Gene rearrangement study for minimal residual disease monitoring in children with acute lymphocytic leukemia

Abstract

ObjectiveTo detect markers for minimal residual disease monitoring based on conventional polymerase chain reaction for immunoglobulin, T-cell receptor rearrangements and the Sil-Tal1 deletion in patients with acute lymphocytic leukemia. MethodsFifty-nine children with acute lymphocytic leukemia from three institutions in Minas Gerais, Brazil, were prospectively studied. Clonal rearrangements were detected by polymerase chain reaction followed by homo/heteroduplex clonality analysis in DNA samples from diagnostic bone marrow. Follow-up samples were collected on Days 14 and 28-35 of the induction phase. The Kaplan-Meier and multivariate Cox methods were used for survival analysis. ResultsImmunoglobulin/T-cell receptor rearrangements were not detected in 5/55 children screened (9.0%). For precursor-B acute lymphocytic leukemia, the most frequent rearrangement was IgH (72.7%), then TCRG (61.4%), and TCRD and IgK (47.7%); for T-acute lymphocytic leukemia, TCRG (80.0%), and TCRD and Sil-Tal deletion (20.0%) were the most common. Minimal residual disease was detected in 35% of the cases on Day 14 and in 22.5% on Day 28-35. Minimal residual disease on Day 28-35, T-acute lymphocytic leukemia, and leukocyte count above 50 x 109/L at diagnosis were bad prognostic factors for leukemia-free survival in univariate analysis. Relapse risk for minimal residual disease positive relative to minimal residual disease negative children was 8.5 times higher (95% confidence interval: 1.02-70.7).ConclusionImmunoglobulin/T-cell receptor rearrangement frequencies were similar to those reported before. Minimal residual disease is an independent prognostic factor for leukemia-free survival, even when based on a non-quantitative technique, but longer follow-ups are needed.

The treatment of acute lymphoblastic leukemia has come a long way but the best is yet to come

“…A low cost, reliable and easy to perform methodology is desired. This was precisely what Assumpção et al are presenting in their paper published in this issue of Revista Brasileira de Hematologia e hemoterapia ( 4 ) . These authors tried to detect markers in MRD monitoring based on conventional polymerase chain reaction (PCR) for immunoglobulin (Ig) and T-cell receptor (TCR) rearrangements, and Sil-Tal1 deletion in patients with acute lymphoblastic leukemia (ALL) treated in three hospitals in Minas Gerais, Brazil.…”

Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

“…Alternatively, some authors have proposed the detection of Ig/TCR rearrangements by conventional PCR using consensus primers and homo/heteroduplex analysis, despite its lower analytical sensitivity, considering that this approach allows identification of patients with greater residual tumor burden, and then at high risk of relapse. 22 , 27 , 49 , 50 , 78 , 79 , 87 , 88 …”

Minimal residual disease in acute leukemia based on the insight of molecular genetics monitoring

“…Another study in acute lymphoblastic leukemia patients measuring Ig/TCR by Real-time PCR found that risk stratification of precursor B-ALL, not T-ALL, could be improved by using MRD measurement on day 15 and day 33 instead of day 33 and day 79 in similar BFM protocols for patients with these diseases. According to Assumpção et al (2013), measuring Ig/TCR by PCR followed by homo/heteroduplex clonality analysis, found MRD independent prognostic factor for leukemia-free survival and overall survival even when based on a non-quantitative technique but longer follow-up always needed. Foroni et al (2005) reported that flow cytometry in childhood T-ALL is a favorable prognostic marker in peripheral blood and bone marrow samples.…”