Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse

Horký, Ondřej; Mayer, Jiřı́; Kablásková, Lenka; Rázga, Filip; Krejčí, Marta; Kissová, Jarmila; Borský, Marek; Ježíšková, Ivana; Dvořáková, Dana

doi:10.1111/j.1751-553x.2010.01249.x

Cited by 24 publications

(18 citation statements)

References 38 publications

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“…This is substantially earlier than most previous reports, although the heterogeneous nature of the literature complicates comparison. Studies in adults have reported a time interval to relapse of about 1 month . Two studies including children report a median of 125 and 144 days from first positive chimerism to relapse of myelodysplastic syndrome and AML, respectively .…”

Section: Discussionmentioning

confidence: 71%

Highly sensitive chimerism detection in blood is associated with increased risk of relapse after allogeneic hematopoietic cell transplantation in childhood leukemia

Haugaard

Madsen

Marquart

et al. 2019

Pediatric Transplantation

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Analysis of chimerism in blood post‐HCT using STR‐PCR is routinely applied in parallel with quantification of MRD to predict relapse of leukemia. RQ‐PCR chimerism is 10‐ to 100‐fold more sensitive, but clinical studies in children are sparse. We analyzed IMC in blood samples following transplantation for acute lymphoblastic or myeloid leukemia in 56 children. IMC was defined as a minimum increase of (a) 0.1% or (b) 0.05% recipient DNA between two samples. The risk of relapse was higher in children with IMC of both 0.1% and 0.05% compared to children without IMC (HR 12.8 [95% CI: 3.9‐41.4; P < .0001] and 7.6 [95% CI: 2.2‐26.9; P < .01], respectively). The first IMC was detected at a median of 208 days prior to relapse. The 5‐year cumulative incidence of relapse for children with a single IMC was 45.5% (CI 12.3‐74.4) and 41.0% (14.2‐66.6) for IMC above 0.1% and 0.05%, respectively. However, in 47 and 38 children never attaining IMC > 0.1% and >0.05%, 10 and 8 children relapsed, respectively. In a landmark analysis, no association was found between IMC prior to 90 days post‐HCT and subsequent relapse by either classification of IMC and AUC for RQ‐PCR chimerism was 54.2% (95 CI 27.7‐ 84.8). Although limited by a retrospective design, these results indicate that monitoring of RQ‐PCR chimerism in peripheral blood may have a role in early detection of relapse in acute childhood leukemia.

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Section: Discussionmentioning

confidence: 71%

Highly sensitive chimerism detection in blood is associated with increased risk of relapse after allogeneic hematopoietic cell transplantation in childhood leukemia

Haugaard

Madsen

Marquart

et al. 2019

Pediatric Transplantation

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“…This finding, however, is controversial because some studies failed to demonstrate a correlation between mixed chimerism after HSCT and a higher risk for relapse [26,28,29]. Nevertheless, several groups established that increasing mixed chimerism is clearly associated with higher frequency of disease relapse in different hematopoietic malignancies [1,2,3,5,6,7]. Taken together, these data illustrate that the routine assessment of chimerism is a useful approach to evaluate post-transplantation prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, achievement of complete donor-derived hematopoiesis is one of the hallmarks of successful HSCT in hematopoietic malignancies. Moreover, several studies indicate that remaining or re-emerging recipient cells after ablation and transplantation are associated with a higher risk of disease relapse [1,2,3,4,5,6,7]. Therefore, the accurate and sensitive quantification of hematopoietic chimerism is a critical aspect of post-transplantation monitoring, since the results strongly influence the therapeutic approach such as donor lymphocyte infusions, additional chemotherapy, or re-transplantation [8].…”

Section: Introductionmentioning

confidence: 99%

Monitoring of Hematopoietic Chimerism by Real-Time Quantitative PCR of Micro Insertions/Deletions in Samples with Low DNA Quantities

