Sidney Farber induces remission in childhood leukemia with aminopterin

Historical milestone — this page describes an event dated 1948. It is not current breaking news.

A pathologist with an idea about a vitamin

Sidney Farber was a pediatric pathologist in Boston. He had noticed something about folic acid. It is a B vitamin the body needs to build DNA. In children with leukemia, giving it seemed to make the disease move faster.

He reasoned backwards from that. If folic acid fed the leukemia cells, a chemical that blocked folic acid might starve them.

The compound he used was 4-aminopteroyl-glutamic acid, known as aminopterin. It is close enough in shape to folic acid that enzymes accept it, then jam.

NCI's milestone list dates the work to 1947, the year the children were treated. Farber and Louis Diamond published it in the New England Journal of Medicine on 3 June 1948. Both years appear in good sources. Each is right about a different thing.

What the paper reported

The title said it: temporary remissions. Children whose leukemia cells fell away, whose blood counts recovered, who felt better and looked better.

None of them were cured. The remissions ran out and the leukemia returned. Farber said as much in the title of his own paper.

That is why this is a landmark rather than a triumph. Before it, no drug had pushed back an advanced cancer in a way that could be measured and repeated. After it, the question changed. It was no longer whether chemotherapy was possible, but how to make it last.

NCI classifies aminopterin as an antimetabolite. These drugs mimic chemicals a cell needs to build DNA. They kill by blocking that work. Our page on chemotherapy explains how the modern versions work.

What came next, quickly

The milestones that follow in NCI's list read like a chain reaction.

In 1949 FDA approved nitrogen mustard for cancer, the first alkylating agent. In 1953 Roy Hertz and Min Chiu Li used methotrexate against choriocarcinoma. It was the first complete cure of a solid tumor by chemotherapy. Methotrexate is aminopterin's close relative, and it is still used today.

In 1958 Emil Frei, Emil Freireich, and James Holland combined 6-mercaptopurine with methotrexate. It produced remissions and longer survival in acute leukemia. Combination therapy is the idea that made Farber's temporary remissions last.

Farber's other legacies were institutional. He introduced actinomycin D for Wilms tumor, a kidney cancer of children. He built the Jimmy Fund and the Children's Cancer Research Foundation, which became the Dana-Farber Cancer Institute.

Childhood ALL today

Acute lymphoblastic leukemia is a cancer of immature white blood cells. It is treated in three phases, and the structure follows directly from what Farber learned.

Remission induction comes first. Its goal is to clear leukemia cells from blood and bone marrow. Consolidation, sometimes called intensification, comes next, aimed at cells that survived. Maintenance follows, often at lower doses, to stop regrowth.

Treatment is tailored. It depends on whether the leukemia started in B or T lymphocytes, on the risk group, and on the child's age. It also depends on chromosome changes such as the Philadelphia chromosome. And on how fast the cell count falls, and whether leukemia reached the brain or spinal cord.

Chemotherapy given by mouth or vein reaches the whole body. Chemotherapy put straight into the fluid around the spine is called intrathecal. It treats the brain and spinal cord, where drugs in the blood struggle to reach. Our page on childhood leukemia covers how families experience these phases.

When to get a child checked

NCI explains that the symptoms of childhood ALL come from too few red cells and platelets, and too many white cells that do not work. Check with a doctor if a child has:

• Fever
• Easy bruising or bleeding
• Flat, pinpoint, dark-red spots under the skin, called petechiae
• Weakness or fatigue
• Pale skin
• Bone or joint pain
• Shortness of breath
• Painless swollen lymph nodes in the neck, underarm, stomach, or groin
• Pain or fullness below the ribs
• Loss of appetite, weight loss, or abdominal pain
• Frequent infections, or infections that do not clear

Petechiae with unexplained bruising is the combination that should prompt a same-week blood count. Most children with these symptoms do not have leukemia. A complete blood count is a quick, cheap way to find out.

The numbers Farber never got to see

For 2026 the American Cancer Society projects 6,250 new cases of acute lymphocytic leukemia in the United States, across all ages, and 1,600 deaths; SEER republishes those projections. NCI's own SEER measurement puts five-year relative survival across all ages at 73.2 percent, based on people diagnosed between 2016 and 2022.

NCI reports that cancer death rates in children aged 0 to 14 fell by 70 percent between 1970 and 2020. Leukemias, brain and central nervous system tumors, and lymphomas remain the most common childhood cancers.

Those are group figures spanning ages, subtypes, and decades of changing treatment. They describe a population, not a child.

What this story cannot tell you

Farber's result was proof of principle. A small, uncontrolled series of children improving for months is not evidence in the sense that word carries now. A 1948 case series would not support an approval today.

Many things closed the gap between his remissions and modern outcomes. Combination therapy, treatment aimed at the brain and spine, dosing matched to risk, better supportive care, and decades of randomized trials. No single discovery did it.

The gains in childhood leukemia are also not matched across all childhood cancers. Some remain very hard to treat. There is still no general screening test for cancer in children. Care starts with taking a child's symptoms seriously.

Sources

• Farber S, Diamond LK, Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid, N Engl J Med 1948;238(23):787-93 — https://pubmed.ncbi.nlm.nih.gov/18860765/
• Miller DR, A tribute to Sidney Farber, the father of modern chemotherapy, Br J Haematol 2006;134(1):20-6 — https://pubmed.ncbi.nlm.nih.gov/16803563/
• NCI, Milestones in Cancer Research and Discovery — https://www.cancer.gov/research/progress/250-years-milestones
• NCI PDQ, Childhood Acute Lymphoblastic Leukemia Treatment (Patient Version) — https://www.cancer.gov/types/leukemia/patient/child-all-treatment-pdq
• NCI, Childhood Cancers — https://www.cancer.gov/types/childhood-cancers
• SEER Cancer Stat Facts, Acute Lymphocytic Leukemia — https://seer.cancer.gov/statfacts/html/alyl.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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