Feature

Non-Hodgkins Lymphoma: the future of stem cell treatment for blood cancer

By Wideacademy - 10.01.2018

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What is Non-Hodgkins Lymphoma?

Non-Hodgkin’s Lymphoma is a cancer of the blood. It begins in a subset of white blood cells called lymphocytes.

Lymphocytes are either B-cells (responsible for making antibodies to fight viruses) or T-cells, which destroys cells infected by viruses or that have become cancerous.

Abnormal lymphocytes become cancerous lymphoma cells, which multiply and collect in your lymph nodes eventually impairing your immune system.

The lymphatic system is composed of lymph nodes in our neck, armpits, groin, chest and abdomen. Lymphoma cancers develop in the nodes and can spread to the lymphatic tissues, such as the spleen, digestive tract and bone marrow. This is called primary extranodal lymphoma.

The most common symptom is a painless swelling, often in the neck, armpit or groin.

A doctor can tell the difference between Hodgkin's lymphoma and Non-Hodgkin's lymphoma by examining the cancer cells under a microscope.

Non-Hodgkin’s Lymphoma isn’t one disease but actually describes a group of 30 blood cancers. There are many different subtypes, categorised as either indolent (slow growth) or aggressive.

Most Non-Hodgkin’s Lymphomas are B-cell lymphomas, of which there are 14 varieties.

The reason these different cancers are combined under the same diagnostic label is due to the fact that they share a single characteristic in how they develop.

Nearly two-thirds (63%) of people diagnosed with Non-Hodgkin lymphoma in England and Wales survive their disease for ten years or more.

From 1975 to 2010 the 5-year survival rate in children aged 15 and younger almost doubled from 45% to 87%.

How do you treat Non-Hodgkin’s Lymphoma?

Treatments for Non-Hodgkin’s Lymphoma include chemo and radiation therapies. However, there are variations in clinical treatment depending on the subtype of Non-Hodgkin’s lymphoma.

Depending on the stage and type, chemotherapy might be used in combination with immunotherapy — chemically engineered antibodies called monoclonal antibodies that can be designed to attack a specific target, such as the surface of a lymphocyte where lymphoma forms.

At the moment it is uncommon for stem cell transplantation to be recommended for initial treatment of Non-Hodgkin’s Lymphoma. This is because of the high, sometimes life-threatening risks to patients.

However, where patients have Non-Hodgkin’s Lymphoma that resists treatment or comes back after previous remission, doctors may recommend a stem cell transplant (also known as a bone marrow transplant).

In these kinds of cases, patients with Non-Hodgkin’s Lymphoma receive a stem cell transplant following intensive chemotherapy which destroys the lymphoma but also destroys the patients’ own bone marrow. The stem cell transplant creates a new bone marrow within the recipient.

Commonly this will be autologous stem cell transplantation, which means a patient’s own non-cancerous stem cells are harvested prior to undergoing intensive drug therapy, such as chemo, and then re-injected into their bodies afterwards.

Allogeneic (from a donor) stem cell transplantation for Non-Hodgkin’s Lymphoma patients is also possible. This is most likely in a situation when lymphoma has spread to the patient’s bone marrow or blood. The donor’s tissue type needs to match the patient’s as closely as possible, which is why a sibling is usually the best option.

How might stem cell therapies help in the future?

T- cell Immunotherapy

Stem cells are used in a branch of immunotherapy that is yielding promising results in clinical trials throughout the world. T-cell engineering enables scientists to reprogramme stem cells into T-cells that can seek out and destroy tumours.

T-cells are distinguished from other lymphocytes by the presence of T-cell receptors (TCRs) on the cell surface. The TCRs enable the T-cells to recognise specific antigens and disable them.

In T-cell immunotherapy, T-cells collected from the patient’s blood can be reprogrammed to allow the patient’s own immune system to fight malignant cells.

This is achieved by engineering the T-cells in the laboratory to produce chimeric antigen receptors (CARs) which are antibody recognition devices. They attach to a specific antigen on cancer cells, meaning they can be targeted and destroyed.

The CAR T-cells can be mass-produced in the lab until there are enough to be re-infused into the patient. Technically these cells are not T-cells, but resemble T-cells. They have added benefits and have the potential to target specific types of cancer cells.

In two recent studies reported in December 2017, CAR T-cell therapy has been found to have long-lasting remissions in patients with Non-Hodgkin’s lymphoma. These advances offer hope of new treatments for Non-Hodgkin’s lymphoma in the future.

Single cell biology research

Although scientists have been examining cells under microscopes for 180 years the characteristics of individual cells remain elusive.

Stem cells may have very diverse functions but do not necessarily look obviously different to other cells.

A study published in Cell Stem Cell reveals the first time researchers have isolated single cells from populations of rare blood cells and used a technique to profile and test these stem cells’ capacity for transplantation.

The study, by Professor Bertie Göttgens and colleagues at the Cambridge University Department of Haematology, the Cambridge Institute for Medical Research and the Wellcome Trust/Medical Research Council Stem Cell Institute, brings with it the possibility of identifying the molecules that operate within a single stem cell and the potential outcomes for a transplant.

Although the exact implications for the treatment of cancers like Hodgkin’s and Non-Hodgkin’s Lymphoma and leukaemia are unclear, the hope is that it will lead to the refinement of stem cell transplants, with targeted individual cells chosen.