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In: Biology of Blood and Marrow Transplantation, Elsevier BV, Vol. 22, No. 3 ( 2016-03), p. S351-S352

Type of Medium: Online Resource

ISSN: 1083-8791

URL: Article

DOI: 10.1016/j.bbmt.2015.11.847

Language: English

Publisher: Elsevier BV

Publication Date: 2016

detail.hit.zdb_id: 3056525-X

detail.hit.zdb_id: 2057605-5

In: Transplantation and Cellular Therapy, Elsevier BV, Vol. 30, No. 2 ( 2024-02), p. S50-S51

Type of Medium: Online Resource

ISSN: 2666-6367

URL: Article

DOI: 10.1016/j.jtct.2023.12.085

Language: English

Publisher: Elsevier BV

Publication Date: 2024

detail.hit.zdb_id: 3056525-X

In: Transplantation and Cellular Therapy, Elsevier BV, Vol. 27, No. 6 ( 2021-06), p. 504.e1-504.e6

Type of Medium: Online Resource

ISSN: 2666-6367

URL: Article

DOI: 10.1016/j.jtct.2020.12.027

Language: English

Publisher: Elsevier BV

Publication Date: 2021

detail.hit.zdb_id: 3056525-X

In: European Journal of Haematology, Wiley, Vol. 76, No. 4 ( 2006-04), p. 342-347

Type of Medium: Online Resource

ISSN: 0902-4441 , 1600-0609

URL: Issue

URL: Article

DOI: 10.1111/ejh.2006.76.issue-4

DOI: 10.1111/j.1600-0609.2005.00601.x

Language: English

Publisher: Wiley

Publication Date: 2006

detail.hit.zdb_id: 2027114-1

In: Blood, American Society of Hematology, Vol. 113, No. 14 ( 2009-04-02), p. 3375-3382

Abstract: Despite recent advances, allografting remains the only potential cure for myeloma. From July 1999 to June 2005, 100 newly diagnosed patients younger than 65 years were enrolled in a prospective multicenter study. First-line treatment included vincristin, adriamycin, and dexamethasone (VAD)–based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m2) followed by a single dose of nonmyeloablative total body irradiation and allografting from an human leukocyte antigen (HLA)–identical sibling. Primary end points were the overall survival (OS) and event-free survival (EFS) from diagnosis. After a median follow-up of 5 years, OS was not reached, and EFS was 37 months. Incidences of acute and chronic graft-versus-host disease (GVHD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) before allografting was associated with achievement of posttransplantation CR (hazard ratio [HR] 2.20, P = .03) and longer EFS (HR 0.33, P 〈 .01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplantation approach allows prolonged survival and long-term disease control in patients with reduced tumor burden at the time of allografting. We are currently investigating the role of “new drugs” in intensifying pretransplantation cytoreduction and posttransplantation graft-versus-myeloma effects to further improve clinical outcomes. (http://ClinicalTrials.gov; NCT-00702247.)

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2008-07-167379

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 106, No. 11 ( 2005-11-16), p. 5311-5311

