Immune reconstitution after unrelated cord blood transplants in adults

Komanduri et al describe a study of immune reconstitution after unrelated HLA-mismatched cord blood (CB) transplants were given to adults with various malignancies. The use of cord blood as an alternative source of stem cells is increasing markedly, since it was shown that HLA incompatibilities were better tolerated after cord blood transplantation (CBT) than after adult hematopoietic stem cell transplantation because of the reduced frequency of graft-versus-host disease (GVHD). In addition to a lower number of cells infused, cord blood lymphocytes differ from adult cells because they are naïve and immature with different subtype composition. They also have different cytokine requirements and express fewer HLA molecules. The mechanism explaining the reduction of GVHD after CBT is not clearly understood. Because of the T cell's functional immune immaturity, there is a concern about a delay of immune reconstitution and increased risk of malignant relapse due to the loss of the graft-versus-leukemia effect.

Here, the authors studied T-cell reconstitution in 32 adults receiving transplants for various malignancies. They found that in the early posttransplantation period there was a profound lymphopenia associated with a compensatory B and NK expansion, an impaired functional response to CMV and superantigens with some exceptions, and thymopoietic failure with a relative paucity of CCR7⁺ naive and central memory cells after CBT, with an apparent association between the preservation of CD4⁺CCR7⁺ T cells and an improved posttransplantation outcome. All these data could explain the high rate of infection after unrelated CBT. They differ from some other published results showing that there was a profound immune deficiency in the early period after transplantation but that in the long term (1 year after transplantation) surviving patients had a better immune reconstitution than did patients who had received an HLA-identical sibling bone marrow transplant.^1,2  One interesting finding is the observation that before transplantation they found an impaired baseline thymopoiesis and a relatively diminished naive T-cell repertoire. This is in line with our previously published study showing that pretransplantation host thymic function was a prognostic factor after HLA-identical sibling bone marrow transplantations.³  In addition to factors related to the source of stem cells, host factors including age, previous treatment, diagnosis, and stage of disease play a major role in outcome after transplantation. Further studies on larger numbers of patients with homogeneous risk factors could determine the individual risks of having delayed immune reconstitution.

Another factor that might modify the results is a study of the influence of number of cells infused and number and type of HLA mismatches. Previous studies have shown that a high number of nucleated cells and CD34⁺ cells in the graft improve the rate of engraftment, decrease transplantation-related mortality, and improve survival. There was also a correlation between the number of HLA mismatches and engraftment, severe GVHD, and survival.⁴  The study of the impact of these differences on immune reconstitution should be important for predicting the outcome and developing new methods for improving immune reconstitution.