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.

Consolidation Chemotherapy Prevents Relapse by Indirectly Regulating Bone Marrow Adipogenesis in Patients with Acute Myeloid Leukemia

“…According to recent studies, the relapse of some fatal haematological malignancies is closely related to the BM microenvironment [3, 4]. As an important component of the BM microenvironment, the number of marrow adipocytes is dramatically decreased in patients with primary acute lymphoblastic leukaemia(ALL) and support ALL cell proliferation and chemo-resistance in the limited BM space [5]. Moreover, obesity is associated with a 50% increase in the recurrence rate in children with ALL [6].…”

Childhood Leukemias in Khyber Pakhtunkhwa and Afghan Children Visiting to Hayatabad Medical Complex Hospital

“…Laboratory diagnosis of childhood leukemia was determined by bone marrow aspiration with trephine biopsy [8]. The exact diagnosis of childhood leukemia was diagnosed through cytogenetic studies, immunohistochemistry, flowcytometry and polymerase chain reaction for responsible gene mutation [9].…”

CD4+ T-cell, CD8+ T-cell, CD4+ /CD8+ ratio, and apoptosis as a response to induction phase chemotherapy in pediatric acute lymphoblastic leukemia

“…Evaluation of bone marrow aspiration after induction phase chemotherapy showed that all the patients were in remission, as determined by leukemic cell clearance from the bone marrow, mainly in the first 2 weeks after induction phase chemotherapy. 13 Mean CD4 + , CD8 + cells, and CD4 + /CD8 + ratio were significantly decreased after induction phase chemotherapy ( Table 2). Verma et al reported a significant decrease in B cells, T cells, and NK cells approximately 2 weeks after chemotherapy.…”

“…Infiltration of hematopoetic cells by leukemic cells accumulated in the bone marrow causes anemia and thrombocytopenia. 1,13 After chemotherapy, leukocyte count decreased, while Hb level and thrombocyte count increased. Evaluation of bone marrow aspiration after induction phase chemotherapy showed that all the patients were in remission, as determined by leukemic cell clearance from the bone marrow, mainly in the first 2 weeks after induction phase chemotherapy.…”