Prevalência do quimerismo após transplante de células hematopoiéticas não-mieloablativo
Palavras-chave:
Repetições mini-satélites, Neoplasia hematológicas, Transplante de medula óssea, Hibridização in situ fluorescente, Quimerismo, LeucemiaResumo
CONTEXTO E OBJETIVO: O transplante de células hematopoiéticas não-mieloablativo é realizado em pacientes com doenças onco-hematológicas que não suportam condicionamentos ablativos devido à elevada idade ou ao acometimento por comorbidades. Esta abordagem não elimina completamente as células do hospedeiro, resultando, inicialmente, em quimerismo misto. A persistência do quimerismo misto na evolução de longo prazo resulta na rejeição ao enxerto e recaída. O acometimento pela doença do enxerto contra hospedeiro é concomitante ao quimerismo completo e ao efeito enxerto versus tumor. O objetivo deste estudo foi avaliar a prevalência do quimerismo em doenças onco-hematológicas tratadas com o transplante não-mieloablativo de células hematopoiéticas. TIPO DE ESTUDO E LOCAL: Estudo clínico observacional do estado de quimerismo após transplante antígenos leucocitários humanos-idêntico nãomieloabaltivo realizado na Disciplina de Hematologia e Hemoterapia da Universidade Federal de São Paulo. MÉTODOS: Analisamos sequencialmente a amplificação dos primers APO-B, D1S80, DxS52, FVW, 33,6, YNZ-22, H-ras pelo VNTR (variable number of tandem repeats) em 17 pares e FISH (fluorescent in situ hybridization) pela sonda XY e do primer SRY em 13 pares de não relacionados a sexo. RESULTADO: A informatividade dos primers pelo VNTR foi de 60% para APO-B; 75% D1S80; 36% DxS52; 14% FVW; 40% YNZ-22 e 16% H-ras. O primer SRY foi informativo em receptores femininos com doadores masculinos. O método XY-FISH foi informativo em 100% dos pares de não relacionado a sexo. CONCLUSÃO: Estes métodos foram sensíveis e informativos. No VNTR, a associação do APO-B com D1S80 mostrou 88% de informatividade. O FISH, método quantitativo, foi mais sensível, porém com desvantagem de ser usado somente nos pares não relacionados a sexo.
Downloads
Referências
Sreenan JJ, Pettay JD, Tbakhi A, et al. The use of amplified variable number of tandem repeats (VNTR) in the detection of chimerism following bone marrow transplantation. A comparison with restriction fragment length polymorphism (RFLP) by Southern blotting. Am J Clin Pathol. 1997;107(3):292-8.
Antin JH, Childs R, Filipovich AH, et al. Establishment of complete and mixed donor chi- merism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings of the International Bone Marrow Transplant Re- gistry and the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2001;7(9):473-85.
Talwar S, Khan F, Nityanand S, Agrawal S. Chimerism monitoring following allogeneic hema- topoietic stem cell transplantation. Bone Marrow Transplant. 2007;39(9):529-35.
Ariffin H, Daud SS, Mohamed Z, Ibrahim K, Lee TF, Chong LA. Evaluation of two short tan- dem repeat multiplex systems for post-haematopoietic stem cell transplantation chimerism analysis. Singapore Med J. 2007;48(4):333-7.
Mackinnon S, Papadopoulos EB, Carabasi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus- host disease. Blood. 1995;86(4):1261-8.
Khan F, Agarwal A, Agrawal S. Significance of chimerism in hematopoietic stem cell trans- plantation: new variations on an old theme. Bone Marrow Transplant. 2004;34(1):1-12.
Hibi S, Tsunamoto K, Todo S, et al. Chimerism analysis on mononuclear cells in the CSF after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1997;20(6): 503-6.
Dewald G, Stallard R, Al Saadi A, et al. A multicenter investigation with interphase fluo- rescence in situ hybridization using X- and Y-chromosome probes. Am J Med Genet. 1998;76(4):318-26.
Lui YY, Chik KW, Chiu RW, Ho CY, Lam CW, Lo YM. Predominant hematopoietic origin of cell- free DNA in plasma and serum after sex-mismatched bone marrow transplantation. Clin Chem. 2002;48(3):421-7.
Sufliarska S, Minarik G, Horakova J, et al. Establishing the method of chimerism monito- ring after allogeneic stem cell transplantation using multiplex polymerase chain reaction amplification of short tandem repeat markers and Amelogenin. Neoplasma. 2007;54(5): 424-30.
Koldehoff M, Steckel NK, Hlinka M, Beelen DW, Elmaagacli AH. Quantitative analysis of chimerism after allogeneic stem cell transplantation by real-time polymerase chain reac- tion with single nucleotide polymorphisms, standard tandem repeats, and Y-chromosome- specific sequences. Am J Hematol. 2006;81(10):735-46.
