Survivorship and Adverse Late Sequelae of Treatment for AML

Cardiac.

Cardiac.

The Childhood Cancer Survivor Study (CCSS) examined 272 survivors of childhood AML who did not undergo an HSCT.[1]

Cardiac. › The Childhood Cancer Survivor Study (CCSS) examined 272 survivors of childhood AML who did not undergo an HSCT.[1]

This study identified second malignancies (cumulative incidence, 1.7%) and cardiac toxic effects (cumulative incidence, 4.7%) as significant long-term risks.

Cardiac. › The Childhood Cancer Survivor Study (CCSS) examined 272 survivors of childhood AML who did not undergo an HSCT.[1]

Cardiomyopathy has been reported in 4.3% of survivors of AML based on Berlin-Frankfurt-Münster studies. Of these, 2.5% showed clinical symptoms.[2]

Cardiac.

A retrospective study examined cardiac function in children treated with United Kingdom Medical Research Council–based regimens at a median of 13 months after treatment.[3]

Cardiac. › A retrospective study examined cardiac function in children treated with United Kingdom Medical Research Council–based regimens at a median of 13 months after treatment.[3]

There was a mean detrimental change in left ventricular stroke volume of 8.4%, compared with baseline values.

Cardiac.

A retrospective study evaluated anthracycline-related cardiomyopathy in children treated for AML.[4]

Cardiac. › A retrospective study evaluated anthracycline-related cardiomyopathy in children treated for AML.[4]

For pediatric patients, the risk of developing early toxicity was 13.7%, and the risk of developing late cardiac toxic effects (defined as 1 year after completing first-line therapy) was 17.4%.

Cardiac. › A retrospective study evaluated anthracycline-related cardiomyopathy in children treated for AML.[4]

Early cardiotoxicity was a significant predictor of late cardiac toxic effects and the development of clinical cardiomyopathy requiring long-term therapy.

Cardiac.

Retrospective analysis of a single study suggests cardiac risk may be increased in children with Down syndrome,[5] but prospective studies are required to confirm this finding.

Psychosocial.

Psychosocial.

A Nordic Society for Pediatric Hematology and Oncology retrospective trial evaluated children with AML who were treated with chemotherapy only. The median follow-up was 11 years.[6]

Psychosocial. › A Nordic Society for Pediatric Hematology and Oncology retrospective trial evaluated children with AML who were treated with chemotherapy only. The median follow-up was 11 years.[6]

Based on self-reported uses of health care services, survivors demonstrated similar health care usage and marital status as their siblings.

Psychosocial.

A population-based study of survivors of childhood AML who had not undergone an HSCT reported the following:[7]

Psychosocial. › A population-based study of survivors of childhood AML who had not undergone an HSCT reported the following:[7]

Equivalent rates of educational achievement, employment, and marital status compared with siblings.

Psychosocial. › A population-based study of survivors of childhood AML who had not undergone an HSCT reported the following:[7]

AML survivors were significantly more likely to take prescription drugs, especially for asthma, than were siblings (23% vs. 9%; P = .03).

Psychosocial. › A population-based study of survivors of childhood AML who had not undergone an HSCT reported the following:[7]

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.

Psychosocial.

A CCSS report evaluated survivors of childhood AML treated between 1970 and 1999 (median age at the time of assessment, 30 to 32 years) and compared their outcomes to data from siblings.[8]

Psychosocial. › A CCSS report evaluated survivors of childhood AML treated between 1970 and 1999 (median age at the time of assessment, 30 to 32 years) and compared their outcomes to data from siblings.[8]

Survivors who received either intensive chemotherapy consolidation (n = 299) or underwent HSCT (n = 183) had statistically significant worse outcomes than did their siblings in somatic symptom measures (prevalence, 8.4%–12%), neurocognitive functioning (prevalence, 17.7%–25.7%), health-related quality-of-life measurements (prevalence, 8.2%–24.6%), and social attainment measures.

Psychosocial. › A CCSS report evaluated survivors of childhood AML treated between 1970 and 1999 (median age at the time of assessment, 30 to 32 years) and compared their outcomes to data from siblings.[8]

In all measures, there was no statistically significant difference in prevalence of problems identified between the two consolidation cohorts.

In a review from one institution, the highest frequency of adverse long-term sequelae for children treated for AML included the following:[10]

In a review from one institution, the highest frequency of adverse long-term sequelae for children treated for AML included the following:[10]

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%).

