10 results on '"Blau, Igor Wolfgang"'
Search Results
2. Hemosiderin deposits in chronic graft-vs.-host disease related myopathy.
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Schmidt-Hieber M, Okuducu AF, Stoltenburg G, Mackert BM, Benzian N, Thiel E, and Blau IW
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- Biopsy, Chronic Disease, Graft vs Host Disease complications, Graft vs Host Disease etiology, Graft vs Host Disease pathology, Hemosiderosis metabolism, Hemosiderosis pathology, Humans, Lipofuscin metabolism, Liver metabolism, Liver pathology, Male, Middle Aged, Muscle, Skeletal metabolism, Muscle, Skeletal pathology, Polymyositis etiology, Polymyositis pathology, Primary Myelofibrosis complications, Primary Myelofibrosis pathology, Sarcolemma metabolism, Sarcolemma pathology, Transplantation, Homologous, Graft vs Host Disease metabolism, Hemosiderin metabolism, Polymyositis metabolism, Primary Myelofibrosis therapy, Stem Cell Transplantation methods
- Abstract
Chronic graft-vs.-host disease (cGVHD) occurs in 20-50% of patients who survive for at least 100 d after allogeneic stem cell transplantation (SCT). cGVHD includes scleroderma-like skin changes, chronic cholangitis, obstructive lung disease and general wasting syndrome. Polymyositis or myopathy are rare manifestations of cGVHD with approximately 40 reported cases. Polymyositis accompanied by hemosiderin deposits in cGVHD has been reported only once, and there are no reports on lipofuscin deposits in skeletal muscle cells in cGVHD. We report here on a 56-yr-old male who underwent allogeneic SCT in 1999 for osteomyelofibrosis and progressive hematopoietic insufficiency. In February 2004, the patient was hospitalized for progressive muscular weakness with loss of the ability to walk. Laboratory tests demonstrated normal values for serum creatine kinase, aldolase and lactic dehydrogenase; the ferritin level was highly elevated. The femoral muscle biopsy showed mostly perifascicular atrophy as well as numerous subsarcolemmal hemosiderin and lipofuscin deposits. Intravenous administration of the chelating agent deferoxamine was ineffective. Three weeks later the patient died of aspiration pneumonia. Interestingly, autopsy disclosed moderate hemosiderin deposits in the liver, the organ usually involved in hemosiderosis.
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- 2005
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3. Continuously improving outcome over time after second allogeneic stem cell transplantation in relapsed acute myeloid leukemia: an EBMT registry analysis of 1540 patients.
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Schmälter, Ann-Kristin, Ngoya, Maud, Galimard, Jacques-Emmanuel, Bazarbachi, Ali, Finke, Jürgen, Kröger, Nicolaus, Bornhäuser, Martin, Stelljes, Matthias, Stölzel, Friedrich, Tischer, Johanna, Schroeder, Thomas, Dreger, Peter, Blau, Igor-Wolfgang, Savani, Bipin, Giebel, Sebastian, Esteve, Jordi, Nagler, Arnon, Schmid, Christoph, Ciceri, Fabio, and Mohty, Mohamad
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STEM cell transplantation ,ACUTE myeloid leukemia ,GRAFT versus host disease - Abstract
Second allogeneic stem cell transplantation (alloSCT2) is among the most effective treatments for acute myeloid leukemia (AML) relapse after first alloSCT (alloSCT1). Long-term EBMT registry data were used to provide large scale, up-to-date outcome results and to identify factors for improved outcome. Among 1540 recipients of alloSCT2, increasing age, better disease control and performance status before alloSCT2, more use of alternative donors and higher conditioning intensity represented important trends over time. Between the first (2000–2004) and last (2015–2019) period, two-year overall and leukemia-free survival (OS/LFS) increased considerably (OS: 22.5–35%, LFS: 14.5–24.5%). Cumulative relapse incidence (RI) decreased from 64% to 50.7%, whereas graft-versus-host disease and non-relapse mortality (NRM) remained unchanged. In multivariable analysis, later period of alloSCT2 was associated with improved OS/LFS (HR = 0.47/0.53) and reduced RI (HR = 0.44). Beyond, remission duration, disease stage and patient performance score were factors for OS, LFS, RI, and NRM. Myeloablative conditioning for alloSCT2 decreased RI without increasing NRM, leading to improved OS/LFS. Haploidentical or unrelated donors and older age were associated with higher NRM and inferior OS. In summary, outcome after alloSCT2 has continuously improved over the last two decades despite increasing patient age. The identified factors provide clues for the optimized implementation of alloSCT2. [ABSTRACT FROM AUTHOR]
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- 2024
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4. PTCy versus ATG as graft-versus-host disease prophylaxis in mismatched unrelated stem cell transplantation.
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Penack, Olaf, Abouqateb, Mouad, Peczynski, Christophe, Boreland, William, Gülbas, Zafer, Gedde-Dahl, Tobias, Castilla-Llorente, Cristina, Kröger, Nicolaus, Eder, Mathias, Rambaldi, Alessandro, Bonifazi, Francesca, Blau, Igor Wolfgang, Stelljes, Matthias, Dreger, Peter, Moiseev, Ivan, Schoemans, Hélène, Koenecke, Christian, and Peric, Zinaida
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STEM cell transplantation ,GRAFT versus host disease ,PREVENTIVE medicine ,OVERALL survival ,PROGRESSION-free survival - Abstract
There is an increased risk of GVHD and of non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) when mismatched unrelated donors (MMUD) are used. In Europe, it is standard practice to use rabbit anti-thymocyte globulin (rATG) to reduce the high NRM and GVHD risks after MMUD alloSCT. As an alternative to rATG, post-transplantation Cyclophosphamide (PTCy) is in increasing clinical use. It is currently impossible to give general recommendations regarding preference for one method over another since comparative evidence from larger data sets is lacking. To improve the evidence base, we analyzed the outcome of rATG vs. PTCy prophylaxis in adult patients with hematologic malignancies undergoing first peripheral blood alloSCT from MMUD (9/10 antigen match) between Jan 2018 and June 2021 in the database of the European Society for Blood and Marrow Transplantation (EBMT). We performed multivariate analyses using the Cox proportional-hazards regression model. We included 2123 patients in the final analyses (PTCy, n = 583; rATG, n = 1540). p values and hazard ratios (HR) presented here are multivariate outcomes. Two years after alloSCT we found a lower NRM in the PTCy group of 18% vs. 24.9% in the rATG group; p = 0.028, HR 0.74. Overall survival in the PTCy cohort was higher with 65.7% vs. 55.7% in the rATG cohort; p < 0.001, HR 0.77. Progression-free survival was also better in the PTCy patients with 59.1% vs. 48.8% when using rATG; p = 0.001, 0.78. The incidences of chronic GVHD and acute GVHD were not significantly different between the groups. We found significantly lower NRM as well as higher survival in recipients of peripheral blood alloSCTs from MMUD receiving PTCy as compared to rATG. The results of the current analysis suggest an added value of PTCy as GVHD prophylaxis in MMUD alloSCT. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Risk factors and characteristics influencing humoral response to COVID-19 vaccination in patients after allogeneic stem cell transplantation.
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Hütter-Krönke, Marie Luise, Neagoie, Adela, Blau, Igor Wolfgang, Wais, Verena, Lam Vuong, Gantner, Andrea, Ahn, Johann, Penack, Olaf, Schnell, Jacqueline, Nogai, Klaus Axel, Eberspächer, Bettina, Saadati, Maral, Benner, Axel, Bullinger, Lars, Döhner, Hartmut, Bunjes, Donald, and Sala, Elisa
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SARS-CoV-2 ,STEM cell transplantation ,COVID-19 pandemic ,HUMORAL immunity ,COVID-19 ,IMMUNE reconstitution inflammatory syndrome - Abstract
Introduction: Vaccination against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is approved and recommended for immunocompromised patients such as patients after allogeneic stem cell transplantation (allo-SCT). Since infections represent a relevant cause of transplant related mortality we analyzed the advent of immunization to SARSCoV-2 vaccination in a bicentric population of allogeneic transplanted patients. Methods: We retrospectively analyzed data of allo-SCT recipients in two German transplantation centers for safety and serologic response after two and three SARS-CoV-2 vaccinations. Patients received mRNA vaccines or vector-based vaccines. All patients were monitored for antibodies against SARS-CoV2-spike protein (anti-S-IgG) with an IgG ELISA assay or an EIA Assay after two and three doses of vaccination. Results: A total of 243 allo-SCT patients underwent SARS-CoV-2 vaccination. The median age was 59 years (range 22-81). While 85% of patients received two doses of mRNA vaccines, 10% had vector-based vaccines and 5% received a mixed vaccination. The two vaccine doses were well tolerated with only 3% patients developing a reactivation of graft versus host disease (GvHD). Overall, 72% of patients showed a humoral response after two vaccinations. In the multivariate analysis age at time of allo-SCT (p=0.0065), ongoing immunosuppressive therapy (p= 0.029) and lack of immune reconstitution (CD4-T-cell counts <200/ml, p< 0.001) were associated with no response. Sex, intensity of conditioning and the use of ATG showed no influence on seroconversion. Finally, 44 out of 69 patients that did not respond after the second dose received a booster and 57% (25/44) showed a seroconversion. Discussion: We showed in our bicentric allo-SCT patient cohort, that a humoral response could be achieve after the regular approved schedule, especially for those patients who underwent immune reconstitution and were free from immunosuppressive drugs. In over 50% of the initial non-responders after 2-dose vaccination, a seroconversion can be achieved by boostering with a third dose. [ABSTRACT FROM AUTHOR]
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- 2023
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6. A Novel Method to Quantify and Characterize Leukemia-Reactive Natural Killer Cells in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation following Conventional or Reduced-Dose Conditioning
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Penack, Olaf, Fischer, Lars, Stroux, Andrea, Gentilini, Chiara, Nogai, Axel, Muessig, Arne, Ganepola, Susanne, Lange, Thoralf, Kliem, Constanze, Marinets, Olga, Blau, Igor Wolfgang, Thiel, Eckhard, and Uharek, Lutz
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- 2007
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7. Untersuchungen des hämatopoetischen Chimärismus nach der allogenen Stammzelltransplantation und Konditionierung mit reduzierter Intensität
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Blau, Igor Wolfgang
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chimerism ,RIC ,stem cell transplantation ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit - Abstract
