Alex's Lemonade Stand Foundation for Childhood Cancer

Leukemia, a cancer of the blood-forming cells in bone marrow, is the most common type of childhood cancer. Over the course of several decades, incredible progress has been made in improving survival rates—from a low of less than 10% in the 1960s to the close to 90% cure rate for children diagnosed with acute lymphoblastic leukemia (ALL) today. This success has happened in high-income countries. In low-income countries, a diagnosis with ALL can still bring a precarious prognosis due to a lack of access to treatments.

Lymphoma, a cancer of the lymphatic system (lymph nodes and related tissues), is grouped with leukemia because both are blood cancers that affect similar immune cells and often behave as systemic diseases requiring similar treatments.

Among childhood cancers in the United States, leukemia stands apart: It has the most FDA-approved treatments and is the only childhood cancer with an FDA-approved CAR T-cell therapy.⁵⁴

While many leukemias and lymphomas are considered cancer therapy success stories, several subtypes continue to be associated with a poor prognosis. For example, acute myeloid leukemia (AML) accounted for 35% of all pediatric leukemia deaths in 2023⁵⁵ but only for 8% of all cases in the United States.⁵⁶

Leukemia

Lymphoma

Breakthroughs and Research Milestones:

1. Chemotherapy (1960s-present):

   The discovery and FDA approval of chemotherapy was a game changer for kids facing leukemia. Years of collaborative research through the Children’s Oncology Group (COG)—an organization made up of childhood cancer experts at more than 220 children’s hospitals, universities, and cancer centers—and its predecessors, the Pediatric Oncology Group (POG) and Children’s Cancer Group (CCG), have defined specific subtypes of leukemia and drug dosing, resulting in improved survival rates. However, chemotherapy brings acute and long-term side effects that can cause cardiac dysfunction, immune system suppression, infertility, hearing loss, and cognitive impairment. Research continues to focus on combination therapies that can protect children from side effects and strategies for lowering the doses of chemotherapy drugs children receive.⁶⁵

2. Stem cell transplants (1960-present):

   Stem cell transplantations are typically performed after treatment with high doses of chemotherapy that deplete both healthy and diseased stem cells, followed by an infusion of healthy stem cells from a donor to replenish the depleted cells.⁶⁶

3. Targeted therapies (2013-present):

   Targeted therapies provide hope for the treatment of rare leukemias:

   • Tyrosine Kinase Inhibitors (TKIs) such as imatinib, dasatinib, nilotinib, and bosutinib. Imatinib is used primarily in the treatment of chronic myeloid leukemia and Ph+ ALL and was FDA approved for the treatment of Ph+ ALL in 2013.^67,68
   • Menin inhibitors, such as revumenib, are showing promise for treating certain leukemias. These drugs work by blocking the protein menin from interacting with KMT2A, a gene that normally helps control how blood cells develop but can drive leukemia when it is altered, helping shut down cancer-driving signals that leukemia cells need to grow and survive.^{71, 72}
4. CAR T-cell Therapy (2017-present):

   The “CAR” in “CAR T-cell” stands for chimeric antigen receptor. The word “chimeric” comes from the Chimera, a strange mixed-up beast from Greek mythology made up of a lion, a goat, and a serpent. In the case of CAR T-cell, the “chimeric” represents a protein (the CAR) made in the lab by stitching parts from different proteins that is then placed on a T-cell, allowing it to see and kill cancer in the body (read more about CAR T-cell in Section 3). In 2017, the approval of the CAR T-cell therapy, tisagenlecleucel (brand name Kymriah), provided kids with relapsed ALL a promising new option with potentially less side effects than chemotherapy.⁷³

5. Immunotherapy (2018-present):

   Beyond CAR T-cell therapy, other types of immunotherapy show promise. Blinatumomab, approved for B-ALL, works to connect T-cells from the patient’s immune system with cancerous B-cells. The drug helps T-cells recognize malignant B-cells and harnesses their power to slow or stop cancer cell growth.⁷⁴ Pembrolizumab, a PD-1 inhibitor, has also been approved in the treatment of relapsed and refractory Hodgkin Lymphoma. Rituximab is a monoclonal antibody that targets a protein specific to B-cells, CD20, and is FDA-approved in numerous B-cell malignancies. Upon binding to CD20, the B-cells bound by rituximab recruit a host of immune cells, such as NK cells and T-cells, which lead to an immune cell–driven killing of the bound cells.⁷⁵ Rituximab was approved by the FDA for treating autoimmune diseases in 1997, and it was approved for pediatric leukemia in 2021.^76,77

6. Antibody-Drug Conjugates (2020-present)

   Antibody-Drug Conjugates (ADCs) are drugs that allow for selective killing of cancer cells. ADCs bind to cancer cells, carrying a small amount of toxin that is delivered directly to the cancer cell. Because it only sticks to cancer cells, healthy cells remain undamaged.

   There are three ADCs that are approved by the FDA for children:

   • Gemtuzumab ozogamicin is used to treat AML.80
   • Inotuzumab ozogamicin has been approved for treating pediatric leukemia, specifically ALL.
   • Brentuximab vedotin has been approved in the treatment of classic Hodgkin lymphoma and subtypes of non-Hodgkin lymphoma.81