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  • 1
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 2678-2678
    Abstract: Background: MDS with del 5q are characterized by profound anemia, which until the recent introduction of lenalidomide (N Engl J Med2005; 352: 549–57, J Clin Oncol2005;16S:5), was considered generally unresponsive to available treatments. In order to reevaluate the outcome of those patients in the pre-lenalidomide era, we analyzed response of anemia in MDS with del 5q treated with EPO ± G-CSF and thalidomide in previous GFM trials. Patients: MDS with del 5q included in 419 MDS treated with EPO or Darbepoetin (DAR) ± G-CSF by GFM centers (including 3 successive GFM trials: Blood2004; 104: 321–7; Blood2005;106 suppl 1: 712a; Br J Haematol2006;133: 513–9 and submitted to ASH 2006), and in 134 MDS treated with thalidomide in two successive GFM trials (Br J Haematol2005; 131: 609–18, and submitted to ASH 2006). Patients received at least 30,000 U/w of EPO or 300 mg/w of DAR and doses ranging from 50 to 800 mg/d of Thalidomide during at least 12 weeks. Results: 48 MDS with del 5q received EPO (or DAR) ± G-CSF, including 30 pts with del 5q alone, 9 with one and 9 with 〉 1 additional cytogenetic abn; 21/48 had marrow blasts ≥5% (7 had 〉 10%). 17 had the “5q- syndrome” according to WHO. Median pre-treatment EPO level was 287 UI/L (range 12–5,665), i.e. significantly more than in non del 5q cases (median 68, p 〈 0.001). 22/48 pts (46%) had erythroid response, including 15 major and 7 minor (11 responses after EPO or DAR alone and 11 after EPO or DAR + G-CSF) vs. 64% in pts without del 5q (p=0.01) (p= 0.066 after adjustment for marrow blasts). The response rate was 52%, 55%, 22% and 33%, respectively in del 5q pts with the 5q- syndrome, one additional cytogenetic abn, 〉 1 additional cytogenetic abn, and marrow blasts ≥5%. Response duration was significantly shorter in MDS with del 5q than in other MDS (mean 12 vs. 24 months, p=0.019) and in pts with 5q- syndrome vs. other MDS with marrow blasts 〈 5% (mean 11vs. 24months, p=0.025). 20 pts with del 5q were treated with thalidomide. 6/20 had an erythroid response (30 %, including 3 major and 3 minor responses) vs. 29% of other MDS (p=NS) Conclusion: MDS with del 5q with ≤1 additional cytogenetic abn and no excess of marrow blasts may have erythroid response to EPO ± G-CSF but responses are generally very short, while response rates to thalidomide are low. Those results are clearly inferior to results obtained with lenalidomide in MDS with del 5q.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 2
    In: Blood, American Society of Hematology, Vol. 111, No. 2 ( 2008-01-15), p. 574-582
    Abstract: We analyzed prognostic factors of response, response duration, and possible impact on survival of epoetin α, epoetin β, or darbepoetin α (DAR) with or without granulocyte colony-stimulating factor in 403 myelodysplastic syndrome (MDS) patients. Sixty-two percent (40% major and 22% minor) and 50% erythroid responses were seen, and median response duration was 20 and 24 months according to IWG 2000 and 2006 criteria, respectively. Significantly higher response rates were observed with less than 10% blasts, low and int-1 International Prognostic Scoring System (IPSS), red blood cell transfusion independence, serum EPO level less than 200 IU/L, and, with IWG 2006 criteria only, shorter interval between diagnosis and treatment. Significantly longer response duration was associated with major response (IWG 2000 criteria), IPSS low to INT-1, blasts less than 5%, and absence of multilineage dysplasia. Minor responses according to IWG 2000 were reclassified as “nonresponders” or “responders” according to IWG 2006 criteria. However, among those IWG 2000 minor responders, response duration did not differ between IWG 2006 responders and nonresponders. Multivariate adjusted comparisons of survival between our cohort and the untreated MDS cohort used to design IPSS showed similar rate of progression to acute myeloid leukemia in both cohorts, but significantly better overall survival in our cohort, suggesting that epoetin or DAR treatment may have a favorable survival impact in MDS.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 3
    In: Cancer Medicine, Wiley, Vol. 12, No. 5 ( 2023-03), p. 5656-5660
    Abstract: Personalized medicine is a challenge for patients with acute myeloid leukemia (AML). The identification of several genetic mutations in several AML trials led to the creation of a personalized prognostic scoring algorithm known as the Knowledge Bank (KB). In this study, we assessed the prognostic value of this algorithm on a cohort of 167 real life AML patients. We compared KB predicted outcomes to real‐life outcomes. For patients younger than 60‐year‐old, OS was similar in favorable and intermediate ELN risk category. However, KB algorithm failed to predict OS for younger patients in the adverse ELN risk category and for patients older than 60 years old in the favorable ELN risk category. These discrepancies may be explained by the emergence of several new therapeutic options as well as the improvement of allogeneic stem cell transplantation (aHSCT) outcomes and supportive cares. Personalized medicine is a major challenge and predictions models are powerful tools to predict patient's outcome. However, the addition of new therapeutic options in the field of AML requires a prospective validation of these scoring systems to include recent therapeutic innovations.