McSweeney PA, Storb R. Mixed chimerism: preclinical studies and clinical applications. Biol Blood Marrow Transplant. 1999;5(4):192-203.
Storb R, Yu C, Zaucha JM, et al. Stable mixed hematopoietic chimerism in dogs given donor antigen, CTLA4Ig, and 100 cGy total body irradiation before and pharmacologic immunosu- ppression after marrow transplant. Blood. 1999;94(7):2523-9.
Bosi A, Bartolozzi B, Guidi S. Allogeneic stem cell transplantation. Transplant Proc. 2005;37(6):2667-9.
Giralt S. Allografting older patients--myths and realities. Biol Blood Marrow Transplant. 2009;15(1 Suppl):146-8.
Khouri IF, Keating M, Körbling M, et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor- cell transplantation as treatment for lymphoid malignancies. J Clin Oncol. 1998;16(8): 2817-24.
Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytore- duction for the treatment of malignant and nonmalignant hematologic diseases. Blood. 1998;91(3):756-63.
Slavin S. New strategies for bone marrow transplantation. Curr Opin Immunol. 2000;12(5):542-51.
Tsirigotis P, Bitan RO, Resnick IB, et al. A non-myeloablative conditioning regimen in allo- geneic stem cell transplantation from related and unrelated donors in elderly patients. Haematologica. 2006;91(6):852-5.
Martinelli G, Trabetti E, Farabegoli P, et al. Early detection of bone marrow engraftment by amplification of hypervariable DNA regions. Haematologica. 1997;82(2):156-60.
Smith AG, Martin PJ. Analysis of amplified variable number tandem repeat loci for eva- luation of engraftment after hematopoietic stem cell transplantation. Rev Immunogenet. 1999;1(2):255-64.
Kraus G, Geffin R, Spruill G, et al. Cross-clade inhibition of HIV-1 replication and cytopa- thology by using RNase P-associated external guide sequences. Proc Natl Acad Sci U S A. 2002;99(6):3406-11.
Richards B, Heilig R, Oberlé I, Storjohann L, Horn GT. Rapid PCR analysis of the St14 (DXS52) VNTR. Nucleic Acids Res. 1991;19(8):1944.
Siva SC, Johnson SI, McCracken SA, Morris JM. Evaluation of the clinical usefulness of isolation of fetal DNA from the maternal circulation. Aust N Z J Obstet Gynaecol. 2003;43(1):10-5.
Stuppia L, Calabrese G, Di Bartolomeo P, et al. Retrospective investigation of hematopoietic chimerism after BMT by PCR amplification of hypervariable DNA regions. Cancer Genet Cytogenet. 1995;85(2):124-8.
Peake IR, Bowen D, Bignell P, et al. Family studies and prenatal diagnosis in severe von Wil- lebrand disease by polymerase chain reaction amplification of a variable number tandem repeat region of the von Willebrand factor gene. Blood. 1990;76(3):555-61.
Ugozzoli L, Yam P, Petz LD, et al. Amplification by the polymerase chain reaction of hyperva- riable regions of the human genome for evaluation of chimerism after bone marrow trans- plantation. Blood. 1991;77(7):1607-15.
Boerwinkle E, Xiong WJ, Fourest E, Chan L. Rapid typing of tandemly repeated hypervariable loci by the polymerase chain reaction: application to the apolipoprotein B 3’ hypervariable region. Proc Natl Acad Sci U S A. 1989;86(1):212-6.
Budowle B, Chakraborty R, Giusti AM, Eisenberg AJ, Allen RC. Analysis of the VNTR locus D1S80 by the PCR followed by high-resolution PAGE. Am J Hum Genet. 1991;48(1): 137-44.
Hassan R, Bonamino MH, Braggio E, et al. A systematic approach to molecular quantitative determination of mixed chimaerism following allogeneic bone marrow transplantation: an analysis of its applicability in a group of patients with severe aplastic anaemia. Eur J Hae- matol. 2004;73(3):156-61.
Muniz ES, Plassa F, Amselem S, Goossens M, Vernant JP. Molecular analysis of polymorphic loci to study chimerism after allogeneic bone marrow transplantation. Heteroduplex analysis in denaturing gradient gel electrophoresis: a new approach to detecting residual host cells. Transplantation. 1994;57(3):451-6.
van Leeuwen JE, van Tol MJ, Bodzinga BG, et al. Detection of mixed chimaerism in flow- sorted cell subpopulations by PCR-amplified VNTR markers after allogeneic bone marrow transplantation. Br J Haematol. 1991;79(2):218-25.
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.
