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  • American Society of Hematology  (4)
  • 2005-2009  (4)
  • 1
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 1250-1250
    Abstract: Graft-vs-host disease (GvHD) is a major obstacle to safe allogeneic haematopoietic stem cell transplantation (HSCT), leading to significant morbidity and mortality. Recently, a subset of interleukin (IL)-17-producing cells, named Th17, have been shown to play a central role in the induction of autoimmune-tissue injuries and inflammation. The aim of our study is to analyze the Th17 population in the peripheral blood of transplanted patients experiencing (6) acute, (7) active chronic and (6) chronic GvHD. Both Elispot assay and intracellular staining showed an augmented population of Th17 (both IL-17+/IFN-g− and IL-17+/IFN-g+ producing cells) in patients with both aGVHD and active cGVHD, that can represent up to 2.4% of CD4+ T lymphocytes. In accordance, an increased IL-17 plasma level was detected both in patients with aGVHD (mean IL17A concentration= 14 pg/ml) and active cGVHD (mean IL17A concentration= 12 pg/ml), compared to healthy donors (mean IL17A concentration & lt; 4 pg/ml). Interestingly, the percentage of TH17 cells drastically decreased in patient with quiescent cGVHD. Th17 cells of patients with aGVHD and active cGVHD, were of donor origin, as demonstrated by genotyping, and, in line with what already described, showed high IL23 receptor expression (mean= 40%, range 30%–52%). Noticeably, in the liver and skin GVHD lesions, the solely CD3 cells spontaneously producing cytokines were double positive for INF-γ and IL-17A. Importantly, we demonstrated a strict correlation between the levels of TH17 cells and the clinical status of patients with GVHD. The better understanding of the role played by TH17 in the GVHD pathogenesis could open the way to new highly targeted strategies for the management of GVHD.
    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
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  • 2
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3074-3074
    Abstract: Aim: To assess the role of autologous transplantation (AT) compared with chemotherapy (CT) for low risk relapsed childhood acute lymphoblastic leukaemia (ALL). Patients and Methods: Since 1997 at a single Institution, 30 pediatric consecutive patients (pts), lacking a compatible related donor, underwent immunologically purified peripheral stem cell AT, for B cell precursor ALL in second remission (CR2) after late ( 〉 30 ms after diagnosis) or extra-medullary (BM) relapse, belonging to S1–S2 BFM risk group. Since 2000 the positivity of minimal residual disease (MRD) at transplant was considered an exclusion criterium. For each AT patient all possible controls were selected among 236 S1 or S2 pts in CR2 treated with CT in all BFM Centers, matched for: site of relapse, CR1 duration, relapse period and waiting time to transplant. Outcome data are expressed according to the KM estimator for the AT group; a weighted version of the KM estimator is used for the CT group in order to account for the variable proportion of matching; a p-value for the comparison at 4 years (ys) is provided by a permutation test. The role of gender and age at relapse are assessed in a multivariate analysis by a Cox model. The impact of MRD is evaluated. Results: 103 CT controls were selected with a median matching ratio of 4 controls (1–8) for each AT patient. Eight pts in the AT group presented with subsequent relapse at a median of 17 ms (11–48) and 50 in the CT group at a median of 22 ms (5–59) after first relapse; 6 of 8 and 18 of 50 relapsed pts in the two groups underwent allogeneic transplant in CR3 and 4 and 15 of them, respectively, are alive. All events were relapses and no pts died of treatment related complications in CR2. The probability of DFS at 4 ys was 71.3% (SE 8.8) for the AT pts and 44.3% (SE 6.2) for the CT group (p-value: 0.0165) and the probability of survival was 85.8% (SE 6.6) and 65.7% (ES 6.5) (p-value: 0.0385) with a median follow-up of 4.9 ys. The advantage of AT was consistent within the subgroups of late BM and extra-BM relapsed pts. Age and gender did not significantly affect DFS (HR male vs female: 1.82, p-value: 0.08; age 〉 10 ys vs 〈 10 ys: 1.24, p-value: 0,53). The time period of relapse seemed to play a role among pts receiving CT, which reported a better survival when relapse occurred after 2000, which could be influenced by MRD driven patient selection. The impact of MRD was striking in the AT pts, among whom all the 4 MRD positive pts transplanted before 2000, relapsed. MRD data after induction were available for 17 of 30 AT and 36 of 103 CT pts; 5 of 9 MRD positive AT pts and 9 of 12 MRD positive CT pts relapsed; 2 of 8 and 5 of 22 MRD negative pts relapsed among the AT and CT pts, respectively. Conclusions: Children treated with autotransplantation reported a better outcome compared to matched patients receiving chemotherapy. These results in low risk relapsed ALL should be confirmed in a prospective controlled study.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 3