    Type of Medium: Online Resource
    ISSN: 2045-7634 , 2045-7634
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
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  • 4
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3083-3083
    Abstract: Abstract 3083 Allogeneic hematopoietic stem cell transplantation (HSCT) is indicated for patients (pts) with acute leukemia (AL) with poor-risk cytogenetics or refractoriness to chemotherapy. For adults requiring HSCT urgently, such as pts in first complete remission (CR1), a single (s) or double unit (d) UCBT is a valid stem cells source. In the sUCBT setting, type of conditioning regimen seems to be associated with better outcome (Sanz BMT 2012). With the aim to compare single vs double UCBT after myeloablative conditioning regimen (MAC) in a homogeneous series of pts, we analyzed 239 adults ( 〉 18years) with AL in CR1. Pts were transplanted with sUCBT (n=156) or dUCBT (n=83) from 2005–2011 in EBMT centers for ALL (n=101) and AML (n=138). Type of MAC was statistically associated with outcomes therefore pts were analyzed in 3 different groups: Group 1: pts receiving sUCBT with TBI-based+Cy (+Flu) (n=68) (performed in 42 transplant centers (TC)), Group 2: pts receiving sUCBT with Bu+Flu+Thiotepa (n=88) (performed in 23 TC) and Group 3: pts receiving dUCBT with Cy+TBI+Flu (n=83) (performed in 47 TC). No statistical differences were found among the 3 groups for pts and disease characteristics (diagnosis, risk, gender, weight, CMV status, year of UCBT and time from diagnosis to UCBT) however pts in group2 were older than in group1 and 3 (median age 38 vs 33 vs 31 years) (p=0.03). Cytogenetic at diagnosis was available for 176 pts, 39% of pts were classified in the intermediate risk and 56% in unfavorable risk group. Forty-two pts had t(9;22) and 26 FLT3/ITD mutation. No differences on cytogenetic were found among the 3 groups. Thirty one percent of CB units were identical to recipient or had 1 HLA disparity (antigen level typing for HLA-A and B and allelic level for DRB1) while 69% had 2–3 HLA disparities. There was no difference on HLA disparities among the 3 groups. Median infused TNC was 2.9×107/kg for group1, 3×107/kg for group2, and 3.7×107/kg for group3 (p=0.01) and median CD34 was 1.2×105/kg, 1.6×105/kg and 1.5×105/kg, respectively (p=0.32). ATG was part of conditioning regimen in 73% of pts. The use of ATG was different in the 3 groups (70%, 90% and 40% for group1, 2 and 3, respectively p 〈 0.001). GVHD prophylaxis consisted either of CSA±MMF or CSA±steroids in 46% and 22% of pts, respectively. All groups had the same median follow-up time: 24 (range 3–74) months. For group1, group2 and group3, the cumulative incidence (CI) of 60 days neutrophil recovery was 82%, 89% and 87% (p=0.15), with median time of 27, 21 and 24 days, respectively (p 〈 0.001). Chimerism analysis performed at day 100 showed full donor chimerism in 87% of pts (data available for 80% of pts who engrafted). No differences in chimerism status were found between the 3 groups (p=0.47). At day 100, CI of acute GVHD (grade II-IV) was 30% vs 20% vs 45% for group1, group2 and group3, respectively (p=0.001). Pts receiving a dUCBT who developed aGvHD (n=38), experienced mainly grade II aGvHD with skin involvement (grade II (n=25), grade III (n=10), grade IV (n=3)). CI of chronic GvHD at 1 year was 29%, with no differences in the incidence among the groups. At 1 year, CI of TRM was 44% for group1, 33% for group2 and 36% for group3 (p=0.46). In multivariate analysis, two factors were associated with higher TRM: diagnosis of ALL (p=0.048) and age 〉 35 years (p=0.049). One-Hundred-six pts died and the causes of death were infection (n=38), GvHD (n=18), other transplant-related events (n=31) or relapse (n=18). CI of 2y relapse was 25% for group1, 18% for group2 and 16% for group3 (p=0.22). No factors were found to be associated with increase relapse incidence in multivariate analysis. The 2y probability of leukemia-free-survival (LFS) was 31% for group1 (sUCBT-TBI based), 48% for group2 (sUCBT-BuFluTT), and 47% for group3 (dUCBT) (p=0.03). No center effect was found for LFS. In multivariate analysis, use of sUCBT using TBI based MAC (HR=0.9, p=0.003), diagnosis of ALL (HR=0.69, p=0.04) and age 〉 35years (HR=1.4, p=0.04) were independently associated with decreased LFS. In this retrospective based registry analysis, in the myeloablative setting for adults with AL in CR1, outcomes (TRM, RI and LFS) after dUCBT were not statistically different from sUCBT using iv-BuFluTT. However, compared to sUCBT using TBI-based MAC, dUCBT was associated with lower RI and better LFS rates. In the MAC setting, the combination of conditioning regimens and type of graft (single vs. double) may have different impact UCBT outcomes. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 5
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2125-2125
    Abstract: Abstract 2125 Background: Over the last three decades, progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has considerably improved the outcome of children, leading to 5-year OS of more than 80%. Numerous comparisons, including the French LALA/FRALLE (Boissel et al. JCO 2001), have reported a better outcome in teenagers treated with pediatric as compared to standard historical adult ALL protocols. Even if modern pediatric-inspired adult ALL protocols have recently reported impressive improvements, especially in younger patients (Huguet et al. JCO 2009), the issue of whether younger adults (YAs) should be treated according to pediatric or adult protocols remains an open one. The aim of this study was first to evaluate the feasibility and the results of a non-modified pediatric protocol (the French FRALLE 2000) in adolescents and younger adults (AYAs, aged 15–29 years) treated in adult departments. Methods: From February 2001 to June 2010, 72 AYAs with Ph-negative ALL were treated according to the pediatric FRALLE 2000-BT protocol in 12 adult hematology units in France and Belgium. After a prednisone prephase and a four-drug induction (prednisone, daunorubicin, vincristine and L-asparaginase), patients in CR received a consolidation, a 1st delayed intensification, an interphase, a 2nd delayed intensification, and a maintenance chemotherapy during two years. Results: The median age was 19 years (range, 15–29 years). The cohort was separated in 2 subgroups: 44 adolescents aged 15–19 years and 28 young adults (YAs) aged 20–29 years. There were no significant differences between the adolescent and the YA populations in term of sex ratio, white blood cell count (WBC), central nervous system involvement, and phenotype (BCP- vs T-ALL). As expected, few recurrent cytogenetical abnormalities were identified in this population and did not differed between both subgroups. In the adolescent group, we identified 2 patients with t(4;11), 1 patient with t(1;19), and 3 patients with hypodiploïdy and/or neartriploïdy, whereas this repartition was 2/2/1 in YAs. Rates of good early response to prednisone were in 68% in adolescents and 61% in YAs (p=.52), while rates of good early response to chemotherapy were 80% and 86%, respectively (p=.51). No patient died during induction. Complete remission (CR) rate did not differ between subgroups (98% vs 100%, p=.42). With a median follow up of 4.8 years, 5-year EFS was 57% (41% in adolescents vs 79% in YAs, p=.03) and 5-year OS was 67% (56% and 82% respectively, p=.09). In patients with BCP-ALL, 5-year EFS was 60% (43% in adolescents vs 91% in YAs, p=.02) and 55% in T-ALL (57% vs 50% respectively, p=.81). Twelve patients (17%) received an allogeneic stem cell transplantation (SCT) in first CR (5 adolescents and 7 YAs). Four patients died in first CR, all after SCT, (2 adolescents and 2 YAs). In univariate analysis, a high WBC (continuous variable, p=.02) and a poor early response to chemotherapy (33% vs 63%, p=.02), but not phenotype or poor early response to prednisone, were significantly associated with a shorter EFS. In multivariate analysis, age (adolescents vs YA, p=.04), WBC (continuous variable, p=.0005), and poor early response to chemotherapy (p=.006) had still an impact on EFS. The poor outcome of adolescents compared to YAs, also observed in the French adult GRAALL protocol (not published), was not explained by differences in ALL characteristics, early response to therapy, or treatment-related toxicity. Conclusion: The pediatric protocol FRALLE 2000 is effective and safe for the treatment of selected AYAs with Ph-negative ALL referred to adult departments. The results observed in the YA population are promising, warranting prospective comparisons with the more recent pediatric-inspired adult protocols. The unexpected poorer outcome of adolescents deserves further investigations to explore a potential impact of the quality of care delivered in an adult environment. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 6
