Detection and role of minimal disseminated disease in children with lymphoblastic lymphoma: The AIEOP experience

Pediatr Blood Cancer. 2015 Nov;62(11):1906-13. doi: 10.1002/pbc.25607. Epub 2015 Jun 24.

Abstract

Background: The use of intensive chemotherapy regimens in children with lymphoblastic lymphoma (LBL) has significantly improved outcome, but the salvage rate for these patients is still poor. The aim of this study was to evaluate the prognostic value of minimal disseminated disease (MDD), studied by multiparametric flow cytometry (MFC), in pediatric patients with T- and B-lineage LBL.

Procedure: We examined bone marrow (BM) and peripheral blood (PB) samples from a series of 65 children affected by T- (52) and B-lineage (13) LBL using an MFC method; 10 of them were also analyzed for clonality of T-cell receptor gene rearrangements.

Results: MDD was detected in 49% (32/65) of BM samples, whereas only 21% (14/65) were positive at standard morphological evaluation. Findings from MFC analyses of paired BM and PB samples were highly concordant. We analyzed the prognostic significance of MDD results detected at diagnosis in morphologically negative patients, as almost all relapsed cases (10/11) did not have any morphological involvement of BM at diagnosis. Using an MDD cut-off level of 3% by FCM (75th percentile), 5-year event-free survival (EFS) was 60% (SE ± 22) for patients with MDD >3% LBL cells versus 83% (SE ± 6) for the remaining patients (P = 0.04). No statistically significant difference in EFS was observed between LBL patients considering all the other clinical characteristics.

Conclusions: Our data demonstrated that MDD studied at diagnosis by MFC could represent a useful prognostic tool in childhood LBL and further application for better stratification is warranted.

Keywords: childhood; flow cytometry; lymphoblastic lymphoma; minimal disseminated disease.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Gene Rearrangement, T-Lymphocyte
  • Humans
  • Male
  • Neoplasm, Residual
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / metabolism
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / pathology
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Survival Rate
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell