Analysis of immune reconstitution in children undergoing cord blood transplantation

Moretta, Antonia; Maccario, Rita; Fagioli, Franca; Giraldi, Eugenia; Busca, Alessandro; Montagna, Daniela; Miniero, R; Comoli, Patrizia; Giorgiani, Giovanna; Zecca, Marco; Pagani, Sara; Locatelli, Franco

doi:10.1016/s0301-472x(00)00667-6

Cited by 113 publications

(97 citation statements)

References 42 publications

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“…These data agree with those previously reported for CBT without the support of TPD-MHSC 9,10 and are consistent with the observed favorable GVT effect and low incidence of GVHD, together with a high incidence of opportunistic infections.…”

Section: Discussionsupporting

confidence: 93%

Immune reconstitution after cord blood transplants supported by coinfusion of mobilized hematopoietic stem cells from a third party donor

Martín-Donaire

Rico

Bautista

et al. 2009

Bone Marrow Transplant

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Low severity of GVHD, substantial graft vs tumor (GVT) and slow development of protective immunity are welldocumented features of cord blood transplants (CBT). We have evaluated the immune reconstitution of adult recipients of single-unit CBT supported by the coinfusion of third party donor (TPD) mobilized hematopoietic stem cells (MHSC), a procedure-'dual CB/TPD-MHSC transplant'-that results in early recovery of circulating granulocytes, high rates of CB engraftment and full chimerism. Cumulative recovery of natural killer and B cells at or above the median values of normal controls were 1.0 and 0.76 by the sixth and ninth months. Recovery of T cells was much slower, naive cells lagging behind those of memory and effector (committed) immunophenotypes. Serial analyses of signal joint TCR excision circles showed a general pattern of very low levels by the third month after CBT, followed by recovery to levels persistently similar or higher than those observed before transplantation and in normal controls. Our results are consistent with the clinical observations of substantial GVT effect together with low incidence of serious GVHD and slow development of protective immunity and suggest that thymic function contributes substantially to the recovery of T-cell populations in adults receiving dual CB/TPD-MHSC transplants.

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Section: Discussionsupporting

confidence: 93%

Immune reconstitution after cord blood transplants supported by coinfusion of mobilized hematopoietic stem cells from a third party donor

Martín-Donaire

Rico

Bautista

et al. 2009

Bone Marrow Transplant

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“…39 Our previously reported Omenn's syndrome patient is the first case successfully treated by UCB transplant. 22 Development of lymphocyte subpopulations and immunologic function in our SCID and non-SCID patients followed the pattern previously described, [34][35][36][37] with early recovery of normal NK cell values followed by CD19, CD3, CD4 and finally CD8. Response to mitogens and immunoglobulin production preceded the development of serologic responses to specific antigens.…”

Section: Discussionmentioning

confidence: 58%

“…19,20 The recovery period of myeloid and lymphoid activity is longer in UCB transplants, 13,17,18,20,[34][35][36][37] which raises the risk of severe infections. In contrast, advantages of UCB include easy availability and lower HLA-compatibility requirements.…”

Section: Discussionmentioning

confidence: 99%

Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies

Heredia

Ortega

Díaz

et al. 2007

Bone Marrow Transplant

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“…This is in accordance with previous reports. 2,6,38,39 In the current model of NK-cell maturation, NKG2A þ cells predate KIR þ cells and CD56 bright cells predate CD56 dim cells. [24][25][26] Using this model, we did not find any difference in NK-cell maturation.…”

Section: Discussionmentioning

confidence: 99%

Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children

Charrier

Cordeiro

Brito

et al. 2012

Bone Marrow Transplant

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Some clinical characteristics of cord blood transplantation (CBT) might be explained by specificities in the reconstitution of immune subsets differing by their maturation stage or their implication in GVHD, tolerance or immune responses against tumor or infectious agents. Here, we compare the immune reconstitution of several of these subsets after CBT and BMT. B-cell count recovery was faster after CBT. There was no difference in the recovery of CD4 þ and CD8 þ cell counts. There was no difference either in the frequency of several subsets: CD45RO þ memory, and CD45RA þ naïve cells within the CD4 þ T-cell compartment, CD27 þ among B cells, CD56 bright , NKG2A þ , and KIR þ cells among natural killer (NK) cells, CD25 þ FOXP3 þ regulatory T cells and invariant NKT cells. The proportion of the thymic naïve CD31 þ CD45RA þ CD4 þ T cells was lower after CBT at 6 months post-transplant, and was still below normal at 1 year in both groups. NK-cell expansion was more sustained after CBT, with fewer double-negative NKG2A À KIR À hyporesponsive cells and more double-positive NKG2A þ KIR þ hyper-responsive NK cells. These results, therefore, indicate that further research to improve CBT outcome should try to improve thymopoieisis and take advantage of the sustained NK-cell reconstitution. INTRODUCTIONAlmost all lethal complications of hematopoietic SCT, including leukemia relapse, and opportunistic infections, result from the post-transplant immune deficiency that lasts for months after transplantation. Therefore, the therapeutic challenge in improving the outcome for transplanted children outcome relies on the enhancement of immune reconstitution and the GVL effect, without increasing the harmful GVHD.Although lower rates of engraftment and GVHD and higher rates of life-threatening infections have been reported in patients who received cord blood transplantation (CBT), similar EFS and leukemia relapse rates have been observed after CBT and BMT. [1][2][3][4][5] These observations indicate that cord blood-derived immune cells have unique immune properties that allow for allogeneic tolerance while preserving the GVL effect.Previous studies have compared the reconstitution of the major immune cell populations after CBT and BMT: CD4 þ and CD8 þ T cells, natural killer (NK) and B cells. They showed that T-cell recovery is delayed, in particular CD8 þ T-lymphopoiesis after CBT, 2,6-9 although T-cell diversity has been shown to be similar in cord blood (CB) and BM recipients beyond 1 year after transplant. 7,10 Conversely, innate immunity recovery has been shown to be similar between CB and BM recipients, with normal cell counts of functional NK cells in the blood as soon as 1-month post-CBT. 2,11,12 Finally, B-cell number recovery appears to be faster after CBT. 6,9,13 Besides these differences in the reconstitution of the major lymphocyte populations, additional changes in the reconstitution of other immune cell subsets might occur and explain some of the clinical differences observed in patients who receive BMT or CBT.

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Analysis of immune reconstitution in children undergoing cord blood transplantation

Cited by 113 publications

References 42 publications

Immune reconstitution after cord blood transplants supported by coinfusion of mobilized hematopoietic stem cells from a third party donor

Immune reconstitution after cord blood transplants supported by coinfusion of mobilized hematopoietic stem cells from a third party donor

Unrelated cord blood transplantation for severe combined immunodeficiency and other primary immunodeficiencies

Reconstitution of maturating and regulatory lymphocyte subsets after cord blood and BMT in children

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