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  • 1
    Language: English
    In: Leukemia, 2020-09, Vol.34 (9), p.2317-2332
    Description: Currently available data on chimeric antigen receptor (CAR)-T cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated multiple myeloma (MM) patients. The CAR-T field in MM is rapidly evolving with 〉50 currently ongoing clinical trials across all phases, different CAR-T design, or targets. Most of the CAR-T trials are performed in China and the United States, while European centers organize or participate in only a small fraction of current clinical investigations. Autologous CAR-T cell therapy against B cell maturation antigen shows the best evidence of efficacy so far but main issues remain to be addressed: duration of response, longer follow-up, prolonged cytopenia, patients who may benefit the most such as those with extramedullary disease, outcome prediction, and the integration of CAR-T cell therapy within the MM treatment paradigm. Other promising targets are, i.a.,: CD38, SLAMF7/CS1, or GPRC5D. Although no product has been approved to date, cost and production time for autologous products are expected to be the main obstacles for broad use, for which reason allogeneic CAR-T cells are currently explored. However, the inherent risk of graft-versus-host disease requires additional modification which still need to be validated. This review aims to present the current status of CAR-T cell therapy in MM with an overview on current targets, designs, and stages of CAR-T cell development. Main challenges to CAR-T cell therapy will be highlighted as well as strategies to structurally improve the CAR-T cell product, and thereby its efficacy and safety. The need for comparability of the most promising therapies will be emphasized to balance risks and benefits in an evidence-based but personalized approach to further improve outcome of patients with MM.
    Subject(s): B-Cell Maturation Antigen - immunology ; Immunotherapy - methods ; Multiple Myeloma - therapy ; Humans ; Receptors, Chimeric Antigen - immunology ; Receptors, Antigen, T-Cell - immunology ; Precision Medicine ; T cells ; Evidence-based medicine ; Index Medicus
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2020-12, Vol.55 (12), p.2286-2293
    Description: Acute graft-versus-host disease (aGVHD) is a serious complication after stem cell transplantation and is associated with high non-relapse mortality. If steroid treatment as first-line therapeutic approach fails, treatment options are limited. In retrospective studies, ruxolitinib, a selective Janus kinase 1/2 inhibitor as well as extracorporeal photopheresis (ECP) could show high efficacy in treatment of steroid refractory acute and chronic GVHD. Here, we report single-center experience of combining JAK-inhibitor treatment with ECP in 18 patients with severe steroid refractory aGVHD of lower GI-tract. The treatment was well tolerated and no severe cytopenia (grade IV) occurred, in three patients grade III cytopenia could be observed. Response was complete or partial in 44% and 11%, respectively, resulting in an estimated 2 year overall survival of 56%. Steroids were tapered rapidly with a median time of 2 days for halving of dosage avoiding additional steroid-associated side effects. Under treatment with ruxolitinib and ECP, an increased level of regulatory T cells could be observed elucidating direct effects of this treatment on immune response.
    Subject(s): Transplantation ; T cells ; Health aspects ; Patient outcomes ; Stem cells ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: Frontiers in immunology, 2021, Vol.12, p.630429-630429
    Description: This analysis aimed to systematically review and synthesize the existing evidence regarding the outcome of tyrosine kinase inhibitor (TKI) maintenance therapy after allogeneic stem-cell transplantation for patients with -ITD-mutated acute myeloid leukemia (AML). We searched publicly available databases, references lists of relevant reviews, registered trials, and relevant conference proceedings. A total of 7 studies comprising 680 patients were included. Five studies evaluated sorafenib and 2 studies evaluated midostaurin, compared with control. The incidence of relapse was significantly reduced after TKI therapy, showing an overall pooled risk ratio (RR) of 0.35 (95% confidence interval [CI], 0.23-0.51; 〈 0.001), with a marked 65% reduced risk for relapse. The overall pooled RR for relapse-free survival and overall survival showed significantly improved outcome after TKI maintenance therapy, being 0.48 (95% CI, 0.37-0.61; 〈 0.001) and 0.48 (95% CI, 0.36-0.64; 〈 0.001). The risk for relapse or death from any cause was reduced by 52% using TKI. No difference in outcome was seen for non-relapse mortality, and the risk for chronic or acute graft-vs. -host disease appeared to be increased, at least for sorafenib. In conclusion, post-transplant maintenance therapy with TKI was associated with significantly improved outcome in relapse and survival in patients with -ITD positive AML.
