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  • Walter de Gruyter GmbH  (2)
  • Unknown  (2)
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  • Walter de Gruyter GmbH  (2)
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  • 1
    In: Clinical Chemistry and Laboratory Medicine (CCLM), Walter de Gruyter GmbH, Vol. 57, No. 5 ( 2019-04-24), p. 641-647
    Abstract: Minimal residual disease (MRD) and hematopoietic chimerism testing influences clinical decision and therapeutic intervention in patients after allogeneic stem cell transplantation (HSCT). However, treatment approaches to induce complete donor chimerism and MRD negativity can lead to complications such as graft-versus-host disease (GvHD) and marrow aplasia. Therefore, there is a need for comprehensive characterization of the molecular remission status after transplantation. Methods We analyzed 764 samples from 70 patients after HSCT for the simultaneous measurement of chimerism and molecular targets used for MRD testing with a digital PCR (dPCR) platform. Results Mixed chimerism (MC) was detected in 219 samples from 37 patients. The mean percentage of host derived DNA in these clinical samples was 4.3%. Molecular relapse with a positive MRD marker and/or increased WT1 expression was observed in 15 patients. In addition to WT1 overexpression, other MRD positive markers were: NPM1 (Type A, B, K), DNMT3A (R882H), MLL-PTD, IDH1 (R132H) and KRAS (G12S). Increasing MC was observed in 15 patients. This group of patients showed either a positive MRD marker, increased WT1 expression or both. Next, we analyzed whether MC or the molecular target for MRD was first detected. MC and MRD marker positivity in this group was first detected in six and two patients, respectively. In the remaining seven patients MC and MRD positivity was detected simultaneously. Conclusions The combination of MRD and chimerism markers in a dPCR platform represents a practical, sensitive and accurate diagnostic tool for the comprehensive assessment of the molecular remission status of patients undergoing HSCT.
    Type of Medium: Online Resource
    ISSN: 1437-4331 , 1434-6621
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2019
    detail.hit.zdb_id: 1492732-9
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 2
    In: Clinical Chemistry and Laboratory Medicine (CCLM), Walter de Gruyter GmbH, Vol. 55, No. 8 ( 2017-07-26), p. 1115-1121
    Abstract: Clinical decision making after allogeneic stem cell transplantation (HSCT) is partially based on hematopoietic chimerism analysis. Polymerase chain reaction amplification of polymorphic short tandem repeats (STR-PCR) is currently considered the gold standard for chimerism surveillance after transplantation. Nevertheless, this method has shown several limitations. Emerging technologies such as digital PCR (dPCR) has been applied to detect hematopoietic chimerism. Despite previous reports, the clinical usefulness of dPCR is unclear because the studies were performed in limited patient populations with short follow-ups. Methods: In order to compare hematopoietic chimerism detection time and rate, we analyzed 591 samples from 155 patients undergoing gender-mismatched HSCT using STR-PCR and dPCR. We also established the correlation between both methods in artificial DNA mixtures prepared in known proportions and in clinical samples. Results: Depending on the artificial DNA mixture analyzed the correlation coefficient between both methods was 0.9946 and 0.9732. The limit of detection for dPCR was 0.01%. Of 157 samples with donor and recipient DNA, mixed chimerism (MC) was detected solely by dPCR in 66 samples. Within the group of patients relapsing after HSCT (n=32) MC was detected earlier in 15 of these patients with dPCR in comparison with STR-PCR. The mean time from MC detection to relapse was 155 days (range: 13–385 days) and 65 days (range: 0–203 days) for dPCR and STR-PCR, respectively. Conclusions: dPCR is a sensitive and accurate method for the quantification of hematopoietic chimerism allowing earlier MC detection compared to STR-PCR.
    Type of Medium: Online Resource
    ISSN: 1437-4331 , 1434-6621
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2017
    detail.hit.zdb_id: 1492732-9
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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