Risk factors for impaired pulmonary function and cardiorespiratory fitness in very long-term adult survivors of childhood acute lymphoblastic leukemia after treatment with chemotherapy only

Acta Oncol. 2018 May;57(5):658-664. doi: 10.1080/0284186X.2017.1423177. Epub 2018 Jan 5.


Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk of late treatment-related side-effects. Data regarding prevalence and risk factors for impairments in pulmonary function and cardiorespiratory fitness are limited, and reported findings are inconsistent and inconclusive.

Material and methods: In a cross-sectional study, 116 ALL survivors (median 5 years at diagnosis, 29 years at follow-up, 53% females) were examined, median 23 years after treatment with chemotherapy only. Individual cumulative doses of cytostatic agents were calculated. Methods included blood tests, echocardiography, pulmonary function tests and cardiorespiratory exercise test.

Results: Females had lower % predicted gas diffusing capacity (DLCO) than males (mean [SD] 84 [13] versus 97 [14], p < .001). Impairment in DLCO was found in 34% females versus 7% males, p < .001. In a multiple linear regression model, female gender, body mass index (BMI) and smoking were risk factors for reduced % predicted DLCO, with a borderline significant effect of left ventricular ejection fraction (LVEF). Impaired cardiorespiratory fitness was found in 42% of the survivors, with a borderline increased risk in females, p = .06. Smoking and BMI were risk factors for reduced % predicted VO2peak. Subjects exposed to anthracyclines had lower LVEF% and % predicted VO2peak than those not exposed, (mean [SD] 56.2 [4.3] versus 59.2 [5.2], p = .01 and 86.9 [18.4] versus 92.8 [18.4], p = .03, respectively).

Conclusions: Impairments in pulmonary function and cardiorespiratory fitness are common in very long-term survivors of childhood ALL. Risk factors are female gender, BMI and smoking. In order to preserve pulmonary function and cardiorespiratory fitness, we suggest increased attention and targeted advice on modifiable lifestyle factors such as smoking, inactivity and overweight.

MeSH terms

  • Adolescent
  • Adult
  • Anthracyclines / adverse effects
  • Antineoplastic Agents / adverse effects*
  • Cardiorespiratory Fitness*
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Cyclophosphamide / adverse effects
  • Echocardiography
  • Exercise Test
  • Female
  • Humans
  • Infant
  • Male
  • Methotrexate / adverse effects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Respiratory Function Tests
  • Respiratory Physiological Phenomena / drug effects*
  • Risk Factors
  • Survivors
  • Vincristine / adverse effects
  • Young Adult


  • Anthracyclines
  • Antineoplastic Agents
  • Vincristine
  • Cyclophosphamide
  • Methotrexate