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Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment (PDQ®): Treatment - Health Professional Information [NCI] - 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).[1] 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.[2] Retrospective analysis of a single study suggests cardiac risk may be increased in children with Down syndrome,[3] but prospective studies are required to confirm this finding.

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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%).[4] 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.[5] 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.[6] 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.

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