Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning

• Published in: Bone marrow transplantation (Basingstoke) Vol. 31; no. 5; pp. 387 - 392
• Main Authors: VALCARCEL, D, MARTINO, R, SAN MIGUEL, J. F, SIERRA, J, CABALLERO, D, MATEOS, M. V, PEREZ-SIMON, J. A, CANALS, C, FERNINDEZ, F, BARGAY, J, MUNIZ-DIAZ, E, GONZALEZ, M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.03.2003
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood; Bone marrow; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Busulfan; Chemotherapy; Chimerism; Conditioning; Disease-Free Survival; Dosage and administration; Female; Fludarabine; Graft rejection; Graft versus host disease; Graft versus host reaction; Graft vs Host Disease - etiology; Grafts; Hematopoietic stem cells; Humans; Leukocytes (granulocytic); Lymphocytes; Lymphocytes T; Male; Medical sciences; Melphalan; Middle Aged; Multivariate analysis; Peripheral blood; Peripheral Blood Stem Cell Transplantation; Physiological aspects; Polymerase chain reaction; Prevention; Prospective Studies; Risk factors; Short tandem repeats; Stem cell transplantation; Stem cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Chimera; Transplantation Conditioning; Transplantation, Homologous; Spain; Human; Immunopathology; Hematology; Stem cell; Hematopoietic cell; Homograft; Graft versus host reaction; reduced-intensity conditioning; Blood; Polymerase chain reaction; allotransplant; Graft; Complication; Evolution; Chimerism; Molecular biology; graft-versus-host disease
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1703846

We have performed a prospective study to evaluate early chimerism and its kinetics after allogeneic peripheral blood stem cell transplantation among 68 patients who received a reduced-intensity conditioning (RIC) regimen with fludarabine plus melphalan (n=40) or busulphan (n=28). Chimerism was analyzed by polymerase chain reaction amplification of short tandem repeats in unfractionated (UF) and/or fractionated nucleated cells from bone marrow and peripheral blood (PB). All of the patients showed initial donor engraftment and no patient presented primary or secondary graft failure. In UF samples, the probability of achieving stable complete donor chimerism (CDC) in PB within the first 6 months was 70% on day +30, 85% on day +100 and 95% on day +180. CDC in granulocytes was observed in nearly all cases from day +30 onwards. CDC in T cells, however, differed among melphalan and busulphan recipients during the first 3 months (100 vs 0% on day +30 and 93 vs 20% on day +90, respectively). In multivariate analysis, the only significant variable associated with the achievement of early CDC was having received more than two lines of chemotherapy pretransplant (P<0.02). No correlation was found between the rate of achieving early CDC and the occurrence of acute graft-versus-host disease (GVHD) or disease progression post-transplant. In multivariate analysis, the only variable that influenced the incidence of disease progression post-transplant was the development of chronic extensive GVHD (P<0.05). In conclusion, a state of CDC is readily obtained within the first 6 months after our RIC protocols. Donor myeloid engraftment occurs rapidly in all cases, while early T-cell CDC is more common in more immunosuppressed hosts and, perhaps, in melphalan recipients.