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Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m was associated with an increased incidence of MDC at day 28 ( P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen. [ABSTRACT FROM AUTHOR]

Lineage-specific chimerism studies are commonly obtained at several time points after nonmyeloablative hematopoietic cell transplantation to assess the tempo and degree of engraftment, and to monitor graft rejection. For patients who receive myeloablative transplants, the value of frequent chimerism analyses using sensitive molecular techniques is less certain. In this study, a retrospective analysis was performed to assess the transplant outcome of 89 adult patients with ALL who had chimerism studies of unfractionated BM cells or peripheral blood subsets performed approximately 80 days after transplantation. These patients received unmanipulated, myeloablative transplants using either HLA-identical or HLA-mismatched, related or unrelated donor stem cells. Incomplete donor engraftment was present only in the CD3+ peripheral blood T cells in a small percentage of patients. There was no correlation of mixed chimerism with transplant outcome. Routine ‘day 80’ chimerism studies in this group of patients who receive intensive, myeloablative conditioning regimens are not recommended.Bone Marrow Transplantation (2008) 42, 271–274; doi:10.1038/bmt.2008.155; published online 26 May 2008 [ABSTRACT FROM AUTHOR]

Summary:Mast cell leukemia (MCL) is a rare form of aggressive mastocytosis with a reported median survival below 6 months. Casuistic reports suggest the effectiveness of allogeneic bone marrow transplantation (BMT) for MCL. However, these reports lack clear evidence for a graft-versus-mast-cell (GvMC) effect. We prospectively investigated the GvMC at different time points after allogeneic BMT and donor-lymphocyte infusions (DLI). Samples were gathered from a patient with MCL treated with allogeneic BMT from an unrelated HLA identical donor. Parameters for detection of a GvMC effect included flow cytometrical analysis of mast cell (MC) populations in peripheral blood and BM, BM smear and histology, chimerism analysis of flow cytometrically sorted BM CD117+/CD34-MC and testing for anti-mast cell reactivity of donor lymphocytes by interferon (IFN)-?ELISPOT. DLIs reduced MC from 5 to 0.5%. MC chimerism analysis demonstrated a complete recipient genotype after BMT, suggesting that the persistent mastocytosis was part of residual neoplastic disease. At 3.7 years after BMT, there is some evidence for relapse. In summary, BMT and DLIs attenuated the mastocytosis from an aggressive to an indolent form and may have improved the patients'prognosis. The in vitro data of our study indicate for the first time the existence of a GvMC effect.Bone Marrow Transplantation (2004) 34, 515-519. doi:10.1038/sj.bmt.1704627 Published online 26 July 2004 [ABSTRACT FROM AUTHOR]

Chimerism analysis is a well-established method for monitoring the state of hematopoietic stem cell transplantation (HSCT) over time by analyzing peripheral blood or bone marrow samples of the recipient in several malignant and non-malignant hematologic diseases. From a clinical point of view, a continuous monitoring is fundamental for an effective early therapeutic intervention. This paper provides a comparative overview of the main molecular biology techniques which can be used to study chimerism after bone marrow transplantation, focusing on their advantages and disadvantages. According to the examined literature, short tandem repeats (STR) analysis through simple PCR coupled with capillary electrophoresis (STR-PCR) is the most powerful method which guarantees a high power of differentiation between different individuals. However, other methods such as real-time quantitative PCR (qPCR), digital PCR (dPCR), and next-generation sequencing (NGS) technology were developed to overcome the technical limits of STR-PCR. In particular, these other techniques guarantee a higher sensitivity, which allows for the detection of chimerism at an earlier stage, hence expanding the window for therapeutic intervention. After a comparative evaluation of the various techniques, it seems clear that STR-PCR still remains the gold standard option for chimerism study, even if it is likely that both dPCR and NGS could supplement or even replace the common methods of STR analysis. [ABSTRACT FROM AUTHOR]