Autologous vs. allogeneic stem cell transplants: key differences in treating malignant lymphoma

Lymphoma is a disease in which lymphocytes, a type of cell, become cancerous and overgrow to form lumps in the body's lymphoid tissue, especially in the lymph nodes. Most lymphomas are malignant.

Benign lymphomas are rarely found, so lymphoma usually refers to malignant lymphoma.

Lymphoma is not a single disease. According to the World Health Organization (WHO) classification, it’s a very complex and diverse disease with more than 50 different subtypes. There are different classifications of lymphomas, and depending on their clinical course, they can be divided into “aggressive lymphomas” and “non-aggressive lymphomas.”

It is commonly thought that aggressive lymphomas have a worse prognosis, but this is not necessarily the case.

“Aggressive lymphoma has a very rapid and dangerous clinical course and can cause death within months or a year if left untreated. On the other hand, however, it responds very well to chemotherapy and can be cured,” said Professor Eom Ki-seong of the Department of Hematology at the Catholic University of Korea Seoul St. Mary's Hospital on the Seoul St. Mary’s Hospital TV.

“Non-aggressive lymphomas, on the other hand, have a slower clinical course, taking years to cause symptoms, sometimes as long as seven or eight years,” Professor Eom said. “This sounds very good, but the problem with non-aggressive lymphoma is that it may respond well to chemotherapy initially but then relapse stubbornly and eventually become incurable.”

The basic treatment for malignant lymphoma is chemotherapy.

“Since blood cells are spread throughout the body, the most important treatment is systemic treatment with chemotherapy,” Eom said. “Surgical methods and radiotherapy usually play a secondary role.”

The treatment consists of cytotoxic anticancer drugs, either alone or in combination, and nowadays, immunotherapy drugs are also added.

Once these first-line treatments have been completed, the patient's response is assessed to determine whether they are in remission. First, if the patient's body is found to be in “complete remission” after the first treatment with no evidence of residual tumor through various clinical tests, physicians only follow up with the patient.

“If chemotherapy fails to achieve complete remission or if the risk of relapse is high, a special treatment called hematopoietic stem cell transplantation is used,” Professor Eom said. “Treatment survival rates vary, depending on the type of lymphoma, its stage, and the patient's health status. Diffuse large B-cell lymphoma, the most common subtype of B-cell lymphoma has an average long-term disease-free survival rate of more than 60 percent with chemotherapy alone.”

The prognostic factors for malignant lymphoma are well known. They include the patient's age, stage, general condition at diagnosis, LDH level in blood tests, and the number of tissues other than the lymph nodes invaded.

“If you have all of these factors, the survival rate is as low as 30 to 40 percent, and if you don't, the survival rate is over 90 percent,” Eom explained.

So, what is the treatment for relapses after treatment of aggressive lymphoma?

“The principle of treatment for relapse is to give a stronger anticancer treatment than the first treatment,” Eom said. “If this treatment results in more than a partial response, that is, partial or complete remission, autologous hematopoietic stem cell transplantation should be done in principle.”

Treatment for relapse can include cytotoxic anticancer drugs, immunotherapy, and radiation therapy, but it usually involves higher doses of these drugs and immunotherapy than were used in the first treatment. Autologous hematopoietic stem cell transplantation, which is performed when a patient achieves partial or complete remission from chemotherapy after relapse, reduces the side effects of high-dose chemotherapy.

“Autologous hematopoietic stem cell transplantation is mainly used for cancers, including lymphoma, where the anticancer effect increases when the dose of chemotherapy is increased. Increasing the dose of chemotherapy kills more cancer cells, but it can also permanently damage tissues in patients that are sensitive to chemotherapy. One of the most sensitive tissues is the hematopoietic stem cells in the bone marrow,” he noted.

“If the high dose of chemotherapy permanently damages the stem cells in the bone marrow, the patient will not be able to recover because they will not be able to hemopoietize. To prevent this, the patient's stem cells are harvested and frozen before the high dose of chemotherapy is administered, and after the high dose of chemotherapy is administered and the cancer cells are killed, the frozen stem cells are thawed and infused back into the patient to replace the destroyed stem cells,” he explained.

On the other hand, allogeneic hematopoietic stem cell transplantation is an entirely different concept from autologous stem cell transplantation. It is often used as a last-resort treatment for patients with malignant lymphoma who have not responded to all other treatments.

“Allogeneic hematopoietic stem cell transplantation involves donating hematopoietic stem cells from a genetically identical person and infusing them into the patient,” Eom said. “The transplanted stem cells attack the patient's cancer cells, increasing the effectiveness of the treatment.”

For this reason, allogeneic stem cell transplantation is a more powerful treatment than chemotherapy. Just as allogeneic stem cell transplantation has a different therapeutic goal than autologous stem cell transplantation, it also has a different treatment procedure.

Before the allogeneic stem cell transplant, the patient is treated with chemotherapy or total body radiation to prevent rejection of other people's stem cells. After the transplant, the patient's immune system cannot reject other people's stem cells, so other people's stem cells are safely engrafted into the bone marrow and form other-derived white blood cells, red blood cells, and platelets.

“Allogeneic hematopoietic stem cell transplantation is a treatment that uses the ‘graft-versus-anti-lymphoma effect’ in which the transplanted other-derived immune cells attack the cancer cells,” Professor Eom said. “This treatment is much stronger than chemotherapy, but the problem is that the immune cells can also attack the patient's normal cells, which can lead to graft-versus-host disease. Therefore, it is usually used as a last resort in lymphoma when all previous treatments have failed.”

Because graft-versus-host disease carries a high risk of death, it is a treatment of last resort for patients with malignant lymphoma who have not responded to other treatment options.

In recent years, there has been a shift in treating malignant lymphoma. Previously, the treatment of malignant lymphoma was chemotherapy based on “cytotoxic anticancer drugs” that cannot distinguish between normal and cancerous cells. In recent years, however, many targeted therapies that attack targets mainly found only in cancer cells have been developed and are used in actual medical practice.

Targeted therapies and immunotherapies have been actively applied to malignant lymphoma. Among the immunotherapies, CAR-T cell therapy has recently been in the spotlight, and monoclonal antibodies have been used to treat patients with malignant lymphoma, either alone or in combination with anticancer drugs.

“Immunotherapy, which uses immune substances naturally present in the body to attack cancer cells, is also being actively used,” Professor Eom said. “Cytotoxic antitumor drugs, targeted therapies, and immunotherapy drugs, used alone or in combination, are the latest treatment trends for lymphoma.”