Habilitationschrift, Die allogene Transplantation von hämatopoetischen Stammzellen ist eine etablierte Behandlungsmodalität bei malignen und einigen nicht malignen hämatologischen Erkrankungen. In der vorliegenden Arbeit wurden die Ergebnisse von 107 allogenen Transplantationen am Campus Benjamin Franklin der Charité analysiert und in zwei Gruppen gegenübergestellt: 55 Patienten erhielten eine Transplantation nach konventioneller Konditionierung und 52 Patienten eine Transplantation nach Konditionierung mit reduzierter Intensität. Diese Therapiemodalität wurde erfolgreich in der Klinik für Hämatologie, Onkologie und Transfusionsmedizin eingeführt und ist jetzt Behandlungsoption für einen Teil der Patienten. In der Analyse wurde gezeigt, dass trotz signifikanter Altersunterschiede beider Gruppen (53 Jahre mittleres Alter nach RIC und 40 Jahre mittleres Alter nach konventioneller Konditionierung), die Therapieergebnisse hinsichtlich des Gesamtüberlebens gleich sind. Zwar treten in der Gruppe nach RIC häufiger Rezidive auf, jedoch sind die Komplikationen, die durch die toxischen Nebenwirkungen der Konditionierung verursacht sind, weniger ausgeprägt. Hinsichtlich akuter und chronischer GvHD und dem Auftreten infektiöser Komplikationen gab es keine Differenzen. Die Wiederhestellung der Hämatopoese hinsichtlich leukozytärer und thrombozytärer Regeneration nach Transplantation läuft gleich schnell. Die seriellen Untersuchungen zum hämatopoetischen Chimärismus an den Tagen 30, 60, 100 und später charakterisierten die Transplantatfunktion und gaben Hinweise auf eine Persistenz bzw. ein Wiederauftreten des maligenen Zellklons des Patienten. Die Ergebnisse der Chimärismusanalyse der Knochenmarkzellen nach Transplantation hämatopoetischer Stammzellen hatten somit einen prädiktiven Wert für den einzelnen Patienten. Sie erlauben eine Vorhersage von Rezidivwahrscheinlichkeit und Gesamtüberleben. In der Multivarianzanalyse ist der komplette Spender-Chimärismus am Tag 60 der stärkste Faktor hinsichtlich eines verbesserten Gesamtüberlebens sowohl in den Gruppen der Patienten nach RIC als auch nach konventioneller Konditionierung. Ein Rezidiv bei Patienten mit einem gemischten Chimärismus an Tag 60 nach Transplantation tritt signifikant häufiger auf als bei Patienten mit komplettem Chimärismus an Tag 60. Die Ergebnisse der Chimärismus-Analyse an Tag 100 korrelierten analog zu den Ergebnissen an Tag 60 mit Rezidivwahrscheinlichkeit und Überleben. Ein früher kompletter Chimärismus an Tag 30 korreliert nicht mit der Häufigkeit eines Rezidivs der Grundkrankheit oder mit der Überlebenswahrscheinlichkeit der Patienten, ebenso nicht ein gemischter Chimärismus an Tag 30. Damit ist die Chimarismusanalyse an Tag 30 ohne prediktiven Wert für den weiteren Verlauf nach der Transplantion. Ein früher Spender-Chimärismus ist aber bedeutend für die Beurteilung der Transplantatfunktion bei fehlendem klinischen Engraftment. Nach den erhobenen Daten ist der Chimärismus zwei Monate nach Transplantation von entscheidender prognostischer Bedeutung und damit für Therapieentscheidungen heranzuziehen. Differenziert werden kann mittels Analyse der minimalen Resterkrankung (MRD) zwischen einer Persistenz und einem Rezidiv der Grundkrankheit oder einer Regeneration der normalen Empfängerhämatopoese. Ohne Chimärismusanalyse ist das Engraftment nach Transplantation mit RIC nicht beurteilbar. Die Wahl der Therapie beinhaltet die Entscheidung zur Induktion einer Graft-versus-leukemia-Reaktion mittels Reduktion der immunsuppressiven Therapie, einer Immunstimulation und der DLI oder die Entscheidung für eine Tumortherapie. Es erwies sich, dass auch Patienten höheren Alters, die sich einer konventionellen komplexen Polychemotherapie eines hämatologischen Malignoms unterziehen, mit einer allogenen Transplantation nach RIC geheilt werden können. Eine Altersgrenze kann somit nicht mehr empfohlen werden. Da Patienten mit einem Alter über 50 Jahre nur in Ausnahmen eine konventionelle Konditionierung mit anschließender Transplantation allogener Stammzellen tolerieren, ist für sie ist eine Konditionierung mit reduzierter Intensität die Therapie der Wahl. Gemäß dieser Analyse und der aktuellen Literatur wird die Transplantation nach Konditionierung mit reduzierter Intensität (RIC) nunmehr als Standardtherapieverfahren genutzt. Die Analyse des hämatopoetischen Chimärismus ist dabei eine wesentliche Voraussetzung für die rechtzeitige Prognostizierung eines Rezidivs der Grunderkrankung und folglich die Basis für einen dauerhaften Erfolg der Transplantation allogener Stammzellen und damit der Heilung der Patienten., Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for various hematological disorders. Antimalignancy