Do quality of life or physical function at diagnosis predict short-term outcomes during intensive chemotherapy in AML?

BACKGROUND: Intensive chemotherapy (IC) used to treat acute myeloid leukemia (AML) is associated with toxicity, particularly in older adults. Emerging data suggest that baseline quality of life (QOL) and physical function may predict outcomes in oncology, although data in AML are limited. We investigated the association between baseline QOL and physical function with short-term treatment outcomes in adults and elderly AML patients. MATERIALS AND METHODS: We conducted a prospective, longitudinal study of adults (age 18+) AML patients undergoing IC. Before starting IC, patients completed the European Organisation for the Research and Treatment of Cancer (EORTC) 30-item questionnaire (QLQ-C30) and Functional Assessment of Cancer Therapy Fatigue subscale (FACT-Fatigue) in addition to physical function tests (grip strength, timed chair stands, 2-min walk test). Outcomes included 60-day mortality, intensive care unit (ICU) admission and achievement of complete remission (CR). Logistic regression was carried out to evaluate each outcome. RESULTS: Of the 239 patients (median age 57.5 years), 56.7% were male and median Charlson comorbidity score was 0. Sixty-day mortality, ICU admission and CR occurred in 9 (3.7%), 15 (6.3%) and 167 (69.9%) patients, respectively. Using univariate regression, neither QOL nor physical function at presentation was predictive of 60-day mortality (all P > 0.05), whereas ICU admission (P < 0.001) and remission status at 30 days (P = 0.007) were. Fatigue (P = 0.004) and role functioning (P = 0.003) were predictors of ICU admission; QOL and physical function were not. A higher Charlson score predicted ICU admission (P = 0.01) and remission status (P = 0.002). The cytogenetic risk group was associated with achievement of CR (P = 0.02); QOL and physical function were not (all P > 0.05). Findings were similar when patients age 60+ were examined. Relationships between fatigue and role functioning with ICU admission deserve further exploration. CONCLUSIONS: Baseline QOL and physical function tests in this prospective study were not associated with short-term mortality, ICU admission or achievement of CR after the first cycle of chemotherapy.

Changes in bone mineral density in men starting androgen deprivation therapy and the protective role of vitamin D.

SUMMARY: Androgen deprivation therapy in 80 men was associated with declines in bone mineral density (BMD), which were greatest in the first year, and in the lumbar spine compared to controls. Vitamin D use was associated with improved BMD in the lumbar spine and in the first year. INTRODUCTION: Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased risk of fractures. Although loss of BMD appears to be greatest within the first year of starting ADT, there are few long-term studies of change in BMD, and risk factors for bone loss are not well-characterized. METHODS: Men aged 50+ with nonmetastatic prostate cancer starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual-energy x-ray absorptiometry at baseline and yearly for 3 years. Matched controls were men with prostate cancer not receiving ADT. Multivariable regression analysis examined predictors of BMD loss. RESULTS: Eighty ADT users and 80 controls were enrolled (mean age 69 years); 52.5 % had osteopenia and 8.1 % had osteoporosis at baseline. After 1 year, in adjusted models, ADT was associated with significant losses in lumbar spine BMD compared to controls (-2.57 %, p = 0.006), with a trend towards greater declines at the total hip (p = 0.09). BMD changes in years 2 and 3 were much smaller and not statistically different from controls. Use of vitamin D but not calcium was associated with improved BMD in the lumbar spine in year 1 (+6.19 %, p < 0.001) with smaller nonsignificant increases at other sites (+0.86 % femoral neck, +0.86 % total hip, p > 0.10) primarily in the first year. CONCLUSIONS: Loss of BMD associated with ADT is greatest at the lumbar spine and in the first year. Vitamin D but not calcium may be protective particularly in the first year of ADT use.

Long-term recovery of quality of life and physical function over three years in adult survivors of acute myeloid leukemia after intensive chemotherapy.

