The CancerWeb Report, What's New In Cancer: September, 1996
Hematologic Malignancies

• Further information on the marrow purging controversy - To an increasing extent, patients with non-Hodgkin's lymphoma (NHL) and other hematologic malignancies are being treated successfully with high-dose chemotherapy, with or without whole-body radiation, and transplantation of the patients' own bone marrow (autologous transplantation) collected before therapy. Stem-cell transplantation using cell isolated from the blood is also used instead of bone marrow. A major controversy has been whether the bone marrow should be purged of tumor cells that may be present among the normal cells before it is given back to the patients. At present, there is no assurance either that the purging procedure is effective, or that it has any effect on progression-free survival of the patients. A report from the European Blood and Marrow Transplant Lymphoma Registry, published in the September, 1996 issue of the Journal of Clinical Oncology, claimed that purging has no clinical effect. When 224 of the patients with NHL who had received purged marrow were compared with a matched group that was given unpurged marrow, overall 5-year survival figures were 54% for the use of purged and 48.3% for unpurged marrow; the more critical progression-free survivals for the corresponding groups were identical at 44.3% and 44.6%, respectively. (Williams, J Clin Oncol 14:2454, 1996)

  Editor's Comment: - While the data are good, I doubt that this study will end the controversy, which extends also to marrow transplantation in the treatment of tumors such as breast cancer. The intuitive concept that the elimination of possible tumor cell contamination is preferable will still outweigh for many the inconvenience of extra in vitro treatment of the marrow preparation. It would help if we could be sure that the in vitro exposure to cytotoxics actually rids the marrow of contaminants. If it does not, then the finding of no difference in progression-free survival with or without purging would not be unexpected. This problem is further complicated by the fact that not all cancer or lymphoma cells circulating in the blood or present in marrow are capable of forming metastases or of becoming reimplanted to form new lymphoma colonies because they lack the necessary biological features. Further study of these aspects, including direct comparison of purging techniques, is needed.

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• High-dose therapy and stem cell transplantation for Burkitt's and Burkitt-like lymphomas - Burkitt's and Burkitt-like lymphomas are somewhat of a paradox in that they show high response rates to treatment schedules used for acute lymphoblastic leukemia, but many patients relapse rapidly despite good initial responses. These diseases are becoming more common in association with HIV infections. The European Blood and Marrow Transplant Lymphoma Registry published the results of ten years' study of such patients in the September, 1996 issue of the Journal of Clinical Investigation. Overall 3-year survival of the whole group treated with high-dose chemotherapy and transplants of stem cells recovered from their blood (rather than from bone marrow) was 72% for patients transplanted in first complete response, 37% for those who had relapsed, and 7% in those who were chemoresistant. Progression-free survival rate was 54% at 3 years for the group as a whole, and 73% (100% in those with less than 5 cm disease) among those who were treated at first complete response. (Sweetenham, J Clin Oncol 14:2465, 1996)

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• Cytarabine and high-dose mitoxantrone in acute lymphoblastic leukemia - Regimens to treat acute leukemia are complex, consisting of an initial intensive treatment to induce remission, and subsequent regimens to consolidate and then maintain the state of remission, with the end result a relatively high cure rate. However, these treatment regimens result in a wide range of side effects from the large number of drugs used. Is it always necessary to use so many drugs? An article by researchers at Memorial Sloan-Kettering Cancer Center and New York Medical College, suggests that high doses of the newer drug mitoxantrone (also discussed under "Breast Cancer" in this month's CancerWeb Report) together with cytarabine, may represent a simpler treatment scheme for the initial induction of remission. In the September, 1996 issue of the Journal of Clinical Oncology, these researchers described use of an induction regimen consisting of high-dose mitoxantrone (80 mg/m2) with cytarabine, and the growth factor G-CSF to stimulate bone marrow recovery. This produced 84% complete responses, which was better rate, and the responses occurred about 20 days sooner, than were achieved with the traditional four-drug induction regimen of vincristine, prednisone, doxorubicin, and cyclophosphamide. (Weiss, J Clin Oncol 14:2480, 1996)

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• Second cancers developing in cured Hodgkin's disease patients may be connected with full-dose radiation treatment - The success achieved in curing about 75% of patients with Hodgkin's disease has come at a price, not only in terms of debilitating side-effects suffered during treatment, but also because of delayed, long-term effects of that treatment. The most serious of these delayed effects is the appearance of second cancers, because radiation and many cancer chemotherapy drugs can themselves be carcinogenic. For this reason, any measures that reduce or eliminate second cancers without jeopardizing the overall cure rate for Hodgkin's disease are worthwhile. It is necessary to compare treatment regimens carefully to identify any factors that may be associated with second tumors. In an article in the September, 1996 issue of the Journal of Clinical Oncology, researchers at Yale identified one such factor. They compared a group of 197 patients who had been successfully treated with full-dose radiotherapy (about 40 Gy) between 1969 and 1985, with another group of 116 who during this time had received multidrug chemotherapy followed by low-dose radiation (15-30 Gy) given only to the areas where there was disease. At follow-up more than 10 years after treatment, 16 of the patients given full-dose radiation treatment had developed second tumors, of which 8 were lung cancers, and 6 had benign tumors; this represented a more than 6-fold increase over the numbers expected. Those receiving chemotherapy and low-dose radiation had 5 cancers, a rate that was not elevated. It is evident that high-dose radiation was the factor responsible for second cancers and tumors among these patients. The effect did not become evident until more than 10 years had elapsed since treatment. (Salloum, J Clin Oncol 14:2435, 1996)

  Editor's Comment: - It is not news that radiation and a number of drugs, particularly the alkylating agents, can produce cancer. The very same features that cause damage to, and eventual death of cancer cells will also damage normal cells. We should bear in mind, of course, that the original disease would have been 100% fatal without treatment, so that despite a significant incidence of second tumors, the overall group of patients is better off. This statistical argument is not, however, of any comfort to those patients who do actually develop second tumors! What is needed is to identify those features of the treatment schedules which are likely to produce normal tissue damage and eliminate them. This study is another step in that process, showing that it is not radiotherapy in and of itself, but the dose and how it is applied that is a critical factor in producing second cancers.