Childhood Acute Myeloid Leukemia Treatment (Professional) (cont.)
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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.)
The Children's Cancer Survivor Study examined 272 survivors of childhood acute myeloid leukemia (AML) who did not undergo a hematopoietic stem cell transplant (HSCT). This study identified second malignancies (cumulative incidence, 1.7%) and cardiotoxicity (cumulative incidence, 4.7%) as significant long-term risks. Cardiomyopathy has been reported in 4.3% of survivors of AML based on Berlin-Frankfurt-Munster studies. Of these, 2.5% showed clinical symptoms. 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.
In a review from one institution, the highest frequency of adverse long-term sequelae for children treated for 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 cataracts (12%). It is noted that most of these adverse sequelae are the consequence of myeloablative, allogeneic HSCT. Although cardiac abnormalities were reported in 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. Another study examined outcomes for children younger than 3 years with AML or acute lymphoblastic leukemia (ALL) who underwent HSCT. The toxicities reported include growth hormone deficiency (59%), dyslipidemias (59%), hypothyroidism (35%), osteochondromas (24%), and decreased bone mineral density (24%). Two of the 33 patients developed secondary malignancies. Of note, survivors had average intelligence but frequent attention-deficit problems and fine-movement abnormalities compared with population controls. In contrast, The Bone Marrow Transplant Survivor Study compared childhood AML or ALL survivors with siblings using a self-reporting questionnaire. The median follow-up was 8.4 years and 86% of patients received total-body irradiation (TBI) as part of their preparative transplant regimen. Compared with siblings, survivors of leukemia who received an HSCT had significantly higher frequencies of several adverse effects, including diabetes, hypothyroidism, osteoporosis, cataracts, osteonecrosis, exercise-induced shortness of breath, neurosensory impairments and problems with balance, tremor, and weakness. The overall assessment of health was significantly decreased in survivors compared with siblings (odds ratio = 2.2; P = .03). Significant differences were not observed between regimens using TBI compared with chemotherapy only, which mostly included busulfan. The outcomes were similar for patients with AML and ALL, suggesting that the primary cause underlying the adverse late effects was undergoing an HSCT.
A population-based study of survivors of childhood AML who had not undergone an HSCT reported equivalent rates of educational achievement, employment, and marital status compared with siblings. AML survivors were, however, significantly more likely to be receiving prescription drugs, especially for asthma, compared with siblings (23% vs. 9%; P = .03). Chronic fatigue has also been demonstrated to be a significantly more likely adverse late effect in survivors of childhood AML than in survivors of other malignancies.
New therapeutic approaches to reduce long-term adverse sequelae are needed, especially for reducing the late sequelae associated with myeloablative HSCT.
Important resources for details on follow-up and risks for survivors of cancer have been developed by the Children Oncology Group's Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers and the National Comprehensive Cancer Network (NCCN) Guidelines for Acute Myeloid Leukemia. Furthermore, having access to past medical history that can be shared with subsequent medical providers has become increasingly recognized as important for cancer survivors. Different templates that address this issue are available, such as those from the Cancer Survivor's Treatment Record and the Cancer Survivor's Medical Treatment Summary.
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