According to a recent article published in the journal Blood, high-dose chemotherapy and autologous stem cell transplantation as initial therapy produces a complete disappearance of cancer in a significant number of patients with advanced follicular lymphoma. Furthermore, this procedure may be safely performed in clinical centers that perform fewer than 3 autologous stem cell transplants a month.

Non-Hodgkin’s lymphoma (NHL) is a cancer of the lymph tissue, which is part of the body’s immune system. Lymph tissue is present in lymph nodes, lymph vessels and bone marrow, which exist throughout the body. It is also present in organs such as the thymus, tonsils and spleen. The main cells in the lymph system are called lymphocytes, of which there are two types: B and T-cells. Each of these cells has a very specific function in aiding the body to fight infection. The large majority of NHL cases, including follicular NHL, involve cancer of the B-lymphocytes and are characterized by excessive accumulation of these atypical cells. This causes overcrowding of blood and lymph tissue, suppressing the formation and function of blood and immune cells that are normally present. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further decrease in the body’s ability to fight infection. Follicular lymphoma is a slow-growing, or indolent, NHL whose cells appear clustered when viewed under the microscope. Treatment for follicular lymphoma includes chemotherapy, radiation therapy, stem cell transplantation and/or biologic therapy (treatment used to stimulate the immune system to fight cancer). Follicular lymphoma is considered incurable with conventional chemotherapy and/or radiation therapy. However, the addition of biologic agents such as Rituxan(R) to chemotherapy are improving responses.

High-dose chemotherapy tends to kill more cancer cells than conventional chemotherapy. However, the high doses also cause more side effects to the patient. One serious side effect that is common with the treatment of high doses of chemotherapy involves the suppression of blood cells. There are three types of blood cells: white blood cells, which help the body fight infection; red blood cells, which transport oxygen to tissues; and platelets, which aid the blood in clotting. All blood cells are derived from a common cell called the stem cell, which is produced in the bone marrow. The high doses of chemotherapy can kill the stem cells in the bone marrow and leave blood cell levels depleted. Researchers have developed a way in which to replenish the low levels of blood cells following high-dose therapy, called an autologous stem cell transplant. Stem cells are collected from the patient either before or sometime during treatment, frozen and re-infused following therapy.

Previous studies have demonstrated that treatment with high-dose chemotherapy and a stem cell transplant could cure some patients with follicular lymphoma who would otherwise be considered incurable with conventional chemotherapy.

1,2 However, high-dose chemotherapy can be difficult to tolerate and is often limited to younger patients who have no other existing medical conditions. In addition, it was previously thought that this procedure could only be safely performed in a large institute that performed many stem cell transplants per year.

Researchers from Italy recently conducted a clinical trial involving 20 medical centers to evaluate the effectiveness and safety of high-dose chemotherapy and autologous stem cell transplantation in 92 patients with previously untreated advanced follicular lymphoma. These patients were younger than 60 years and had a poor prognosis. Treatment consisted of intensified induction chemotherapy followed by high-dose chemotherapy and an autologous stem cell transplant. Nearly 40% of patients were treated at small institutions that performed 31 or few autologous stem cell transplants per year for blood-related cancers. Following treatment, 88% of patients had no clinical evidence of cancer (complete remission) and only 3% of patients progressed while on therapy. The estimated four-year overall survival for these patients is 84% and cancer-free survival is 67%. Presently, 78 patients (85%) are still alive and 56 have no evidence of disease progression (55 in complete remission and one in partial remission). Two patients died from treatment-related complications.

These researchers concluded that high-dose chemotherapy with autologous stem cell transplantation is an effective and safe treatment option for patients younger than 60 years with poor prognosis advanced follicular lymphoma, even in facilities that perform few transplants per year. Patients with advanced follicular lymphoma may wish to speak with their physician about the risks and benefits of high-dose chemotherapy and autologous stem cell transplantation or the participation in a clinical trial further evaluating this treatment or other promising therapeutic options. Two sources of information regarding ongoing information include the National Cancer Institute ( cancer.gov) and www.eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients.

Reference: Ladetto M, Corradini P, Vallet S, et al. High rate of clinical and molecular remissions in follicular lymphoma patients receiving high-dose sequential chemotherapy and autografting at diagnosis: a multicenter, prospective study by the Gruppo Italiano Trapianto Midollo Osseo (GITMO).

Blood. 2002;100:1559-1565.

1.Gribben JG. Molecular basis for stem cell transplantation in indolent lymphomas.

Cancer J Sci Am. 1998;4 (suppl 2):S37-S45.

2.Corradini P, Ladetto M, Pileri A, Tarella C. Clinical relevance of minimal residual disease monitoring in non-Hodgkin's lymphomas: a critical reappraisal of molecular strategies.

Leukemia. 1999;13:1691-1695.

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