In a review from one institution, the highest frequency of adverse long-term sequelae for children treated for AML included the following:[10]

Most of these adverse sequelae are the consequence of myeloablative, allogeneic HSCT. Although cardiac abnormalities were reported in 8% of patients, this issue 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.[11]

Another study examined outcomes for children younger than 3 years with AML or acute lymphoblastic leukemia (ALL) who underwent HSCT.[11]

The toxicities reported include growth hormone deficiency (59%), dyslipidemias (59%), hypothyroidism (35%), osteochondromas (24%), and decreased bone mineral density (24%).

Another study examined outcomes for children younger than 3 years with AML or acute lymphoblastic leukemia (ALL) who underwent HSCT.[11]

Two of the 33 patients developed secondary malignancies.

Another study examined outcomes for children younger than 3 years with AML or acute lymphoblastic leukemia (ALL) who underwent HSCT.[11]

Compared with population controls, survivors had average intelligence but had frequent attention-deficit problems and fine-movement abnormalities.

In contrast, the Bone Marrow Transplant Survivor Study compared childhood AML or ALL survivors with siblings using a self-reporting questionnaire.[12] The median follow-up was 8.4 years, and 86% of patients received total-body irradiation (TBI) as part of their preparative transplant regimen.

In contrast, the Bone Marrow Transplant Survivor Study compared childhood AML or ALL survivors with siblings using a self-reporting questionnaire.[12] The median follow-up was 8.4 years, and 86% of patients received total-body irradiation (TBI) as part of their preparative transplant regimen.

Survivors of leukemia who received an HSCT had significantly higher frequencies of several adverse effects than did siblings. These effects included diabetes, hypothyroidism, osteoporosis, cataracts, osteonecrosis, exercise-induced shortness of breath, neurosensory impairments, and problems with balance, tremor, and weakness.

In contrast, the Bone Marrow Transplant Survivor Study compared childhood AML or ALL survivors with siblings using a self-reporting questionnaire.[12] The median follow-up was 8.4 years, and 86% of patients received total-body irradiation (TBI) as part of their preparative transplant regimen.

The overall assessment of health was significantly decreased in survivors compared with siblings (odds ratio, 2.2; P = .03).

In contrast, the Bone Marrow Transplant Survivor Study compared childhood AML or ALL survivors with siblings using a self-reporting questionnaire.[12] The median follow-up was 8.4 years, and 86% of patients received total-body irradiation (TBI) as part of their preparative transplant regimen.

Significant differences were not observed between regimens using TBI compared with chemotherapy only, which mostly included busulfan.

In contrast, the Bone Marrow Transplant Survivor Study compared childhood AML or ALL survivors with siblings using a self-reporting questionnaire.[12] The median follow-up was 8.4 years, and 86% of patients received total-body irradiation (TBI) as part of their preparative transplant regimen.

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 Children's Oncology Group (COG) study compared health-related quality-of-life outcomes in survivors of childhood AML.[13]

A Children's Oncology Group (COG) study compared health-related quality-of-life outcomes in survivors of childhood AML.[13]

Of 5-year survivors, 21% had a severe or life-threatening chronic health condition. When compared by type of treatment, this percentage was 16% for the chemotherapy-only group, 21% for the autologous HSCT group, and 33% for those who received an allogeneic HSCT.

A CCSS cohort analysis examined the long-term mortality and health statuses of 856 children (5-year survivors) previously treated for AML, with or without HSCT, between 1970 and 1999.[14]

A CCSS cohort analysis examined the long-term mortality and health statuses of 856 children (5-year survivors) previously treated for AML, with or without HSCT, between 1970 and 1999.[14]

Cumulative rates of grades 3 to 5 chronic health conditions significantly declined among HSCT recipients between the 1970s and 1990s (from 76.1% to 43.5%; P = .04) but remained stable for chemotherapy-only recipients (from 12.2% to 27.6%; P = .06).

A CCSS cohort analysis examined the long-term mortality and health statuses of 856 children (5-year survivors) previously treated for AML, with or without HSCT, between 1970 and 1999.[14]

There was a significant decrease in cumulative all-cause late mortality over the same time frame for HSCT recipients (from 38.9% to 8.5%; P < .0001). This decrease was primarily a result of a reduction in relapse, whereas no significant decrease in late mortality was seen in the chemotherapy-only survivors (from 38.9% to 8.5%; P < .0001).

A CCSS cohort analysis examined the long-term mortality and health statuses of 856 children (5-year survivors) previously treated for AML, with or without HSCT, between 1970 and 1999.[14]

In self-reports, health status among all survivors was excellent, very good, or good in 85% of HSCT recipients and in 90% of chemotherapy-only recipients. However, survivors' health status in both treatment groups was significantly worse than that of their siblings (hazard ratio [HR], 3.8; 95% confidence interval [CI], 2.7–5.4 vs. HR, 2.6; 95% CI, 1.8–3.6, respectively).