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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.
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Impact of early chimerism status on clinical outcome in children with acute lymphoblastic leukaemia after haematopoietic stem cell transplantation
Lejman, M., Zaucha-Prazmo, A., Zawitkowska, J., Mroczkowska, A., Grabowski, D., Kowalczyk, J. R., Drabko, K.
BMC cancer. 2019;19(1):1141
Abstract
BACKGROUND The significance of very early chimerism assessment before day + 28, which is considered the moment of engraftment, is still unclear. In this retrospective study, we evaluated the clinical impact of very early chimerism on the clinical outcome after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukaemia (ALL). METHODS The study group included 38 boys and 18 girls. Very early chimerism was evaluated on days + 7, + 14, + 21 and + 28 after the transplant. Short tandem repeat polymerase chain reaction (STR PCR) was used to analyse chimerism. RESULTS Overall survival (OS) and event-free survival (EFS) were 84 and 80%, respectively. The OS in the group of 24 patients with complete donor chimerism on day + 14 was 83%, and it did not differ statistically compared to the 32 patients with mixed chimerism on day + 14 (OS was 84%). In our cohort of patients, the matched unrelated donor, male gender of donor, number of transplanted cells above 4.47 x 10(6) kg and no serotherapy with anti-thymocyte globulin (ATG) were statistically related to a higher level of donor chimerism. The immunophenotypes of disease, age of patient at time HSCT, recipient sex, stem cell source (peripheral blood/bone marrow) and conditioning regimen had no impact on early chimerism. Acute graft versus host disease grades II-IV was diagnosed in 23 patients who presented with donor chimerism levels above 60% on day 7. CONCLUSIONS The data presented in this study provide valuable insight into the analysis of very early chimerism in children with ALL treated with HSCT.
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Early achievement of full donor chimerism after allogeneic hematopoietic stem cell transplantation predicts lower relapse risk in patients with acute lymphoblastic leukemia
Chen, C. T., Gau, J. P., Liu, J. H., Chiou, T. J., Hsiao, L. T., Liu, Y. C.
Journal of the Chinese Medical Association : JCMA. 2018
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Abstract
BACKGROUND Acute lymphoblastic leukemia (ALL) remains one of the most difficult-to-cure hematological malignancies. Allogeneic hematopoietic stem cell transplantation (HSCT) provides curative potential but a substantial proportion of patients eventually will relapse. It is unknown if there are any modifiable factors exists that could improve survival or predict relapse immediately after HSCT is unknown. The aim of this study was to explore whether achieving early (<30 days) full donor chimerism (FDC) could predict disease relapse after allogeneic HSCT in ALL patients. A second objective is to examine the impact of achieving early donor chimerism on survival. METHODS This study retrospectively enrolled 55 ALL patients undergoing allogeneic HSCT during the 10-year period from 1999 to 2008. Analysis of short tandem repeats (STR) was used to determine donor chimerism, and was prospectively followed at the time of engraftment and on days 30. Patients with early treatment-related mortality (<30 days), without STR analysis, or who were lost to follow-up before FDC were excluded. Survival analyses were performed using Kaplan-Meier Methods. Cox proportional hazard analyses were performed for poor prognostic factors associated with overall survival (OS) and relapse-free survival (RFS). RESULTS The general characteristics were comparable between patients with early donor chimerism (n = 31) and those with late donor chimerism (n = 24). Survival analyses showed patients with early FDC had both lower probability of relapse (chi(2) = 5.770, p = 0.022) and longer RFS than those with late chimerism. The OS was not different according to the chimerism status on days 30. In the Cox proportional hazard analyses, early FDC is a significant factor predictive for longer RFS (HR = 0.264, p = 0.010). CONCLUSION Our results indicate that the achievement of early FDC within 30 days after allogenic HSCT can be used as a significant predictor of RFS. The results underscored the need to improve outcome in ALL patients with late FDC.
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Risk assessment of relapse by lineage-specific monitoring of chimerism in children undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia
Preuner, S., Peters, C., Potschger, U., Daxberger, H., Fritsch, G., Geyeregger, R., Schrauder, A., von Stackelberg, A., Schrappe, M., Bader, P., et al
Haematologica. 2016;101(6):741-6
Abstract
UNLABELLED Allogeneic hematopoietic stem cell transplantation is required as rescue therapy in about 20% of pediatric patients with acute lymphoblastic leukemia. However, the relapse rates are considerable, and relapse confers a poor outcome. Early assessment of the risk of relapse is therefore of paramount importance for the development of appropriate measures. We used the EuroChimerism approach to investigate the potential impact of lineage-specific chimerism testing for relapse-risk analysis in 162 pediatric patients with acute lymphoblastic leukemia after allogeneic stem cell transplantation in a multicenter study based on standardized transplantation protocols. Within a median observation time of 4.5 years, relapses have occurred in 41/162 patients at a median of 0.6 years after transplantation (range, 0.13-5.7 years). Prospective screening at defined consecutive time points revealed that reappearance of recipient-derived cells within the CD34(+) and CD8(+) cell subsets display the most significant association with the occurrence of relapses with hazard ratios of 5.2 (P=0.003) and 2.8 (P=0.008), respectively. The appearance of recipient cells after a period of pure donor chimerism in the CD34(+) and CD8(+) leukocyte subsets revealed dynamics indicative of a significantly elevated risk of relapse or imminent disease recurrence. Assessment of chimerism within these lineages can therefore provide complementary information for further diagnostic and, potentially, therapeutic purposes aiming at the prevention of overt relapse. This study was registered at clinical. TRIALS gov with the number NC01423747.