Comparison of donor chimerism following myeloablative and nonmyeloablative allogeneic hematopoietic SCT

Abstract

Surveillance of hematopoietic chimerism following hematopoietic SCT (HSCT) with nonmyeloablative (NMA) preparative regimens is standard to assess the need for clinical intervention. Monitoring of donor chimerism following HSCT with myeloablative (MA) preparative regimens is, however, not considered useful because engraftment is thought to occur rapidly and consistently. This study compares the timing of donor hematopoietic cell engraftment in patients undergoing NMA conditioning with fludarabine and TBI with those receiving MA conditioning with BU-or TBI-based regimens. Achievement of X90% donor leukocyte chimerism occurred rapidly and consistently in all three groups and time to achievement of X90% donor T cells was similar among the three groups (P ¼ 0.57). Achievement of X90% donor leukocyte chimerism was not associated with risk of acute or chronic GVHD, graft rejection, relapse or all cause mortality in multivariate analyses. Donor T-cell chimerism of X90% was significantly associated with development of extensive chronic GVHD. The value of routine surveillance of chimerism following any of the preparative regimens used in this study should be reevaluated.

Reduced-intensity allografting in patients with therapy-related myeloid neoplasms and active primary malignancies

“…When no full donor chimaerism was achieved by day þ 28 or graft failure was suspected, the analysis was repeated at regular intervals. 25 DNA was extracted from both peripheral blood granulocytes and sorted CD3 þ T-lymphocytes, and STR sequences were analysed with a commercially available kit (AmpFlSTR Profiler Plus KIT, Applied Biosystems, Warrington, UK). Complete donor chimaerism was defined as more than 99% donor cells.…”

The practical application of chimerism analyses in allogeneic stem cell transplant recipients: Blood chimerism is equivalent to marrow chimerism

“…In reduced-intensity conditioning SCT, which is known to have a greater rate of graft loss than myeloablative SCT, chimerism is a measure of engraftment and can predict graft loss (Ozyurek et al, 2008). A recent study showed, however, that those receiving RIC conditioning generally attained full donor chimerism at a similar rate as those receiving myeloablative conditioning (Mickelson et al, 2011). The authors rightly assert that the role of chimerism surveillance is unclear at this time and, given the great variability of institutional practices, the issue needs to be addressed.…”

Rapid single nucleotide polymorphism based method for hematopoietic chimerism analysis and monitoring using high-speed droplet allele-specific PCR and allele-specific quantitative PCR

“…FAM, fluorescein amidite; BHQ, black hole quencher. receiving a nonmyeloablative conditioning regimen, donor lymphocyte infusions, or second transplantation [24,25]. In the present study, we developed a rapid SNP-based chimerism analysis method involving SNP genotyping by droplet-AS-PCR pre-HSCT samples and quantitation of recipient DNA using AS-qPCR for SNP genotype following HSCT.…”