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2929-2929
    Abstract: Abstract 2929 Background: Azacitidine (AZA) has changed the outcome of patients (pts) with myelodysplastic syndromes (MDS) or acute myeloid leukemia with multi-lineage dysplasia (AML-MLD) unfit for intensive chemotherapy. AZA is a hypomethylating agent providing about 50% of responses in MDS and AML with low blast count (Fenaux et al., Lancet Oncol 2009, JCO 2010). To date, no consensus genetic predictor of response has been reported. Methods: In MDS (including RAEB-t) and AML-MLD ( 〉 30% blasts) patients treated by AZA in 5 centers, we performed genomewide single nucleotide polymorphism (SNP) analysis using SNP 6.0 arrays (Affymetrix, High Wycombe, U.K.) on bone marrow (BM) samples. Patients having received ≥ 1 cycle of AZA and who had bone marrow evaluation after ≥ 4 cycles, or who died or progressed before completion of 4 cycles were considered evaluable (the last 2 groups were considered as treatment failures). Responses were scored according to IWG 2006 criteria for MDS and to Cheson et al. (JCO 2003) for AML. DNA were prepared for hybridization according to the manufacturers' recommendations. Affymetrix CEL files for each sample were analyzed using the Genotyping Console software (v3.0.2). Genotyping was performed using Birdseed V2 algorithm. Unpaired Copy Number and LOH analysis was performed with Regional GC correction. Copy number and UPD were also analyzed using the Copy Number Analyzer for GeneChip (CNAG version 3.3.0.1) algorithm (http://www.genome.umin.jp/CNAGtop2.html). Results: The study population included 92 pts: F/M: 41/51; median age 72 (range 35–88). Diagnosis at AZA onset was MDS in 54 (RAEB-1 n=6, RAEB-2 n=37, RAEB-t=11, IPSS int-1 in 7, int-2 in 15, high in 32, undetermined in 2) and AML-MLD in 38 pts. Cytogenetic according to IPSS was favorable in 33, intermediate in 19, unfavorable in 28, unknown in 11. Median number of cycles was 6 (range 1–41). All pts received the approved (75 mg/m2 for 7 days every 4 weeks) or a reduced AZA schedule (75 mg/m2 for 5 days every 4 weeks). Median overall survival (OS) of our cohort was 22 months. DNA samples from 52 patients were available for SNP analysis. There were no significant differences between the SNP and no SNP subgroups in term of median age, sex ratio, disease status at AZA onset, cytogenetic according to IPSS, median number of cycles, responses and OS. We listed aneuploidies (CNA) and uniparental disomies (UPD) detected by SNP analysis in the samples, and focused on 18 chromosomal bands (1p13.2, 2q34, 3p14.2, 3q26, 4q24, 5q33.1, 5q35, 6p21.3, 7q36.1, 9p21.3, 11p13, 11q23.3, 13q12.2, 15q21, 15q26.2, 20q11.21, 21q22.1) containing genes implicated in MDS or AML. Preliminary results show correlations between some CNA/UPD and response to AZA and OS, such as 1/a UPD at 9p21 (6% of patients) associated to a better hematologic improvement (X2, p=0.037), 2/an amplification at 20q11.21 (8% of patients) correlated with a poorer response (X2, p=0.048) and a trend toward poorer OS (Log-Rank, p=0.091), and 3/deletion and UPD at 15q21 (6% of patients) strongly correlated to poorer OS (Log-Rank, p=0.001). Several additional CNA and UPD of potential interest are presently under investigation. Conclusion: SNP analysis using SNP 6.0 is a powerful tool to decipher genome complexity in BM samples of MDS and AML patients treated with AZA. Our data suggest that this approach could allow characterizing profiles of responder versus non responder pts. Our study must be extended to a larger cohort and relevant anomalies must be confirmed by more sensitive techniques such as high-scale sequencing. Disclosures: Cluzeau: Celgene: Consultancy. Raynaud:Celgene: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 7
    In: Medical Mycology, Oxford University Press (OUP), Vol. 59, No. 5 ( 2021-05-04), p. 486-497
    Abstract: Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain.