effects result from cytoreduction by the pretransplantation preparative regimen and the immune- mediated graft-versus-leukemia (GvL) effect. The latter effect plays the predominant role for a variety of hematological malignancies and was the basis for introducing reduced-intensity conditioning (RIC) regimens in the allogeneic SCT setting. This made the approach applicable for patients previously ineligible due to advanced age or comorbidity. It has been suggested that, compared to conventional conditioning, RIC might be associated with delayed engraftment and mixed donor hematopoietic chimerism. Mixed chimerism was found to result in a higher relapse risk than complete chimerism in patients with severe aplastic anemia and chronic myeloid leukemia. However, the prognostic value of the degree of chimerism remains controversial in patients with acute leukemia. The nucleoside analogue fludarabine was established in RIC protocols in 1997. Its favorable toxicity profile and immunosuppressive effects, particularly in relation to T-cell activity, makes the substance suitable as part of a RIC regimen prior to allogeneic SCT. The alkylating agent treosulfan offers due to its low non-hematological toxicity a promising alternative to conventional conditioning agents in the autologous and allogeneic SCT setting. Therefore, this conditioning regimen might be considered as “reduced-toxicity” and discriminated from truly “reduced- intensity” regimens. Despite previous evidence substantiating the feasibility of conditioning with fludarabine and treosulfan, limited data are available on engraftment kinetics and the significance of hematopoietic chimerism in terms of relapse, acute graft-versus-host disease (GvHD) and survival. To clarify these open questions we analyzed between 2001 and 2005 the outcomes of 107 patients with different hematological malignancies who underwent allogeneic stem cell transplantation from HLA identical (10 loci) donor were analyzed according to 2 types of conditioning: reduced-intensity conditioning (RIC) in 52 patients (42 of them received Treosulfan containing regimen), and convention myeloablative conditioning (CMC) in 55 patients. The mean age was 53 years (18-72) in RIC group and 40 years (17-64) in CMC group (p
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- 2007
8. Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid-refractory acute graft- versus-host disease.
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Schmidt-Hieber, Martin, Fietz, Thomas, Knauf, Wolfgang, Uharek, Lutz, Hopfenmüller, Werner, Thiel, Eckhard, and Blau, Igor Wolfgang
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INTERLEUKIN-2 ,STEM cell transplantation ,GRAFT versus host disease ,TRANSPLANTATION of organs, tissues, etc. ,CELL transplantation ,HEMATOLOGY - Abstract
Acute graft- versus-host disease (aGVHD) occurs in up to 80% of patients who undergo allogeneic stem cell transplantation (SCT) and contributes significantly to transplant-related mortality (TRM). We conducted a prospective phase II trial to assess the efficacy and feasibility of treating steroid-refractory aGVHD with basiliximab, a chimaeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor. Basiliximab was administered intravenously at a dose of 20 mg on days 1 and 4. Twenty-three patients were enrolled between October 1999 and July 2004. We found a primary overall response rate of 82·5% with four patients (17·5%) showing a complete response and 15 patients (65%) a partial response. Six patients were again treated successfully with an IL-2 receptor antagonist because of recurrence of aGVHD. The rates of infections, chronic GVHD, malignancy recurrence and 1-year TRM following immunosuppression with basiliximab were comparable with those found with other treatment modalities for aGVHD. We conclude that basiliximab is efficient and feasible for steroid-refractory aGVHD and merits further evaluation. [ABSTRACT FROM AUTHOR]
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- 2005
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9. Shear Wave Elastography in the Detection of Sinusoidal Obstruction Syndrome in Adult Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation.
