The CancerWeb Report, What's New In Cancer: June, 1996
Childhood Leukemia

• Is autologous bone marrow transplantation of value in childhood acute myeloid leukemia (AML)? - The Pediatric Oncology Group set out to answer this question. Their results, published in the May 30, 1996 issue of the New England Journal of Medicine, indicated that the event-free survival rates for children receiving autologous (their own marrow) transplantations were the same as for those given intensive consolidation chemotherapy. Initially, 552 of 649 patients were brought into remission with one course of daunorubicin, cytarabine and thioguanine, followed by a course of high-dose cytarabine. The 232 patients who were eligible and evaluable for study were randomly assigned to autologous bone- marrow transplantation or to six courses of intensive chemotherapy with daunorubicin and cytarabine (course 1), daunorubicin, cytarabine and thioguanine (courses 2 and 5), etoposide and azacytidine (courses 3 and 6), or high-dose cytarabine (course 4). While transplantation gave a lower relapse rate (31% versus 58%) it also produced a higher treatment-related mortality rate (15% versus 2.7%) than did chemotherapy, and the end results, the event-free three-year survival rates, were the same (38% and 36%) for both treatments. The researchers noted that the non-randomized chemotherapy- treated patients from the original group had an event-free survival rate of 39%, and a separate group of patients receiving bone-marrow from sibling donors (allogeneic transplants) showed a 52% rate. (Ravindranath, New England J Medicine 334:1428, 1996)

  Editor's Comment: - As with many other studies in children, randomization presented problems with a high drop-out rate before randomization could take place due to early relapses, so that only 232 of the original 649 patients could go through with the study. The survival figures in two other studies (UK Medical Research Council and Children's Cancer Study Group) have shown no advantage of allogeneic over autologous marrow transplants, while one (Amadori, J Clinical Oncology 11:1046, 1993) showed similar survival with either autologous transplants using unpurged marrow or with intensive chemotherapy, as in the Pediatric Oncology Group study.

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• Epidemiology of childhood leukemia, a viral factor? - Viral or other infectious factors have often been invoked as causes of leukemias and lymphomas, with so-called clustering in both space and time commonly claimed as an indicator. For relatively rare diseases such as leukemia, it has been difficult to prove statistically in many cases that the clustering is a real phenomenon. In addition, there is the complicating factor of population migration. A study carried out in Greece, and reported in the May, 1996 issue of the British Journal of Cancer, described the occurrence of clusters of childhood leukemia among the total of 872 cases diagnosed in Greece over the period 1980- 1989. There was highly significant (p values 0.004 or below) statistical evidence for clustering both space and time, with the observed numbers exceeding those expected by 5.2% for all children and 9.4% for those aged below 4 years; in the case of acute lymphoblastic leukemia (ALL) the excess was over 19%. Urban (with mixing due to population influx) and rural (with relative isolation) findings differed in that the rural results showed older and broader age groups for clustering, compatible with delayed development of immunity against an infectious agent. The authors considered that the data supported the possibility that a significant proportion of childhood leukemia results as a rare sequel to exposure to an infectious agent, probably a virus. (Petridou, Br J Cancer 73:1278, 1996)