Palavras-chave
biomarkers
chimerism
genetics
leukemia
Como Citar
Resumo
Background: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is considered a potential therapy for long-term survival, used as post-remission therapy in leukemias whose response to earlier treatments was not effective. Relapse and associated disease progression are some of the main complications after the transplantation period that may lead to uncertain clinical endings. Transplantation monitoring markers must be effective in the follow-up disease [1-5]. Aim: This study aimed to evaluate the presence of mixed chimerism (MC) in peripheral blood along the follow-up of patients after Allo-HSCT to optimize the predictive value of recurrence of the underlying disease. Methods: Peripheral blood samples from 143 individuals with Acute Myeloblastic Leukemia (AML) and 80 individuals with B/T Cell Acute Lymphoblastic Leukemia (LLB/T) between January 2013 and December 2019. Chimerism conditions were performed at the first moment of evidence of MC and one year after transplantation, using a PCR multiplex (Mentype® Chimera®) from Biotype. Results: The mean age of patients undergoing transplantation was 43.8 and 31 years and the mean survival was 11,1 and 12 months for AML and LLB/T patients, respectively. After 1 year of HSCT, 30% and 31,7% of LLB/T and AML patients showed complete chimerism (CC), opposed 70% and 68,3% exhibit MC. However, 68% and 72% of that denote a progressive MC. On LLB/T and AML patients, 50% and 60% keeped MC; 39% and 33% evolved from MC to CC; 11% and 5% regressed from CC to MC, respectively. Conclusions: The evaluation of chimerism over one year of Allo-HSCT in both leukemias, concluded that although the percentage of CC was lower than the MC, the percentage of progressive chimerism was significantly more evident than decreasing chimerism, which may indicate a decrease probably of recurrence and a better prognosis. Most patients maintained stable MC, supporting the idea of balance between donor and recipient cells, or evolved from MC to CC, which shows a positive evolution in transplant engraftment [6-12].
Referências
[1] Koreth, J; Kim, HT; Nikiforow, S; Milford, EL; Armand, P; Cutler, C., et al. Donor chimerism early after reduced-intensity conditioning hematopoietic stem cell transplantation predicts relapse and survival. Biology of Blood and Marrow Transplantation 2014, 20(10), 1516–1521. https://doi.org/10.1016/j.bbmt.2014.05.025
[2] Ozdemir, ZN; Civriz Bozdağ, S. Graft failure after allogeneic hematopoietic stem cell transplantation. Transfusion and Apheresis Science 2018, 57(2), 163–167. https://doi.org/10.1016/j.transci.2018.04.014
[3] Rautenberg, C; Germing, U; Haas, R; Kobbe, G; Schroeder, T. Relapse of acute myeloid leukemia after allogeneic stem cell transplantation: Prevention, detection, and treatment. In International Journal of Molecular Sciences 2019, 20(1), 228. https://doi.org/10.3390/ijms20010228
[4] Reshef, R; Hexner, EO; Loren, AW; Frey, NV; Stadtmauer, EA; Luger, SM; et al. Early donor chimerism levels predict relapse and survival after allogeneic stem cell transplantation with reduced-intensity conditioning. Biology of Blood and Marrow Transplantation 2014, 20(11), 1758–1766. https://doi.org/10.1016/j.bbmt.2014.07.003
[5] Selim, AG; Moore, AS. Molecular Minimal Residual Disease Monitoring in Acute Myeloid Leukemia: Challenges and Future Directions. In Journal of Molecular Diagnostics 2018, 20(4), 389–397. https://doi.org/10.1016/j.jmoldx.2018.03.005
[6] Döhner, H; Estey, E; Grimwade, D; Amadori, S; Appelbaum, FR; Büchner, T; et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017, 129(4), 424–447. https://doi.org/10.1182/blood-2016-08-733196
[7] Hansrivijit, P; Gale, RP; Barrett, J; Ciurea, SO. Cellular therapy for acute myeloid Leukemia – Current status and future prospects. Blood Reviews 2019, 37, 100578. https://doi.org/10.1016/j.blre.2019.05.002
[8] Knight-Perry, J; Miller, WP; Orchard, PJ; Smith, AR. Peripheral Blood Lymphoid and Myeloid Chimerism after Hematopoietic Stem Cell Transplant for Non-Malignant Disorders. Biology of Blood and Marrow Transplantation 2018, 24(3), S309. https://doi.org/10.1016/j.bbmt.2017.12.356
[9] Koreth, J.; Antin, J.H.; Cutler, C. Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome in Adults. In Hematology: Basic Principles and Practice, Seventh Ed.; Elsevier, 2018; pp. 970-980. https://doi.org/10.1016/B978-0-323-35762-3.00061-5
[10] Sanz-Piña, E; Santurtún, A; Zarrabeitia, MT. Forensic implications of the presence of chimerism after hematopoietic stem cell transplantation. Forensic Science International 2019, 302, 109862. https://doi.org/10.1016/j.forsciint.2019.06.020
[11] Tsirigotis, P; Byrne, M; Schmid, C; Baron, F; Ciceri, F; Esteve, J; et al. Relapse of AML after hematopoietic stem cell transplantation: Methods of monitoring and preventive strategies. A review from the ALWP of the EBMT. Bone Marrow Transplantation 2016, 51(11), 1431–1438. https://doi.org/10.1038/bmt.2016.167
[12] Tyler, J; Kumer, L; Fisher, C; Casey, H; Shike, H. Personalized Chimerism Test that Uses Selection of Short Tandem Repeat or Quantitative PCR Depending on Patient’s Chimerism Status. Journal of Molecular Diagnostics 2019, 21(3), 483–490. https://doi.org/10.1016/j.jmoldx.2019.01.007
Este trabalho encontra-se publicado com a Licença Internacional Creative Commons Atribuição-NãoComercial-SemDerivações 4.0.
Direitos de Autor (c) 2025 C. Serra, G. Martins, B. Fernandes, I. Godinho, C. Palmeira, M.E. Sousa