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Schulz, Marten, Vuong, Lam Giang, Müller, Hans Peter, Maibier, Martin, Tacke, Frank, Blau, Igor Wolfgang, and Wree, Alexander
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HEMATOPOIETIC stem cell transplantation ,SHEAR waves ,HEPATIC veno-occlusive disease ,STEM cell transplantation ,ELASTOGRAPHY ,FRICTION velocity ,ADULTS ,DIAGNOSIS - Abstract
Hepatic sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD) can be a life-threatening complication after hematopoietic stem cell transplantation (HSCT). Diagnosis is often difficult and traditionally based on clinical parameters. Shear wave elastography (SWE) is a modern non-invasive liver stiffness measurement technique using ultrasound. In this monocentric study, we evaluated the role of SWE in diagnosing SOS/VOD in 63 adult patients undergoing HSCT from February 2020 to August 2020 in real world settings. Three patients developed SOS/VOD. This was accompanied by an increase in shear wave velocity in all three patients, indicating that this method may contribute to establishing the diagnosis SOS/VOD after HSCT. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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10. FLAMSA-Based Reduced-Intensity Conditioning versus Myeloablative Conditioning in Younger Patients with Relapsed/Refractory Acute Myeloid Leukemia with Active Disease at the Time of Allogeneic Stem Cell Transplantation: An Analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Rodríguez-Arbolí, Eduardo, Labopin, Myriam, Tischer, Johanna, Brecht, Arne, Ganser, Arnold, Finke, Jürgen, Blau, Igor Wolfgang, Kröger, Nicolaus, Kalhs, Peter, Forcade, Edouard, Bunjes, Donald, Spyridonidis, Alexandros, Savani, Bipin, Nagler, Arnon, and Mohty, Mohamad
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FLUDARABINE , *BUSULFAN , *ACUTE myeloid leukemia , *STEM cell transplantation , *ACUTE leukemia , *ALEMTUZUMAB , *GRAFT versus host disease , *CELL analysis - Abstract
• FLAMSA (fludarabine, Ara-C, and amsacrine) sequential chemotherapy followed by total body irradiation (TBI)-based reduced-intensity conditioning (RIC) and myeloablative conditioning (MAC) led to similar transplantation outcomes in relapsed/refractory active acute myeloid leukemia. • FLAMSA sequential chemotherapy followed by TBI-free RIC was associated with lower nonrelapse mortality resulting in increased overall survival. • There were no significant differences in relapse incidence between FLAMSA sequential chemotherapy followed by RIC and MAC. The use of myeloablative conditioning (MAC) in the setting of active relapsed/refractory (R/R) acute myeloid leukemia (AML) has been hindered by high historical rates of nonrelapse mortality (NRM). FLAMSA (fludarabine, Ara-C, and amsacrine) chemotherapy (CT) followed by reduced-intensity conditioning (RIC) has been proposed as an effective and potentially safer alternative in this scenario. As improvements in supportive care have contributed to decreasing NRM rates after MAC, a comparative reassessment of these two strategies was performed. This was a registry-based analysis by the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Eligibility criteria included age 18 to 50 years, primary refractory, first or second relapsed active AML, first allogeneic stem cell transplantation from a matched sibling donor (MSD) or an unrelated donor (UD) performed between 2005 and 2018, MAC or FLAMSA-RIC. A total of 1018 patients were included. The median patient age was 39 years (range, 18 to 50). Two hundred and fifty-eight patients received busulfan (Bu)/cyclophosphamide (Cy), 314 received Cy/total body irradiation (TBI), 318 received FLAMSA-TBI, and 128 received FLAMSA-CT. The median duration of follow-up was 50 months. In univariate analysis, the 2-year relapse incidence (RI) (54%; 95% confidence interval (CI), 50%-57%), leukemia-free survival (LFS) (30%; 95% CI, 27%-33%), and refined graft-versus-host disease-free, relapse-free survival (GRFS) (21%; 95% CI, 18%-24%) were not significantly different between cohorts. Lower 2-year NRM was observed in the FLAMSA-CT group (7% versus 16% in Bu/Cy, 19% in Cy/TBI, and 18% in FLAMSA-TBI; P =.04), as well as increased 2-year overall survival (OS) (50% versus 33% in Bu/Cy, 34% in Cy/TBI, and 36% in FLAMSA-TBI; P =.03). These results were maintained in the multivariate analysis (hazard ratio [HR] for NRM:.40, P =.01; HR for OS:.65, P =.01; Bu/Cy as reference). These data suggest that FLAMSA-CT may be a preferred conditioning regimen in patients with active R/R AML due to lower NRM. Yet, the high relapse rates observed in our analyses emphasize the need for novel therapeutic strategies in this clinical setting. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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