Correlation between the kinetics of CD3+ chimerism and the incidence of graft-versus-host disease in patients undergoing allogeneic hematopoietic stem cell transplantation.
ABSTRACT Graft-versus-host disease (GvHD) remains a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT). Early diagnosis and treatment may improve patient outcomes. A prospective study to investigate the relationship between chimerism kinetics and the development of acute or chronic GvHD was carried out. Split chimerism in association with the onset of GvHD was also analyzed.
Thirty-three patients with hematologic diseases treated with allogeneic HSCT were analyzed. They were conditioned with myeloablative or reduced intensity regimens and grafted with peripheral blood (PB) or bone marrow stem cells. GvHD prophylaxis consisted of cyclosporine and methotrexate. Chimerism evaluation was performed on PB mononuclear cells and purified cell subsets consisting of separated CD3(+) T cells, monocytes (CD14(+)), and granulocytes (CD15(+)). Chimerism analysis was performed at 30, 60, 120, and a median of 200 days after HSCT.
Acute GvHD was diagnosed in 19 patients and chronic GvHD in 16. On day 30, no relation was found between the level of donor chimerism and aGvHD. Upon univariate analysis, decreasing mixed chimerism among CD3(+) and infused CD34(+) cell numbers was significantly correlated with acute GvHD development, while the PB stem cell source, reduced-intensity conditioning regimen, and female donor sex were associated with an increased risk of chronic GvHD. In multivariate analysis, the risk of acute GvHD correlated only with the CD34(+) cell dose, while the risk of extensive chronic GvHD was associated with high CD3(+) donor chimerism on day 30. Patients with versus without split chimerism (T cell vs myeloid lines) did not differ statistically in their incidence of acute GvHD or chronic GvHD.
Our results supported the belief that chimerism kinetics or longitudinal chimerism evaluation is of greater significance than isolated absolute values of the percentage of chimerism at a single point after HSCT. The observations suggest that longitudinal monitoring of chimerism in CD3(+) T-cell subsets is an acceptable method to predict the development of GvHD among patients undergoing HSCT.
- SourceAvailable from: Anne Sproul
Article: Monitoring of chimerism following allogeneic haematopoietic stem cell transplantation (HSCT): Technical recommendations for the use of Short Tandem Repeat (STR) based techniques, on behalf of the United Kingdom National External Quality Assessment Service for Leucocyte Immunophenotyping Chimerism Working Group.[Show abstract] [Hide abstract]
ABSTRACT: Analysis of short tandem repeats (STR) is the predominant method for post-transplant monitoring of donor engraftment. It can enable early detection of disease relapse, level of engraftment and provide useful information on the graft-versus-host disease (GVHD)/graft-versus-tumour (GVT) effect, facilitating therapeutic intervention. Harmonization and standardization of techniques and result interpretation is essential to reduce the impact of laboratory variability on both clinical management and the results of multi-centre clinical trials. However, the United Kingdom National External Quality Assessment Service for Leucocyte Immunophenotyping (UK NEQAS LI) has highlighted significant issues inherent in STR testing that impact upon inter- and intra- laboratory variation. We present here consensus best practice guidelines and recommendations for STR chimerism testing, data interpretation and reporting that have been drawn up and agreed by a consortium of 11 UK and Eire clinical laboratories. This document uses data obtained from the UK NEQAS LI Post-Stem Cell Transplant (SCT) Chimerism Monitoring Programme.British Journal of Haematology 08/2014; · 4.94 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: Chimerism defines the amount of donor versus recipient hematopoiesis following allogeneic stem cell transplant (SCT). PCR-based analyses of short tandem repeats (STRs) are commonly used and are accurate and applicable to allogeneic transplant recipients. These analyses are performed on blood and marrow aspirates, but it is unknown if analyses of both are required. We performed a retrospective analysis of 42 consecutive adult allogeneic SCT recipients at our institution to determine if both sample types are needed. METHODS: Chimerism status was determined by multiplex PCR and capillary electrophoresis of STRs. Analyses were performed at 30, 60, and 90days after SCT on both unfractionated blood and unfractionated marrow aspirate. RESULTS: PCR analyses of STRs for chimerism performed on unfractionated blood highly correlated with results obtained using unfractionated marrow aspirates at 30, 60, or 90days following transplant (p<0.0001 for each time point). Overall and relapse-free survival of patients experiencing full donor chimerism was not statistically different from patients demonstrating mixed chimerism at days 30, 60, and 90 following SCT. CONCLUSIONS: PCR-based chimerism analyses on blood provide similar information as marrow aspirate analyses. These are unique results suggesting that chimerism analyses may be assessed on peripheral blood alone.Experimental and Molecular Pathology 07/2012; · 2.88 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: This study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99·9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post-transplant outcome. Ninety-four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post-transplant dates, using a real-time polymerase chain reaction method with 0·1% sensitivity. Cumulative incidence of cDC at 1 year post-transplantation was 61·8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0·03), older age (above 2·16 years, the first quartile of age, P = 0·0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5-6/6, P < 0·001) increased the probability of post-transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99·9% donor chimerism on days 15–30 post-transplant) appeared useful to predict engraftment (P = 0·003) as well as acute and chronic graft-versus-host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ≤99·9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT.British Journal of Haematology 04/2014; · 4.94 Impact Factor