LLS | History of Leukemia

The history of leukemia is a fascinating journey through time, marked by scientific breakthroughs that have transformed our understanding of this blood cancer. Unlike some other cancers, leukemia doesn’t form solid tumors but affects the blood and bone marrow, leading to the production of abnormal leukemia cells, and because of that, it is known as a blood cancer. Leukemia has been studied for centuries, and researchers have made significant strides in diagnosing, treating, and improving the survival rate of those affected.

Tracing the roots of leukemia back to its origins will help us better understand the advancements that have been made in leukemia research and how they’ve shaped modern treatments for both children and adults.

First Studies of Blood and the Origin of Leukemia

The earliest insights into blood date back to ancient times, when people believed that blood held the body's vital force.

Blood has always been essential for life, but early doctors didn't have good tools to study it scientifically. Things began to change with the invention of the microscope in the late 16th century. Although simple magnifying lenses were already in use, it was the compound microscope, developed by Hans and Zacharias Janssen around 1590, that really let scientists take a closer look at blood (Mualla, Aubreville, and Maier 2018)(Wollman et al. 2015).

In 1658, a Dutch naturalist named Jan Swammerdam was the first to see red blood cells under a microscope, which was a huge step forward for blood research (Ajmani 2020)(Gurkan 2021). Following him, Anton van Leeuwenhoek described how red blood cells looked and even drew the first picture of them in 1695 (Da Silva 2017)(Davis 2022). By the 18th century, Joseph Lieutaud discovered white blood cells, paving the way for future studies on blood diseases like leukemia (Mughal and Barbui 2020)(Thomas 2013).

The earliest hints of what we now call leukemia showed up in the 19th century when doctors found unusually high levels of white blood cells in some patients' blood. These observations were key to defining the disease, even though it took a while longer to really understand what leukemia was (Mualla, Aubreville, and Maier 2018)(Wollman et al. 2015).

Early Leukemia Discoveries

In the 1840s, doctors began noticing patients with symptoms like swollen bellies, fever, weight loss, and weakness—signs we now know are linked to leukemia. By examining bodies after death, these doctors discovered that some patients had way too many white blood cells, which they called "white blood." This led to the disease being named "leukemia," from the Greek words "leukos" (white) and "haima" (blood) (Deininger 2008)(Tremblay, Yacoub, and Hoffman 2021).

One of the first doctors to describe this was John Hughes Bennett from Scotland. In 1845, while working in Edinburgh, he reported on a patient with a big spleen and lots of white blood cells. Bennett thought it was an infection causing pus in the blood. Although he was wrong, his work was crucial in starting to understand leukemia (Deininger 2008)(Tremblay, Yacoub, and Hoffman 2021).

At the same time, German pathologist Rudolf Virchow was also studying patients with high white blood cell counts. In the 1850s, Virchow suggested that leukemia started in organs like the spleen and bone marrow, where white blood cells are made. He was the first to use the term "leukemia" to describe this disease (Deininger 2008)(Handgretinger 2022).

A big leap in leukemia research came in 1877 thanks to Paul Ehrlich, a German medical student. Ehrlich developed a new way to stain blood cells so they could be studied more easily. This technique helped him find "primitive cells," early forms of blood cells, which we now understand as stem cells. This discovery was a key moment in studying leukemia at a cellular level (Kay 2017)(Kay 2016).

Early Leukemia Classification

Paul Ehrlich's work went on to influence the classification of leukemia, differentiating the disease based on the types of cells it affected. His research helped distinguish between lymphocytic leukemia, which affects cells that would develop into lymphocytes (a type of white blood cell), and myeloid leukemia, which affects cells that become red blood cells, platelets, or other types of white blood cells.

Ehrlich also helped classify leukemia into acute and chronic forms. In acute leukemia, the blood is filled with immature cancer cells known as myeloblasts or lymphoblasts, while chronic leukemia involves more mature, but still abnormal, cancer cells. These distinctions laid the foundation for the modern understanding of leukemia, which is divided into four major subtypes:

Acute lymphocytic leukemia (ALL), also known as acute lymphoblastic leukemia.
Acute myeloid leukemia (AML), also known as acute myeloblastic leukemia.
Chronic lymphocytic leukemia (CLL).
Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia.

