GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • 2005-2009  (2)
  • 1
    Online Resource
    Online Resource
    American Society of Hematology ; 2005
    In:  Blood Vol. 106, No. 11 ( 2005-11-16), p. 3232-3232
    In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 3232-3232
    Abstract: Epstein Barr Virus (EBV) reactivation occurs in about 50% of the allogeneic hematopoietic stem cell transplantation (HSCT) population in the first year post-transplantation. About 1-7% of these patients run the risk of developing a post-transplant lymphoproliferative disorder (PTLD). Several authors have thus advocated systematic screening by EBV real time PCR (RT-PCR) to initiate pre-emptive treatment of reactivations using Rituximab (van Esser 2002). However, the positive predictive value of EBV RT-PCR is only of 40% (van Esser 2001), implying that this algorithm overtreats a number of patients. Methods: We have retrospectively analyzed 60 consecutive allogeneic HSCT patients transplanted in our center between 1/1/2004 and 31/3/2005. Four patients were excluded because of absence of EBV follow-up (n=2) or autologous reconstitution (n=2). EBV reactivation (EBV (+)) was defined by at least two consecutive episodes of EBV RT-PCR above 1000 copies/ml of whole blood. Any other result was considered as negative (EBV (−)). Results: 1175 EBV RT-PCR samples were collected over a median follow up of 215 days (range: 21–511). The population observed was essentially adults (median age 42 years, range: 1–65) with leukemia (29 leukemia, 11 lymphomas, 16 other diseases), mixed graft types (26 matched sibling donors, 26 matched unrelated donors, 4 haploidentical donors; 77% peripheral blood stem cells; 20% CD34+ selection) and mixed conditioning (52% non-myeloablative conditioning containing ATG, and 48% full conditioning). The EBV(+) and EBV(−) cohorts were similar for all characteristics analyzed. We observed a median of 18 EBV RT-PCR per patient (range: 4–105), with a median interval between two tests of 7 days (range: 3–45). There were 30 true reactivations, 2 intermittent reactivations (non consecutive EBV titer rises above threshold), 8 isolated reactivations and 16 patients with no reactivation episode. EBV RT-PCR was first performed at a median of 6 days post HSCT (range: 0–245), and reactivation was noted at a median of 44 days post HSCT (range: 6–375). There were no significant difference in PCR follow up (first day of screening, median test interval and length of biological follow up) except for the total number of screening tests per patient, which was higher in the EBV(+) group (p= 0.01). There was only one case of biopsy-proven PTLD in the EBV(+) cohort. No patient was administered Rituximab post- HSCT. Survival curves of the two cohorts were similar regardless of EBV reactivation (log-rank, p= 0.201). Discussion: The incidence of EBV reactivation (n= 30; 54%) and of PTLD (n=1;1.7%) were standard compared to previous studies, resulting in a standard specificity of 47% for EBV screening. However, within our limited group of patients, we could not show any significant differences in mortality between the EBV(+) and EBV (−) cohorts. Therefore, absence of preventive treatment for EBV reactivation did not result in an increase in mortality in our EBV reactivating cohort. This suggests that systematic prophylactic use of Rituximab may not affect overall mortality, whilst potentially increasing the risk of other opportunistic infections. Conclusion: Further prospective studies are needed to better define the patients at risk for developing EBV-related PTLD, within the EBV reactivating allogeneic transplant patients group, before prophylactic treatment of reactivation becomes a routine procedure.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2005
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 1409-1409
    Abstract: A recent transcriptome analysis of human umbilical cord blood and bone marrow (BM) CD34+CD33−CD38−ckit+Rholo (Rholo) vs. CD34+CD33−CD38−ckit+Rhohi (Rhohi) cells identified the gene RASSF8, to be more highly expressed in the hematopoietic stem cell (HSC) rich compartment (Rholo) versus committed progenitor cells (Rhohi). In a subsequent screen for the function of differentially expressed genes in hematopoiesis, the knockdown of RASSF8 using morpholinos in zebrafish embryos resulted in decreased blood formation and reduced expression of early (scl and gata1) and late (hbae1 and lcp1) hematopoietic markers. To test the function of RASSF8 in mammalian hematopoiesis, we overexpressed RASSF8 cDNA in lineage depleted murine bone marrow cells (Lin−) by retroviral transduction using the MSCV-RASSF8-IRES-GFP vector (rMIG-RASSF8). Sorted transduced GFP+ cells were cultured in serum-free medium (supplemented with SCF, TPO, Flt3L and Il-3) for three to five days. No significant differences were seen in overall cell expansion, cell death (7-AAD staining) or cell proliferation (thymidine incorporation assay and propidium iodide staining) between rMIG-RASSF8 transduced cells and cells transduced with the control vector (rMIG). However, we noted a significant accumulation of the stem cell enriched cKit+Lin−Sca1+ (KLS) population in rMIG-RASSF8 transduced cells (43+/−9%) compared to control cells transduced with rMIG (13+/−8%, p=0.003; n=4) after five days. The total number of colony forming cells (CFCs) produced by 750 rMIG-RASSF8 transduced Lin− cells (24+/−7) was significantly lower than in rMIG transduced cells (54+/−8, p=0.008; n=3). CFCs from rMIG-RASSF8 transduced cells were morphologically smaller and more compact, consistent with the morphology of primitive blast-forming colonies. Competitive repopulation assays using 25 000 rMIG-RASSF8 or rMIG transduced C57/Bl6 CD45.1 Lin- cells versus 100 000 C57/Bl6 CD45.2 mononuclear BM cells were performed to evaluate HSC engraftment potential. Four weeks after transplantation only 1+/−0.96% CD45.1 cells were found in the peripheral blood (PB) of the animals receiving rMIG-RASSF8 transduced cells vs. 23+/−12% CD45.1 cells in animals that had received rMIG transduced cells (p & lt; 0.05; n=3). Likewise, PB analysis at 3 months demonstrated nearly no reconstitution of rMIG-RASSF8 transduced CD45.1 cells (1+/−1.7%) vs 30+/−23% rMIG transduced CD45.1 cells (p=0.02). In conclusion, constitutive overexpression of RASSF8 increases the retention/expansion of KLS cells in vitro, blocks differentiation of progenitors giving rise to CFC and inhibits engraftment of HSC. These studies thus suggest that short term overexpression of RASSF8 might ultimately lead to new methods of HSC expansion.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...