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

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.
Competing Interests: Dan Hauzenberger is founder and co‐owner of Devyser AB. He is also part‐time employed by the company. Stephan Mielke has received speakers fee from Novartis and DNA Prime SA, has received travel support from and served in expert panel for Gilead/KITE, has received travel support and speakers fee from Celgene/BMS, has received research funding, travel support, and speakers fee from Kiadis Pharma, has served in expert panel for Bellicum, has received travel support and speakers fee from and has served in data safety monitoring board for Miltenyi, and has served in data safety monitoring board for Immunicum. The remaining authors have no conflict of interest to declare.
(© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)