Abstract
Hematopoietic chimerism (HpC) was assayed monthly using a sensitive, polymerase chain reaction (PCR) -based method in consecutive patients. Between January 1998 and April 2002, 181 patients underwent non-T cell depleted allogeneic hematopoietic cell transplantation (HCT). A total of 163 patients were evaluable for HpC at 1 month (11 early deaths; no informative band for HpC analysis/no genomic DNA in seven). In all, 53 of 163 patients (33%, median recipient DNA of 15% (range 5-95)), 39 of 151 patients (26%), and 27 of 142 patients (19%) showed mixed chimerism (MC) at 1, 2, and 3 months after HCT, respectively. Conditioning regimen (busulfan-fludarabine-ATG vs BuCy, relative risk 3.99 (95% CI 1.16-10.92)), neutrophil engraftment (>/=day 17 vs </=day 16, relative risk 2.49 (95% CI 1.14-5.41)), and acute graft-versus-host disease within 30 days (none vs yes, relative risk 4.78 (95% CI 1.50-15.17)) were independent variables that showed significant correlation with having >/=5% recipient DNA at 1 month. Five patients experienced secondary graft failure. All five patients showed MC at 1 month with median recipient DNA of 40%. None of the 109 patients with complete chimerism experienced graft failure (P=0.002). Our study showed that MC shown on monthly analysis of HpC after allogeneic HCT is a significant predictor of secondary graft failure. Bone Marrow Transplantation (2003) 32, 423-431. doi:10.1038/sj.bmt.1704147
Highlights
Pre and post transplant factors associated with mixed chimerism (MC) based on multivariate analysis The variables that showed a significance level of P-value o 0.1 on univariate analysis, as well as the patient age and sex, were considered in the variable selection process: conditioning regimen (Bu–Flu–ATG vs BuCy, relative risk 3.99); neutrophil engraftment day (day 17 or later vs day 16 or sooner, relative risk 2.49), and the presence of acute graft-versus-host disease (GVHD) within 30 days after hematopoietic cell transplantation (HCT) (none vs yes, relative risk 4.78) were independent variables that showed a significant correlation with the likelihood of having recipient DNA of 5% or over at 1 month after HCT (Table 2)
Four patients relapsed before day 120 of HCT and were excluded from the analysis, since a relapsing leukemic clone could interfere with the interpretation of the effect of early Hematopoietic chimerism (HpC) on the relapse of leukemia
Our study showed that hematopoietic chimerism at 1 month after HCT had a predictive value for subsequent occurrence of secondary graft failure (Table 3)
Summary
Consecutive patients who underwent allogeneic HCT at the University of Ulsan, Asan Medical Center in Seoul, Korea, Hemotopoietic chimerism after allogeneic HCT K-H Lee et al[424] beginning in January 1998, were enrolled in the study. same dose of G-CSF was administered daily when ANC. The HPRTB, vWA, and F13B (GenePrintt STR Systems, regimen for the prophylaxis of GVHD consisted of Promega, Madison, WI, USA) was used in the initial cyclosporine 1.5 mg/kg by intravenous infusion every 12 h screening process to identify the most informative STR starting on day À1, switched to an oral dose when oral locus in a given donor/recipient pair. The initial 19 patients who received Bu–Flu–ATG those of the donor alleles was chosen to avoid misinterfor conditioning and those who were included in a pretation of results by artifacts of the donor alleles These randomized trial comparing cyclosporine plus methotrex- artifacts are commonly generated and usually located at ate vs cyclosporine alone for the GVHD prophylaxis and one or two repeat units below the original bands by the who were assigned to the cyclosporine alone arm did not mechanism known as slipped mispairing in PCR amplificareceive methotrexate. Assays of HpC at one plotted using the Kaplan-Meier method and were com- month after HCT revealed that 54 of 163 evaluable patients pared using a log-rank test
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