Cord-Blood Transplantation in Patients with Minimal Residual Disease

Hourigan, Christopher S.; Haferlach, Torsten; Hokland, Peter

doi:10.1056/nejmc1612872

Cited by 10 publications

(4 citation statements)

References 32 publications

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“…Umbilical Cord Blood (CB), obtained at the time of delivery, is a good source of hematopoietic stem cells and a useful tool for stem cell transplantation for a variety of hematological and nonhematological malignancies and disorders (1,2). Compared to the conventional adult stem cell sources of bone marrow and peripheral blood, CB are associated with lower incidences of acute and chronic graft versus host disease (GVHD), while maintaining good graft versus leukemia (GVL) activity (3,4), possibly because of their tolerogenic cell composition, with a majority of naïve T cells and a high proportion of highly suppressive regulatory T cells (5,6).…”

Section: Introductionmentioning

confidence: 99%

Factors Predicting the Presence of Maternal Cells in Cord Blood and Associated Changes in Immune Cell Composition

et al. 2021

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BackgroundCord blood (CB) samples are increasingly used as a source of hematopoietic stem cells in transplantation settings. Maternal cells have been detected in CB samples and their presence is associated with a better graft outcome. However, we still do not know what influences the presence of maternal microchimerism (MMc) in CB samples and whether their presence influences CB hematopoietic cell composition.Patients and MethodsHere we test whether genetic, biological, anthropometric and/or obstetrical parameters influence the frequency and/or quantity of maternal Mc in CB samples from 55 healthy primigravid women. Mc was evaluated by targeting non-shared, non-inherited Human Leukocyte Antigen (HLA)-specific real-time quantitative PCR in whole blood and four cell subsets (T, B lymphocytes, granulocytes and/or hematopoietic progenitor cells). Furthermore CB samples were analyzed for their cell composition by flow cytometry and categorized according to their microchimeric status.ResultsMMc was present in 55% of CB samples in at least one cell subset or whole blood, with levels reaching up to 0.3% of hematopoietic progenitor cells. Two factors were predictive of the presence of MMc in CB samples: high concentrations of maternal serological Pregnancy-Associated-Protein-A at first trimester of pregnancy (p=0.018) and feto-maternal HLA-A and/or –DR compatibility (p=0.009 and p=0.01 respectively). Finally, CB samples positive for MMc were significantly enriched in CD56+ cells compared to CB negative for MMc.ConclusionsWe have identified two factors, measurable at early pregnancy, predicting the presence of maternal cells in CB samples at delivery. We have shown that MMc in CB samples could have an influence on the hematopoietic composition of fetal cells. CD56 is the phenotypic marker of natural killer cells (NK) and NK cells are known to be the main effector for graft versus leukemia reactions early after hematopoietic stem cell transplantation. These results emphasize the importance of MMc investigation for CB banking strategies.

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Section: Introductionmentioning

confidence: 99%

Factors Predicting the Presence of Maternal Cells in Cord Blood and Associated Changes in Immune Cell Composition

et al. 2021

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“…Thus, cord blood transplants pose a minimal risk of clonal heterogenenity with the possibility of a final, dominant mutant clone. Retrospective studies looking at cord blood transplants have shown that they can perform well enough to minimize the difference in survival in patients with and without minimal residual disease at the time of transplantation [63]. This result is notable because it is a direct test of the clonal competitiveness of transplanted cord blood populations against a known leukemic population (minimal residual disease).…”

Section: Discussionmentioning

confidence: 99%

Clonal hematopoiesis of indeterminate potential and its impact on patient trajectories after stem cell transplantation

et al. 2019

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Clonal hematopoiesis of indeterminate potential (CHIP) is a recently identified process where older patients accumulate distinct subclones defined by recurring somatic mutations in hematopoietic stem cells. CHIP’s implications for stem cell transplantation have been harder to identify due to the high degree of mutational heterogeneity that is present within the genetically distinct subclones. In order to gain a better understanding of CHIP and the impact of clonal dynamics on transplantation outcomes, we created a mathematical model of clonal competition dynamics. Our analyses highlight the importance of understanding competition intensity between healthy and mutant clones. Importantly, we highlight the risk that CHIP poses in leading to dominance of precancerous mutant clones and the risk of donor derived leukemia. Furthermore, we estimate the degree of competition intensity and bone marrow niche decline in mice during aging by using our modeling framework. Together, our work highlights the importance of better characterizing the ecological and clonal composition in hematopoietic donor populations at the time of stem cell transplantation.

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“…These findings led to the initiation of clinical trials using peripheral blood stem cell (PBSC) grafts depleted of naïve T cells, which showed lower rates of aGvHD and chronic GvHD (cGvHD) in HLA-matched HCT, with no apparent increase in relapse rates ( 14 ). On the other hand, cord blood grafts (in which almost all T cells are naïve) show great anti-leukaemic potential with reduced relapse risk but a similar likelihood of developing GvHD when compared to bone marrow grafts ( 15 ), indicating that T-cell intrinsic factors are contributing to the risk of GvHD development and anti-leukemic efficacy as well. Most significant associations between IR and clinical events were described for CD4 + rather than for CD8 + T cells, maybe because CD8 + T cell numbers fluctuate more swiftly in response to infections (e.g., CMV) or other events post-transplant ( 16 ).…”

Section: Distinct Importance Of Naïve and Memory T Cells And Significance Of T-cell Receptor Diversitymentioning

confidence: 99%

Immune Reconstitution After Allogeneic Haematopoietic Cell Transplantation: From Observational Studies to Targeted Interventions

Yanir

Schulz²,

Lawitschka

et al. 2022

Front. Pediatr.

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Immune reconstitution (IR) after allogeneic haematopoietic cell transplantation (HCT) represents a central determinant of the clinical post-transplant course, since the majority of transplant-related outcome parameters such as graft-vs.-host disease (GvHD), infectious complications, and relapse are related to the velocity, quantity and quality of immune cell recovery. Younger age at transplant has been identified as the most important positive prognostic factor for favourable IR post-transplant and, indeed, accelerated immune cell recovery in children is most likely the pivotal contributing factor to lower incidences of GvHD and infectious complications in paediatric allogeneic HCT. Although our knowledge about the mechanisms of IR has significantly increased over the recent years, strategies to influence IR are just evolving. In this review, we will discuss different patterns of IR during various time points post-transplant and their impact on outcome. Besides IR patterns and cellular phenotypes, recovery of antigen-specific immune cells, for example virus-specific T cells, has recently gained increasing interest, as certain threshold levels of antigen-specific T cells seem to confer protection against severe viral disease courses. In contrast, the association between IR and a possible graft-vs. leukaemia effect is less well-understood. Finally, we will present current concepts of how to improve IR and how this could change transplant procedures in the near future.

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Cord-Blood Transplantation in Patients with Minimal Residual Disease

Abstract: BACKGROUND-The majority of patients in need of a hematopoietic-cell transplant do not have a matched related donor. Data are needed to inform the choice among various alternative donorcell sources.

Cited by 10 publications

References 32 publications

Factors Predicting the Presence of Maternal Cells in Cord Blood and Associated Changes in Immune Cell Composition

Factors Predicting the Presence of Maternal Cells in Cord Blood and Associated Changes in Immune Cell Composition

Clonal hematopoiesis of indeterminate potential and its impact on patient trajectories after stem cell transplantation

Immune Reconstitution After Allogeneic Haematopoietic Cell Transplantation: From Observational Studies to Targeted Interventions

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