Short Tandem Repeats (STRs) as Biomarkers for the Quantitative Follow-Up of Chimerism after Stem Cell Transplantation: Methodological Considerations and Clinical Application

• Published in: Genes 2020-08, Vol.11 (9), p.993
• Main Authors: Navarro-Bailón, Almudena, Carbonell, Diego, Escudero, Asunción, Chicano, María, Muñiz, Paula, Suárez-González, Julia, Bailén, Rebeca, Oarbeascoa, Gillen, Kwon, Mi, Díez-Martín, José Luis, Martínez-Laperche, Carolina, Buño, Ismael
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological markers; Biomarkers; Biomarkers - metabolism; Bone marrow; Bone Marrow - metabolism; Capillary electrophoresis; Child; Chimerism; Complications and side effects; Deoxyribonucleic acid; Diagnosis; Disease; DNA; DNA - genetics; Female; Follow-Up Studies; Genetic aspects; Genetic disorders; Health aspects; Hematology; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; Male; Microsatellite Repeats - genetics; Middle Aged; Patients; Peripheral blood; Polymerase chain reaction; Real-Time Polymerase Chain Reaction - methods; Recurrence; Retrospective Studies; Risk factors; Short tandem repeats; Stem cell transplantation; Stem cells; Transplants & implants; Young Adult
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes11090993

Chimerism refers to the relative proportion of donor and recipient DNA after hematopoietic stem cell transplantation (HSCT) and its quantitative follow-up is of great clinical utility in this setting. PCR of short tandem repeats (STR-PCR) constitutes the gold standard method for chimerism quantification, although more sensitive PCR techniques (such as qPCR) have recently arisen. We compared the sensitivity and the quantification capacity of both techniques in patient samples and artificial mixtures and demonstrated adequate performance of both methods, with higher sensitivity of qPCR and better quantification skills of STR-PCR. By qPCR, we then prospectively followed up 57 patients that were in complete chimerism (CC) by STR-PCR. Twenty-seven patients (59%) showed 0.1-1% recipient DNA in the bone marrow. Only 4 patients presented 0.1-1% recipient DNA in peripheral blood (PB), and one of them relapsed. Finally, by qPCR, we retrospectively studied the last sample that showed CC by STR-PCR prior to relapse in 8 relapsed patients. At a median of 59 days prior to relapse, six patients presented mixed chimerism by qPCR in PB. Since both approaches have complementary characteristics, we conclude that different techniques should be applied in different clinical settings and therefore propose a methodological algorithm for chimerism follow-up after HSCT.