    Subject(s): Analysis ; Transplantation ; Stem cells ; Index Medicus ; midostaurin ; Immunology ; allogeneic stem cell transplantation ; sorafenib ; acute myeloid leukemia ; graft-vs.-host disease ; FLT3-internal tandem duplication ; maintenance
    ISSN: 1664-3224
    E-ISSN: 1664-3224
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: British journal of haematology, 2021-01, Vol.192 (2), p.e60-e63
    Description: Byline: Panagiotis Karagiannis, Winfried Alsdorf, Ann-Christin Tallarek, Martin E. Blohm, Jennyfer Oelrich, Jonas S. Waizenegger, Christine Wolschke, Kurt Hecher, Dominique Singer, Carsten Bokemeyer, Walter Fiedler
    Subject(s): Pregnant women ; Care and treatment ; Index Medicus
    ISSN: 0007-1048
    E-ISSN: 1365-2141
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: European journal of haematology, 2020-08, Vol.105 (2), p.126-137
    Description: Objectives During allogeneic hematopoietic stem cell transplantation (allo‐SCT), infections significantly contribute to morbidity and mortality. A monocentric prospective analysis was performed to assess epidemiology, risk factors, and outcomes of infections during the peri‐transplant period. Methods Data were recorded prospectively using a predefined questionnaire. Results In 2015, 163 consecutive patients, 37.4% female, median age 59 (range 18‐79) years received 166 allo‐SCT. Median duration of leukopenia 〈109/L was 14.5 days (range 4‐43 days). Fever of unknown origin (FUO) occurred in 118/166 patients (71.1%). Severe sepsis developed in 95, and septic shock developed in 26 patients. Intensive diagnostic workup helped to identify causative microorganisms only in a small number of infectious courses. All but 13 patients needed antibiotic therapy, each according to the standard operating procedures of the department. Cumulative incidence of death by infection after 1 year was 16.6% (95% CI: 11.3‐22.7). The only risk factor for FUO in neutropenia was duration of neutropenia 〈/≥14 days (55.4% vs 85.5%, P 〈 .001). Conclusion Results of an elaborate diagnostic workup of infections in the peri‐transplant period are scarce. Attention to risk factors might help to identify patients at risk for severe infections.
    Subject(s): FUO ; neutropenia ; infection ; allogeneic stem cell transplantation ; Index Medicus
    ISSN: 0902-4441
    E-ISSN: 1600-0609
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: Bone marrow transplantation (Basingstoke), 2020-09, Vol.55 (9), p.1817-1820
    Subject(s): Chemotherapy ; Relapse ; Medical centers ; Immunotherapy ; Stem cells ; Transplantation ; Drug therapy, Combination ; Cancer ; Diseases ; Index Medicus
    ISSN: 0268-3369
    E-ISSN: 1476-5365
    Source: Nature Open Access
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: British journal of haematology, 2019-08, Vol.186 (3), p.484-489
    Description: Summary Allogeneic stem cell transplantation (alloSCT) is a curative procedure for myelofibrosis. Elderly people are mainly affected, limiting the feasibility of myeloablative regimens. The introduction of reduced‐intensity conditioning (RIC) made alloSCT feasible for older patients. Nevertheless, the incidence of myelofibrosis is not negligible in young patients, who are theoretically able to tolerate high‐intensity therapy. Very few data are available about the efficacy of RIC‐alloSCT in younger myelofibrosis patients. This study included 56 transplanted patients aged 〈55 years. Only 30% had a human leucocyte antigen (HLA)‐matched sibling donor, the others were transplanted from a fully‐matched (36%) or partially‐matched (34%) unrelated donor. All transplants were conditioned according the European Society for Blood and Marrow Transplantation protocol: busulfan‐fludarabine + anti‐thymocyte globulin, followed by ciclosporin and mycophenolate. One patient experienced primary graft failure. Incidence of graft‐versus‐host disease grade II‐IV was 44% (grade III/IV 23%). One‐year non‐relapse mortality was 7% and the 5‐year cumulative incidence of relapse was 19%. After a median follow‐up of 8·6 years, the estimated 5‐year progression‐free survival and overall survival (OS) was 68% and 82%, respectively. Patients with fully‐matched donor had a 5‐year OS of 92%, in contrast to 68% for those with a mismatched donor (P = 0·03). The most important outcome‐determining factor is donor HLA‐matching. In conclusion, RIC‐alloSCT ensures optimal engraftment and low relapse rate in younger myelofibrosis patients, enabling the possibility of cure in this group.
