Double Umbilical Cord Blood Transplantation: A Study of Early Engraftment Kinetics in Leukocyte Subsets using HLA-Specific Monoclonal Antibodies

Abstract

Single cord blood unit (CBU) predominance is usually established within the first month after double umbilical cord blood transplantation (UCBT). However, the kinetics of engraftment of the different leukocyte subsets and the mechanism of graft predominance is largely unknown. To investigate whether a differential engraftment might reveal a specific subset that could play a key role in the mechanism of graft predominance, we studied early engraftment kinetics of different leukocyte subpopulations by flow cytometry using human monoclonal antigen-specific human leukocyte antigen antibodies, directed against mismatched human leukocyte antigen-A or -B antigens between recipient and CBUs. Twenty-two patients, who had received a double UCBT preceded by a reduced-intensity conditioning regimen, were evaluated at days +11, +18, +25, and +32 posttransplantation. Single CBU predominance in the various leukocyte subsets was established within 18 days posttransplantation. CD4+ T cells of the dominant CBU showed early peripheral blood expansion. Moreover, chimerism in CD4+ and CD8+ T cell and natural killer cell subsets at day +11 was predictive of ultimate graft predominance. These findings show that engraftment kinetics of the various leukocyte subsets vary considerably after double UCBT and may suggest an important role for CD4+ T cells in a presumed alloreactive graft-versus-graft rejection.

Rapid induction of single donor chimerism after double umbilical cord blood transplantation preceded by reduced intensity conditioning: results of the HOVON 106 phase II study

“…27 Predominance of one grafted unit over another was established within 11 days in most patients. In a previous study in a subcohort of these patients using flow cytometry with HLA-monoclonal antibodies 25 we observed that early CD4 + T-lymphocyte chimerism was predictive of ultimate graft predominance, which may suggest a role for CD4 + lymphocytes in a graftversus-graft reaction. This is in line with several reports suggesting the presence of a T-cell-mediated unit-versusunit allo-immune reaction.…”

“…Results were reported earlier as a part of a larger group of patients. 25 In brief, at day +11, the median percentages of cells derived from the surviving unit within CD4 + T cells, CD8 + T cells, natural killer cells, monocytes and granulocytes in peripheral blood were 89% (range, 46-100), 98% + T-cell numbers were below the detection limit in 7/10 patients, precluding the prediction of donor chimerism, but chimerism in the three remaining patients was concordant with ultimate graft predominance.…”

The increase of the global donor inventory is of limited benefit to patients of non-Northwestern European descent

“…13 If no 6/6 or 5/6 mismatched units with sufficient total nucleated cells were identified, a run for two mismatches was performed, for both single and double CBU searches.…”

Natural killer cell licensing after double cord blood transplantation is driven by the self-HLA class I molecules from the dominant cord blood

“…Nicolas Guillaume, 1,2 Pascale Loiseau, 1,3,4 Katia Gagne, 5,6,7 Hélène Moins-Teisserenc, 1,3,4,8 Jean-Michel Cayuela, 8,9 Guylaine Henry, 3 Marie Robin, 10 Régis Peffault de Latour, 10 Eliane Gluckman, 11 Gérard Socié, 1,10 Table S1). …”

“…Usually, one CB unit dominates the other in the 2CBT. It is presumed that alloreactive graftversus-graft rejection occurs, depending on the status of CD4 + T cells 8 or CD8 + T cells. 9 The dose of CD34 + cells 10 and the cell banking procedures 11 may also influence CB unit dominance which appears to be independent of the KIR-HLA mismatch.…”