The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 20, 1996
Philadelphia, PA, May 18, 1996-- Exciting new research that better defines the role and timing of bone marrow transplantation was presented at the 32nd Annual Meeting of the American Society of Clinical Oncology (ASCO). Bone marrow transplantation is commonly used in cancer of the blood and lymphatic systems, and is being increasingly used in poor prognosis cancers, such as metastatic breast cancer.
The bone marrow is the source of all blood cells (white blood cells, red blood cells and platelets) in the human body. Bone marrow transplantation (BMT), the removal and re-insertion of bone marrow, is usually derived from the patient (autologous) or another person (allogeneic). While high dose chemotherapy followed by BMT offers the hope of ridding the body of cancerous cells, it involves potentially serious risks including infection, malfunction of the lungs, liver, kidneys and heart, and excessive bleeding.
For autologous bone marrow transplantation (ABMT) to be successful, the patient's marrow must be free of cancer cells when it is reinfused. To this end, the marrow often is treated to remove cancer cells ("purged") before transplantation. Not all patients undergoing ABMT receive purged marrow because it is not clear whether purging truly reduces the risk of relapse after transplantation. In addition, purging with anticancer drugs may result in delayed recovery of bone marrow function after transplantation because normal stem cells in the harvested marrow may be destroyed along with cancer cells.
Allogeneic bone marrow transplantation (alloBMT) involves a different set of risks. While the transplanted marrow is free of tumor cells, it is a foreign body. Despite efforts to ensure a close match between marrow donors and recipients (especially through the use of family members), the recipient's body can develop graft-versus-host-disease (GVHD), one of the most serious potential complications of alloBMT. In GVHD, the transplanted marrow launches an attack against the patient. Severe cases of GVHD can be fatal.
A new study by the Children's Cancer Group (CCG) has found that allogeneic bone marrow transplantation (alloBMT) is the best treatment option for children with acute myelogenous leukemia who have achieved remission. The second-best option is aggressive post-remission chemotherapy, which provides better outcomes than autologous bone marrow transplantation (ABMT) in this patient population. The results are reported by William G. Woods, M.D., professor and director, Pediatric Hematology-Oncology Division, University of Minnesota Cancer Center (Minneapolis, MN), for the CCG.
Acute Myelogenous Leukemia (AML), cancer in the bone marrow and blood cells, is the most common form of aggressive leukemia in adults, and affects almost 500 children in the United States each year. (As cancer studies can be conducted more effectively in children than in adults, important information can be obtained by studying even rare cancers in children.)
Previous studies have suggested that once remission is achieved in children with AML, the best way to achieve long term cure is to perform an alloBMT if a suitable family donor exist. In the absence of a matched family donor, there has been controversy over the best way to treat patients who have achieved remission: with large doses of chemotherapeutic drugs, or an ABMT with marrow that has been removed and treated to remove any residual leukemia cells.
CCG, the largest childhood cooperative group in the world, undertook a Phase III randomized trial of 450 children with AML in remission to determine the optimum form of post-remission therapy. The patients were treated with alloBMT if an appropriate family donor was present, or were randomized to ABMT with purging versus chemotherapy utilizing high-dose cytarabine and other drugs.
Overall survival for three years from the end of remission was 76% for the 140 patients allocated to alloBMT; 59% for the 160 patients receiving high-dose chemotherapy and 45% for the 150 patients treated with ABMT. Disease-free survival for three years post-remission was 70% for the alloBMT group; 50% for the high-dose chemotherapy group; and 40% for the ABMT group.
"There has been a lot of focus on the potential promise of ABMT," Elizabeth j. Shpall, M.D., associate director, Bone marrow Transplant Program, University of Colorado Health Sciences Center (Denver, CO), said at a press briefing today. "This study demonstrates that ABMT is not the best course of treatment for children with AML in remission."
BMT is an Effective Therapy for Metastatic Breast Cancer -- And Timing Appears to Play an Important Role in Outcome
High-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT) can make a significant impact on disease-free survival compared to standard doses fo chemotherapy, and the timing of the HDC/AMBT can have an impact on overall survival, according to the results of a study presented by William P. Peters, M.D., Ph.D., director, Karmanos Cancer Institute (Detroit, MI). Dr. Peters and his colleagues conducted the study while he was director of the Duke University Bone Marrow Transplant Program.
The prognosis for women diagnosed with metastatic breast cancer is not promising: fewer than 5% of women whose disease is not responsive to hormonal therapy are alive and disease-free five years after conventional-dose chemotherapy. While numerous studies have demonstrated that high-dose chemotherapy will increase the frequency of regression in hormone-insensitive metastatic breast cancer, randomized comparative data evaluating the effectiveness of HDC has not been available.
In the prospective, randomized trial of 423 patients with hormone-insensitive metastatic breast cancer, the researchers set out to determine whether HDC plus AMBT improved the duration and frequency of remission compared to conventional dose therapy, and whether the timing of HDC/ABMT affedts the overall survival of patients.
Patients were treated with intensively-timed chemotherapy with doxorubicin, 5-flurouracil, and methotrexate at conventional doses. Remissions were seen in 98 patients, who were then randomized to immediate treatment with high-dose chemotherapy (HDC) with cyclophosphamide, cisplatin, and carmustine follwed by an autologous bone marrow transplant (ABMT), or to observation with HDC/ABMT if there was a recurrence of disease. Forty-nine patients were randomized to each group.
Disease-free survivial was significantly higher in the patients who went on to treatment with HDC/ABMT than those treated with the conventional chemotherapy only -- an average of one year compared to an average of four months. In addition, approximately 22% of transplant patients were alive and disease-free at five years, compared to only 8% of those treated with conventional chemotherapy.
With regard to the timing of HDC/ABMT (at remission vs. at recurrence), patients randomized to observation followed by ABMT only when relapse occurred had a superior overall survival (40% at five years) than those receiving immediate transplantion (20% at five years). Patients randomized to observation had an overall survival of 3.2 years, compared to 1.9 years for those receiving transplants immediately.
"These data indicate that the timing of intensive therapy in certain patient populations may have a considerable impact on the effectiveness of the treatment regimen," Elizabeth J. Shpall, M.D., associate director, Bone Marrow Transplant Program, University of Colorado Health Sciences Center (Denver, CO), said at a press briefing today. "The more we understand about how dose, timing, and combination of cancer treatments affect treatment outcomes, the better oncologists should be able to tailor therapies to achieve optimal results.