Regenerating normal B-cell precursors during and after treatment of acute lymphoblastic leukaemia: implications for monitoring of minimal residual disease.

Autor: van Wering ER; Dutch Childhood Leukaemia Study Group, The Hague, The Netherlands. snwlk@wxs.nl, van der Linden-Schrever BE, Szczepański T, Willemse MJ, Baars EA, van Wijngaarde-Schmitz HM, Kamps WA, van Dongen JJ
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2000 Jul; Vol. 110 (1), pp. 139-46.
DOI: 10.1046/j.1365-2141.2000.02143.x
Abstrakt: We studied 57 childhood acute lymphoblastic leukaemia (ALL) patients who remained in continuous complete remission after treatment according to the Dutch Childhood Leukaemia Study Group ALL-8 protocols. The patients were monitored at 18 time points during and after treatment [640 bone marrow (BM) and 600 blood samples] by use of cytomorphology and immunophenotyping for the expression of TdT, CD34, CD10 and CD19. Additionally, 60 BM follow-up samples from six patients were subjected to clonality assessment via heteroduplex polymerase chain reaction (PCR) analysis of immunoglobulin VH-JH gene rearrangements. We observed substantial expansions of normal precursor B cells in regenerating BM not only after maintenance therapy but also during treatment. At the end of the 2-week intervals after consolidation and reinduction treatment, B-cell-lineage regeneration was observed in BM with a large fraction of immature CD34+/TdT+ B cells. In contrast, in regenerating BM after cessation of maintenance treatment, the more mature CD19+/CD10+ B cells were significantly increased, but the fraction of immature CD34+/TdT+ B cells was essentially smaller. Blood samples showed a profound B-cell lymphopenia during treatment followed by a rapid normalization of blood B cells after treatment, with a substantial CD10+ fraction (10-30%). Heteroduplex PCR analysis confirmed the polyclonal origin of the expanded precursor B cells in regenerating BM. This information regarding the regeneration of BM is essential for the correct interpretation of minimal residual disease studies.
Databáze: MEDLINE