Bach

Tomova

Goldmann

et al. 2015

Transfus Med Hemother

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Background: Sensitive and accurate methods to detect hematopoietic chimerism after hematopoietic stem cell transplantation (HSCT) are essential to evaluate engraftment and to monitor response to therapeutic procedures such as donor lymphocyte infusion. Continuous long-term follow up, however, requires large amounts of pre-HSCT samples limiting the application of many widely used techniques for sensitive chimerism monitoring. Methods: DNAs from 42 normal healthy donors and 16 HSCT donor/recipient pairs were employed to validate the use of allele-specific insertion/deletion (indel) quantitative real-time polymerase chain reaction (qPCR) to quantify chimerism in samples with low amounts of DNA. Consequently, indel-qPCR analyses of samples from 16 HSCT patients were compared to short-tandem repeat (STR) specific PCR analyses. Results: Typing with reduced amounts of input DNA (15 vs. 60 ng) allowed for the reliable distinction of positive (mean threshold cycle (ct) 28.05) and negative (ct >36) signals. The high informativity of primer/probe sets, with 12 out of 19 markers exceeding 20% informativity, was confirmed in our cohort (n = 74). Importantly, a fourfold reduction of input DNA compared to published protocols did not alter PCR efficiencies and allowed for a more sensitive detection of chimerism in 7 of 16 HSCT patients compared to results obtained by STR-PCR. Conclusions: Our data suggest that indel-qPCR is a more sensitive technique for the detection of hematopoietic chimerism compared to STR-PCR and works efficiently for samples with low amounts of DNA.

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“…Quantitative PCR analysis using insertion/deletion polymorphism (indel qrtPCR) is a well-characterized and simple technique, which can be performed in peripheral blood with a better sensitivity compared with standard STR-PCR (0.01-0.1% vs 1-5%). 22,23 While this technique has been previously used by others, [24][25][26] its usefulness to predict relapse at the recipient's cell level o1% has never been clearly evaluated.…”

Section: Introductionmentioning

confidence: 99%

Chimerism analysis in peripheral blood using indel quantitative real-time PCR is a useful tool to predict post-transplant relapse in acute leukemia

Jacque

Nguyen

Golmard

et al. 2014

Bone Marrow Transplant

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Detection of increasing mixed chimerism (IMC) using standard PCR correlates with relapse after allo-SCT for acute leukemias (ALs). Quantitative real-time PCR of insertion/deletion polymorphism (indel qrtPCR) is a much more sensitive method, which can be performed on peripheral blood. We studied the significance of low increases of recipient cells (0.1%) detected by indel qrtPCR in a cohort of 89 transplants. We did not observe relapse among the 32 patients with no IMC. Fifty-seven patients presented a first IMC, which was followed by four different scenarios: a decreasing MC (26 cases, no relapse), a stable MC (1 case, 1 relapse), a second IMC (24 cases, 15 relapse) or no control of chimerism (6 cases, 5 relapses). In multivariate analysis, detection of two successive IMCs was strongly associated with relapse (hazard ratio (HR): 9.4, 95% confidence interval (CI): 3.8-23; Po0.0001). Among the 57 patients who presented at least one IMC, 27 underwent immunomodulation (tapering of immunosuppression or donor lymphocyte injection), leading to a 1-year relapse rate of 15.7% vs 57.6% in the 30 other patients (P = 0.0007). Altogether, these results indicate that chimerism analysis using indel qrtPCR in peripheral blood is a useful tool for detection of relapse in patients transplanted for AL.

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Increasing hematopoietic microchimerism is a reliable indicator of incipient AML relapse

Abstract: Within this paper, we emphasize the importance of microchimerism monitoring as a reliable indicator of incipient AML relapse, especially in patients where no other specific molecular marker is available.

Cited by 24 publications

References 38 publications

Highly sensitive chimerism detection in blood is associated with increased risk of relapse after allogeneic hematopoietic cell transplantation in childhood leukemia

Highly sensitive chimerism detection in blood is associated with increased risk of relapse after allogeneic hematopoietic cell transplantation in childhood leukemia

Monitoring of Hematopoietic Chimerism by Real-Time Quantitative PCR of Micro Insertions/Deletions in Samples with Low DNA Quantities

Chimerism analysis in peripheral blood using indel quantitative real-time PCR is a useful tool to predict post-transplant relapse in acute leukemia

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