Treatment of Leukemias and Lymphomas: New Approach to Blood Cell Transplants May Offer Effectiveness with Reduced Side Effects

For many persons with cancers of the blood, bone marrow, and lymph system, a peripheral stem cell transplant offers a hope for cure. However, the risk associated with such a transplant can be great, especially for those who are elderly. In a recent study, researchers reported that a new transplant approach, using a moderate dose of total-body radiation therapy with drugs to suppress the immune system, may dramatically reduce the risk of treatment-related side effects and death.

In healthy persons, the bone marrow produces different types of blood cells in the appropriate quantities, and these cells mature to perform their jobs in the body. Red blood cells carry oxygen to the tissues, platelets help with blood clotting, and white blood cells help the body to fight infection. In persons with a cancer of the blood, bone marrow, and lymph system—such as acute or chronic myelogenous leukemia, acute or chronic lymphocytic leukemia, Hodgkin’s or non-Hodgkin’s lymphoma, and multiple myeloma—there is an uncontrolled growth of 1 type of blood cell, which can affect the ability of all the blood cells to perform their jobs in the body properly. Many treatment options are available to help control these types of cancer, including chemotherapy, radiation therapy, and biologic therapy (also called immunotherapy) to help the immune system. In some cases, a peripheral stem cell transplant may be the only curative treatment available.

A peripheral stem cell transplant, also referred to as a bone marrow transplant, involves the removal of bone marrow that has been damaged by chemotherapy or radiation therapy. The unhealthy bone marrow is then replaced with stem cells (young blood cells) from healthy bone marrow. The healthy bone marrow cells may be donated by 1 of 3 sources: an allogeneic transplant uses bone marrow donated by someone who may or may not be a relative of the patient; a syngeneic transplant uses bone marrow donated by an identical twin of the patient; and an autologous transplant uses bone marrow directly from the patient.

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The researchers at Fred Hutchinson Cancer Research Center treated 45 patients (average age 56 years) with advanced cancer of the blood, bone marrow, or lymph system with an allogeneic peripheral stem cell transplant, using a new approach to help reduce treatment-related side effects and death. Instead of receiving the full doses of radiation and/or chemotherapy usually administered, these patients received low-dose total body radiation therapy before the transplant. After the transplant, they received the drugs, cyclosporine and mycophenolate mofetil, to suppress the immune system and help the body accept the new stem cells. While these lesser doses of radiation are not sufficient to eradicate the cancer, the researchers relied on the body’s reaction to receiving the new stem cells to also cause an anti-cancer effect. Thirty-two patients were able to be treated as outpatients; half of the patients required no hospitalization in the first 2 months. For those who did require hospitalization, the stay was an average of only 10 days.

The study results showed that all patients’ bodies initially accepted the new stem cells; 20% ultimately rejected the transplant, but their condition was no worse than it was before the transplant. This was an improvement over outcomes with previous transplant strategies; patients who have rejection after a transplant with full-dose radiation and/or chemotherapy can die from a lack of blood cell production. A potentially serious side effect, called graft-versus-host disease, occurred in almost half of those whose bodies accepted the transplant, but this side effect was less severe than normally seen in those having a transplant with full-dose radiation and/or chemotherapy. Overall, 74% of patients survived, and 50% had complete acceptance of the new stem cells and were in complete remission from the cancer. In 7 persons, most with chronic myelogenous leukemia, laboratory molecular tests before the treatment showed markers for cancer in the bone marrow. After treatment, these same tests showed a remission, suggesting effectiveness in eradicating cancer cells.

The researchers concluded that this new approach to peripheral stem cell transplantation holds promise for dramatically reducing the side effects related to this treatment. Future studies will evaluate ways to use the immune system to kill cancer cells in persons who do not have graft-versus-host disease, such as using infusion of donor blood cells, called lymphocytes. ( Proceedings of the American Society of Hematology, Vol 94, No 10, Supplement 1, pp 347a, Abstract No 1551, 1999)

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