Minimal residual disease (MRD) detection using rearrangement of immunoglobulin/T cell receptor genes in adult patients with acute lymphoblastic leukemia (ALL)

• Published in: Annals of hematology 2018-04, Vol.97 (4), p.585-595
• Main Authors: Shahkarami, Sepideh, Mehrasa, Roya, Younesian, Samareh, Yaghmaie, Marjan, Chahardouli, Bahram, Vaezi, Mohammad, Rezaei, Nima, Nikbakht, Mohsen, Alimoghaddam, Kamran, Ghavamzadeh, Ardeshir, Tavakkoly-Bazzaz, Javad, Ghaffari, Seyed H.
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Female; Follow-Up Studies; Gene Rearrangement, T-Lymphocyte - drug effects; Hematology; Hospitals, University; Humans; Immunoglobulins; Induction Chemotherapy; Iran; Leukemia; Male; Medicine; Medicine & Public Health; Multiplex Polymerase Chain Reaction; Neoplasm Proteins - chemistry; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplasm, Residual - diagnosis; Neoplasm, Residual - genetics; Neoplasm, Residual - metabolism; Neoplasm, Residual - pathology; Oligonucleotides - chemistry; Oligonucleotides - metabolism; Oncology; Original Article; Precursor Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; Prospective Studies; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; Survival Analysis; T cell receptors; Tumor Burden - drug effects
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-018-3230-z

MRD detection with allele-specific oligonucleotide-quantitative polymerase chain reaction (ASO-qPCR) and using clone-specific immunoglobulin/T cell receptor rearrangements is considered as a powerful prognostic factor in acute lymphoblastic leukemia (ALL). In the present study, we evaluated an ASO-qPCR assay for MRD quantification in peripheral blood (PB) samples of adult patients with ALL. DNA was isolated from PB samples of patients with newly diagnosed ALL. They were first investigated by multiplex-PCR assay to identify V/J usage. An ASO-qPCR technique was then applied for 2.5-year monthly MRD quantification for detection of patient-specific Ig/TCR receptor rearrangements as a molecular target. From 98 patients who were diagnosed as ALL, 72 (73.5%) were enrolled in the present study for MRD detection. MRD was successfully quantified in patients with 1-month interval time. MRD level at the end of induction therapy up to day 88 was the only significant prognostic factor. Regarding MRD level, patients were categorized into two groups of low and high-risk. 2.5-year OS in all three time points (days 28, 58 and 88) were significantly lower in high-risk group ( P