Lymphocyte subset reconstitution after unrelated cord blood or bone marrow transplantation in children

Abstract

SummaryWe report the post‐transplant lymphocyte subset recovery of 226 children treated with Unrelated Cord Blood transplant (UCBT) (n = 112) or Unrelated Bone Marrow Transplant (UBMT) (n = 114) for malignant or non‐malignant diseases. Absolute numbers of natural killer (NK), B and T cells were monitored by flow cytometry up to 5 years post‐transplant. Immunological endpoints were: time to achieve a CD3+ cell count >0·5 and 1·5 × 109/l, CD4+ > 0·2 and 0·5 × 109/l, CD8+ > 0·25 × 109/l, CD19+ > 0·2 × 109/l, NK > 0·1 × 109/l. These endpoints were analysed through the use of cumulative incidence curves in the context of competing risks. CD8+ T cell recovery was delayed after UCBT with a median time to reach CD8+ T cells > 0·25 × 109/l of 7·7 months whereas it was 2·8 months in UBMT (P < 0·001). B cell recovery was better in UCBT, with a median time to reach CD19+ cells > 0·2 × 109/l of 3·2 months in UCBT and 6·4 months in UBMT (P = 0·03). Median time for CD4+ T cell and NK cell recovery was similar in UCBT and UBMT. CD4+ T cells recovery was negatively correlated to age (better reconstitution in younger patients, P = 0·002). CD8+ T cells recovery was shorter in recipients with a positive cytomegalovirus serology (P = 0·001).

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

“…Indeed, B-cell number recovery was more rapid after CBT, but the proportion of CD27 þ memory B cells was identical at any time point, and still remains below the normal range for children at 1-year post transplant. Rapid recovery of B-cell numbers after CBT, already described by others, 2,6,8,9 can be attributed to a higher proportion of B-cell precursors in cord blood. 37 B-cell maturation after CBT remains suboptimal at 1-year post-transplant, as already described with other graft sources.…”

“…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.…”

“…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. …”

Better outcomes of modified myeloablative conditioning without antithymocyte globulin versus myeloablative conditioning in cord blood transplantation for hematological malignancies: A retrospective (development) and a prospective (validation) study

“…The reduction of ATG after CBT could achieve an early CD4+ T‐cell immune reconstitution and no exposure to ATG results in even exceptional immune reconstitution potential, as recently shown 31. NK cells typically recover within the first month after transplant and are therefore one of the first lymphocytes to recover after transplant, regardless of stem‐cell source 32. Due to the delay of T‐cell immune recovery, NK cells are a vital lymphocyte subset exerting GVL effects and have been associated with superior OS, less CMV infection and reduced relapse rate 33.…”

Rituximab treatment may disturb the normal pattern of lymphopoiesis after cord blood SCT

“…For instance, earlier and more intense B-cell reconstitution after cord blood transplantation (CBT) compared with BM or PB allo-SCT has been recognized. 4 Detection of immature CD34 þ B cells has been identified as a normal phenomenon in murine models after CBT, with secondary reconstitution occurring exclusively in the CD34 þ population. 5 Furthermore, heterogeneous B-cell lymphoproliferation, with complex morphological and phenotypical features, has been recently described in patients with AML after allo-cord blood SCT.…”