Near infrared spectroscopy (NIRS) as a new non-invasive tool to detect oxidative skeletal muscle impairment in children survived to acute lymphoblastic leukaemia

Francesca Lanfranconi, Luca Pollastri, Alessandra Ferri, Donatella Fraschini, Giuseppe Masera, Giuseppe Miserocchi, Francesca Lanfranconi, Luca Pollastri, Alessandra Ferri, Donatella Fraschini, Giuseppe Masera, Giuseppe Miserocchi

Abstract

Background: Separating out the effects of cancer and treatment between central and peripheral components of the O2 delivery chain should be of interest to clinicians for longitudinal evaluation of potential functional impairment in order to set appropriate individually tailored training/rehabilitation programmes. We propose a non-invasive method (NIRS, near infrared spectroscopy) to be used in routine clinical practice to evaluate a potential impairment of skeletal muscle oxidative capacity during exercise in children previously diagnosed with acute lymphoblastic leukaemia (ALL). The purpose of this study was to evaluate the capacity of skeletal muscle to extract O2 in 10 children diagnosed with ALL, 1 year after the end of malignancy treatment, compared to a control group matched for gender and age (mean±SD = 7.8±1.5 and 7.3±1.4 years, respectively).

Methods and findings: Participants underwent an incremental exercise test on a treadmill until exhaustion. Oxygen uptake ([Formula: see text]), heart rate (HR), and tissue oxygenation status (Δ[HHb]) of the vastus lateralis muscle evaluated by NIRS, were measured. The results showed that, in children with ALL, a significant linear regression was found by plotting [Formula: see text] vs Δ[HHb] both measured at peak of exercise. In children with ALL, the slope of the HR vs [Formula: see text] linear response (during sub-maximal and peak work rates) was negatively correlated with the peak value of Δ[HHb].

Conclusions: The present study proves that the NIRS technique allows us to identify large inter-individual differences in levels of impairment in muscle O2 extraction in children with ALL. The outcome of these findings is variable and may reflect either muscle atrophy due to lack of use or, in the most severe cases, an undiagnosed myopathy.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Individual and mean values of…
Figure 1. Individual and mean values of body mass index percentile (BMI) in ALL (n = 10) and CTRL (n = 10) children.
Statistical significance level was defined as p

Figure 2. Individual and mean values of…

Figure 2. Individual and mean values of relative to predicted in ALL (n = 10)…

Figure 2. Individual and mean values of relative to predicted in ALL (n = 10) and CTRL (n = 10) children.
Statistical significance level was defined as p

Figure 3. Individual skeletal muscle O 2…

Figure 3. Individual skeletal muscle O 2 extraction, Δ[HHb], expressed as the ratio of the…

Figure 3. Individual skeletal muscle O2 extraction, Δ[HHb], expressed as the ratio of the values obtained during limb ischemia, are presented for children with ALL as a function of speed.
CTRL values (thick line) are shown as mean±SE. Speed is expressed relative to peak value. Statistical significance level was defined as p

Figure 4. Regression between and skeletal muscle…

Figure 4. Regression between and skeletal muscle O 2 extraction at peak of exercise, Δ[HHb]…

Figure 4. Regression between and skeletal muscle O2 extraction at peak of exercise, Δ[HHb] peak, expressed as the ratio of the values obtained during limb ischemia for children with ALL (n = 10).
CTRL values are shown as mean±SE. Statistical significance level was defined as p

Figure 5. Individual regression for heart rate…

Figure 5. Individual regression for heart rate (HR) vs the corresponding for one ALL and…