We previously described impairments in quality of life (QOL) and physical function among acute myeloid leukemia (AML) survivors between diagnosis and 1 year. The aim of the current study is to describe and compare to normative data QOL and physical function recovery over 3 years from diagnosis and treatment with intensive chemotherapy (IC). At assessments done at baseline (pre-IC) and at 11 time points over 3 years, QOL, fatigue, and 3 physical performance measures (PPMs; grip strength, 6-min walk test (6MWT), and timed chair stands) were collected. Long-term recovery was defined by reaching scores within the minimum clinically important difference of normative data. Global QOL recovery was seen in 79% at 1 year, 75% at 2 years, and 86% at 3 years. At 3 years, the QLQ-C30 subscales with the greatest recovery were physical and emotional functioning. For FACT-fatigue, recovery was seen in 68% at 1 year and 77% at 3 years. Recovery on PPMs was poorer on average, with only 17% on the 6MWT and 42% in grip strength returning to normal at 3 years. The vast majority of AML survivors after IC achieve recovery in QOL and fatigue by three years. However, recovery in physical performance remained blunted.

A phase II exercise randomized controlled trial for patients with acute myeloid leukemia undergoing induction chemotherapy.

Curative treatment for acute myeloid leukemia (AML) involves induction chemotherapy (IC) which is associated with bed rest and toxicities, leading to worsening quality of life (QOL), fatigue, and fitness. Exercise during IC may ameliorate declines but has not been rigorously tested. We examined the efficacy of supervised exercise during IC on QOL, fatigue, and fitness. Eighty-three inpatients age 18-80 scheduled to receive IC for newly diagnosed or relapsed AML were randomized 2:1 (exercise intervention:control group). Study measures were completed at baseline, post-IC, and following the first cycle of consolidation. The intervention consisted of a supervised mixed-modality, moderate-intensity exercise program (4-5 days per week, 30-60min per session) throughout admission. Recruitment was good (56%), retention excellent (96%), and adherence was 54%. Global QOL improved similarly in both groups from baseline to post-IC (between-group difference 3.0 points, p=0.62). Fatigue improved in the exercise group from baseline to post-IC (potentially clinically important between-group difference of 3.6 points, p=0.23). Aerobic fitness, lower body strength, and grip strength improved in the exercise group (between-group differences p=0.005, p<0.001, p=0.03, respectively). Supervised exercise for patients with AML undergoing IC is feasible, safe, and appears effective at improving fitness and possibly fatigue. A larger trial is warranted.

Older age is associated with similar quality of life and physical function compared to younger age during intensive chemotherapy for acute myeloid leukemia.

We examined the quality of life (QOL) and physical function over the first three cycles of intensive chemotherapy in 103 newly diagnosed younger (18-59 years, n=64) and older adults (age 60 or older, n=39) with acute myeloid leukemia. Both QOL and physical function were worse than normative data. QOL was fairly stable over time and similar in both age groups, whereas physical function generally improved over time, although the improvement was somewhat greater in younger than older adults. Compared to younger adults, older adults tolerate intensive chemotherapy quite well from QOL and physical function perspectives.

Levels of sex hormones have limited effect on cognition in older men with or without prostate cancer.

Androgen deprivation therapy is commonly used to treat prostate cancer, but by lowering testosterone levels it may affect cognitive function. However, the relationship between testosterone and cognition remains unclear. We examined the relationship between sex hormones (total testosterone, bioavailable testosterone, and estradiol) and cognition in a cross-sectional study of 198 older men (mean age 69.2 years, median education 16 years) with and without prostate cancer, none of who had started androgen deprivation therapy. We found relationships between total testosterone and two of four measures of working memory. Similar relationships were found in regression analyses adjusted for age and education with both total testosterone and estradiol. Neither hormone was related to other cognitive domains, nor was bioavailable testosterone level. Although cognitive function was not generally related to sex hormone levels in older men, there may be a weak association with working memory. These results may help guide future studies.