Acute Leukemia of Childhood and Adolescence

Acute Leukemia of Childhood and Adolescence

Leukemia is a malignancy or cancer of the bone marrow. All of the cells in the bloodstream are normally produced in the bone marrow. In leukemia, there is an unrestrained proliferation of a "clone" of immature white blood cells. These abnormal white blood cells gradually crowd out the normal blood cells. This can lead to anemia, an increased risk of infection, and bleeding.

Leukemia is the most common form of childhood cancer, responsible for approximately 30% of cancers in children under age 16, according to the American Cancer Society. The disease will strike approximately 2,600 children in 1995. The cause of most cases of leukemia is unclear, although there appears to be a relationship between leukemia and exposure to radiation, genetic and congenital factors, exposure to chemicals such as benzene, and perhaps even infection with certain viruses.

In the article that follows, Lorrie F. Odom, M.D., a nationally recognized pediatric oncologist, discusses progress that has been made in treatment of this most frightening disease.

Acute Leukemia of Childhood and Adolescence:
by Lorrie F. Odom, M.D.

Over the past three decades, significant strides have been made in the treatment of children and adolescents with acute leukemia. It has also become apparent that there are many different types of leukemia and that these differences have relevance to both treatment and outcome. The two general categories are acute lymphoid leukemia (ALL), which comprises about 70% to 75% of acute leukemias in this age group, and acute myeloid leukemia (AML), which comprises about 25% to 30% of these leukemias. ALL is diagnosed in approximately 2,000 children and adolescents in the United States each year and AML is diagnosed in about 500 young individuals annually.

Within the category of ALL, there is a subtype of children which has a very good response to only moderately intensive treatment with a very favorable outcome - a cure rate of 85% to 90%. In this category are children between the ages of two and ten with certain other favorable features at diagnosis such as low white count, a particular morphologic appearance of the leukemic cells under the microscope, presence of certain antigens on the surface of the leukemia cells which lead to a classification of so-called "early pre-B cell ALL," and an overabundance of chromosome material within each leukemia cell, termed "hyperdiploidy" of the DNA content with no other chromosome aberrations. About 20% of children with ALL are in this very favorable category.

Children under two years of age and over ten years of age generally have a more biologically aggressive form of ALL, requiring more intensive therapy and with increased likelihood of relapsing in the bone marrow or in so-called "sanctuary sites," such as the central nervous system or testicles. ALL in children between the ages of two and ten can also behave very aggressively, especially if it is associated with a high white count, large burden of leukemia outside the bone marrow (lymphomatous involvement), and/or certain unfavorable cytogenetic abnormalities in the leukemic cells. Overall, up to 70% of children and adolescents with ALL may be cured using current therapeutic regimens.

AML is actually more common than ALL in the first few months of life despite the fact that it occurs much less frequently than ALL throughout childhood and adolescence. AML is generally more resistant to chemotherapy than ALL. There are eight subtypes of AML, each of which has special clinical and laboratory features. The distinguishing clinical features vary from tendency to have bulky disease outside the bone marrow such as the central nervous system and skin, to bleeding tendencies and response to particular therapies. Examples of laboratory variations at diagnosis include different degrees of white count elevation, the presence of abnormalities in coagulation parameters, distinctive morphologic features of the leukemic cells under the microscope, and distinct non-random patterns of chromosome abnormalities in the leukemic cells. Chemotherapy in general must be much more intensive to optimize the chance for a favorable outcome, unfortunately resulting in greater side effects.

Even with current modern approaches to treatment, long-term survival tantamount to cure is achievable in only about 40% of children and adolescents with AML. Treatment of young people with this type of leukemia may involve a bone marrow transplant in early first remission, especially if there is an identically matched (histocompatible) sibling.

Because AML encompasses such a heterogeneous group of leukemias, progress in the future will most likely involve tailoring treatment to each individual subtype. Thus, the treatment of patients with certain subtypes may involve the use of only chemotherapy or the addition of biologic agents such as retinoic acid or Interleukin-2 and the treatment of other subtypes may include early bone marrow transplantation.

If there is recurrence or relapse of disease in a child or adolescent with ALL or AML who has not previously been transplanted, some form of bone marrow transplantation is usually recommended to offer the best possible chance of cure. In such a situation, if a fully matched (histocompatible) sibling donor is not available, a matched unrelated donor or mismatched related donor is considered if a second remission of the leukemia can be achieved.

Although progress in treatment of acute leukemia in children and adolescents has been substantial over the past few decades, there is considerable need for further improvement in outcome. Additionally, minimizing the long-term sequelae of treatment of young people is also of great importance. It is likely that additional improvements in therapy, perhaps even methods of preventing certain forms of childhood leukemia, will come only after careful, systematic clinical investigations and close collaboration with basic researchers wherein mechanisms of malignant transformation and response to chemotherapeutic/biologic agents can be better understood. Toward this end, treatment on cooperative group protocols (such as protocols originating from the Children's Cancer Group or Pediatric Oncology Group) is recommended to offer the most modern therapeutic approach as well as the opportunity for dedicated clinical and basic science researchers to collaborate in improving therapy for the future.

Lorrie F. Odom, M.D. is a Professor of Pediatrics at the University of Colorado Health Sciences Center, Department of Pediatrics, Denver, Colorado USA, and Director, Clinical Oncology, The Children's Hospital, Denver. In addition, Dr. Odom serves as Principal Investigator, the largest cooperative group of pediatric cancer centers in the USA, with headquarters in Los Angeles, California. She is Board Certified by the American Board of Pediatrics and the American Board of Pediatric Hematology-Oncology, and a member of the American Society of Clinical Oncology and the American Society of Pediatric Hematology-Oncology.

For additional information on leukemia, go to:

http://cancer.med.upenn.edu/disease/leukemia/
OncoLink, Pediatric Leukemias, at The University of Pennsylvania

Or contact: The Leukemia Society of America, Inc., Toll-free National Resource Line:
1-800-955-4LSA

733 Third Avenue
New York, NY 10017
(212) 573-8484

American Cancer Society, 1-800-ACS-2345
1599 Clifton Road, NE
Atlanta, Georgia 30329-4251
http://www.cancer.org/

For further reading:

The Cure of Childhood Leukemia: Into the Age of Miracles, by John Laszlo, M.D., American Cancer Society National Vice President for Research (1995, Rutgers University Press). To order the book, contact your local bookstore, or Rutgers Press at 1-800-446-9323. All royalties from sale of the book will be donated to the American Cancer Society.

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