title: Bone Marrow Recovery by Morphometry during Induction Chemotherapy for Acute Lymphoblastic Leukemia in Children.
abstract: Bone marrow architecture is grossly distorted at the diagnosis of ALL and details of the morphological changes that accompany response to Induction chemotherapy have not been reported before. While marrow aspirates are widely used to assess initial response to ALL therapy and provide some indications, we have enumerated marrow components using morphometric analysis of trephine samples with the aim of achieving a greater understanding of changes in bone marrow niches. Morphometric analyses were carried out in the bone marrow trephine samples of 44 children with ALL, using a NanoZoomer HT digital scanner. Diagnostic samples were compared to those of 32 control patients with solid tumors but without marrow involvement. Samples from patients with ALL had significantly increased fibrosis and the area occupied by bony trabeculae was lower than in controls. Cellularity was higher in ALL samples due to leukemic infiltration while the percentage of normal elements such as megakaryocytes, adipocytes, osteoblasts and osteoclasts were all significantly lower. During the course of Induction therapy, there was a decrease in the cellularity of ALL samples at day 15 of therapy with a further decrease at the end of Induction and an increase in the area occupied by adipocytes and the width of sinusoids. Reticulin fibrosis decreased throughout Induction. Megakaryocytes increased, osteoblasts and osteoclasts remained unchanged. No correlation was found between clinical presentation, early response to treatment and morphological changes. Our results provide a morphological background to further studies of bone marrow stroma in ALL.
authors.affiliation: Erasmus University, Rotterdam, The Netherlands; SA Pathology at Women's and Children's Hospital, Adelaide, Australia.
authors.forename: Tuong-Vi
authors.initials: TV
authors.lastname: Nguyen
authors.affiliation: Women's and Children's Research Institute, Adelaide, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Melville
authors.affiliation: SA Pathology, Frome Road, Adelaide, Australia.
authors.forename: Shriram
authors.initials: S
authors.lastname: Nath
authors.affiliation: SA Pathology at Women's and Children's Hospital, Adelaide, Australia.
authors.forename: Colin
authors.initials: C
authors.lastname: Story
authors.affiliation: Data Management & Analysis Centre, Discipline of Public Health, University of Adelaide, Adelaide, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Howell
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, UNSW, Randwick, NSW, Australia.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Sutton
authors.affiliation: Faculty of Health Science, University of Adelaide, Adelaide, Australia; Centre for Cancer Biology, SA Pathology, Adelaide, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zannettino
authors.affiliation: SA Pathology at Women's and Children's Hospital, Adelaide, Australia; Faculty of Health Science, University of Adelaide, Adelaide, Australia.
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001706:Biopsy; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D060828:Induction Chemotherapy; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology*