, UK: Macmillan Cancer Support; 2008.
  • Margolin, J.F., Steuber, C.P. and Poplack, D.G . Acute lymphoblastic leukemia. Pizzo, P. A. & Poplack, D. G. (Eds.). Principles and Practice of Pediatric Oncology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2006: 19:pp. 538-590.
  • National Cancer Institute. Cancer Currents Blog: FDA Approval of Rylaze Will Address Drug Shortage for Childhood ALL. National Institutes of Health; 2021:
  • National Cancer Institute. Childhood Acute Lymphoblastic LeukemiaTreatment (PDQ®) Patient Version. Bethesda, MD: National Cancer Institute; 2012.
  • National Cancer Institute. Childhood Acute Lymphoblastic LeukemiaTreatment (PDQ®) Health Professional Version. Bethesda, MD: National Cancer Institute; 2012.
  • National Cancer Institute. Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®) Patient Version. 2018.
  • How is acute lymphoblastic leukemia treated . National Childhood Cancer Foundation & Children's Oncology Group . CureSearch . Bethesda, MD : 2006 .
  • Acute lymphoblastic leukemia (ALL). St. Jude Children's Research Hospital. Cure4Kids. Memphis, TN: St. Jude Children's Research Hospital; 2008.
  • Tomlinson, Deborah . Leukemia. Tomlinson, D. & Kline, N. E. Pediatric Oncology Nursing: Advanced Clinical Handbook. Germany: Springer; 2005: 1: pp. 2-23.
  • Weinblatt ME. Medscape Reference: Pediatric Acute Lymphoblastic Leukemia Treatment and Management. 2017:
  • Westlake, S.K. and Bertolone, K.L . Acute lymphoblastic leukemia. Baggott, C. R., Kelly, K. P., Fochtman, D. et al. Nursing Care of Children and Adolescents with Cancer. 3rd ed. Philadelphia, PA: W. B. Saunders Company; 2002: 19: pp.466-490.

Medical disclaimer

The information that the Canadian Cancer Society provides does not replace your relationship with your doctor. The information is for your general use, so be sure to talk to a qualified healthcare professional before making medical decisions or if you have questions about your health.

We do our best to make sure that the information we provide is accurate and reliable but cannot guarantee that it is error-free or complete.

The Canadian Cancer Society is not responsible for the quality of the information or services provided by other organizations and mentioned on, nor do we endorse any service, product, treatment or therapy.

1-888-939-3333 | | © 2024 Canadian Cancer Society