Lymphocyte reconstitution following allogeneic hematopoietic stem cell transplantation: a retrospective study including 148 patients

Abstract

Here we investigated the influence of parameters known before hematopoietic stem cell transplantation (HSCT) as well as the relevance of graft-versus-host disease (GvHD) and cytomegalovirus (CMV) reactivation on post transplant lymphocyte reconstitution in 148 patients treated in our institution between 1996 and 2003. Median patient age was 42 (19-68) years, HSCT followed standard high dose (n ¼ 91) or reduced-intensity conditioning regimens (n ¼ 57) with bone marrow (BM, n ¼ 67) or peripheral blood stem cells (PBSC, n ¼ 81) from related (n ¼ 71) or unrelated (n ¼ 77) donors. In the first months, we observed a partially faster reconstitution of CD3 þ 4 þ , CD3 þ 8 þ and CD4 þ 45RA þ T cells in patients following peripheral blood stem cell transplantation when compared to bone marrow transplantation. Prolonged CD3 þ 4 þ and CD4 þ 45RA þ lymphopenia was noted after unrelated donor HSCT and GvHD prophylaxis containing anti-T-lymphocyte globulin. Lymphocyte subset counts in patients older than the median age were comparable to those in patients transplanted at a younger age and not influenced by the conditioning regimen. CD3 þ 8 þ T cell reconstitution was strongly correlated with CMV reactivation, but not significantly affected by CMV serostatus before HSCT. Incidence or extent of GvHD did not significantly influence lymphocyte reconstitution. Therefore, the source of graft is the most predictive parameter in early lymphocyte reconstitution, but the differences in lymphocyte recovery completely resolved within the first year after HSCT.

Improved outcome in relapsed and refractory myeloid malignancies for unrelated vs related donor allogeneic peripheral blood-derived hematopoietic cell transplantation

“…Peripheral blood-derived grafts, as opposed to BMderived grafts, have been shown to be advantageous in terms of a faster hematopoietic and immune reconstitution. 30 Furthermore, although not statistically significant, Ringden et al 29 observed a higher RFS in unrelated recipients compared with related HCT in patients with acute GVHD in contrast to patients without acute GvHD. In addition, in that study, NRM accounts for more deaths than does disease relapse, and unrelated recipients had a higher NRM than related transplant recipients.…”

Impact of lymphocyte and monocyte recovery on the outcomes of allogeneic hematopoietic SCT with fludarabine and melphalan conditioning

“…4 Other studies have not demonstrated significantly improved immune reconstitution with RIC, 5,6 making this area a subject of continued debate (reviewed by Jimenez et al 7 ). While many previous studies of immune reconstitution post HSCT have focused on lymphocyte subset recovery, [8][9][10][11][12][13][14][15][16] we have previously shown that combined monocyte and lymphocyte recovery also has an impact on survival post myeloablative HSCT in acute leukemia due to a reduction in nonrelapse mortality. 17 Here, we test the hypothesis that both lymphocyte and monocyte recovery are similarly associated with survival in patients undergoing RIC allogeneic HSCT with fludarabine and melphalan.…”

Six cases of leprosy associated with allogeneic hematopoietic SCT

“…26 Thus, we hypothesize that this reaction occurred by the regeneration of CD4 þ T cell, provided that in the setting of SCT the regeneration of this subset of cells generally occurs between 6 and 12 months after the transplantation. 22 This clinical and immunological picture may be similar to a new clinical syndrome known as immune reconstitution inflammatory syndrome (IRIS) 27 observed in HIV-infected patients receiving highly active antiretroviral therapy. Those patients exhibit paradoxical deterioration in their clinical status, generally induced by exuberant inflammatory responses toward opportunistic pathogens and often associated with a rapid increase in CD4 lymphocyte count after satisfactory control of viral replication.…”

“…CD4 þ T cells regenerate later and only 21% of the patients reach normal counts within the first year. 22 The situation after allogeneic HSCT mimics that of severe combined immunodeficient (SCID) mice, which are increasingly susceptible to leprosy 23,24 and clear the infection when reconstituted with BM cells from immunocompetent mice. 25 We hypothesized that the severity of the immunosupression that occurs in the context of the SCT, specifically the delayed normalization of CD4 þ T cells, may explain the opportunistic infections in cases 1-3.…”

“…Moreover, in SCT, the immune reconstitution has been found to be influenced by the source of graft (PBSC vs BM), CMV reactivation after the SCT and the use of anti-thymocyte globulin in unrelated transplants. 22 Thus, owing to these differences, no meaningful comparisons between SCT and SOT can be made regarding the incidence, presentation, course and prognosis of leprosy.…”