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2217-2217
    Abstract: Abstract 2217 Poster Board II-194 Introduction: Allogeneic haemopoietic-stem-cell transplantation (HSCT) is the treatment of choice for many malignant and non-malignant disorders. Despite the recent advances in post-transplantat immunosuppressive therapy, Graft-versus-Host Disease (GVHD) still represents the major life-threatening complication, developing in a substantial number of HSCT patients and resulting in poor outcome. The basis of GVHD pathophysiology are still poorly understood and its current diagnosis depends mainly on clinical manifestations and invasive biopsies. Specific biomarkers for GVHD would facilitate the early and accurate recognition of this invalidating disease as well as the monitoring of patient response to adopted anti-GVHD pharmacological treatment. With the aim to explore new reliable markers for predicting and monitoring GVHD course, we focused on pentraxin-3 (PTX-3), an acute-phase protein, that has been shown to play a crucial role in orchestrating inflammatory immune responses. Patients and Methods: Having obtained an informed consent, we collected plasma samples from 46 patients who received unmanipulated HSCT and from 9 healthy donors (HD) volunteers. After HSCT, 25/46 patients developed skin GVHD (18 acute GVHD and 7 chronic GVHD), while 21/46 never experienced it. Concerning GVHD patients, blood samples were collected at the day of GVHD onset/ flare, before the beginning of GVHD-specific drug therapy. PTX-3 plasma levels were monitored by ELISA assays. Results: Patients who did not develop GVHD after HSCT showed augmented PTX-3 plasma levels (mean=3.3 ng/ml, range=1.1-8.6 ng/ml) if compared to HD (mean=1.2 ng/ml, range=0.3-2.5 ng/ml, p 〈 0.01). Interestingly, we observed a strong increase of PTX-3 plasma levels in patients with acute GVHD (mean=42.2 ng/ml, range=6.7-218.2 ng/ml) or with flair-ups of chronic GVHD (mean=15.8 ng/ml, range=9-44.3 ng/ml). The increase of PTX-3 levels in patients with acute and active chronic GVHD was statistically significant (p 〈 0.01 and p 〈 0.05 respectively) when compared to both HD and HSCT patients without GVHD. Conclusions: These preliminary results suggest that PTX-3 plasma levels increase very rapidly in patients experiencing active GVHD, thus candidating PTX-3 as an easily measurable soluble factor useful to corroborate clinical observations in a disease in which signs and symptoms are often protean. Further studies are needed to clarify if PTX-3 could represent a good diagnostic and/or prognostic factor rapidly indicating therapy responsiveness. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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  • 4
    In: Blood, American Society of Hematology, Vol. 106, No. 3 ( 2005-08-01), p. 925-928
    Abstract: Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor–cleaving protease, ADAMTS13. The presence of anti-ADAMTS13 autoantibodies is considered a factor predisposing to relapses. Despite close monitoring and intensive plasma treatment, in these patients acute episodes are still associated with substantial morbidity and mortality rates, and the optimal therapeutic option should be prevention of relapses. This study was conducted in a patient with recurrent TTP due to high titers of ADAMTS13 inhibitors, who used to have 2 relapses of TTP a year. The study compared the standard treatment plasma exchange with rituximab. Results documented that plasma exchange had only a small transient effect on ADAMTS13 activity and inhibitors; on the contrary, prophylaxis with rituximab was associated with disappearance of anti-ADAMTS13 antibodies, a progressive recovery of protease activity, and it allowed the patient to maintain a disease-free state during a more than 2-year follow-up.
    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
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