Figure 5. Individual regression for heart rate (HR) vs the corresponding for one ALL and one CTRL child (A graph).
Regression between the individual slopes of the HR vs relationship, obtained in children with ALL (n = 10) and skeletal muscle O2 extraction at peak of exercise Δ[HHb]peak, expressed as the ratio of the values obtained during limb ischemia with the corresponding regression line (B graph). CTRL values are given as mean±SE. Statistical significance level was defined as p<0.05.
Similar articles
References
    1. Dama E, Rondelli R, De Rosa M, Aricò M, Carli M, et al. (2008) Patterns of domestic migration and access to childhood cancer care centres in Italy: a report from the hospital based registry of the Italian Association of Pediatric Haematology and Oncology (AIEOP). Eur J Canc 44: 2101–105. - PubMed
    1. Aricò M, Valsecchi MG, Rizzari C (2008) Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy. J Clin Oncol 26 (2) 283–9. - PubMed
    1. Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, et al. (2010) Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood 115 (16) 3206–14. - PubMed
    1. Benedetti G, Camnasio M, Fioredda F, Fraschini D, Haupt R, et al. (2003) A system for the informatics charge of the follow up of recovered cancer child. CILEA bulletin 86: 15–16.
    1. van Brussel M, Takken T, Lucia A, van der Net J, Helders PJM (2005) Is physical fitness decreased in survivors of childhood leukemia? A systematic review. Leukemia 19: 13–17. - PubMed
Show all 38 references
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All the sources of funding are related to the Department of health sciences of University of Milano-Bicocca. The senjor researcher, prof. G. Miserocchi, who provided this fund, was involved in study design and preparation of the manuscript.
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Figure 2. Individual and mean values of…
Figure 2. Individual and mean values of relative to predicted in ALL (n = 10) and CTRL (n = 10) children.
Statistical significance level was defined as p

Figure 3. Individual skeletal muscle O 2…

Figure 3. Individual skeletal muscle O 2 extraction, Δ[HHb], expressed as the ratio of the…

Figure 3. Individual skeletal muscle O2 extraction, Δ[HHb], expressed as the ratio of the values obtained during limb ischemia, are presented for children with ALL as a function of speed.
CTRL values (thick line) are shown as mean±SE. Speed is expressed relative to peak value. Statistical significance level was defined as p

Figure 4. Regression between and skeletal muscle…

Figure 4. Regression between and skeletal muscle O 2 extraction at peak of exercise, Δ[HHb]…

Figure 4. Regression between and skeletal muscle O2 extraction at peak of exercise, Δ[HHb] peak, expressed as the ratio of the values obtained during limb ischemia for children with ALL (n = 10).
CTRL values are shown as mean±SE. Statistical significance level was defined as p

Figure 5. Individual regression for heart rate…

Figure 5. Individual regression for heart rate (HR) vs the corresponding for one ALL and…

Figure 5. Individual regression for heart rate (HR) vs the corresponding for one ALL and one CTRL child (A graph).
Regression between the individual slopes of the HR vs relationship, obtained in children with ALL (n = 10) and skeletal muscle O2 extraction at peak of exercise Δ[HHb]peak, expressed as the ratio of the values obtained during limb ischemia with the corresponding regression line (B graph). CTRL values are given as mean±SE. Statistical significance level was defined as p<0.05.
Similar articles
References
    1. Dama E, Rondelli R, De Rosa M, Aricò M, Carli M, et al. (2008) Patterns of domestic migration and access to childhood cancer care centres in Italy: a report from the hospital based registry of the Italian Association of Pediatric Haematology and Oncology (AIEOP). Eur J Canc 44: 2101–105. - PubMed
    1. Aricò M, Valsecchi MG, Rizzari C (2008) Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy. J Clin Oncol 26 (2) 283–9. - PubMed
    1. Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, et al. (2010) Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood 115 (16) 3206–14. - PubMed
    1. Benedetti G, Camnasio M, Fioredda F, Fraschini D, Haupt R, et al. (2003) A system for the informatics charge of the follow up of recovered cancer child. CILEA bulletin 86: 15–16.
    1. van Brussel M, Takken T, Lucia A, van der Net J, Helders PJM (2005) Is physical fitness decreased in survivors of childhood leukemia? A systematic review. Leukemia 19: 13–17. - PubMed
Show all 38 references
Publication types
MeSH terms
Grant support
All the sources of funding are related to the Department of health sciences of University of Milano-Bicocca. The senjor researcher, prof. G. Miserocchi, who provided this fund, was involved in study design and preparation of the manuscript.
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM

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The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

Follow NCBI
Figure 3. Individual skeletal muscle O 2…
Figure 3. Individual skeletal muscle O2 extraction, Δ[HHb], expressed as the ratio of the values obtained during limb ischemia, are presented for children with ALL as a function of speed.
CTRL values (thick line) are shown as mean±SE. Speed is expressed relative to peak value. Statistical significance level was defined as p

