Stem Cell Transplants for Non-Hodgkin’s Lymphoma


In patients with aggressive non-Hodgkin’s lymphoma, early stem cell transplants do not improve the overall survival in high-risk patients, but are beneficial in those patients who are at the highest risk.

Lymphomas are cancers of the lymphocytes, which are a specific group of white blood cells. A particular type of lymphoma known as Non-Hodgkin’s lymphoma is more common than the other general type of lymphoma — Hodgkin lymphoma. There are several different subtypes of non-Hodgkin’s lymphoma. The most common non-Hodgkin’s lymphoma subtypes include diffuse large B-cell lymphoma and follicular lymphoma.

The symptoms of non-Hodgkin’s lymphoma include Non-Hodgkin’s lymphoma symptoms may include: swollen lymph nodes in the neck, armpits or groin, swelling of the abdomen and abdominal pain, Chest pain, coughing or trouble breathing, fatigue (tiredness), fever, night sweats, and weight loss.

The usual treatment for aggressive non-Hodgkin’s lymphoma is a combination of four different chemotherapeutic agents designated as “CHOP,” which stands for Cyclophosphamide (alkylating agent that rituximabdamages DNA), Hydroxydaunorubicin (also called doxorubicin or Adriamycin, also a DNA-damaging agent), Oncovin (vincristine, which binds to microtubules and prevents cells from dividing duplicating by binding to the protein tubulin), and Prednisone or prednisolone (corticosteroids). Recently, many oncologists are adding Rituximab to this drug regimen (but only if the lymphoma is of B-cell origin). Rituximab is a monoclonal antibody that binds to the surface of B-lymphocytes (the very cells that have become cancerous) and facilitates their destruction. This new five-drug regimen, R-CHOP, can drive many patients into remission. However, some relapse and go on to receive stem cell transplants.

This present study, which was directed by Patrick Stiff from the Loyola University Medical Center’s Cardinal Bernardin Cancer Center, was designed to determine if an early stem cell transplant before the patient relapsed increase patient survival. This study examined patients from 40 different clinical sites in the United States and Canada.

397 patients who were in defined groups of high risk or intermediate-high risk of relapsing. After initial chemotherapy treatment, those patients who responded to treatment were randomly assigned to receive an autologous stem cell transplant (125 patients) or to a control group (128 patients) who received three additional cycles of the R-CHOP regimen.

After two years, 69 percent of the transplantation patients had no disease progression, compared with 55 percent of the control group. This is a statistically significant difference, but the two-year survival rates in the transplantation group was 74 percent versus 71 percent in the control group, which was not statistically significant. However, patients in the control group who relapsed were later offered stem cell transplants, which is probably why the differences are not statistically significant.

However, mining the data further reveals something even more interesting. While the stem cell transplants did not improve overall survival among the entire group of high-risk and high-intermediate risk patients, the high-risk patients as an isolated subset rather clearly received a remission and survival benefit from the early stem cell transplants. The two-year survival rate was 82 percent in the stem cell transplant group and 64 percent in the control group, which is statistically significant.

Patrick Stiff and his colleagues concluded: “Early transplantation and late transplantation achieve roughly equivalent overall survival in the combined risk groups.” However, “early transplantation appears to be beneficial for the small group of patients presenting with high-risk disease.”

Stiff hopes that this finding will “trigger discussions between such patients and their physicians as to the feasibility of doing early transplants.”

Patients who receives doses of their own stem cells (so-called autologous stem cell transplants), can tolerate very high doses of chemotherapy and/or radiation. This high-dose treatment kills off many cancer cells, but it also destroys the patient’s immune system. Therefore, prior to the treatment, stem cells are removed from the blood or bone marrow of he patient and infused back into the patient. These stem cells then form a new immune set of immune cells that replace the ones destroyed by the chemotherapy.

Previous studies have shown that patients who undergo autologous stem cell transplants have a higher risk of developing secondary cancers that are caused by the chemotherapy or the radiation. However, this new study did not find a statistically significant difference (11 percent in the control group and 12 percent in the stem cell transplant group) in secondary tumor formation between the two groups.

Stiff and his crew are continuing to crunch the numbers and mine the data. “As years go by, there may be additional analysis that may help fine-tune the results so that we will be able to more carefully and concisely define any potential benefit,” said Stiff.

See Patrick J. Stiff, et al, New England Journal of Medicine 2013; 369(18):1681.

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Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).