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Chronic Lymphoid Leukaemia (CLL): new treatment prospects

By Edited Nov 13, 2013 0 0

Chronic lymphoid leukaemia (CLL) is one of the most common types of blood cancer. Its treatment relies on the use of special types of chemotherapy. Here we will go through most of them, covering the new advances in th field.

Chronic Lymphoid Leukaemia(CLL)

CLL affects lymphocytes: B and T cells, the blood cell lineages responsible for the adaptive response (i.e. producing tailor-made antibodies or substances to fight viral or bacterial invasion), and natural killer cells (NKC) that carry out the cell-mediated immunity. CLL is most common in older patients, and can be divided into two subtypes: the one where the protein level expression of ZAP-70 and CD38 is low and the one where it is higher. In the first case, the progression of the disease is very slow (patients can survive 15 years), while in the second it is less slow (patients survive 8 years). The reason why it is called chronic is precisely because it develops over a longer period of time. This is due to the fact that CLL cells partly mature and therefore are of use for the body to some extent. This is not the case for acute leukaemias, where the abnormal population suddenly starts proliferating, while not maturing – resulting in the bone marrow (the blood factory of our body) and the blood being overcrowded with useless cells.

CLL: current treatment

There are five different approaches that can be taken individually or in parallel for each patient.

Watchful waiting

The patient is not given any specific treatment (as usually the symptoms are mild and don’t entail an abnormal lifestyle). He is just treated for any side-diseases that he might suffer from (like infection).


Radiation therapy

This type of therapy is based on the use of X-rays, which kill the abnormal cells. They are given either outside the body (with an X-ray machine) or inside the body by injecting radioactive substances that result in the same effect.



It is a partially selective treatment, in that it kills proliferating cells or stops them from growing, but can also affect healthy proliferating cells (depending on the drug given). Fludarabine is the drug most typically used, as it accumulates in blood cells in general but also affects preferentially lymphocytes, and more particularly in T-cells.



Splenectomy (the surgery involving the removal of the spleen) can be performed if the patient requires it.


Targeted therapy

This is the area where the most research is taking place. A therapy that affects only the cancer cells is the ideal solution. There are currently several therapies in the market that include monoclonal antibodies. Monoclonal antibodies are targeted and capable of detecting cancer cells, and are equipped with a substance that interferes with the abnormal cell identified. However, they are not always effective and they highly rely on the antibodies expressed on the cells, which vary greatly between patients.

Monoclonal antibodies against CD20 cells (cells of the B cell lineage at further stages of maturation) are commercially available and used in certain therapies. Two common types are rituximab and ofatumumab.

GA101 (obinutuzumab): A new horizon

On the 16th May 2013, results from a clinical trial with GA101[1] in combination with chlorambucil (chemotherapy) in phase III showed that it reduced the risk of disease progression by 86%. This new drug is a monoclonal antibody that acts against CD20 positive cells. It is unique in the way that it labels the B cells expressing this marker and helps by telling the body to eradicate them. It is now under expedited review from the Food and Drug Administration (FDA), although it will still undergo several more phase III clinical trials to ensure there are no unexpected effects.

The drug has been developed by Roche, a pharmaceutical company with extensive research expertise in the area of chronic lymphoid leukemia.

List of drugs approved for use in CLL

·       Alemtuzumab (Campath): monoclonal antibody that binds to CD52 positive cells

·       Ambochlorin/Amboclorin/Leukeran/Linfolizin (Chlorambucil): it’s a type of chemotherapy that is tolerated by most patients

·       Arzerra (Ofatumumab): monoclonal antibody that binds to CD20 positive cells and is used specifically for refractory CLL to fludarabine and alemtuzumab.

·       Treanda (Bendamustine Hydrochloride): it is an alkylating agent that interferes with the DNA of the cells

·       ChlorambucilClafen/Cytoxan/Neosar (Cyclophosphamide): it is a chemotherapeutic agent, it acts against DNA, killing the cells

·       Fludara (Fludarabine Phosphate): this chemotherapy treatment is given to patients that are younger. It acts against proliferating and quiescent cells. Because of its phosphorylated state, it is easily converted into ions at the pH of blood and stays there, which creates some specificity for blood cells.

Other types of leukaemia

Chronic myeloid leukaemia (CML): It affects myeloid cells and usually grows slowly at first. There are approximately 5,000 new cases of this type of leukaemia each year. It mainly affects adults.

Acute Lymphocytic (lymphoblastic) leukaemia: It affects lymphoid cells and it develops very quickly. There are over 5,000 new cases of ALL each year. ALL is the most common type of leukemia in young children, although it also affects adults.

Acute myeloid leukaemia (AML): It affects myeloid cells and it appears very suddenly. It consists of immature myeloid cells that are highly proliferative. These cells build up in the bone marrow and are released into the bloodstreams, making it very difficult for the patient to maintain sufficient levels of functioning cells. There are more than 13,000 new cases of AML each year. It affects both adults and children.

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  1. "Roche's obinutuzumab (GA101) significantly reduced the risk of disease progression or death in people with one of the most common forms of blood cancer." Roche. 16/05/2013 <Web >

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