    Type of Medium: Online Resource
    ISSN: 1369-3786 , 1460-2709
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 8
    In: British Journal of Haematology, Wiley, Vol. 166, No. 5 ( 2014-09), p. 749-757
    Type of Medium: Online Resource
    ISSN: 0007-1048
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2014
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  • 9
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 187-187
    Abstract: Double umbilical cord blood transplantation (dUCBT) has extended the applicability of UCBT for hematologic disorders especially to adult patients (pts) for whom the low cellular content of a single unit is a limiting factor. However the use of dUCBT has been, recently, associated with a higher incidence of acute graft-versus-host disease (aGVHD) when compared with single UCBT (sUCBT). Moreover, several retrospective and prospective studies have addressed risk factors for aGVHD with some conflicting results. Whether the number of total nucleated cells, HLA disparities, type of conditioning regimen or GVHD prophylaxis have an impact on aGVHD incidence in dUCBT is yet to be established in a larger series of patients. With this background, this report analyzed 921 adult recipients who underwent dUCBT for hematologic malignancies from 2005-2012 in EBMT centers. Median age was 46 (range, 18-72) years (yrs) and 59% were males. Diagnosis was acute leukemia in 56%, MDS/CML in 19% and lymphoid malignancies in 25%; 22% of pts received at least one prior autologous HSCT. Reduced-intensity conditioning (RIC) was used in 68% of pts and the most common regimen for both myeloablative conditioning (MAC) and RIC was Cyclophosphamide-Fludarabine-TBI (TCF) (40% and 78%, respectively). ATG was used in 30% of pts. GVHD prophylaxis consisted of a MMF based regimen in 774 pts (84%); cyclosporine±steroids in 103 (11%) and MTX-based regimen in 44 (5%). HLA incompatibilities were classified using the cord blood unit bearing the highest degree of mismatch with the recipient: 1% were HLA matched 6/6, 25% were 5/6, 67% were 4/6, and 7% 〈 4/6. Median TNC collected was 4.8x10e7/kg. With a median follow-up of 26 months (range, 3-98) aGVHD was absent in 418 patients (46%), 169 pts developed grade I (18%), 194 grade II (21%), 103 grade III (11%) and 37 grade IV (4%). One-hundred day cumulative incidence (CI) of aGVHD grade II-IV was 36%±2% and III-IV 15%±2%, with a median time of onset of 28 days (range, 4-97). Of those pts with grade II-IV aGVHD, 82% had skin, 66% gastro-intestinal tract (GIT) and 25% liver involvement. The most common organ involvement in pts with grade III-IV aGVHD was GIT (89%) followed by skin (71%) and liver (39%). Treatment of grade II-IV aGVHD was steroid alone in 91% of pts. For pts with grade III-IV aGVHD steroid was used alone in 77% of pts, 11% received steroid+monoclonal antibodies, 3% steroid+MTX and 9% other treatments (figure 1). At day 60, CI of neutrophil engraftment was 84%. Out of the 712 pts at risk, 218 developed chronic GVHD (cGVHD) with a CI at 2 yrs of 25%±5%. Of these, 102 pts (47%) had previous aGVHD grade II-IV and 116 (53%) had de novo cGVHD. CI of early NRM (at day 100) was 13%. At 2 yrs, the probability of PFS was 37%, NRM 35% and relapse 28%. In multivariate analysis, the following factors were associated with an increased incidence of grade II-IV GVHD: use of MAC (HR: 1.45 (1.12-1.91), p=0.005), absence of ATG (HR: 2.39 (1.78-3.30), p 〈 0.001) and ≥2 HLA mismatches (HR: 1.35 (1.01-1.81), p=0.048) – figure 2; whereas advanced stage disease at transplantation (HR: 1.76 (1.10-2.80), p=0.02) and absence of ATG (HR: 2.54 (1.56-4.13), p 〈 0.001) were associated with increased incidence of aGVHD grade III-IV. Presence of 2 or higher HLA mismatches was associated with increased incidence of cGVHD (HR: 1.5 (1.1-2.05), p=0.01). In a time dependent model the presence of grade II-IV aGVHD was associated with lower relapse risk (HR: 0.71 (0.54-0.94), p=0.02), higher NRM (HR: 1.4 (1.1-1.76), p=0.005) and