1. ¹Department of Clinical Sciences, Pediatrics, Umea University, Umea, Sweden
2. ²Department of Medical Biosciences, Pathology, Umea University, Umeå, Sweden
3. ³Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden
4. ⁴Department of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden
5. ⁵Department of Pathology, Karolinska University Hospital, Stockholm, Sweden
6. ⁶Childhood Cancer Research Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden

Correspondence: Dr U Norén-Nyström, Department of Clinical Sciences, Pediatrics, Umeå University, Umeå S-901 87, Sweden. E-mail: ulrika.norennystrom@pediatri.umu.se

Received 28 September 2007; Revised 19 November 2007; Accepted 20 November 2007; Published online 20 December 2007.

Abstract

We retrospectively evaluated reticulin fiber density (RFD) in 166 diagnostic bone marrow (BM) biopsies and 62 biopsies obtained at treatment day 29 from children with acute lymphoblastic leukemia (ALL). Patients with B-cell precursor (BCP)-ALL showed higher RFD as compared to patients with T-cell ALL (P<0.001). RFD correlated negatively with white blood cell count (P=0.008) in BCP-ALL patients. Patients with high-hyperdiploid ALL (51–61 chromosomes), no high-risk criteria and low RFD showed a favorable outcome when compared to similar patients with high RFD (P=0.002). In BCP-ALL patients, RFD at diagnosis correlated to the levels of minimal residual disease (MRD) analyzed by flow cytometry on treatment day 29 (P=0.001). Accordingly, patients with MRD10^-4 presented higher RFD at diagnosis compared to patients with MRD<10^-4 (P=0.003). BCP-ALL patients with low RFD at diagnosis and a rapid reduction of RFD on day 29 had a favorable outcome compared to patients with the same baseline RFD level at diagnosis but a slow RFD reduction (P=0.041). To our knowledge, these findings are novel and may indicate BM fibrosis as a new valuable prognostic marker in childhood ALL. Expanded use of BM biopsy both at diagnosis and during follow-up is suggested.