Abstract: The introduction of non myeloablative/reduced intensity conditioning regimens for allografting has broadened the application of a potentially curative treatment to patients who, for age or medical controindications, could not tolerate conventional high dose preparative regimens. However, pulmonary causes account for a high percentage of post transplant complications. Between May 2001 and December 2004, lung function tests, methacholine inhalation challenge and eNO were evaluate pre transplant and then at 3, 6 and 12 months post allografting in 31/40 of patients affected by hematological malignancies and undergoing non myeloablative transplant at our Institution. Median age was 56 (23–64). Conditioning regimens consisted of fludarabine (90mg/m2 total) and low dose (200 cGy) TBI in 16 patients, TBI only in 14, and penthostatin + TBI in 1. Donors were matched-siblings in all but 4 patients whose donor was matched unrelated. Post-grafting immunosuppression consisted of oral cyclosporine and mycophenolate mofetil. Nine patients died within 6 months from transplant (group A); causes of death were pulmonary infection in 3, mesothelioma in 1, cerebral toxicity in 3, and progressive disease in 2. Nine died after 12 months from transplant (group B) from bronchiolites obliterans (BO), 1, lung cancer, 1, myocardial ischemia, 1, progressive disease, 4. The remaining 13 are alive (group C) after a median follow-up of 26 months (18–49 months). Patients in groupA were evaluated at baseline only. Overall, baseline rate of carbon monoxide uptake (KCO) was mildly decreased (median 65%, range 42–118%), but significantly lower when compared group A to group C (61% vs 72% p=0.01). A decline of KCO was also observed in group B. Table 1. KCO % Baseline 3 months 6 months 12 months * n=3 in group B; n=7 in group A Group A (range) 60 (45–69) - - - Group B (range) 62 (42–118) 56 (40–82) 55 (36–117) 67 (64–76) GroupC (range) 72 (51–105) 63 (29–65) 72 (61–123) 66 (45–123) Despite similar baseline values, at 6 months, there was evidence of higher eNO in group B when compared to group C (12 vs 31 ppb, p=0.02). Patients who received 2 or more lines of chemotherapy before allografting showed significant higher increases of eNO at 3 and 6 months post transplant: 12 vs 21 ppb (p=0.01) and 12 vs 37 ppb (p=0.0003), respectively. Co-morbidities, disease status, donor type, conditioning regimen and GVHD did not influence any of the parameters studied. BO developed in 2 patients who showed progressive worsening lung function tests and raising eNO. In summary, reduced KCO appeared to be associated with increased transplant related mortality. Previous heavy chemotherapy might predispose transplant patients to higher risk of tissue inflammation as suggested by increased eNO. Moreover, the clinical impact of elevated eNO should be further investigated as it might define a subset of patients at higher risk of pulmonary inflammation and lethal transplant related complications.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V106.11.5311.5311

