Monitoring of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia — Preliminary Data from a Prospective Study
Minimal residual disease (MRD) was evaluated in bone marrow samples prospectively obtained from children with acute lymphoblastic leukemia (ALL) during complete remission (CR), using allele-specific markers based on junctional regions generated through the recombination of T-cell receptor δ (TCRδ), TCRγ, immunoglobulin K (IgK) chain or sil-tal genes. Suitable TCRδ, TCRγ, IgK and sil-tal recombinations were identified by Southern blot analysis in 27/29 (93%) T-ALL and 152/174 (87%) precursor-B ALL patients. Two or more independent markers were available in 156/203 (77%) cases. Allele-specific oligonucleotides (ASO) were used either as clonospecific probes or primers and reached a detection level between 10−4 to 10−6 in 192/212 (91%) recombined alleles. Six hundred and forty-one remission samples from 112 cases (20 relapsed, 92 in continuous CR) have been analyzed so far. MRD was demonstrated during a period of 6 months after diagnosis in the vast majority of patients who relapsed during the course of treatment. In contrast, 88% of the patients who remained in continuous CR became PCR-negative within 3 months of treatment. Remarkably, 58% of them achieved PCR-negativity within 1 month. Our data suggest that the MRD status at 3 and 6 months after diagnosis may represent a clinically relevant parameter for a second stratification of childhood ALL.
KeywordsLymphoma Leukemia Recombination Oncol Stratification
Unable to display preview. Download preview PDF.
- 1.Reiter A, Schrappe M, Ludwig WD, Hiddemann W, Sauer S, Henze G, Zimmermann M, Lampert F, Havers MW, Niethammer D, Odenwald E, Ritter J, Mann G, Welte K, Gadner H, Riehm H (1994) Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86. Blood 84: 3122–3133PubMedGoogle Scholar
- 3.Yamada M, Hudson S, Tournay D, Bittenbender S, Shane SS, Lange B, Tsujimoto Y, Caton AJ, Roy-era G (1989) Detection of minimal residual disease in hematopoietic malignancies of the B-cell lineage by using third-complementary-determining region (CDR-III)- specific probes. Proc. Natl. Acad. Sci USA 86: 5123–5127PubMedCrossRefGoogle Scholar
- 10.van der Does-van der Berg A, Bartram CR, Basso G, Benoit YCM, Biondi A, Debatin KM, Haas OA, Harbott J, Kamps WA, Köller U, Lampert F, Ludwig W-D, Niemeyer CM, van Wering ER (1992) Minimal requirements for the diagnosis, classification and evaluation of the treatment of childhood acute lymphoblastic leukemia (ALL) in the “BFM Family” cooperative group. Med. Pediatr. Oncol. 20: 497–505Google Scholar
- 16.Breit TM, Mol EJ, Wolvers-Tettero ILM, Ludwig WD, van Wering ER, van Dongen JJM (1993) Site-specific deletions involving the tal-1 and sil genes are restricted to cells of the T cell receptor a/13 lineage: T cell receptor S gene deletion mechanism affects multiple genes. J Exp. Med. 177: 965–977PubMedCrossRefGoogle Scholar
- 17.Seriu T, Yokota S, Nakao M, Misawa S, Takaue Y, Koizumi S, Kawai S, Fujimoto T (1995) Prospective monitoring of minimal residual disease during the course of chemotherapy in patients with acute lymphoblastic leukemia, and detection of contaminating tumor cells in peripheral blood stem cells for autotransplantation. Leukemia 9: 615–623PubMedGoogle Scholar
- 20.Seriu T, Erz D, Stark Y, Bartram CR. T-cell receptor D62D63 rearrangement: a suitable allele-specific marker for the detection of minimal residual disease in childhood acute lymphoblastic leukemia. Leukemia 1997, in press.Google Scholar