Among reported advantages of umbilical cord blood (CB) in transplantation is lower leukemia relapse probability. Underlying cellular mechanisms of graft-vs.-leukemia (GVL) are thought to include a prominent role for T cells. Cells of the CB's mother, maternal microchimerism (MMc), were recently strongly, but indirectly, implicated in this GVL benefit. We assayed MMc directly and hypothesized benefit accrues from CB maternal T cells. MMc was quantified in 51 CBs and, within memory T, naïve T, B, NK cells, and monocytes in 27 CBs. Polymorphism-specific quantitative-PCR assays targeted maternal genotypes non-shared with CBs. Overall MMc was common and often at substantial levels. It was present in 52.9% of CB and in 33.3-55.6% of tested subsets. Remarkably, MMc quantities were greater in memory T cells than other subsets ( < 0.001). Expressed as genome equivalents (gEq) per 10 total gEq tested (gEq/10), memory T cell MMc averaged 850.2 gEq/10, while other subset mean quantities were 13.8-30.1 gEq/10. After adjustment for proportionality in CB, MMc remained 6-17 times greater in memory T, and 3-9 times greater in naïve T, vs. non-T-cell subsets. Further, CB-origin MMc was detected in a patient up to 6 mo post-transplantation, including among T cells. Overall, results revealed levels and phenotypes of CB MMc with potential relevance to CB transplantation and, more broadly, to offspring health.
Background Sickle cell disease (SCD) is a complex genetic disorder that manifests in infancy and progresses throughout life in the form of acute and chronic complications. As the upfront costs of potentially curative, genetic therapies will likely be high, an assessment and comprehensive characterization of the medical and non-medical cost burden will inform future decision making. Objective We sought to systematically summarize the existing literature surrounding SCD medical and non-medical costs. Methods We searched MEDLINE and EMBASE (2008-2020) and identified US-based studies that detailed medical or non-medical costs. Eligible studies provided empirical estimates about any aspect of cost or SCD individuals of all ages and their caregivers. Study quality was assessed using the Newcastle-Ottawa Scale, and costs were adjusted to 2019 US$. Results Search queries returned 479 studies, with 342 from medical burden searches and 137 from non-medical burden searches, respectively. Herein, we report the results of the 40 studies that contained relevant cost information: 39 detailed medical costs and 1 detailed non-medical costs. Costs were higher for SCD patients when compared with non-SCD individuals
Cord blood transplantation (CBT) is associated with low risk of leukemia
relapse. Mechanisms underlying antileukemia benefit of CBT are not well
understood, however a previous study strongly but indirectly implicated cells
from the mother of the cord blood (CB) donor. A fetus acquires a small number of
maternal cells referred to as maternal microchimerism (MMc) and MMc is sometimes
detectable in CB. From a series of 95 patients who underwent double or single
CBT at our center, we obtained or generated HLA-genotyping of CB mothers in 68.
We employed a technique of highly sensitive HLA-specific quantitative-PCR assays
targeting polymorphisms unique to the CB mother to assay CB-MMc in patients
post-CBT. After additional exclusion criteria, CB-MMc was evaluated at multiple
timepoints in 36 patients (529 specimens). CB-MMc was present in 7 (19.4%)
patients in bone marrow, peripheral blood, innate and adaptive immune cell
subsets, and was detected up to 1-year post-CBT. Statistical trends to lower
relapse, mortality, and treatment failure were observed for patients with vs.
without CB-MMc post-CBT. Our study provides proof-of-concept that maternal cells
of the CB graft can be tracked in recipients post-CBT, and underscore the
importance of further investigating CB-MMc in sustained remission from leukemia
following CBT.
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