Deficient reconstitution of early progenitors after allogeneic bone marrow transplantation

Abstract

Summary:time required for stem cells to reconstitute sufficiently a large reservoir; later, hematopoiesis is maintained by the Allogeneic bone marrow transplant recipients maintain progeny of relatively few cells. 5 normal peripheral blood counts long term, suggestingLethally irradiated individuals engrafted with adequate durable support from engrafted stem cells. In order to numbers of allogeneic stem cells, achieve normal peripheral investigate late hemopoietic reconstitution at the level cell counts and good marrow cellularity in a short period of committed and early progenitors (LTC-IC), we studof time. 6,7 Recovery of committed progenitors is much ied 64 long-term survivors at a median interval of 6 slower and may remain permanently below the normal years (range: 2-20) after allogeneic bone marrow transrange 8,9 in patients with otherwise normal graft function. plant. CFU-GM and BFU-E numbers did not differThese data can be explained with a prolonged defect in the from normal controls; CFU-GEMM were found to be production of colony-forming cells (CFCs) from multisignificantly decreased (1.2 ؎ 0.2/10 5 vs 3.1 ؎ 0.4, potent and very early progenitors together with an impaired P ‫؍‬ 0.001). The most remarkable defect was however, or limited capacity of self-renewal of the latter 10 and an the low frequency of LTC-IC (3.2 ؎ 0.6/10 6 vs increased proportion of cells in cycle. 11,12 In addition, the 54.2 ؎ 9.3, P ‫؍‬ 0.0001) that did not improve with time host stromal microenvironment may be defective due to and did not correlate with phase of the disease, conexposure to chemotherapy and radiotherapy: in 58% of ditioning regimen, CMV infections or GVHD. Number patients studied after allogeneic bone marrow transplants, of infused cells and CFU-GM content of marrow grafts the stroma is considerably compromised in its ability to did not seem to influence the number of LTC-IC. This support early uncommitted hemopoietic cells and this study documents a significantly reduced number of defect lasts for several years. 13 These data are confirmed early progenitors in BMT patients despite normal numin patients transplanted with autologous marrow where bers of committed progenitors and normal peripheral difficulties or poor engraftment due to histocompatibility blood counts. This finding may suggest a permanent barriers can be excluded. 14 reduction of the stem cell reservoir after allogeneic boneThe information concerning the recovery of early and marrow transplantation.committed stem cell compartments in long-term survivors

Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy

“…High telomerase and telomere shortening in leukemia a telomeric DNA decline after high-dose chemotherapy. 61 Therefore, of great interest for future studies are long-term and ST specimens supports the concept that telomerase was turned on late in tumorigenesis after a high number of popueffects on telomere dynamics after chemotherapy and highdose protocols. lation doublings (PDs) has occurred.…”

“…Thus, the analysis of peak values early progenitors despite normal numbers of committed cells and normal peripheral blood counts. 61 This suggests a permaallowed the detection of tumor cells with short telomeres.…”

Replicative stress after allogeneic bone marrow transplantation: changes in cycling of CD34+CD90+ and CD34+CD90− hematopoietic progenitors

“…However, recipients have profound deficits in hematopoietic progenitors (determined by functional assays and absolute CD34 ϩ cell enumeration) persisting for more than 10 years after BMT. [1][2][3][4][5] The demonstration of accelerated telomere shortening in leukocytes of BMT recipients, [6][7][8] reflecting an increase in the mitotic rate of bone marrow progenitors and/or stem cells, suggests that hematopoietic reconstitution imposes a "replicative stress" upon the graft. The distribution of this stress within the hematopoietic hierarchy is unknown and is of considerable importance.…”

Haematopoietic damage persists 1 year after autologous peripheral blood stem cell transplantation

“…However, in the present study when different patient subgroups were screened, it was found that in patients with HD, only haematopoietic progenitor cells were significantly affected. Soligo et al 10 have recently reported on a decreased number of LTC-IC immature progenitors after haematopoietic stem cell transplantation and Podestá et al 11 showed a similar feature in patients after allogeneic transplantation. Our results using two-stage LTBMC are similar to those observed by these authors.…”

“…When an appropriate number of progenitor cells was not reached, a second mobilization using 10 g/kg of G-CSF was performed. Patients reached more than 0.5 × 10 9 /l granulocytes and 20 × 10 9 /l platelets in a median of 11 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)) and 13 (7-28) days, respectively.…”