Kevin C. Oeffinger, MD Debra A. Eshelman, RN, MSN, CPNP Gail E. Tomlinson, MD, PhD Michael Tolle, MD Gregory W. Schneider, MD Dallas, Texas Submitted, revised, August 27, 2000. From the Department of Family Practice and Community Medicine (K.C.O., M.T., G.W.S.), the Center for Cancer and Blood Disorders (D.A.E.), and the Department of Pediatrics, Division of Hematology-Oncology (G.E.T.), the University of Texas Southwestern Medical Center at Dallas, and Children’s Medical Center of Dallas, the After the Cancer Experience (ACE) Young Adult Program. Reprint requests should be addressed to Kevin C. Oeffinger, MD, the University of Texas Southwestern Medical Center at Dallas, Department of Family Practice and Community Medicine, 5323 Harry Hines Blvd, Dallas, TX 75390-9067. E-mail: kevin.oeffinger@email.swmed.edu.
References
Obesity in ALL survivors may be due in part to reduced physical activity. In a small cross-sectional study with sibling controls, ALL survivors had decreased activity levels and total daily energy expenditures that correlated with their percentage of body fat.41 Maximal and submaximal exercise capacity were reduced in another cross-sectional study.42 Similarly, in a study of 53 ALL survivors with a longer interval from ALL diagnosis (mean=10.5 years), 25% and 31%, respectively, were unable to reach normal maximal oxygen uptake and normal oxygen uptake at the anaerobic threshold.43
Changes in gross motor skills may also affect the physical activity level of ALL survivors. Balance, strength, running speed and agility, and hand grip strength were decreased in a cohort of 36 ALL survivors with a median age of 9.3 years.44 In a follow-up of this cohort, Wright and coworkers45 reported that the ALL survivors had significantly less active and passive dorsiflexion range of motion of the ankle than did controls. Younger age at diagnosis and female sex were significant predictors, while treatment with CRT did not increase risk. These studies suggest that ALL survivors should be assessed for gross motor deficits that might alter exercise choices.
In the general population, obesity and physical inactivity are risk factors for cardiovascular disease. Obesity (an especially important risk factor during young adulthood) enhances the development of hypertension, dyslipidemia, and insulin resistance.46-48 Because the median age of ALL survivors is still relatively young, there are no cohort or case-control studies evaluating the treatment-related risk of premature onset of coronary artery disease. Talvensaari and coworkers40 reported that 50 childhood cancer survivors (including 28 ALL survivors) had an increased risk of fasting hyperinsulinemia and reduced high-density lipoprotein (HDL) cholesterol compared with 50 age- and sex-matched controls. Eight of the cancer survivors with reduced spontaneous growth hormone (GH) secretion (4/8 had received CRT) had obesity, hyperinsulinemia, and reduced HDL cholesterol, fitting the criteria for cardiac dysmetabolic syndrome, a clustering of metabolic problems associated with a markedly increased risk of cardiovascular disease.49
Studies of noncancer populations may shed light on the cardiovascular risk of ALL survivors with GH deficiency. Hypopituitarism with GH deficiency in adults is associated with increased vascular mortality.50-52 Adults with GH deficiency also have an increased prevalence of dyslipidemia53,54 and insulin resistance,55 that may improve with GH therapy.56,57
Counseling on the benefits of proper diet and exercise is an important component of long-term care for ALL survivors. Periodic analysis of lipoproteins has not been prospectively studied in ALL survivors, but the US Preventive Services Task Force states that adolescents and young adults who have major risk factors for cardiovascular disease should be screened.58
Psychosocial well-being of all survivors
The long-term psychosocial welfare of ALL survivors is complex. A population-based sibling-matched control study of 93 ALL survivors who were at least 15 years postdiagnosis showed no difference in quality of life or mental health.59 Similarly, no differences were found in symptoms of anxiety and posttraumatic stress in 130 leukemia survivors and 155 controls.60 In contrast, a large cooperative study of the Children’s Cancer Group and the National Institutes of Health evaluated 580 adult survivors and 396 sibling controls and reported that survivors had greater negative mood and reported more tension, depression, anger, and confusion.61 Female, minority, and unemployed survivors reported the highest total mood disturbance. Issues related to late effects, especially cognitive dysfunction, obesity, and physical inactivity, may have an impact on the mental health of survivors.
Few data are available on the risk behavior of ALL survivors. In a cohort study of 592 young adult ALL survivors and 409 sibling controls, Tao and colleagues62 reported that ALL survivors were less likely to start smoking, but once they started they were no more likely to quit than their siblings. Fourteen percent of the ALL survivors were smokers. Although no prospective studies have evaluated the effect of smoking on the incidence and severity of late effects of ALL treatment, it will have an impact on survivors with cardiovascular risk factors, restrictive pulmonary disease, and osteopenia. Counseling on smoking cessation is imperative in the long-term health care of ALL survivors.
Osteopenia and osteoporosis
Several well-designed small to medium-size cross-sectional studies of childhood cancer survivors63-65 and ALL survivors66-71 with median ages at evaluation ranging from 12 to 25 years consistently showed reduction in bone mineral density, bone mass content (BMC), and/or age-adjusted bone mass. Age at diagnosis, interval since treatment, sex, and cumulative dosages of MTX and corticosteroids have not been consistently associated with reduction in bone mass. In contrast, CRT has consistently been identified as a risk factor, although the 3 studies that evaluated GH status showed variation in the relationship of GH deficiency and reduced bone mass.69-71 Impairment of peak bone mass is likely multifactorial in etiology, with predisposing risk factors including altered bone metabolism at the time of onset of leukemia, interference in bone metabolism by corticosteroids and MTX, and impaired bone growth and skeletal maturation caused by pituitary dysfunction/GH deficiency. In an ongoing prospective cohort study, Atkinson and coworkers72 reported that by 6 months of therapy for ALL, 64% of the children had a reduction from baseline measures of BMC, and by the end of 2 years of therapy 83% were osteopenic. Hypomagnesemia due to renal wasting of magnesium after treatment with high-dose corticosteroids and/or aminoglycosides was associated with the progression in changes and may be a key factor in the alteration of bone metabolism.
