Run-Ming Jin, Hong-Bao Fei

Wuhan, China

Author Affiliations: Department of Pediatrics, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China (Bai Y, Yu H, Lin W, Zhou DF, Xiao Y, Wu XY, Jin RM, Fei HB)

Corresponding Author: Yan Bai, MD, Department of Pediatrics, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China (Tel: 86-27-85726002; Fax: 86-27-85726002; Email: swcathy32@yahoo.com.cn)

Background: At diagnosis, leukemic cell burden reaches 10¹² in patients with acute lymphoblastic leukemia (ALL). When patients get the first complete remission (CR) after induction chemotherapy, less than 5% of lymphoblasts are found in bone marrow smear by light microscopy. But an amount of 10⁹ or less residual leukemic cells may be left, thus the disease is known as minimal residual disease (MRD), which is proven to be responsible for clinical relapse. Detection and quantification of MRD in ALL patients after chemotherapy might improve therapeutic results and prognosis. 

Methods: Polymerase chain reaction (PCR) and nested-PCR were used to detect rearranged immunoglobulin heavy-chain (IgH) CDRIII gene and T lineage cell receptor (TCR) Vδ2Dδ3 gene for 71 ALL patients. Cerebral spinal fluid (CSF) samples from 67 patients at CR were also detected by the same methods. Leukemic clones were quantified by limiting dilution analysis.

Results: IgH CDRIII rearrangements were found positive in 43 (82.7%) of 52 patients with B lineage ALL and 3 (15.8%) of 19 patients with T lineage ALL. TCR Vδ2Dδ3 positive rearrangements were present in 17 (32.7%) patients with B lineage ALL and 12 (63.2%) with T lineage ALL. MRD was quantified with the nested-PCR through limiting dilution of DNA samples from these rearrangement positive patients. Patients with MRD level above 2×10^-3 in the first CR were found to have a high relapse rate and this situation was also found in patients with a slow decrease or a high level of MRD. Whereas patients with undetectable or detected less than 2×10^-5 level of MRD in the first CR had a good prognosis. Of the 67 CSF samples, 9 were positive for IgH CDRIII rearrangement and 4 positive for TCR Vδ2Dδ3 rearrangement; 5 of them eventually developed central nervous system leukemia.

Conclusions: The relationship between MRD detection and outcome is significant for ALL patients. Early quantification of leukemic cells after chemotherapy may be an effective strategy for predicting ou tcome and hence individualizing ALL treatment in childhood.

Key words: minimal residual disease; acute lymphoblastic leukemia; polymerase chain reaction; immunoglobulin heavy-chain; T lineage cell receptor; gene rearrangement

World J Pediatr 2007;3(4):290-294