Two sequential doses of high-dose chemotherapy each supported by autologous peripheral blood stem cell transplantation was shown to be very effective in the treatment of advanced neuroblastoma in children, according to a study performed by researchers at the University of Pennsylvania and several other medical centers.
Neuroblastoma is a rare cancer of the tissues that form the sympathetic nervous system (the division of the nervous system that involuntary regulates different body functions by constricting blood vessels, increasing heart rate and blood pressure and stimulating certain hormones). There is a network of this nerve tissue throughout the body that carries messages from the brain to specific destinations in the body. Neuroblastoma is often diagnosed in children under 2 years old when they begin to show symptoms, but it is often already present at birth. It commonly begins in the adrenal gland located directly on top of each kidney, chest, and neck and may extend to the spine. Depending on the stage, or extent of the disease, neuroblastoma can be treated with surgery, chemotherapy and/or radiation. When cancer is localized (stage I or II, without involvement of lymph nodes), meaning that it is present only in the area of the body in which it first developed, surgery alone can provide a high cure rate. In fact, the survival rate for these children is excellent. However, children with neuroblastoma that has spread from the area in which it first started to different areas in the body are considered to have an advanced stage of cancer and are at high risk for recurrence (return of cancer) after treatment with standard doses of chemotherapy.
Chemotherapy targets and kills rapidly dividing cells, such as cancer cells. Although chemotherapy is effective at killing cancer cells, treatment does not differentiate between cancer cells and healthy cells. High-dose chemotherapy kills more cancer cells than lower dose conventional chemotherapy. Unfortunately, high-dose chemotherapy also kills more normal cells, especially the blood producing stem cells in the bone marrow. The treatment strategy utilizing stem cell transplant is an attempt to restore the blood producing stem cells after high-dose chemotherapy has reduced them to dangerously low levels. Stem cells are immature, cells produced in the bone marrow (spongy material inside bones). Stem cells eventually become either red blood cells, which provide Oxygen to tissues, white blood cells, which fight infection, or platelets, which aid in blood clotting. When high-dose chemotherapy is destroying cancer cells it is also killing the bone marrow stem cells. When bone marrow is destroyed, stem cell stores are depleted leading to low levels of circulating blood cells. When these cells reach critically low levels, complications such as anemia, infection and bleeding can occur which may result in death. Thus, it is imperative to restore stem cell levels as quickly as possible. In autologous (self) stem cell transplantation, the patient’s own stem cells are collected before chemotherapy treatment, frozen, and infused back into the patient after treatment to “rescue” the bone marrow. Stem cells were historically collected from the bone marrow but can be collected in greater quantities from the blood. Stem cells collected from blood restore blood cell production faster than cells collected from bone marrow.
A clinical trial conducted by the Children’s Cancer Group previously demonstrated that patients with advanced neuroblastoma receiving one course of high-dose chemotherapy with autologous stem cell transplantation have improved survival compared to patients undergoing standard chemotherapy treatment. Despite the improvement, 50% of patients experienced cancer recurrence and died. Thus, further improvements in high-dose treatment regimens are needed to cure more children with advanced neuroblastoma. The goal in designing new regimens is to use effective drug combinations while safely increasing the doses and ensuring rapid bone marrow reconstitution with autologous stem cells. (The New England Journal of Medicine, Vol 341, No 16, pp 1165-1173, 1999).
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A preliminary study conducted by researchers from several pediatric centers CSG utilized the treatment strategy of administering two sequential high-dose chemotherapy treatments followed by bone marrow stem cell transplantation in children. This treatment proved to be too toxic with the major setback being the slow rate of restoration of blood cells. Because peripheral blood stem cells restore blood cell counts faster than bone marrow, this study was repeated with the use of autologous peripheral blood stem cells. Thirty-nine children with advanced neuroblastoma received 2 courses of high-dose chemotherapy, 4 to 6 weeks apart, each followed by autologous blood peripheral stem cell transplantation. Recovery of blood cells after high-dose treatment was rapid and complete. Three years after treatment, 58% of patients survived without cancer recurrence. The doctors concluded that two courses of high-dose chemotherapy treatment each followed by peripheral autologous stem cell transplantation was an effective treatment strategy for children with advanced neuroblastoma and appears to improve survival and the chance of cure.
Parents of children with advanced neuroblastoma may wish to talk with their doctor about high-dose chemotherapy treatment with stem cell transplantation or other promising, new treatments. Sources of information on ongoing clinical trials that can also be discussed with a doctor include comprehensive, easy to use clinical trials listing services provided by the National Cancer Institute (cancer.gov). (Journal of Clinical Oncology, Vol 18, No 13, pp 2567-2575, 2000).