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USE OF VOXEL-BASED MORPHOMETRY TO DETECT CEREBRAL VOLUMES ABNORMALITIES IN LONG TERM SURVIVORS OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA.
Author(s): ,
Giuseppina Aloj
Affiliations:
Pediatric Hemato-Oncology Department,Santobono-Pausilipon Children’s Hospital,Naples,Italy
,
Grazia Pastorino
Affiliations:
Child Neuropsychiatry Unit, Traslational Medical Science Department,“Federico II” University,Naples,Italy
,
Federica Mazio
Affiliations:
Neuroradiology Unit, Advanced Biomedical Science Department,“Federico II” University,Naples,Italy
,
Nilde Di Paolo
Affiliations:
Neuroradiology Unit, Advanced Biomedical Science Department,“Federico II” University,Naples,Italy
,
Maria Pia Riccio
Affiliations:
Child Neuropsychiatry Unit, Mental and Fisical Health and Preventive medicine Department,Second University of Naples,Naples,Italy
,
Alessandra D'Amico
Affiliations:
Neuroradiology Unit, Advanced Biomedical Science Department,“Federico II” University,Naples,Italy
,
Carmela Bravaccio
Affiliations:
Child Neuropsychiatry Unit, Traslational Medical Science Department,“Federico II” University,Naples,Italy
,
Rosanna Cuccurullo
Affiliations:
Pediatric Hemato-Oncology Department,Santobono-Pausilipon Children’s Hospital,Naples,Italy
,
Rosanna Parasole
Affiliations:
Pediatric Hemato-Oncology Department,Santobono-Pausilipon Children’s Hospital,Naples,Italy
Vincenzo Poggi
Affiliations:
Pediatric Hemato-Oncology Department,Santobono-Pausilipon Children’s Hospital,Naples,Italy
(Abstract release date: 05/19/16) EHA Library. Parasole R. 06/09/16; 132411; E862
Dr. Rosanna Parasole
Dr. Rosanna Parasole
Contributions
Abstract
Abstract: E862

Type: Eposter Presentation

Background
Improvements in therapeutic strategies of pediatric Acute Lymphoblastic Leukemia(ALL) over the last decades have highly increased survival rates; consequently, there is a growing population of ALL Long Term Survivors(ALL-LTS). Treatment protocols include Central Nervous System directed Chemotherapy(CT) associated, in selected patients, to Cranial Irradiation(CI). These treatments appear able to determine neurocognitive late effects in ALL-LTS. The anatomical and molecular basis of these alterations are still largely unknown, and neuroimaging studies, such as automated whole brain segmentation of MRI images through Voxel-Based Morphometry(VBM), may be helpful in their understanding. Aim of this study was to better define neuroanatomic regions involved in neurocognitive impairment of a population of ALL-LTS, and to evaluate possible relationships of these abnormalities with type of therapy.

Aims
The primary objective was to detect the neuroanatomical alterations in ALL-LTS who received either CT alone or in combination with CI during childhood.  Secondary objective was to assess the neurocognitive performance in the same two groups of LTS.

Methods
In this cross-sectional, controlled study, twentysix ALL-LTS were recruited from the ALL-LTS cohort of patients followed up in the Hemato-Oncology Department of Santobono-Pausilipon Children’s Hospital of Naples. Thirteen subjects received CT and CI (group A) while thirteen received CT alone (group B). All signed written informed consent. The two groups were matched for age, sex, ethnicity, education, number of right-handed and left-handed subjects, use of glasses, age at ALL diagnosis, years since therapy-discontinuation and type of therapeutic protocol used.  People who underwent HSCT and relapsed subjects were excluded.Imaging were collected using a 3T Siemens Scanner. VBM analyses were conducted on MPRAGE T1 3D images in Statistical Parametric Mapping 8. Analyses of brain volumes were performed as global Gray Matter(GM), White Matter(WM) and Cerebro Spinal Fluid(CSF) volumes and as regional voxel-by-voxel analyses.Neurocognitive performance was assessed through the Wechsler Adult Intelligence Scale–Revised(WAIS-R) for over 16 years and through the Wechsler Intelligence Scale for Children–4th Edition(WISC-4th) for age 9-16 years. d2-R test and Wisconsin Card Sorting Test(WCST) were used to assess respectively attention and concentration abilities and executive function.A two sample t-test was employed for all the between group comparisons.

