- Clustering of childhood leukemia cases, a new study from Hong Kong - Childhood leukemia,
especially the acute lymphoblastic form, has frequently been found to show clustering of cases -
an above average concentration of cases in specific areas over a limited time-span. While this
has often been held as evidence of an infection as the cause of the disease, clustering can be
difficult to prove or disprove statistically, and there have been few specific studies. A report
from Hong Kong, in the February, 1997 issue of the British Journal of Cancer, described
significant clustering of acute lymphoblastic leukemia in the 1 to 4- and 2 to 7-year-old groups
in specific census tracts where extreme population mixing may have occurred. Such mixing has
been described in earlier British studies of leukemia clustering (Kinlen, Br J Cancer 64:549,
1991, and Br Med J 306:743, 1995), and would tend to expose the preexisting population to new
unaccustomed strains of viruses or even bacteria. (Alexander, Br J Cancer 75:457, 1997)
Editor's Comment: - This paper presents one more piece of evidence suggesting an abnormal
immune response to an infectious agent as the root cause of the leukemia. This pattern of origin
is increasingly being suspected not only for leukemias and lymphomas, but also for non-cancer
diseases like Type I diabetes and some forms of arthritis.
- Long-term psychological outcome of adults treated for acute leukemia as children - As we
have stated before, childhood cancers represent the main success story of chemotherapy. In a
number of issues we have touched on fairly long-term effects of these intensive treatment
schedules on growth and other physical processes, and on mental development. Now comes an
even more long-term study that looked at more subtle effects. The Children's Cancer Group
looked at 580 adult survivors of acute lymphoblastic leukemia who were treated as children,
reporting their findings in the February, 1997 issue of the Journal of Clinical Oncology.
Survivors, when matched with their siblings, scored significantly higher in tests for negative
mood, tension, depression, anger, and confusion; this was especially pronounced in females,
minorities and the unemployed. Unemployment and part-time employment were significantly
more common among the survivors. (Zeltzer, J Clin Oncol 15:547, 1997)
- The value of bone marrow transplants for children with acute leukemia - Two articles in the
February, 1997 issue of the Journal of Clinical Oncology emphasize the value of performing
bone marrow transplants as early as possible in children beyond their second complete
remission, even if only unrelated donors are available. A study from the University of
Minnesota in Minneapolis found that unrelated donor marrow transplants provided disease-free
survival figures at 1 and 2 years of 37% and 30% for acute lymphoblastic, and 53% and 33% for
acute myelocytic leukemia, respectively. Reaction to the graft (graft-versus-host disease)
occurred in 50% of those who were matched and 57% in those who were mismatched (Davies, J
Clin Oncol 15:557, 1997), a relatively small difference. The European Working Group studied
children with acute myelomonocytic leukemia, finding a 5-year event-free survival of 31%.
Interestingly, in the group receiving compatible or only one-mismatched antigen, the survival
rate rose to 62% for those receiving pretransplant conditioning with busulfan and other drugs
compared with only 11% for total body radiation. However, unlike the US researchers, the
Europeans found significantly more graft rejection disease in unrelated and mismatched relatives
than in compatible or one-antigen mismatched relatives, 87% versus 23%; the mismatched
group also a high transplant-related mortality rate of 46% (Locatelli, J Clin Oncol 15:566, 1997).
Editor's Comment: - Although both studies used donors who were not all compatible, and
emphasized the need for early transplants, the high graft-versus-host disease and mortality rates
for unrelated donors in the European study underlines the need for intensive supportive care.
There is no easy way of evaluating how this factor varied among 20 institutions in a number of
European countries; only one institution was involved in the US study.
- Measuring residual leukemia cells after treatment - Although a high proportion of children
with acute lymphoblastic leukemia respond to treatment with long-term survival and apparent
cure, there is a significant recurrence rate. This is believed to result from residual leukemic cells
that escape detection by conventional microscopic examination. Availability of new molecular
biological techniques such as polymerase chain reaction amplification (PCR) might enable
doctors to detect much lower numbers of leukemia cells and give additional therapy to kill them.
In an article in the January 30, 1997 issue of the New England Journal of Medicine, researchers
at the M.D. Anderson Cancer Center in Houston, described their study of PCR in acute
lymphoblastic leukemia (ALL). Their general results for chemotherapy patients with ALL
showed an overall 4-year survival of 59%. In 24 patients who had PCR tests, 7 relapsed and 17
remained in remission for 2-35 months. Levels of leukemia cell DNA in the bone marrow were
significantly different between relapsing patients and those in remission. However, PCR
detected leukemic DNA in 15 of the 17 patients in remission suggesting that eradicating all
leukemia cells may not be necessary for cure. (Roberts, New Engl J Med 336:317, 1997)
Editor's Comment: - The nature and fate of these silent' leukemia cells seen by PCR was
discussed in an editorial that accompanied this article, by Dr. Greaves from the Institute of
Cancer Research in London. The detected cells might be preleukemic cells that had features in
common with the leukemic cells that had evolved from them and been eliminated by
chemotherapy, or they might be normal cells that happen to possess specific features the same as
those on the leukemic clones. These normal cells with leukemia-like features would be
harmless, but the test still would classify them as leukemic cells. Only further study and
application will answer these questions and determine the ultimate value of this new technology
in managing leukemic patients
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