Transplantation of allogeneic CD34+ blood cells

Abstract

Pluripotent stem cells of hematopoiesis and lymphopoiesis are among the CD34+ cells in blood or bone marrow. After granulocyte-colony stimulating factor (G-CSF) treatment, 1% to 2% of the mononuclear cells in blood are CD34+ cells, which can be procured by leukapheresis. We investigated the potential of CD34+ blood cells for reconstituting hematopoiesis and lymphopoiesis after allogeneic transplantation. HLA- identical sibling donors of 10 patients with hematologic malignancies were treated with G-CSF (filgrastim), 5 microgram/kg subcutaneously twice daily for 5 to 7 days. CD34+ cells were selected from the apheresis concentrates by immunoadsorption, concomitantly the number of T cells was reduced 100- to 1,000-fold. After transplantation, five patients received cyclosporine A for graft-versus-host disease (GvHD) prophylaxis (group I); five patients additionally received methotrexate (group II). G-CSF and erythropoietin were given to all patients. Mean numbers of 7.45 x 10(6) CD34+ and 1.2 x 10(6) CD3+ cells per kilogram were transplanted. In group I, the median times of neutrophil recovery to 100, 500, and 1,000 per mm3 were 10, 10, and 11 days, respectively. Group II patients reached these neutrophil levels after 10, 14, and 15 days, respectively. Platelet transfusions were administered for a median of 18 days in group I and 30 days in group II, and red blood cells for 9 and 12 days, respectively. Between day 30 and 60, lymphocytes reached levels of 353 +/- 269 cells per mm3. The median grades of acute GvHD were III in group I and I in group II. Two patients in group I died from acute GvHD. Two leukemic relapses occurred in group II. Complete and stable donor hematopoiesis was shown in all patients with a median follow up of 370 (45 to 481) days. Allogeneic blood CD34+ cells can successfully reconstitute hematopoiesis and lymphopoiesis. Reduction of T cells by CD34+ blood cell enrichment and cyclosporine A alone might not be sufficient for prophylaxis of severe acute GvHD.

Review

“…Several series of CD34 þ selected PBPC have now been published (Link et al, 1996;Bensinger et al, 1996a;Urbano-Ispizua et al, 1997). Two studies (Link et al, 1996;Bensinger et al, 1996a) reported a high incidence of severe (grade II-IV) acute GVHD (60-80%) in patients receiving a CD3 þ cell dose of approximately 1 × 10 6 /kg when post-transplant cyclosporin alone was used for GVHD prophylaxis. Urbano-Ispizua et al (1997) recently updated the Spanish experience in 20 patients undergoing CD34 þ selected PBSC using CSA combined with prednisolone post-transplant.…”

Transplantation of HLA‐mismatched CD34+ selected cells in patients with advanced malignancies: severe immunodeficiency and related complications

“…The overall incidence and severity of acute GvHD was unexpectedly low: two patients developed no GvHD (grades 0-I), seven patients developed grade II GvHD and only one patient had grade III GvHD, this was the only patient who did not receive prophylactic CyA. It is puzzling that a recent paper has reported a relatively high incidence of acute GvHD in patients receiving HLA-identical marrow or peripheral blood or both, after CD34-positive selection, despite the use of CyA and methotrexate for GvHD prophylaxis (Link et al, 1996). In that series of 10 patients the only manipulation was a Ceprate column which apparently produced a greater number of residual T cells compared to our experience: the median number of infused CD3 þ cells was 1 .…”

“…5 × 10 6 /kg CD3 þ cells. It is unclear whether this difference may have been responsible for the increased incidence and severity of acute GvHD, since Link et al (1996) were dealing with HLA-matched grafts.…”

“…A continuous flow column selection system designed for haemopoietic progenitors is now available; harvested marrow or peripheral blood are labelled with biotinylated mouse anti-CD34 and rapidly passed through a column of avidin coated beads, the CD34 þ cells are selected by immune-absorption and released by gentle agitation. This device has been used to concentrate haemopoietic progenitors for autologous bone marrow and peripheral blood transplantion (Brugger et al, 1994) and more recently for HLA-identical sibling transplants (Link et al, 1995(Link et al, , 1996Bensinger et al, 1996).…”

In vitro generation of murine myeloid dendritic cells from CD34‐positive precursors

“…In humans, CD14 þ monocytes or CD34 þ cells stimulated with specific cytokines in vitro differentiate into DCs (Caux et al, 1992). In contrast to humans and other primates in which long-term HSCs express CD34, murine long-term HSCs have been described as CD34 À and short-term HSCs as CD34 þ cells (Link et al, 1996;Osawa et al, 1996). Transgenic studies showed that human CD34 transgene is expressed in long-term murine CD34 À and CD34 low HSCs (Okuno et al, 2002).…”