1.
Early relapse prediction after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia (ALL) using lineage-specific chimerism analysis
Lindahl, H., Valentini, D., Vonlanthen, S., Sundin, M., Björklund, A. T., Mielke, S., Hauzenberger, D.
EJHaem. 2022;3(4):1277-1286
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.
2.
Lineage-specific early complete donor chimerism and risk of relapse after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia
Lindahl, H., Vonlanthen, S., Valentini, D., Björklund, A. T., Sundin, M., Mielke, S., Hauzenberger, D.
Bone marrow transplantation. 2022
Abstract
Recipient-donor chimerism is routinely analyzed after allogeneic hematopoietic stem cell transplantation (HSCT) to monitor engraftment and graft rejection. For malignancies, chimerism can also be used to screen for disease relapse post-HSCT but methodology and interpretation of results are not standardized and likely depend on underlying diagnosis. We have implemented highly sensitive and accurate methodologies for chimerism analysis for the purpose of improving relapse prediction. Here, we report an exploratory retrospective analysis of clinical routine chimerism results from all 154 HSCTs for acute myeloid leukemia (AML) performed at our center during the years 2015-2020 with the aim of suggesting a clinically useful threshold at which risk of relapse is high. Relapse was not reliably predicted based on single elevated chimerism values obtained before time of overt relapse. However, early complete donor chimerism, here defined as recipient DNA < 0.2% in CD33(+) cells in any blood or bone marrow sample taken during the first 60 days after HSCT, correlated inversely with relapse during the observation time (log-rank test P = 0.033). We propose that achievement of complete chimerism determined early after HSCT using sensitive methods can be used for risk-stratification of AML patients.