Survivorship and Adverse Late Sequelae
While the issues of long term complications of cancer and its treatment cross many disease categories, there are several important issues that relate to the treatment of myeloid malignancies that are worth stressing. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information.)
In a review from one institution, the highest frequency of adverse long-term sequelae for children treated for acute myeloid leukemia (AML) included the following incidence rates: growth abnormalities (51%), neurocognitive abnormalities (30%), transfusion acquired hepatitis (28%), infertility (25%), endocrinopathies (16%), restrictive lung disease (20%), chronic graft-versus-host disease (20%), secondary malignancies (14%), and cataract (12%).[1] Of note is that most of these adverse sequelae are the consequence of myeloablative, allogeneic, hematopoietic stem cell transplantation. Although cardiac abnormalities were reported in only 8% of patients, this is an issue that may be particularly relevant with the current use of increased anthracyclines in clinical trials for children with newly diagnosed AML. For children who were treated with hematopoietic stem cell transplantation for acute leukemias when they were younger than 3 years, growth disturbances and dyslipidemias were the most frequently observed late sequelae (about 60%), while quality of life and intelligence scores were in the normal range.[2] Cardiomyopathy has been reported in 4.3% of survivors of AML based on Berlin-Frankfurt-Munster studies. Of these, 2.5% showed clinical symptoms.[3] Retrospective analysis of a single study suggests cardiac risk may be increased in children with Down syndrome, but prospective studies are required to confirm this finding.[4] New therapeutic approaches to reduce long-term adverse sequelae are needed, but without reducing the antileukemic efficacy of treatment as relapsed leukemia is still the primary cause of death in patients with AML.
References
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Leung W, Hudson MM, Strickland DK, et al.: Late effects of treatment in survivors of childhood acute myeloid leukemia. J Clin Oncol 18 (18): 3273-9, 2000.
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Perkins JL, Kunin-Batson AS, Youngren NM, et al.: Long-term follow-up of children who underwent hematopoeitic cell transplant (HCT) for AML or ALL at less than 3 years of age. Pediatr Blood Cancer 49 (7): 958-63, 2007.
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Creutzig U, Diekamp S, Zimmermann M, et al.: Longitudinal evaluation of early and late anthracycline cardiotoxicity in children with AML. Pediatr Blood Cancer 48 (7): 651-62, 2007.
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O'Brien MM, Taub JW, Chang MN, et al.: Cardiomyopathy in children with Down syndrome treated for acute myeloid leukemia: a report from the Children's Oncology Group Study POG 9421. J Clin Oncol 26 (3): 414-20, 2008.
[PUBMED Abstract]
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