    Subject(s): myelofibrosis ; allogeneic stem cell transplantation ; younger age ; reduced‐intensity conditioning ; Transplantation ; Stem cells ; Index Medicus
    ISSN: 0007-1048
    E-ISSN: 1365-2141
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 8
    Language: English
    In: Annals of hematology, 2017-08, Vol.96 (8), p.1379-1388
    Description: The optimal parameters and time points for the measurement of iron overload (IO) in allogeneic stem cell transplantation (ASCT) patients are still under discussion. Hyperferritinemia and IO are poor prognostic factors in ASCT. We hypothesize that non-transferrin-bound iron (NBTI) is possibly a better marker to predict the effect of IO on the outcome than serum ferritin (SF), which however is not specific for IO. The aim of this prospective observational trial was to evaluate the influence of NBTI in comparison to SF on the outcome of ASCT patients [overall survival, bloodstream infections (BSIs), and invasive fungal infections (IFIs)]. We analyzed daily transferrin saturation (TSAT), SF, and NTBI (if TSAT exceeded 70%) in 100 patients who received ASCT during conditioning, and on day 0, +7, and +14 post-ASCT. After a median NTBI level of 0 μmol/l at baseline, the median of the area under the curve (AUC) of NTBI between conditioning and ASCT (d0) increased to 17 μmol*d/l, and between ASCT and day +14 to 56.3 μmol*d/l. Higher NTBI-AUC d0 resulted in a higher risk of BSI (HR 1.042, p = 0.009) and IFI (HR 1.070, p = 0.001) and showed a trend of inferior 1-year survival (65 vs. 76%, p = 0.09). Baseline SF did not influence BSI, but higher levels resulted in more IFI (HR 1.26, p 〈 0.001). In conclusion, NTBI possibly better predict for a higher risk of bloodstream infections than SF and needs further investigation.