Language: English

Publisher: American Society of Hematology

Publication Date: 2005

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 23-24

Abstract: Background SEA-CD70 is being developed in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Current treatment options are limited for patients (pts) with relapsed or refractory (r/r) MDS or r/r AML and outcomes remain poor. SEA-CD70 is an investigational humanized, non-fucosylated monoclonal antibody targeting CD70. Expression of CD70 is limited in normal tissue, but is aberrantly expressed on malignant myeloid blasts while absent from healthy hematopoietic progenitor cells. CD70 and its ligand, CD27, may play a role in malignant blast cell survival and/or tumor immune evasion. SEA-CD70 uses a novel sugar-engineered antibody (SEA) platform to produce a non-fucosylated antibody with enhanced effector function. The proposed mechanism of action of SEA-CD70 includes elimination of CD70 positive cells via enhanced antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and mediation of complement-dependent cytoxicity (CDC). Additionally, SEA-CD70 has the potential to block the interaction of CD70 with CD27, which may disrupt signals that enhance blast proliferation and survival and may modulate the immune system to limit immune evasion and increase antigen specific T cell responses. Methods SGNS70-101 is a phase 1, open-label, multicenter, dose-escalation, and cohort expansion study designed to establish the safety, tolerability, and preliminary activity of SEA-CD70 in pts with myeloid malignancies (NCT04227847). Dose escalation is ongoing. In dose escalation, pts must have r/r MDS with 5-20% blasts which has failed prior treatment with a hypomethylating agent (HMA), and have no other therapeutic options known to provide clinical benefit for MDS. After conclusion of dose escalation, monotherapy expansion cohorts will be opened for pts with MDS and for pts with AML. Primary objectives are to evaluate the safety and tolerability, and to determine the maximum tolerated dose (MTD) or recommended expansion dose of SEA-CD70. Secondary objectives are to assess antitumor activity, PK, and immunogenicity of SEA-CD70. Once dose escalation is complete and the recommended monotherapy dose is identified, combination cohorts will be considered in AML and MDS. The study is currently enrolling with sites opening in the US and EU. Disclosures Aribi: Seattle Genetics: Consultancy. Advani:OBI: Research Funding; Takeda: Research Funding; Novartis: Consultancy, Other: advisory board; Pfizer: Honoraria, Research Funding; Kite: Other: Advisory board/ honoraria; Amgen: Consultancy, Other: steering committee/ honoraria, Research Funding; Seattle Genetics: Other: Advisory board/ honoraria, Research Funding; Immunogen: Research Funding; Glycomimetics: Consultancy, Other: Steering committee/ honoraria, Research Funding; Macrogenics: Research Funding; Abbvie: Research Funding. Donnellan:Kite Pharma/Gilead: Research Funding; Janssen: Research Funding; Karyopharm Therapeutics: Research Funding; AstraZeneca: Research Funding; Astex Pharmaceuticals: Research Funding; Incyte: Research Funding; MedImmune: Research Funding; TCR2 Therapeutics: Research Funding; Genentech: Research Funding; PTC Therapeutics: Consultancy, Research Funding; Pfizer: Research Funding; Daiichi Sankyo: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Consultancy; Abbvie: Consultancy, Research Funding; Bellicum Pharmaceuticals: Research Funding; CTI Biopharma: Research Funding; Celgene: Research Funding; Celularity: Research Funding; Forma Therapeutics: Research Funding; Forty Seven: Research Funding; Takeda: Research Funding; H3 Biomedicine: Research Funding; Ryvu Therapeutics: Research Funding; Seattle Genetics: Consultancy, Research Funding. Fathi:Astellas: Consultancy; Agios: Consultancy, Research Funding; Amphivena: Consultancy, Honoraria; AbbVie: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Celgene: Consultancy, Research Funding; Forty Seven: Consultancy; Jazz: Consultancy, Honoraria; Kite: Consultancy, Honoraria; NewLink Genetics: Consultancy, Honoraria; Novartis: Consultancy; PTC Therapeutics: Consultancy; Takeda: Consultancy; TrovaGene: Consultancy; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Blue Print Oncology: Consultancy; Boston Biomedical: Consultancy; Kura: Consultancy; Trillium: Consultancy; Seattle Genetics: Consultancy, Research Funding. Rotta:Merck: Speakers Bureau; Jazz Pharma: Speakers Bureau. Vachani:Blueprint: Consultancy; CTI Biopharma: Consultancy; Daiichi Sankyo: Consultancy; Incyte: Consultancy, Research Funding; Jazz: Consultancy; Astellas: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy; Abbvie: Consultancy. Yang:AROG: Research Funding; Protagonist: Research Funding; Jannsen: Research Funding; AstraZeneca: Research Funding. Ho:Seattle Genetics: Current Employment, Current equity holder in publicly-traded company. Garcia-Manero:Novartis: Research Funding; Helsinn Therapeutics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Jazz Pharmaceuticals: Consultancy; Onconova: Research Funding; Amphivena Therapeutics: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Acceleron Pharmaceuticals: Consultancy, Honoraria; AbbVie: Honoraria, Research Funding; Astex Pharmaceuticals: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; H3 Biomedicine: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136203