Results
Absolute volumes of GM, WM and CSF segments of group A vs group B did not differ significantly. Group A showed significantly smaller volumes than group B in superior frontal gyrus, posterior medial frontal gyrus, paracentral lobule, inferior parietal lobule, precuneus, temporal medial gyrus, parahippocampal gyrus, medial and posterior cingulate cortex.Significant differences between groups were found for intelligence, performance, attention and memory measures of WAIS-R. No significant differences were observed for WISC-4th, d2-R and WCST, but in both groups, working memory, processing speed, concentration and attention were worse than population norm.

Conclusion
In our study some neuroanatomic structures showed smaller volumes in ALL-LTS treated with CT in combination with CI than in those treated with CT alone. These findings could be related to specific neurocognitive alterations observed in these subjects, and represent an initial attempt in elucidating their anatomical basis. Further studies on more extensive pediatric series are needed to confirm our observations.

Session topic: E-poster

Keyword(s): Acute lymphoblastic leukemia, Long-term follow-up
Abstract: E862

Type: Eposter Presentation

Background
Improvements in therapeutic strategies of pediatric Acute Lymphoblastic Leukemia(ALL) over the last decades have highly increased survival rates; consequently, there is a growing population of ALL Long Term Survivors(ALL-LTS). Treatment protocols include Central Nervous System directed Chemotherapy(CT) associated, in selected patients, to Cranial Irradiation(CI). These treatments appear able to determine neurocognitive late effects in ALL-LTS. The anatomical and molecular basis of these alterations are still largely unknown, and neuroimaging studies, such as automated whole brain segmentation of MRI images through Voxel-Based Morphometry(VBM), may be helpful in their understanding. Aim of this study was to better define neuroanatomic regions involved in neurocognitive impairment of a population of ALL-LTS, and to evaluate possible relationships of these abnormalities with type of therapy.

Aims
The primary objective was to detect the neuroanatomical alterations in ALL-LTS who received either CT alone or in combination with CI during childhood.  Secondary objective was to assess the neurocognitive performance in the same two groups of LTS.

Methods
In this cross-sectional, controlled study, twentysix ALL-LTS were recruited from the ALL-LTS cohort of patients followed up in the Hemato-Oncology Department of Santobono-Pausilipon Children’s Hospital of Naples. Thirteen subjects received CT and CI (group A) while thirteen received CT alone (group B). All signed written informed consent. The two groups were matched for age, sex, ethnicity, education, number of right-handed and left-handed subjects, use of glasses, age at ALL diagnosis, years since therapy-discontinuation and type of therapeutic protocol used.  People who underwent HSCT and relapsed subjects were excluded.Imaging were collected using a 3T Siemens Scanner. VBM analyses were conducted on MPRAGE T1 3D images in Statistical Parametric Mapping 8. Analyses of brain volumes were performed as global Gray Matter(GM), White Matter(WM) and Cerebro Spinal Fluid(CSF) volumes and as regional voxel-by-voxel analyses.Neurocognitive performance was assessed through the Wechsler Adult Intelligence Scale–Revised(WAIS-R) for over 16 years and through the Wechsler Intelligence Scale for Children–4th Edition(WISC-4th) for age 9-16 years. d2-R test and Wisconsin Card Sorting Test(WCST) were used to assess respectively attention and concentration abilities and executive function.A two sample t-test was employed for all the between group comparisons.

Results
Absolute volumes of GM, WM and CSF segments of group A vs group B did not differ significantly. Group A showed significantly smaller volumes than group B in superior frontal gyrus, posterior medial frontal gyrus, paracentral lobule, inferior parietal lobule, precuneus, temporal medial gyrus, parahippocampal gyrus, medial and posterior cingulate cortex.Significant differences between groups were found for intelligence, performance, attention and memory measures of WAIS-R. No significant differences were observed for WISC-4th, d2-R and WCST, but in both groups, working memory, processing speed, concentration and attention were worse than population norm.

Conclusion
In our study some neuroanatomic structures showed smaller volumes in ALL-LTS treated with CT in combination with CI than in those treated with CT alone. These findings could be related to specific neurocognitive alterations observed in these subjects, and represent an initial attempt in elucidating their anatomical basis. Further studies on more extensive pediatric series are needed to confirm our observations.

Session topic: E-poster

Keyword(s): Acute lymphoblastic leukemia, Long-term follow-up

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