Figure 4. Regression between and skeletal muscle…

Figure 4. Regression between and skeletal muscle O 2 extraction at peak of exercise, Δ[HHb]…

Figure 4. Regression between and skeletal muscle O2 extraction at peak of exercise, Δ[HHb] peak, expressed as the ratio of the values obtained during limb ischemia for children with ALL (n = 10).
CTRL values are shown as mean±SE. Statistical significance level was defined as p

Figure 5. Individual regression for heart rate…

Figure 5. Individual regression for heart rate (HR) vs the corresponding for one ALL and…

Figure 5. Individual regression for heart rate (HR) vs the corresponding for one ALL and one CTRL child (A graph).
Regression between the individual slopes of the HR vs relationship, obtained in children with ALL (n = 10) and skeletal muscle O2 extraction at peak of exercise Δ[HHb]peak, expressed as the ratio of the values obtained during limb ischemia with the corresponding regression line (B graph). CTRL values are given as mean±SE. Statistical significance level was defined as p<0.05.
Similar articles
References
    1. Dama E, Rondelli R, De Rosa M, Aricò M, Carli M, et al. (2008) Patterns of domestic migration and access to childhood cancer care centres in Italy: a report from the hospital based registry of the Italian Association of Pediatric Haematology and Oncology (AIEOP). Eur J Canc 44: 2101–105. - PubMed
    1. Aricò M, Valsecchi MG, Rizzari C (2008) Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy. J Clin Oncol 26 (2) 283–9. - PubMed
    1. Conter V, Bartram CR, Valsecchi MG, Schrauder A, Panzer-Grumayer R, et al. (2010) Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood 115 (16) 3206–14. - PubMed
    1. Benedetti G, Camnasio M, Fioredda F, Fraschini D, Haupt R, et al. (2003) A system for the informatics charge of the follow up of recovered cancer child. CILEA bulletin 86: 15–16.
    1. van Brussel M, Takken T, Lucia A, van der Net J, Helders PJM (2005) Is physical fitness decreased in survivors of childhood leukemia? A systematic review. Leukemia 19: 13–17. - PubMed
Show all 38 references
Publication types
MeSH terms
Grant support
All the sources of funding are related to the Department of health sciences of University of Milano-Bicocca. The senjor researcher, prof. G. Miserocchi, who provided this fund, was involved in study design and preparation of the manuscript.
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 4. Regression between and skeletal muscle…
Figure 4. Regression between and skeletal muscle O2 extraction at peak of exercise, Δ[HHb] peak, expressed as the ratio of the values obtained during limb ischemia for children with ALL (n = 10).
CTRL values are shown as mean±SE. Statistical significance level was defined as p

Figure 5. Individual regression for heart rate…

Figure 5. Individual regression for heart rate (HR) vs the corresponding for one ALL and…

Figure 5. Individual regression for heart rate (HR) vs the corresponding for one ALL and one CTRL child (A graph).
Regression between the individual slopes of the HR vs relationship, obtained in children with ALL (n = 10) and skeletal muscle O2 extraction at peak of exercise Δ[HHb]peak, expressed as the ratio of the values obtained during limb ischemia with the corresponding regression line (B graph). CTRL values are given as mean±SE. Statistical significance level was defined as p<0.05.
Figure 5. Individual regression for heart rate…
Figure 5. Individual regression for heart rate (HR) vs the corresponding for one ALL and one CTRL child (A graph).
Regression between the individual slopes of the HR vs relationship, obtained in children with ALL (n = 10) and skeletal muscle O2 extraction at peak of exercise Δ[HHb]peak, expressed as the ratio of the values obtained during limb ischemia with the corresponding regression line (B graph). CTRL values are given as mean±SE. Statistical significance level was defined as p<0.05.

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    1. Aricò M, Valsecchi MG, Rizzari C (2008) Long-term results of the AIEOP-ALL-95 Trial for Childhood Acute Lymphoblastic Leukemia: insight on the prognostic value of DNA index in the framework of Berlin-Frankfurt-Muenster based chemotherapy. J Clin Oncol 26 (2) 283–9.
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