Patients with leukaemia were among the first to be given a treatment where transplants of blood stem cells made it possible to obtain cures. Today this form of therapy is given to thousands of patients with leukaemia around the world. But many difficulties remain. Ongoing research aims to increase our understanding of the disease and improve treatments. What are the latest advances and what are the remaining challenges? 

Leukaemia is a group of blood cancers that produce large numbers of immature, non-functional white blood cells that weaken (or completely block) the immune system.

Present stem cell treatments for severe leukaemias include blood stem cell transplants (also known as haematopoietic stem cell transplants or bone marrow transplants).

Thousands of leukaemia patients worldwide have received successful blood stem cell transplants, but these treatments carry very serious risks. However, these risks have greatly decreased over the years as researchers learn more about leukaemia and blood stem cells.

Researchers still don’t know what gene mutations cause most types of leukaemia. Studies continue to examine haematopoietic stem cells (HSCs) and what turns HSCs into cancerous leukaemia cells.  

To reduce problems associated with HSC transplants, researchers are examining new approaches such as, treatments with immune cells, ways to boost patient immunity with growth factors and the use of induced pluripotent stem cells (iPSCs).

There is a general shortage of donors to supply HSCs for transplants. Researchers are working to develop ways of creating large numbers of HSCs using iPSCs.

Immediately before new HSCs are transplanted the immune system of a patient is completely destroyed by chemotherapy. An ongoing challenge is reducing the vulnerability of patients to infection while transplanted HSCs rebuild the patient’s immune system.

Immune system incompatibilities between a patient’s body and transplanted HSCs from a donor cause many complications. Even when donor and patient tissue types are matched, incompatibilities can occur and lead to transplant rejections or graft-versus-host disease, which can be fatal in extreme cases.

Leukaemia is a term used to describe many different kinds of cancers of the blood. However, in all of these, too many white blood cells (also called leukocytes) are produced and these leukemic cells do not mature normally. As a result, they look like immature cells called blasts. These leukaemic blasts are not able to perform the functions of normal mature blood cells which is to defend the body against infection and disease. In most forms of acute leukaemia, these leukaemic blasts accumulate in the bone marrow as well as in the blood and and suppress the formation of normal white blood cells. The production of excessive numbers of cells in the blood and the lost ability to fight infection is what makes leukaemia rapidly fatal if not successfully treated.

Blood sample from a patient with acute leukaemia
Blood sample from a patient with acute leukaemia

Leukaemias are grouped according to the severity of the disease (how fast it is growing) and the types of white blood cells that become abnormal:

  • Acute leukaemias are rapidly growing leukaemias that progress very quickly and therefore need to be treated right away and cause a sudden increase in the number of malignant (cancerous) immature white blood cells. They are usually sub-classified as acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) depending on the types of white blood cells that are affected.
  • Chronic leukaemias are more slowly developing leukaemias that may escape diagnosis for several years before they are detected. They are usually sub-classified as either chronic lymphocytic leukaemia (CLL) or chronic myeloid leukaemia (CML).
  • There are also less common types and subtypes of leukaemia.

Like most cancers, leukaemias are caused by a series of rare mutations (changes) in certain genes inside primitive blood cell precursors. Very rarely, a mutated form of one of these genes may be inherited. When this happens the individual is predisposed to develop leukaemia. Other known causes include accidental exposure to radiation and treatment with some types of anti-cancer drugs. However, in order for a full blown leukemia to develop, it is thought that several changes must be accumulated to alter the molecular programs that control cell behaviour. A large number of gene mutations have been linked to human leukaemias, and in some cases, the same mutation is consistently and uniquely associated with a particular type of leukaemia. Chronic myeloid leukaemia (CML) is an example of such a leukaemia where knowledge of a shared driver mutation led to the development of a drug (Gleevec) that is very successful in killing the leukemic cells in CML patients. However, in most patients with leukaemia, it is not yet known which mutation or group of mutations are actually driving their disease.


Healthy blood sample showing two white blood cells (neutrophils) and many red cells
Healthy blood sample showing two white blood cells (neutrophils) and many red cells
'Blast crisis' in chronic myeloid leukaemia
'Blast crisis' in chronic myeloid leukaemia





Because many types of leukaemia are thought to require several rare mutations in order to develop, the first change is assumed to occur in a cell that will remain in the body for a long time. A prime candidate group of cells are the most primitive blood cell precursors - also called haematopoietic stem cells (HSCs). HSCs are responsible for making new blood cells in our bodies for our entire lives. If a stem cell is affected by a genetic change, all the cells it produces will inherit the same mutation. It has been shown that CML starts with a particular mutation in HSCs. However, cells go through a number of steps to develop from HSCs into specialised cells such as white blood cells. Mutations might happen at any of these steps. For many leukaemias, a complex series of events is probably involved and it is not yet clear where the first important mutation occurs.

