General Information
The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.
Cancer in children and adolescents is rare. Children and adolescents with
cancer should be referred to medical centers that have a multidisciplinary team
of cancer specialists with experience treating the cancers that occur during
childhood and adolescence. This multidisciplinary team approach incorporates the skills
of the primary care physician, pediatric surgical subspecialists, radiation
oncologists, pediatric medical oncologists/hematologists, rehabilitation
specialists, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation
that will achieve optimal survival and quality of life. (Refer to the PDQ Supportive Care summaries for specific information about supportive care for children and adolescents with cancer.)
Guidelines for
pediatric cancer centers and their role in the treatment of pediatric patients
with cancer have been outlined by the American Academy of Pediatrics.[1] Since
treatment of children with acute lymphoblastic leukemia (ALL) entails many potential complications and
requires intensive supportive care (e.g., transfusions; management of infectious
complications; and emotional, financial, and developmental support), this
treatment is best coordinated by pediatric oncologists and performed in cancer
centers or hospitals with all of the necessary pediatric supportive care
facilities. Specialized care is essential for all children with ALL, including
those for whom specific clinical and laboratory features might confer a
favorable prognosis. It is equally important that the
clinical centers and the specialists directing the patient’s care maintain
contact with the referring physician in the community. Strong lines of
communication optimize any urgent or interim care required when the child is at
home.
In recent decades, dramatic improvements in survival have been achieved in children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ Late Effects of Treatment for Childhood Cancer summary for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
ALL is the most common cancer diagnosed in children and represents 23% of cancer
diagnoses among children younger than 15 years. ALL occurs at an
annual rate of approximately 30 to 40 per million.[2] There are approximately 2,400
children and adolescents younger than 20 years diagnosed with ALL each
year in the United States,[3] and there has been a gradual increase in the incidence of ALL in the past 25 years.[4,5] A sharp peak in ALL incidence is observed among
children aged 2 to 3 years (>80 per million per year), with rates decreasing
to 20 per million for ages 8 to 10 years. The incidence of ALL among children
aged 2 to 3 years is approximately fourfold greater than that for infants and
is nearly tenfold greater than that for adolescents who are 19 years old. For
unexplained reasons, the incidence of ALL is substantially higher in white
children than in black children, with a nearly threefold higher incidence from age 2
to 3 years in white children compared with black children.[3] The incidence of ALL appears to be highest in Hispanic children (43 per million).[6]
There are few identified factors associated with an increased risk of ALL.[3] The
primary accepted nongenetic risk factors for ALL are prenatal exposure to
x-rays and postnatal exposure to high doses of radiation (e.g., therapeutic
radiation as previously used for conditions such as tinea capitis and thymus
enlargement).[7] Children with Down syndrome have increased risk of
developing both ALL [8] and acute myeloid leukemia (AML),[9] with a cumulative risk of
developing leukemia of approximately 2.1% by age 5 years and 2.7% by age 30
years.[10] Approximately one-half to two-thirds of the cases of acute leukemia in children
with Down syndrome are ALL. Patients with ALL and Down syndrome have a lower incidence of both favorable and unfavorable cytogenetic findings and a lower incidence of T-cell phenotype.[8,10-13] While the vast majority of cases of AML in children with Down syndrome occur before the age of 4 years (median age, 1 year),[10,13] ALL in children with Down syndrome has an age distribution similar to that of ALL in non–Down syndrome children, with a median age of 3 to 4 years.[10,13] Outcome in Down syndrome children with ALL has generally been reported as poorer than that of non–Down syndrome children.[11,12,14] The lower event-free survival and overall survival in children with Down syndrome appear to be related to higher rates of treatment-related mortality, especially during induction therapy,[12,13] and to the absence of favorable biological features.[13,11] Increased occurrence of ALL is also associated
with certain genetic conditions, including neurofibromatosis,[15] Shwachman
syndrome,[16,17] Bloom syndrome,[18] and ataxia telangiectasia.[19]
Many cases of ALL that develop in children have a prenatal origin. Evidence in support of this comes from the observation that the immunoglobulin or T-cell receptor antigen rearrangements that are unique to each patient’s leukemia cells can be detected in blood samples obtained at birth.[20,21] Similarly, there are data to support that patients with ALL characterized by specific chromosomal abnormalities had blood cells carrying the abnormalities at the time of birth.[20-22] Genetic studies of identical twins with concordant leukemia further support the prenatal origin of some leukemias.[23]
Among children with ALL, more than 95% attain remission and 75% to 85% survive free of leukemia recurrence at least 5 years from
diagnosis with current treatments that incorporate systemic therapy (e.g.,
combination chemotherapy) and specific central nervous system preventive
therapy (i.e., intrathecal chemotherapy with or without cranial
radiation).[2,3,24-27][Level of evidence: 2Di][28-32]
Despite the treatment advances noted in childhood ALL, numerous important
biologic and therapeutic questions remain to be answered to achieve
the goal of curing every child with ALL. The systematic investigation of these
issues requires large clinical trials, and the opportunity to participate in
these trials is offered to most patients/families. Clinical trials for
children and adolescents with ALL are generally designed to compare potentially
better therapy with therapy that is currently accepted as standard. Much of
the progress made in identifying curative therapies for childhood ALL and other
childhood cancers has been achieved through investigator-driven discovery, tested in carefully randomized, controlled clinical trials.[33,34]
Information about ongoing clinical trials is available from the NCI
Web site.
References
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Yagi T, Hibi S, Tabata Y, et al.: Detection of clonotypic IGH and TCR rearrangements in the neonatal blood spots of infants and children with B-cell precursor acute lymphoblastic leukemia. Blood 96 (1): 264-8, 2000.
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Greaves MF, Wiemels J: Origins of chromosome translocations in childhood leukaemia. Nat Rev Cancer 3 (9): 639-49, 2003.
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