The following is a summary of “Minimal residual disease detection by next-generation sequencing of different immunoglobulin gene rearrangements in pediatric B-ALL,” published in the November 2023 issue of Hematology by Chen et al.

This study investigates the prognostic significance of immunoglobulin heavy chain locus (IGH) and light chain loci (IGK/IGL) rearrangements in detecting minimal residual disease (MRD) among pediatric patients with B-acute lymphoblastic leukemia (B-ALL). While the role of IGH in MRD prognosis has been previously acknowledged, the impact of IGK/IGL remains uncertain.

Utilizing next-generation sequencing (NGS), the researchers evaluated the prognostic value of IGH and IGK/IGL rearrangement-based MRD after the induction (EOI) and consolidation (EOC) phases. IGK/IGL rearrangements identified 5.5% of patients without identifiable IGH clones. The concordance rates for IGH and IGK/IGL at EOI were 79.9% (cutoff 0.01%), increasing to 81.0% (cutoff 0.0001%) at EOC.

Patients exhibiting NGS-MRD levels below 0.01% at EOI or below 0.0001% at EOC demonstrated excellent outcomes, boasting 3-year event-free survival rates exceeding 95%. Specifically, IGH-MRD proved prognostic at both EOI and EOC, while IGK-MRD at both phases and IGL-MRD solely at EOI did not exhibit prognostic significance.

NGS analysis at EOI identified 26.2% of higher-risk patients whose MRD levels were below 0.01% by flow cytometry. However, the inclusion of IGK/IGL alongside IGH failed to identify additional higher-risk patients at EOI and EOC.

In conclusion, while IGH is paramount in MRD monitoring, IGK and IGL remain relatively limited in determining MRD prognosis among pediatric B-ALL patients. This study underscores the pivotal role of IGH and the comparatively lesser impact of IGK/IGL rearrangements in MRD assessment, shedding light on their differential prognostic values in pediatric B-ALL management.

Source: nature.com/articles/s41467-023-43171-9