Acute leukaemia usually requires immediate and intensive treatment. Depending on the particular type of leukaemia and many other things about the individual patient, treatment options might include chemotherapy, steroids or a more intensive procedure involving high-dose chemotherapy followed by a transplant of healthy haematopoietic stem cells.

Two acute lymphocytic leukemia patients who are receiving chemotherapy; they are demonstrating some of the procedures used with chemotherapy
Two acute lymphocytic leukemia patients who are receiving chemotherapy; they are demonstrating some of the procedures used with chemotherapy

High-dose chemotherapy is the most effective currently established method to kill leukaemic cells and can cure some patients. However, it also severely damages the remaining normal blood-forming cells in the bone marrow. To replace these cells, patients are given a haematopoietic stem cell transplant (HSCT). The cells for the transplant can be collected from the blood or bone marrow of a healthy donor. In fact, such transplants are effective because they contain important immune cells that help to kill the leukaemic cells in addition to HSCs that rescue blood production. A patient’s own cells can sometimes be used for the transplant, if it is possible to collect enough healthy cells before the treatment is performed. If a different donor is needed, they must match the patient’s tissue type. Otherwise the transplanted donor cells can be attacked by the patient’s residual immune system and rejected.

Intensive chemotherapy followed by a HSC transplant is very effective for treating many types of acute leukaemia. However, the side effects of the procedure itself make it risky with the potential for early fatality and usually substantial after effects in long-term survivors, particularly in the case of children.Therefore, this type of stem cell transplant is only considered when standard-dose chemotherapy fails to eradicate the disease.

Despite the successes of HSC transplant-based treatments of leukaemia, the use of cells from a normal donor can have serious side effects:

Infections - The transplanted stem cells need time to produce the necessary new blood cells for the body.  In the interval that inevitably precedes recovery, the patient is highly vulnerable to infections. Careful observation, restricted access to other people and preventative treatment with antibiotics are used to reduce infection risks.

Graft-versus-host disease (GvHD) – This complication occurs when donor blood cells attack the patient’s own normal tissues. Symptoms include rashes, diarrhoea, blisters and fever. GvHD is a serious complication and can be life-threatening. It is minimized by closely matching the tissue type of the donor to the patient. This is easiest to achieve if the patient has a matched sibling. Other strategies to prevent GvHD include suppressing the immune system with drugs and removing a specific type of white blood cells (lymphocytes) from the transplant.

Researchers and doctors are investigating ways to improve current transplantation approaches in order to address these limitations.  Another challenge is the shortage of donors and several organisations are working to increase the number of volunteers in donor registries.

The high dose of chemotherapy given to leukaemia patients before a transplant destroys both the leukaemic cells and the patient's healthy bone marrow cells. Newer forms of transplantation called mini-allografts or reduced-intensity allografts have been developed to reduce the risk. These procedures allow lower doses of chemotherapy to be used, which helps reduce the extent of damage to the bone marrow. Instead, donor immune cells are transplanted with and after the donor HSCs to attack and eliminate any remaining leukaemic cells. This is called a graft-versus-leukaemia effect. This type of transplant has fewer side effects but some serious ones remain, particularly GvHD.

Several new techniques are now being tested in patients to see if they will prevent or reduce the severity of GvHD. Certain types of immune cells (regulatory T lymphocytes) that have a suppressive effect on the immune system may be administered to the patient. This can help prevent the donor immune cells from attacking the patient’s own cells. Alternatively, attempts are being made to selectively remove the immune cells that cause GvHD from the transplant.

Scientists and doctors are also currently investigating treatments that might reduce the time it takes for the patient’s immune system to recover after a HSC transplant. One option is to treat the patient with selected proteins called growth factors, which can enhance the production of the particular immune cells needed to fight infections. This can help reduce the risk of infection while the patient recovers.

Stem cell research is a rapidly developing field. New technologies such as induced pluripotent stem cells are already being used to study leukaemia in the lab. They provide a tool for producing large numbers of leukaemic cells in a dish. Researchers can then study the cells to learn more about how the disease arises and is maintained, and to design and test new, potentially more effective and less toxic therapies. In the future, new methods for the lab-based production of HSCs that can be used in transplant patients may also be developed. This could revolutionize many of the current shortcoming of current transplants and lack of matched donors.

This factsheet was created by Christine Weber and reviewed by Connie Eaves and Linda Barber.

Lead image of blood in chronic myeloid leukaemia by Junia Melo/Wellcome Images. Healthy blood by Spike Walker/Wellcome Images. Chronic meyloid leukaemia blast crisis by CDC/ Stacy Howard. Acute leukaemia blood sample image by Wellcome Images. Leukaemia patients demonstrating chemotherapy procedures released into the public domain by Bill Branson.