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4548-4548

Abstract: Recent studies have reported that statin use is associated with improved outcomes in immunocompetent patients with bacterial sepsis and respiratory virus disease. We have reported previously that statin use in donors or recipients was associated with reduced risks of severe acute graft-versus-host disease (GVHD) or chronic GVHD, respectively, after allogeneic hematopoietic cell transplantation (HCT). In the present study, we analyzed the influence of donor and recipient statin use on the incidence of infections and infection-outcomes after allogeneic HCT. Patients and Methods A previously reported cohort of HCT recipients (BBMT 16:1463-6, 2010) was used for the analyses. The cohort included 1206 allogeneic HCT recipients (no statin treatment: n=1130; statin treatment: n=76) transplanted between 2001 and 2008 at the Fred Hutchinson Cancer Research Center. Recipients were considered “statin-treated” when a statin was used to treat hyperlipidemia before and after HCT-conditioning. In addition, for all 567 sibling donors in the same cohort, the statin treatment status at the time of stem cell donation was assessed by review of medical records (no statin treatment: n=480, statin treatment: n=87; Blood 115:1288-95, 2010). The associations between statin use and risks of incident infections or infection-related mortality were evaluated using Cox proportional hazards models. Results Among 1206 HCT recipients, the following proportions experienced first infectious events within 100 days after HCT: bacteremia, 23% (n=275); CMV reactivation, 23% (n=277); respiratory viral infection with upper and/or lower respiratory tract involvement, 8.0% (n=97), and with only lower respiratory tract involvement (LRI), 1.8% (n=22). Within 1 year after HCT, 13% (n=153) developed invasive fungal infections and 3.7% (n=45) developed CMV disease. The overall incidences of bacteremia, invasive fungal infection, CMV reactivation, CMV disease, and LRI were not impacted by recipient or donor statin use. Recipient statin-use, however, was associated with a significantly increased cumulative incidence of gram-negative bacteremia (adjusted HR 2.15 [95% CI, 1.1-4.1], p=0.02), an association not observed with donor statin use. The risk of 30-day mortality attributable to gram-negative bacteremia was not significantly affected by recipient or donor statin use. Finally, the risk of respiratory viral infections was increased in recipients transplanted from statin-treated donors compared with those transplanted from donors not treated with a statin (adjusted HR 2.7 [95% CI, 1.3-5.6] , p=0.01). There were no progressions to LRI among recipients transplanted from statin-treated donors (0% vs. 15%, p=0.15). Conclusions Recipient or donor statin use did not alter incidence of most infections after allogeneic HCT. However, while recipient statin use was associated with an increased risk of gram-negative bacteremia, donor statin use was associated with an increased risk of recipient respiratory viral infections without affecting mortality or progression to LRI. The mechanisms underlying these associations remain unknown. Validation of the findings in other large cohorts and, ultimately, randomized trials are needed. Disclosures: Boeckh: Merck: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.4548.4548

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 525-525

Abstract: Abstract 525 Background: Role and timing of allografting in myeloma are hotly debated. Before the introduction of new drugs, we carried out a trial where the treatment assignment was based only on the presence/absence of an HLA-identical sibling (Bruno et al, N Engl J Med 2007). Methods: Overall, 162/199 (81%) of patients with at least one sibling were HLA-typed. First-line treatments included induction with VAD-based regimens and a cytoreductive autograft, followed by a nonmyeloablative allograft (Tandem auto-allo) or a second melphalan-based autograft (Double-auto). We now report an update at a median follow up of 7.1 years. Results: Response rates [complete (CR) and partial remissions (PR)] at the time and after the non-myeloablative allograft and at the time and after the second autograft did not differ between the two cohorts: 76% and 86%, and 76% and 91% respectively (p=1 and p=0,54). However, CR rate was significantly higher after the non-myeloablative allograft than after the second autograft: 55% versus 26% (p=0,0026). At a median follow up of 7.1 years (range 2.5 – 10.7+), by intention-to-treat analysis, median overall survival (OS) and event free survival (EFS) were significantly longer in patients with HLA-identical siblings (No.80) as compared with those without (No.82): not reached vs. 4.25 years (HR 0.51, CI 95% 0.34–0.76, p=0.001) and 2.8 vs. 2.4 years (HR 0.62, CI 95% 0.44–0.87, p=0.005). By multivariate analysis, independent of age, gender, myeloma protein isotype, Durie & Salmon stage, and disease status at the first autograft; the presence of an HLA-identical sibling was significantly associated with longer OS (HR 0.5, CI 95% 0.3–0.8, p=0.001) and EFS (HR 0.63, CI 95% 0.4–0.9, p=0.01). At a median follow up of 7.3 (range 5.4 – 10.7+ years), median OS was not reached in the 58 patients who received a non-myeloablative allograft and 5.3 years in the 46 who received a second high-dose melphalan autograft (HR 0.55, CI 95% 0.32–0.94, p=0.02), whereas EFS was 39 months and 33 months (HR 0.62, CI 95% 0.40–0.96, p=0.02) respectively. Cumulative incidence of transplant related mortality was 11% and 2% at 2 years respectively. At median follow-ups of 7.3 years from diagnosis (range 5.4 – 10.4+) and 6.5 years from the allograft (range 4.2 – 9.4+), and 7.4 years from diagnosis (range 5.6 – 10.7+) and 6.2 years from the second autograft (range 4.7 – 9.1+), 30/58 (52%) and 37/46 (80%) patients, respectively, were treated for disease relapse/progression. Salvage therapies included bortezomib- or thalidomide-containing regimens in most patients of both cohorts. After 1–3 lines of therapy, 22/30 (73%) had a response, including 5 CR and 17 PR, in the tandem auto-allo group, whereas 21/37 (54%) had a response, including 4 CR and 16 PR after the second autograft. Of note, at a median follow up of 3.9 years from the start of the first salvage therapy, OS was not reached and was 1.7 years in patients who had relapsed/progressed after the allograft and the second high-dose melphalan (HR 0.44, CI 95% 0.24–0.82, p=0.01) respectively. Conclusions: In this study, allografting conferred a long term survival advantage over standard autografting. Salvage therapy was associated with longer OS perhaps due to a synergistic effect between new drugs and residual graft-vs.-myeloma effects. In prospective clinical trials, the combination of graft-vs.-myeloma effects with “new drugs” should be explored and may increase the cure rate of myeloma patients. Disclosures: Bringhen: Celgene: Honoraria; Janssen-Cilag: Honoraria. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.525.525

