Hodgkin’s lymphoma in adults: What is the benefit of stem cell transplantation with an unrelated donor?

Blood stem cell transplantation can be a treatment option for people with Hodgkin’s lymphoma, if other therapies were unsuccessful. However, there are not enough studies on the chances and risks of stem cell transplantation with unrelated donors.

Hodgkin’s lymphoma, also known as Hodgkin’s disease, is a cancer of the lymphatic system. The lymphatic system includes lymph vessels and lymph nodes. Similar to blood vessels, lymph vessels form a network through the entire body to transport a fluid called lymph. Lymph nodes are small tissue nodes that filter out and destroy germs and other harmful substances from the body. You can read more about the lymphatic system here.

Hodgkin’s lymphoma is a rare disease. About 2,000 people, most of them adults, are newly affected in Germany every year. Men are affected more often than women. What causes Hodgkin’s lymphoma is still unknown. Gradual, painless enlargement of the lymph nodes is often the first sign of this disease. Usually the lymph nodes in the neck area are the first ones to get larger, but lymph nodes in the armpits, the groin or other parts of the body can also be affected. Other symptoms can include fever, severe itching, weight loss and increased night sweats.

Treatment options for Hodgkin’s lymphoma

What kind of therapy is used to treat Hodgkin’s lymphoma depends on the stage of the disease. When Hodgkin’s lymphoma is diagnosed for the first time, it is usually treated with chemotherapy, often combined with radiation therapy. This therapy aims to destroy the affected lymph tissue. Because of this type of therapy the chances of survival are very high: nowadays it is successful in more than 80% of all patients – including the ones with an advanced stage of disease. In other patients, tumor cells do not respond sufficiently to treatment, or the tumor returns after initially successful therapy, which doctors call “relapse”. Subsequent treatment with high-dose chemotherapy in combination with blood stem cell transplantation is then usually recommended. Sometimes additional radiation is applied.

In high-dose chemotherapy and radiation, the patient’s bone marrow is first destroyed – this part of therapy is called “conditioning”. Blood stem cell transplantation (or stem cell transplantation for short) is used to replace the vitally important blood stem cells that have been destroyed by the conditioning. This makes it possible to apply a higher dose of chemotherapy and, hopefully, better treat the cancer. Conditioning and subsequent blood stem cell transplantation is a risky treatment. It puts a lot of strain on people, both physically and mentally, and can have serious, sometimes life-threatening complications. The body is more vulnerable to infections, for example, or there can be life-threatening bleeding.

If people decide to have this type of therapy, the blood stem cells used for transplantation will be stem cells taken from their own body, if possible. This is called autologous blood stem cell transplantation. In this procedure, blood stem cells are taken from a person and later transplanted back into their body. The advantage of autologous stem cell transplantation, compared with stem cells taken from a donor, is that the body will accept its own cells. There remains a small risk, however, that the transplanted blood stem cells do not settle in the bone marrow.

If autologous stem cell transplantation is not possible or is unsuccessful, blood stem cells from a donor are used (allogeneic blood stem cell transplantation). These donors can be related or unrelated persons whose tissue types match the recipient’s tissue type as closely as possible.

After allogeneic stem cell transplantation, cells taken from the donor might attack and damage cells in the recipient’s body. Cells of the liver, the intestine and the skin are the most affected. This reaction is called graft-versus-host disease (GVHD) and can be a potentially life-threatening complication. It can lead to serious inflammations or skin changes, for example. GVHD can be acute, which means starting shortly after transplantation. But it can also last a long time, or start only after a few months for the first time. It is then called chronic GVHD. A graft-versus-host disease can considerably compromise quality of life and is hard to treat.

You can find more detailed information on blood stem cell transplantation in the treatment of cancer in our fact sheet.

Studies on blood stem cell transplantation with an unrelated donor

Researchers from the German Institute for Quality and Efficiency in Health Care (IQWiG) have assessed trials on adults with Hodgkin’s lymphoma who have received blood stem cells from an unrelated donor. They particularly looked for trials that compared this treatment with other therapies – autologous blood stem cell transplantation, and standard-dose chemotherapy without subsequent stem cell transplantation. In addition, the researchers compared the consequences of stem cell transplantation with a related donor with transplantation with an unrelated donor. They also analyzed the effects of different chemotherapy dosages before blood stem cell transplantation. Trials that did not compare therapies were also considered.

The researchers wanted to find out whether the treatment can prolong life or prevent the cancer from progressing or from relapsing. Risks of the treatment and its effect on quality of life and psychosocial aspects were other aspects the researchers assessed.

The researchers found 8 trials with a total of 454 patients. Of these 454 patients, 245 received transplantation from an unrelated donor. Most of the other participants received blood stem cells from a related donor. The researchers did not find any trials that compared blood stem cell transplantation with unrelated donors with autologous stem cell transplantation or with chemotherapy without transplantation. Therefore only two variants of therapy could be compared: stem cell transplantation with an unrelated donor and stem cell transplantation with a related donor. Most patients in the trials received so-called reduced-intensity conditioning. You can read more about this further below.

Benefit of the transplantation remains unclear

Unfortunately, the study results did not offer a reliable answer to what benefit blood stem cell transplantation with an unrelated donor has compared with a related donor.

The trials examined the effects these treatments have on survival. The results were inconsistent, and it remained unclear whether treatment with blood stem cells from a related donor is better than treatment with blood stem cells from an unrelated donor. However, this does not imply that both treatments are equally good. This question remains open. No trial examined the effects on quality of life and on psychosocial aspects.

Transplantation of blood stem cells from related donors and from unrelated donors both led to more or less severe graft-versus-host diseases in some patients. It remains unclear whether this complication occurred more often in one of the treatments. The trials do not give any information on more severe complications.

Possible benefit of transplantation after reduced-intensity conditioning

IQWiG identified a few trials on allogeneic blood stem cell transplantation that were, however, not included in the assessment, as the results did not distinguish between related and unrelated donors. In these trials, patients received a reduced-intensity conditioning regimen – chemotherapy and sometimes radiation at a lower dosage than the one normally applied – and subsequent blood stem cell transplantation with stem cells from another person. These patients were then compared with patients who had been treated with chemo- and/or radiotherapy alone. The reduced-intensity variant is a type of high-dose chemotherapy. People receive a lower dose of the chemotherapeutic than in standard high-dose chemotherapy, but still more than in normal chemotherapy. This treatment variant puts less strain on patients and also destroys fewer stem cells in the bone marrow. The trials indicate that patients who received allogeneic blood stem cell transplantation with a reduced-intensity conditioning survived longer than patients who had been treated with chemo- and/or radiotherapy alone.

In the IQWiG researchers’ opinion it is therefore justified to offer blood stem cell transplantation from unrelated donors to certain patients. These patients include people with relapse and/or who have undergone unsuccessful therapy attempts, including autologous transplantation. For this treatment, however, people will have to be fit enough and need to be thoroughly informed about the uncertainties of available data before they decide for or against transplantation.

Author: German Institute for Quality and Efficiency in Health Care (IQWiG)

Note

This health information is a summary of a scientific report published by IQWiG. It is not an assessment of the right to have health care services reimbursed by statutory health insurance funds in Germany. By law, decisions about the reimbursement of diagnostic and therapeutic procedures can only be made by the German Federal Joint Committee (G-BA). The Federal Joint Committee takes IQWiG reports into consideration in its decision-making process. You can find information about the decisions of the German Federal Joint Committee on its English-language website, www.english.g-ba.de.

Next planned update: March, 2014. You can find out more about how our health information is updated here.

© IQWiG (Institute for Quality and Efficiency in Health Care)