    Subject(s): Outcome Assessment (Health Care) - methods ; Multivariate Analysis ; Prognosis ; Prospective Studies ; Humans ; Middle Aged ; Proportional Hazards Models ; Male ; Bacteremia - diagnosis ; Transplantation, Homologous ; Iron Overload - blood ; Transferrin - analysis ; Young Adult ; Ferritins - blood ; Survival Analysis ; Bacteremia - blood ; Mycoses - diagnosis ; Adult ; Female ; Aged ; Mycoses - blood ; Hematopoietic Stem Cell Transplantation - methods ; Iron Overload - diagnosis ; Iron - blood ; Transferrin ; Analysis ; Stem cells ; Ferritin ; Mycoses ; Transplantation ; Epidemiology ; Medical prognosis ; Infections ; Index Medicus
    ISSN: 0939-5555
    E-ISSN: 1432-0584
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: Cancers, 2020-11-01, Vol.12 (11), p.1
    Description: Currently, the only curative therapy in myelofibrosis is allogeneic hematopoietic stem cell transplantation. Donor lymphocyte infusion and second stem cell transplantation are the two main treatment options for myelofibrosis patients who relapse after the first transplantation. The optimal conditioning regimen for the second transplantation in myelofibrosis patients is not well defined. Our study aimed to address this question and showed that treosulfan-based conditioning for second allograft in relapsed myelofibrosis patients resulted in longtime freedom from disease in about 50% of the patients. This data supports the second allogeneic hematopoietic stem cell transplantation with a less toxic treosulfan-based conditioning regimen that is effective in relapsed, donor lymphocyte infusion resistant myelofibrosis patients with long term low transplant-related mortality and relapse rates. Relapse after allogeneic hematopoietic stem cell transplantation (AHSCT) in myelofibrosis (MF) patients remains as a significant issue despite advances in transplantation procedures and significant prolongation in survival. Second AHSCT is a potential treatment option but associated with high treatment-related mortality and novel less toxic conditioning regimens are needed. In 33 MF patients with relapse after AHSCT and failure to donor lymphocyte infusion (DLI) we investigated treosulfan (36-42 g/[m.sup.2]) in combination with fludarabine and anti-thymocyte globulin (ATG) as conditioning regimen for a second AHSCT with matched related (n = 2), unrelated (n = 23), or mismatched unrelated (n = 8) donors. All patients achieved leukocyte engraftment after a median of 11 days, and 56 [+ or -] 13% experienced acute GVHD grade II-IV at day 100. The therapy-related mortality at day 100 and at 3 years was 16% and 31%, respectively. The cumulative incidence of relapse at 5 years was 16%, resulting in a 5-year disease-free and overall survival of 45% and 47%, respectively. Treosulfan-based conditioning for second allograft in relapsed MF patients resulted in about 50% of the patients in long-term freedom from disease. Keywords: treosulfan; myelofibrosis; second allogeneic transplant; stem cell transplantation
    Subject(s): Drug therapy ; Patient outcomes ; Myelofibrosis ; myelofibrosis ; treosulfan ; stem cell transplantation ; second allogeneic transplant
    ISSN: 2072-6694
    E-ISSN: 2072-6694
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: Directory of Open Access Journals
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Language: English
    In: European journal of haematology, 2020-12, Vol.105 (6), p.722-730
    Description: Objectives Major complications affecting the central nervous system (CNS) present a challenge after allogeneic stem cell transplantation (allo‐SCT). Methods Incidence, risk factors, and outcome were retrospectively analyzed in 888 patients in a monocentric study. Results Cumulative incidence (CI) of major CNS complications at 1 year was 14.8% (95%CI 12.3%‐17.2%). Median follow‐up is 11 months. CNS complications were documented in 132 patients: in 36 cases, classified metabolic; 26, drug‐related neurotoxicity (14 attributed to cyclosporine A, 4 to antilymphocyte globulin); 11, cerebrovascular (ischemic n = 8, bleeding n = 3); 9, infections; 9, psychiatric; and 9, malignant. The cause of CNS symptoms remained unclear for 37 patients (28%). Multivariate analysis demonstrated an association of CNS complication with patient age (P 〈 .001). The estimated OS of patients with any CNS complication was significantly lower than in patients without neurological complications (P 〈 .001), and the CI of non‐relapse mortality (NRM) was higher for patients with CNS complication (P 〈 .001). A significant negative impact on survival can only be demonstrated for metabolic CNS complications and CNS infections (NRM, P 〈 .0001 and P = .0003, respectively), and relapse (P 〈 .0001). Conclusion CNS complications after allo‐SCT are frequent events with a major contribution to morbidity and mortality. In particular, the situations of unclear neurological complications need to be clarified by intensive research.
    Subject(s): complications ; allogeneic transplantation ; central nervous system
    ISSN: 0902-4441
    E-ISSN: 1600-0609
    Source: Alma/SFX Local Collection
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