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  • 1
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 4310-4310
    Abstract: In the era of novel drugs, the role of RIC AT for relapsed Multiple Myeloma (MM) remains to be determined. In this retrospective study we analyzed the results of RIC AT performed in 36 patients with relapsed MM in our institution between June 1999 and August 2007. At diagnostic our population consisted of 27 males and 9 females. Twenty-eight patients had stage III, 4 patients had stage II and 4 patients had stage I DS. B2-micoglobuline was ≤ 3 mg/l in 16 patients and & gt; 3 mg/l in 11 patients. Del 13 was present in 7/18 patients evaluated. Nineteen received at least 2 HDM with autologous stem cell transplantation, 15 received only one and 2 didn’t received HDM as part of frontline treatment. The median age at time of AT was 56 years (range: 44–64). The “pre-AT” treatments consisted in “standard chemotherapy” for 13 patients and targeted treatments, represented by thalidomide or lenalidomide, or bortezomib w or wo dexamethasone in 23 patients. At the time of AT, 29 patients were responder (3 complete response (CR), 6 very good partial response (VGPR) and 20 partial response (PR)), and 7 patients were not responder (6 stable disease (SD) and 1 progressive disease (PD)). RIC regimen consisted of fludarabine associated with busulfan (n=22), treosulfan (n=2), total body irradiation (n=10), idarubicine and cytosine arabinoside (n=1) or melphalan (n=1). In addition, 25 patients received ATG as part of the conditioning. The donor was an HLA-identical sibling in 20 cases or an unrelated donor in 16 cases. GVH Prophylaxis consisted of CSA alone (n=16), CSA with MMF (n=7), or CSA with MTX (n=13). The median delay between AT and the first response evaluation was 3.8 months, 15 patients achieved CR, 3 patients achieved VGPR, 9 patients achieved PR, 2 patients were in SD and 4 in PD. Twenty one patients developed acute GVHD (grade 1–4) and 14 patients developed chronic GVHD. With a med FU of 42 months, 11 patients are alive. The 3-year event free survival (EFS) and overall survival (OS) from AT are 17, 5% (+/−7.2%) and 32% (+/− 8.3%) respectively. The causes of death were transplant-related complications in 11 patients, relapse or progression in 13 patients, and second malignancy in 1 patient. The TRM at Day 100 and Day 365 was 19 % (+/− 6.6 %) and 32 % (+/− 8%) respectively. Among the numerous factors that were evaluated for their prognostic influence, only two were significantly associated with a better OS and EFS (in univariate and multivariate analysis): the achievement of a CR or VGPR after AT (median OS: 31m vs 5; p & lt;0.0001; median EFS: 56m vs 9; p=0.005) and the occurrence of a chronic GVHD (median OS: 31m vs 9; p=0.0003; median EFS: 56m vs 21; p=0.007). The achievement of a CR or a VGPR after the RIC AT was significantly associated with the result achieved before RIC AT. In our small cohort of patients we were unable to identify factor associated with the occurrence of a cGVH. When targeted treatments were used as salvage, the rate of CR+VGPR before and after RIC AT was higher (before:35% vs 7%; after: 61% vs 31%) however, this did not turned in a significant improvement of the OS, the EFS and the TRM. Conclusion: The disease response remains a major goal to improve the results of RIC AT in relapsed Multiple myeloma. The targeted therapies are able to improve the disease response in patients who relapse after HDM and were never treated with such drugs. However we did not document a significant improvement of the overall results of RIC AT following such salvage as compared to chemotherapy salvage.
    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. 114, No. 22 ( 2009-11-20), p. 502-502
    Abstract: Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.
    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
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  • 3
    Online Resource
    Online Resource
    Cambridge University Press (CUP) ; 2009
    In:  Recusant History Vol. 29, No. 3 ( 2009-05), p. 341-354
    In: Recusant History, Cambridge University Press (CUP), Vol. 29, No. 3 ( 2009-05), p. 341-354
    Abstract: Recent discussion about confessional divisions in England before the Civil War concerns questions of toleration, loyalty, and politics. While the historiography of early modern Catholicism concentrates on matters of persecution, Michael Questier has demonstrated that the Catholic community in England was not as powerless, leaderless and frustrated as some have suggested. In particular, he portrays Anthony Browne, first Viscount Montague, as an influential Catholic who successfully projected a public persona of loyalism to a Protestant monarch. Catholic aristocrats faced a perpetual dilemma. On one hand they existed in confessional opposition to their monarch and society, on the other they were often servants of the Crown in their county or at Court and great landowners who seldom suffered complete social ostracism, or experienced the full penalties the law prescribed for Catholics. How did individual peers attempt to reconcile this paradox?
    Type of Medium: Online Resource
    ISSN: 0034-1932
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2009
    detail.hit.zdb_id: 2815587-7
    SSG: 1
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  • 4
    Online Resource
    Online Resource
    Elsevier BV ; 2009
    In:  Journal of Proteomics Vol. 72, No. 3 ( 2009-4), p. 475-483
    In: Journal of Proteomics, Elsevier BV, Vol. 72, No. 3 ( 2009-4), p. 475-483
    Type of Medium: Online Resource
    ISSN: 1874-3919
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
    detail.hit.zdb_id: 2400835-7
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