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Minimal residual disease levels in bone marrow and peripheral blood are comparable in children with T cell acute lymphoblastic leukemia (ALL), but not in precursor-B-ALL

Leukemia volume 16, pages 1432–1436 (2002)Cite this article

Abstract

Sensitive and quantitative detection of minimal residual disease (MRD) in bone marrow (BM) samples of children with acute lymphoblastic leukemia (ALL) is essential for evaluation of early treatment response. In this study, we evaluated whether the traumatic BM samplings can be replaced by peripheral blood (PB) samplings. MRD levels were analyzed in follow-up samples of 62 children with precursor-B-ALL (532 paired BM-PB samples) and 22 children with T-ALL (149 paired BM-PB samples) using real-time quantitative PCR (RQ-PCR) analysis of immunoglobulin and T cell receptor gene rearrangements with sensitivities of 10−3 to 10−5 (one ALL cell in 103 to 105 normal cells). In 14 of the 22 T-ALL patients, detectable MRD levels were found in 67 paired BM-PB samples: in 47 pairs MRD was detected both in BM and PB, whereas in the remaining pairs very low MRD levels were detected in BM (n = 11) or PB (n = 9) only. The MRD levels in the paired BM-PB samples were very comparable and strongly correlated (rs = 0.849). Comparable results were obtained earlier by immunophenotyping in 26 T-ALL patients (321 paired BM-PB samples), which also showed a strong correlation between MRD levels in paired BM and PB samples (rs = 0.822). In 39 of the 62 precursor-B-ALL patients, MRD was detected in 107 BM-PB pairs: in 48 pairs MRD was detected in both BM and PB, in 47 pairs MRD was solely detected in BM (at variable levels), and in 12 pairs only the PB sample was MRD-positive at very low levels (≤10−4). Furthermore, in the 48 double-positive pairs, MRD levels in BM and PB varied enormously with MRD levels in BM being up to 1000 times higher than in the corresponding PB samples. Consequently, BM samples cannot easily be replaced by PB sampling for MRD analysis in childhood precursor-B-ALL, in line with their BM origin. In T-ALL, which are of thymic origin, BM sampling might be replaced by PB sampling, because the dissemination of T-ALL cells to BM and PB appears to be comparable.

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Acknowledgements

This study was supported by the Dutch Cancer Foundation/Koningin Wilhelmina Fonds (grant SNWLK 97-1567 and grant SNWLK 2000-2268), the Ank Van Vlissingen Foundation, and the Rotary Zwolle. We acknowledge Daniëlle Korpershoek, Marcia Reintjes and Annella Boon for their secretarial support, Dr Ton Langerak for critically reading the manuscript, and Dr Wim CJ Hop (Department of Epidemiology and Biostatistics) for help with the statistical analyses. We thank Phary Hart for technical assistance, the pediatric oncologists of the Department of Pediatrics, Sophia Children‘s Hospital Rotterdam, for the collection of bone marrow and blood samples at diagnosis and during follow-up, and the Dutch Childhood Leukemia Study Group for kindly providing additional ALL cell samples.

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Authors and Affiliations

  1. Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands

    VHJ van der Velden, DCH Jacobs, AJM Wijkhuijs, WM Comans-Bitter, MJ Willemse & JJM van Dongen

  2. Department of Pediatrics, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands

    K Hählen

  3. Dutch Childhood Leukemia Study Group, The Hague, The Netherlands

    WA Kamps & ER van Wering

  4. Department of Pediatrics, Beatrix Children's Hospital, Groningen, The Netherlands

    WA Kamps

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van der Velden, V., Jacobs, D., Wijkhuijs, A. et al. Minimal residual disease levels in bone marrow and peripheral blood are comparable in children with T cell acute lymphoblastic leukemia (ALL), but not in precursor-B-ALL. Leukemia 16, 1432–1436 (2002). https://doi.org/10.1038/sj.leu.2402636

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