These classifications remain essential for diagnosing and treating the different forms of leukemia.

Early Leukemia Diagnosis and Treatments

By the late 1800s and early 1900s, doctors started using X-rays, a new technology back then, to treat leukemia. This treatment, called radiation therapy, worked better for slow-progressing leukemias than for fast-acting ones. It could help patients with chronic leukemia feel better for a while, but unfortunately, the disease usually came back (Santos et al. 2011).

Another big step in treating leukemia came from research during World War I. Scientists found out that mustard gas, a chemical used in the war, could stop blood cells from being made. This discovery led to the creation of the first chemotherapy drugs, like chlorambucil and busulfan. These drugs were used for a long time to treat types of chronic leukemia (Amjad, Chidharla, and Kasi 2023)(Singh et al. 2018).

In the 1940s, a new chemotherapy drug called aminopterin was introduced to treat childhood leukemia. Aminopterin was improved into another drug called methotrexate, which is still used today to treat people with leukemia and other blood cancers (Amjad, Chidharla, and Kasi 2023)(Bertino 2009).

Bone Marrow and Stem Cell Transplantation

As the understanding of leukemia evolved, scientists began to explore the possibility of using bone marrow transplants to treat the disease. The idea was to replace diseased marrow with healthy marrow capable of producing normal stem cells. Early transplants in animals showed promise, but human transplants faced the challenge of graft-versus-host disease due to mismatched bone marrow types.

Over time, improvements in bone marrow matching techniques and pre-transplant chemotherapy regimens made bone marrow transplants a standard treatment for diseases like acute myeloid leukemia (AML) (Onida and Chalandon 2024)(Jain and Van Besien 2011). Though still a risky procedure, these transplants are now used to treat people whose leukemia hasn’t responded to chemotherapy.

Improved Leukemia Prognosis and Treatment

By the 1970s, chemotherapy had become a standard treatment for leukemia, marking a significant shift in cancer care. Leukemia research led to the development of combination chemotherapy, which used multiple drugs to maximize the treatment's effectiveness. This advancement was crucial in improving the survival rate for both leukemia and other blood cancers.

In the late 1990s, a new type of leukemia treatment came about when scientists figured out that certain cancerous cells, called B cells, had a special marker named CD20 on them. This discovery led to the creation of a drug called Rituxan (rituximab), which specifically targets those markers and is used to treat chronic lymphocytic leukemia (CLL) and other types of lymphoma (Casan et al. 2018).

At the same time, researchers made another huge leap forward by identifying the Philadelphia chromosome in people with chronic myelogenous leukemia (CML). This genetic glitch was important because it helped scientists develop imatinib (or Gleevec), a medicine that specifically blocks the abnormal protein made by this gene. With early support from LLS, imatinib was incredibly effective in trials, where everyone who took it showed improvement. This drug changed the game and led to more targeted treatments like ibrutinib and venetoclax, which are now used for various types of leukemia (Flynn and Gerriets 2023)(Wu et al. 2024).

Over the past 50 years, the five-year survival rate for leukemia in the United States has risen from 14% to about 66%, thanks to advancements in leukemia research and treatments (Yang et al. 2021). Today, leukemia, once considered a fatal disease, is now highly treatable, and in many cases, curable.

Conclusion

The history of leukemia is a remarkable story of scientific discovery and medical advancement. From the early identification of abnormal white blood cells to the modern development of targeted therapies like imatinib, the understanding of leukemia has come a long way. Thanks to relentless leukemia research, today’s treatments offer hope and survival to countless individuals affected by the disease. As science continues to advance, the future of leukemia treatment holds even more promise.

If you or a loved one has been affected by leukemia, The Leukemia & Lymphoma Society (LLS) is here to support you. Visit LLS for trusted resources, expert guidance, and the latest information on treatments and research. Together, we can help navigate the path to hope and healing.

About the author: Dr. Ali is a medical journalist and copywriter.

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