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3391-3391

Abstract: Abstract 3391 Poster Board III-279 BACKGROUND: We previously reported on the outcome of unrelated donor nonmyeloablative hematopoietic cell transplantation (HCT) in 24 patients (pts) with poor-risk multiple myeloma treated by Seattle Consortium Centers (Georges et al BBMT 2007). Here we update our observation to 43 pts with a median follow up of 3.3 years after allografting. PATIENTS: Pts with stage II-III MM (n=43) received AlloHCT at 9 centers between May 2000 and September 2008. Forty pts (93%) were matched with their donors for 10 of 10 HLA alleles, and 3 (7%) had single HLA-C allele-level mismatches. Median age at allotransplant was 53 (range 35–67) years. Median number of prior treatments was 2 (1–3), and median number of prior treatment cycles was 8 (5–22). All pts but 2 received at least 1 (range 1-3) high dose-Autograft regimen. Fifteen pts (35%) received planned tandem Auto/AlloHCT as consolidation to first line therapy. Allogeneic conditioning was with 2 Gy TBI plus fludarabine 90 mg/m2 and post allografting immunosuppression was with mycophenolate mofetil (MMF) and cyclosporine or tacrolimus. Disease status at allogeneic HCT included complete remission (CR, 6 pts, 14%), very good partial remission (VGPR, 12 pts, 28%), partial remission (PR, 14 pts, 33%) and refractory disease (RD, 11 pts, 26%). RESULTS: All pts had sustained donor engraftment. Twenty-eight (65%) developed grade 2 to 4 acute graft-versus-host-disease (GVHD) and 6 pts (14%) developed 3 to 4 acute GVHD. Twenty-six pts (60%) had extensive chronic GVHD. The overall response rate was 86%, with 18 pts (42%) achieving CR, 14 (33%) VGPR and 5 (12%) PR. With a median follow-up of 3.3 (0.3–8.1) years from allografting, median time to progression was 1.1 years. Median overall survival (OS) has not been reached. Median progression-free survival (PFS) was 1.5 years. Five-year estimated OS and PFS were 51% and 21% respectively. Cumulative incidence of nonrelapse mortality (NRM) at 100 days, 1 and 5 years were 2%, 16% and 19% respectively. The subgroup of 15 pts receiving upfront tandem Auto/AlloHCT had five-year estimated OS and PFS of 72% and 37%, respectively. These results are similar to the outcomes we observed in a series of 102 patients with MM who received upfront tandem Auto/AlloHCT from HLA-identical sibling donor (Rotta et al, Blood 2009) where five-year OS and PFS were 64% and 36%, respectively. CONCLUSION: The use of unrelated donors leads to sustained donor engraftment and is associated with a low 1-year NRM (16%). As consolidation of first remission, Tandem Auto/Allo HCT leads to similar 5-year outcomes as HCT from HLA-identical sibling donors. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.3391.3391

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

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detail.hit.zdb_id: 80069-7