Early relapse prediction after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia (ALL) using lineage‐specific chimerism analysis

Abstract

Relapse is a major cause of treatment failure after hematopoietic stem cell transplantation (HSCT) for acute leukemia. Here, we report a monocentric retrospective study of all HSCTs for B cell acute lymphoblastic leukemia (ALL) performed during the years 2005–2021 (n = 138, including 51 children), aiming to identify the optimal use of lineage‐specific recipient‐donor chimerism analysis for prediction of relapse. In adults, relapse was associated with increased recipient chimerism in CD3+ bone marrow cells sampled at least 30 days before a relapse. Relapse could be predicted with a sensitivity of 73% and a specificity of 83%. Results were similar for children but with a higher recipient chimerism cutoff. Additionally, adults that had at least one chimerism value <0.12% in CD3+ peripheral blood cells within the first 60 days after HSCT had 89% probability of being relapse‐free after 2‐years compared to 64%. Results were similar for children but again necessitating a higher chimerism cutoff. These results suggest that high‐sensitive lineage‐specific chimerism analysis can be used for (1) early ALL relapse prediction by longitudinal chimerism monitoring in CD3+ bone marrow cells and (2) relapse risk stratification by analyzing CD3+ blood cells early post‐HSCT.

Highly-sensitive chimerism analysis in blood after allogeneic hematopoietic cell transplantation in childhood leukemia: Results from the Nordic Microchimerism Study

“…Furthermore, two children had a detectable IMC not included in the analysis because it occurred within 30 days of relapse. Our results thus suggest that causes of falsenegative results could be explained by non-adherence to sample protocol and a rapid development of the relapse (57). As illustrated in online Supplemental Material Table A, protocol adherence declined during follow-up and could to some extent explain false negative as well as true negative results.…”

Prospects and Potential for Chimerism Analysis after Allogeneic Hematopoietic Stem Cell Transplantation

“…Various hematopoietic cells, such as whole-blood and bulk BM cells, as well as lineage-specific cells—including T cells, myeloid cells, B cells, natural killer cells, and hematopoietic progenitor cells (HPCs)—are applicable to chimerism analysis ( Table 2 ) [ 45 , 51 , 52 ]. Lineage-specific chimerism analysis may show higher sensitivity compared to whole-blood chimerism analysis [ 4 , 42 , 53 ].…”