increased incidence of cGVHD (HR: 1.92 (1.59-2.63), p 〈 0.001). Despite previous analysis showing increased incidence of acute and chronic GVHD after dUCBT, our study demonstrated that the GVHD incidence remains relatively low in dUCBT setting when compared to published data on HLA matched adult donor. In pts developing grade II-IV aGVHD, skin was the most common organ affected, followed by GIT and liver. Steroid alone was the backbone treatment of aGVHD and the association of steroid and other therapies (mainly monoclonal antibodies) was mostly seen in pts affected by grade III-IV aGVHD. Acute GVHD grade II-IV seems to be influenced by the intensity of the conditioning regimen, the use of ATG, and HLA compatibility; therefore prospective trials evaluating the role of these factors in dUCBT should be addressed. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 10
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4428-4428
    Abstract: Abstract 4428 The Fas death receptor (CD95/TNFSFR6) conveys death and non-death signals through binding to its cognate ligand, FasL (CD95L)1,2. Fas is expressed constitutively in CD34+ cells of patients with chronic myeloid leukemia3. In order to explore the implication of Fas in CML patient's response, we aimed at analyzing expression and function of Fas in the imatinib-sensitive human Bcr-abl+ Fas+ AR 230S cell line, and in its imatinib-resistant counterpart AR 230R. We analysed the Fas-mediated apoptosis of AR230S and showed that not only imatinib (Figure 1) but also nilotinib and dasatinib (data not shown) potentiate Fas-L mediated apoptosis. This potentiation is dose dependent (Figure 2). Interestingly, there is no potentiation of TKI-mediated apoptosis by FasL in the imatinib-resistant counterpart AR 230R which is Fas negative. The Fas knockdown with a lentivirus-expressing a FAS-shRNA in AR 230S was associated with a disappearance of potentiation effect, whereas the up regulation of Fas expression in AR230 S cell line using lentivirus-expressing human Fas (hFas) induced an emphasized potentiation effect confirming the pivotal role of Fas in the potentiation of TKI-mediated apoptosis. Notably, IFN-α is able to enhance expression of Fas on CD34+ cells from CML patients3. We thus explored the action of IFN-α on the Fas potentiation of TKI-mediated apoptosis. We observed that preincubation with IFN-α increased potentiation in a dose-dependant manner (Data not shown). In conclusion, our preliminary results demonstrate the pivotal role of Fas in the potentiation of TKI-mediated apoptosis and highlight the role of IFN-α in the design of CML treatments. Figure 1: Percentage of FasL-mediated apoptosis in AR230 cell line. Apoptosis induced by FasL in presence or in absence of imatinib was analyzed by propidium iodide staining of cellular DNA content and shown as percentage of sub-G1 to the whole population. Figure 1:. Percentage of FasL-mediated apoptosis in AR230 cell line. Apoptosis induced by FasL in presence or in absence of imatinib was analyzed by propidium iodide staining of cellular DNA content and shown as percentage of sub-G1 to the whole population. Figure 2: Dose-dependentof FasL mediated apoptosis in absence or in combination with imatinib. Apoptosis induced by FasL in presence or in absence of imatinib analyzed by propidium iodide staining of cellular DNA content and shown as percentage of sub-G1 to the whole population. Each point represents the mean ± S.E.M. of 3 experiments. Figure 2:. Dose-dependentof FasL mediated apoptosis in absence or in combination with imatinib. Apoptosis induced by FasL in presence or in absence of imatinib analyzed by propidium iodide staining of cellular DNA content and shown as percentage of sub-G1 to the whole population. Each point represents the mean ± S.E.M. of 3 experiments. Disclosures: Legros: Novartis: Research Funding, Speakers Bureau; BMS: Speakers Bureau; Celgene: Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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