Immunological reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation for advanced ovarian cancer

Summary:The cytolytic T lymphocyte (CTL) response has often been used to assess the reconstitution of T cell function after allogeneic or autologous bone marrow transplantation (BMT). Less is known, however, about the reconstitution of the CTL response after peripheral blood stem cell transplantation (PBSCT). Therefore, we investigated the CTL response against Epstein-Barr virus (EBV) of patients undergoing autologous PBSCT. CTLs of six patients with relapsed non-Hodgkin's lymphoma and multiple myeloma were established before and at different times after PBSCT by in vitro stimulation of peripheral blood lymphocytes with autologous EBVtransformed lymphoblastoid cell lines (LCLs). The efficiency of T cell priming by LCLs was assessed at the time of initiation of CTL lines; the proliferative response was strongly reduced during the first 4 months and increased 5 months or more following PBSCT. Cytolytic activity was measured after three or four restimulations of CTLs. All patients investigated had a detectable EBV-specific CTL response which was poor during the first weeks after transplantation, accompanied by a strong non-MHC-restricted cytotoxic activity and a high proportion of CD56-positive T cells. Five or more months after PBSCT, a specific CTL response against EBV was seen which was similar to the situation prior to PBSCT, while the unspecific cytotoxic response decreased. Blocking experiments with monoclonal anti-CD3, anti-CD8 or anti-MHC I antibodies resulted in substantial inhibition of autologous LCL lysis, whereas anti-CD4 or anti-MHC II antibodies had no effect. Finally, autologous PHA blasts of a patient with the HLA haplotype A1/9+, B5/8+, Cw4/7+, were loaded with various EBNA-derived nonapeptides known to be presented by HLA B8 or A11, and exposed to autologous, EBV-directed In the last few years, autologous peripheral blood stem cell transplantation (PBSCT) has been established as a standard treatment for relapsed aggressive non-Hodgkin's lymphoma and has proven advantageous when compared with autologous or allogeneic bone marrow transplantation (BMT). 1-5 However, in contrast to autologous or allogeneic BMT, little information is available concerning the reconstitution of the immune system following autologous peripheral blood stem cell transplantation (PBSCT). As after BMT, the CD4/CD8 ratio seems to be inversed after PBSCT, but lymphocyte subpopulations and functions recover more rapidly, including the proliferative response to mitogens and the cytotoxic activity of lymphocytes after stimulation with high-dose IL-2 (lymphocyte-activated killer cells, LAK). [6][7][8][9][10] Previous investigations mainly examined non-specific lymphocyte functions in patients undergoing autologous PBSCT and the reconstitution of the antigen-specific cytolytic T lymphocyte (CTL) response has not been evaluated so far. Therefore, we examined the CTL response of these patients to Epstein-Barr virus (EBV), a widespread lymphotropic herpes virus. Most people are infected with EBV by adulthood, and the life-long persist...

Section: Discussionsupporting

confidence: 89%

Assessment and characterization of the cytolytic T lymphocyte response against Epstein–Barr virus in patients with non-Hodgkin’s lymphoma after autologous peripheral blood stem cell transplantation

Nolte

Buhmann

Straka

et al. 1998

“…29,30 In our study NK cells were present at timeafter PBSCT may partly explain the faster regeneration of B lymphocytes, following PBSCT. The regeneration of naive points of first determination and above normal at day +20, returning to normal values at day +100 in both groups.…”

Section: Discussionsupporting

confidence: 53%

Phenotype of lymphocyte subsets after autologous peripheral blood stem cell transplantation

Koehne

Zeller

Stockschlaeder

et al. 1997

Summary:blood stem cell transplantation than after allo-BMT, resulting in less morbidity and mortality. 3,4 There are relatively little data about the reconstitution of lymphocyte subThe expression of CD45RA + and CD45RO + isoforms on T cells and the recovery of B lymphocytes and NK cells sets after PBSCT. 5 B cell reconstitution is severely compromised for months to years after allo-BMT, 6 especially in after autologous peripheral blood stem cell transplantation (PBSCT) were studied during the early period patients with chronic graft-versus-host disease (GVHD). CD45RA+ subset. The regeneration in the second post-transplant year. Storek et al 12 showed that a second round of B cell ontogeny occurred in transof the CD4 + cells was markedly delayed, but was faster in the PBSCT recipients, mainly because of the faster plant recipients without chronic GVHD. Does a faster recovery of B lymphocytes after PBSCT imply a faster recovery of the mature CD4 + CD45RO + subset. The pattern of surface antigens on T lymphocytes after transrecapitulation of ontogeny following PBSCT than after allo-BMT without cGVHD? Or, does a different T lymphoplantation did not resemble the antigen pattern on cord blood cells. The CD19 + CD20 + cells recovered earlier in cyte regeneration after PBSCT influence the faster B cell recovery, since a lack of appropiate T cell support is proven the PBSCT group and remained compromised after allo-BMT during the time studied. The faster B lymphoto contribute to deficiencies of B cell function. 13-17To date, the mechanisms of T cell regeneration are not cyte regeneration correlates with the faster reconstitution of the mature CD4 with CD45RA monoclonal antibodies. The CD45RO + isoforms increase thereafter to reach about 50% in adult life. 18Keywords: lymphocyte reconstitution; PBSCT; T cell isoforms; CD4 + CD45RO +The expression of CD45RO receptors characterizes a T cell as a mature cell of the memory type, responding to antigen stimulation, 19 whereas the CD45RA receptor-positive cells are considered to be immature and naive. They may convert Allogeneic bone marrow transplantation and peripheral to mature CD45RO + cells after stimulation. The expression blood stem cell transplantation have been proved to be of the CD45RO antigen, however, seems to be bidirectional effective therapies for patients with hematopoietic maligand may revert to the CD45RA + isoform. 18nancies and a variety of solid tumors. 1 Intensive chemoThere is no evidence of recapitulation of ontogeny of T therapy with and without total body irradiation severely and cells post-transplant, but it appears that the thymus plays an irreversibly damages the bone marrow, which can be reconimportant role in T cell ontogeny.

“…We reported previously the advantage of adding rh-EPO to myelopoietic growth factors which translates into a potentiation of their effects in vitro and in vivo. 29,30 In the present study, we demonstrated that the combination of three growth factors did not yield any improvement in hematologic recovery or in the clinical management of patients with respect to the use of rh-G-CSF plus rh-EPO or rh-GM-CSF plus rh-EPO. Instead, patients who received the three factors experienced a longer period of fever, and required a higher number of red blood cell and platelet transfusions as compared to the groups receiving only two factors.…”

Section: Discussionmentioning

confidence: 51%

High-dose chemotherapy as a consolidation approach in advanced ovarian cancer: long-term results

Salerno

Ferrandina

Greggi

et al. 2001