Minimal residual disease analysis for the prediction of relapse in children with standard‐risk acute lymphoblastic leukaemia

Abstract

Summary. We report a largely retrospective analysis of minimal residual disease (MRD) in a cohort of 66 children suffering from acute lymphoblastic leukaemia (ALL). All patients lacked high-risk features at diagnosis, i.e. the presenting white cell count was <50 × 10 9 /l, age 1-16 years and translocations t(9;22) and t(4;11) were not present. All were treated according to either the MRC protocols UKALL X or XI. PCR of IgH, TCRd and TCRg gene rearrangements and allele-specific oligoprobing were employed for the detection of MRD. Sensitivity was at least 10 ¹4 in 78/82 (93%) probes examined. A total of 33 patients relapsed (seven on therapy and 26 off) and 33 remain in continuing complete remission (CCR) (median follow-up 69 months from diagnosis). Of those who remain in CCR, MRD was present in the bone marrow in 32%, 10% and 0% at 1, 3 and 5 months into therapy respectively. This is in marked contrast to the presence of MRD at these times in 82%, 60% and 41% of patients who relapsed (P<0·001, P<0·005 and P<0·005). These results provide further evidence of a strong correlation between clearance of MRD early in therapy and clinical outcome in childhood ALL.

Leukemia lineage-specific chimerism analysis is a sensitive predictor of relapse in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic stem cell transplantation

“…In patients with ALL, MRD analysis of BM is also unreliable for predicting EMR. 48 However, in two patients in this study, both suffering from EMR after SCT, an increase in the MC pattern in BM was found, indicating an impending relapse. In UPN 672, with MC detected only in the BM at the time of relapse 8 months after SCT, no BM sample was available at 6 months for chimerism analysis.…”

Evaluation of immunomodulatory treatment based on conventional and lineage-specific chimerism analysis in patients with myeloid malignancies after myeloablative allogeneic hematopoietic cell transplantation

“…38 Therefore, EMR is a potential problem with chimerism monitoring and must be considered in suggestive clinical courses. MC in BM without any evidence of a relapse suggests residual recipient hematopoiesis.…”

Flow cytometry and allele-specific oligonucleotide PCR are equally effective in detection of minimal residual disease in ALL

“…2,23 MRD detection levels obtained with our ASO primers varied in dilution experiments between 10 −3 and 10 −6 (Table 3), which is in agreement with other studies applying similar methods 34 and other PCR-based approaches. 10,13,35,36 Therefore, in practice, the MRD detection level by PCR is often one log higher than that of flow cytometry. This is illustrated by our case No.…”

“…13 In other studies applying only slightly less sensitive methods there were patients with PCR-negative samples at the end of treatment and subsequent relapse. 6,8,36,37 Some of the latter discrepancies may be explained by the disappearance of some leukemic clones, or the presence of PCR inhibitors, but in the majority of cases reported, at least one PCR target remained stable. 6 Most of the previous studies where semi-quantitative PCR methods were applied suggested that the clinically significant level of MRD would be above 1 per 10 3 BM cells.…”