Minimal Residual Disease (MRD) Detection with Translocations and T-Cell Receptor and Immunoglobulin Gene Rearrangements in Adult Acute Lymphoblastic Leukaemia Patients: A Pilot Study

Turk J Haematol. 2008 Sep 5;25(3):124-32.

Abstract

Monitoring minimal residual disease has become increasingly important in clinical practice of ALL management. Break-point fusion regions of leukaemia related chromosomal aberrations and rearranged immunoglobulin (Ig) and T cell-receptor (TCR) genes, which can be detected by polymerase chain reaction (PCR), are used as leukaemia specific markers in genetic studies of MRD. A total of 31 consecutive patients with newly diagnosed ALL were screened for eligibility criteria. Of those 26 were included in the study. One patient with partial response following induction therapy and four patients who were lost to follow-up after induction were excluded from the study; thus 21 patients were evaluated for MRD. Chromosomal aberrations were detected in 5 (24%) of the patients and were used for MRD monitoring. Three patients had t(9;22) translocation, the other 2 had t(4;11) and t(1;19). MRD-based risk stratification of the 16 patients analysed for Ig/TCR rearrangements revealed 3 low-risk, 11 intermediate-risk and 2 high-risk patients. MRD monitoring is progressively getting to be a more important predictive factor in adult ALL patients. As reported by others confirmed by our limited data there is a good correlation between MRD status and clinical outcome in patients receiving chemotherapy. The pilot-study presented here is the first that systematically and consecutively performs a molecular MRD monitoring of ALL patients in Turkey.

Minimal rezidüel hastalığın (MRH) takibi, ALL tedavisinin klinik uygulamalarında giderek önem kazanmaktadır. Lösemide sıklıkla görülen kromozomal kırık noktaları, immunglobulin (Ig) ve T-hücre reseptörleri (THR), polimeaz zincir reaksiyonu (PCR) kullanılarak, MRH takibinde lösemiye özgü marker olarak kullanılmaktadır. Yeni ALL tanısı almış toplam 31 hasta çalışmaya alındı, kriterlere uygun 26 hasta ile çalışma gerçekleştirildi. 5 hasta çalışma sürecinde takip dışı kaldı ve 21 hasta MRH açısından değerlendirilmeye alındı. Bu hastalardan 5 (%24) tanesinde kromozomal translokasyonlar tespit edildi. 3 hastada t(9;22), 1 hastada t(4;11) ve 1 hastada da t(1;19) translokasyonları belirlendi. MRH’a dayalı risk tespitinde 16 hasta Ig/THR yeniden yapılanmaları için analiz edildi ve 3 tanesi düşük risk gurubu, 11 tanesi orta risk gurubu ve 2 tanesi de yüksek risk gurubuna dahil edildi. Elde ettiğimiz sonuçlar, kemoterapi alan hastalarda klinik sonuçların, MRH durumları ile iyi korelasyon gösterdiğini desteklemektedir. Bu pilot çalışma ile ülkemizde ilk defa sistematik olarak tanı ve takip örneklerinde MRH takibi gerçekleştirilmiştir.