Clinical Presentation of Patients with Adult Late-Onset Telomere Biology Disorders - Results from the Aachen Telomeropathy Registry

Introduction: Telomere biology disorders (TBD) are caused by mutations affecting proper telomere maintenance resulting in premature telomere shortening. Telomere length (TL) assessment is currently being used for screening and diagnosis of TBD of which Dyskeratosis congenita (DKC) is the most promin...

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Published inBlood Vol. 138; no. Supplement 1; p. 1130
Main Authors Beier, Fabian, Tometten, Mareike, Kirschner, Martin, Halfmeyer, Insa, Vieri, Margherita, Kricheldorf, Kim, Maurer, Angela, Roeth, Alexander, Platzbecker, Uwe, Radsak, Markus P., Schafhausen, Philippe, Corbacioglu, Selim, Hoechsmann, Britta, Wilk, C. Matthias, Hinze, Claas, Chromik, Jörg, Egle, Alexander, Heuser, Michael, Kreuter, Michael, Kurth, Ingo, Koschmieder, Steffen, Panse, Jens, Meyer, Robert, Isfort, Susanne, Brummendorf, Tim H
Format Journal Article
LanguageEnglish
Published Elsevier Inc 23.11.2021
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Abstract Introduction: Telomere biology disorders (TBD) are caused by mutations affecting proper telomere maintenance resulting in premature telomere shortening. Telomere length (TL) assessment is currently being used for screening and diagnosis of TBD of which Dyskeratosis congenita (DKC) is the most prominent TBD subtype typically found in children and adolescents. In adults, TBDs are characterized by a broad spectrum of more “cryptic” diverging mono- or oligosymptomatic clinical manifestations such as bone marrow failure (BMF), hepatopathy or interstitial lung disease (ILD). However, despite growing general clinical awareness and exertion of improved TL screening strategies, insufficient data are available about the clinical course of adult, late-onset TBDs. Here, we present a series of 41 consecutive adult TBD cases from 2014 to 2021 identified through the Aachen Telomeropathy registry. Methods and Patients: Median follow-up of the cohort was 2.0 (range 0-6.2) years. In 39/41 patients TBD diagnosis was established based on coexistence of the following three criteria: 1.) Identification of pathogenic variant in a known TBD-related gene via next-generation panel sequencing (NGS) or sequential whole exome sequencing (WES). 2.) The presence of prematurely shortened TL below the 1% percentile (39/41) or 5% percentile (2/41) in the lymphocyte gate detected by flow-FISH and 3.) the presence of BMF or ILD as predominant clinical manifestation. In 2 out of 41 cases, WES did not identify a definitive pathogenic variant. Here, diagnosis of TBD was established due to short telomere below the 1% percentile, BMF and the presence of typical DKC stigmata, other TBD symptoms and a positive family history. Results: Mean age of our cohort was 35.9 ± 17.6 years. 49% (n=20) of patients were females. Results of the genetic screening revealed heterozygous pathogenic variants in TERC (n=14) and TERT (n=11) as the most frequent variants, followed by RTEL1 (n=6), TIN2 (n=1), CTC1 (n=1) and DKC1 (n=1). Homozygous or compound heterozygous pathogenic variants were found for CTC1 (n=2), NHP2 (n=2) or TCAB1 (n=1). 46% (n=19) of patients had a positive family history. BMF was the most frequent symptom with 93% (n=38) presenting with leukopenia, 78% (n=32) with anemia and 76% (n=31) with thrombocytopenia. ILD was suspected/confirmed clinically in 44% (n=18), hepatopathies in 29% (n=12) and cancer in 12% of the patients in past medical history (n=5, liposarcoma, breast cancer, Hodgkin lymphoma, diffuse large B-cell lymphoma, endometrial cancer). Symptoms of the typical DKC triad (leukoplakia, nail dystrophy, abnormal skin pigmentation) were observed in 41% (n=17). Of those, 76% (13/17) presented with only one or two clinical signs. Based on past medical history, the onset of first TBD manifestation was observed at a mean age of 26.9 ± 18.3 years. Time from first symptom observed to the diagnosis of TBD was 8.2 ± 9.5 years. 22% (n=9) patients died during follow-up with mean time of 11.7 ± 10.1 years from first manifestation of TBD to death. Regarding treatment, 39% (n=16) were listed for allogeneic stem cell transplantation (allo Tx), but only 38% (6/16) of these eventually received allo Tx. Immunosuppressive therapy with ATG and CSA was carried out in 12% (n=5) of the patients with no patient responding to treatment. Eltrombopag was given in 5% of cases (n=2) without response. 15% (n=6) received androgen treatment with danazol as the most frequently used drug in five of the six reported cases. All patients showed a response at least in one hematological lineage. Conclusions: Our data support the notion that despite the recent progress in screening and genetic diagnostics, late-onset TBD is still frequently underdiagnosed with several years from first manifestation of disease to diagnosis. Implementation of routine screening for TBD might improve the rate of correct TBD diagnosis and could help to avoid ineffective treatments. Beier: Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Other: Travel reembursement; Alexion: Speakers Bureau. Roeth: Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Kira: Consultancy, Honoraria; Bioverativ, a Sanofi company: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Apellis Pharmaceuticals: Consultancy, Honoraria; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria. Platzbecker: AbbVie: Honoraria; Novartis: Honoraria; Celgene/BMS: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Geron: Honoraria. Radsak: Novartis: Consultancy, Honoraria, Other: e.g. travel support; JAZZ: Other: e.g. travel support; Takeda: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria, Other: e.g. travel support; Daiichi Sankyo: Consultancy, Honoraria, Other: e.g. travel support; Astellas: Other: e.g. travel support; Incyte: Consultancy, Honoraria; Corat: Consultancy, Honoraria; Cogent Biosciences: Consultancy, Honoraria; TEVA: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; Amgen: Other: e.g. travel support; Abbvie: Other: e.g. travel support. Schafhausen: Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Swedish Orphan Biovitrum AB: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Corbacioglu: Gentium/Jazz Pharmaceuticals: Consultancy, Honoraria. Heuser: AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; BergenBio: Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer Pharma AG: Research Funding; Astellas: Research Funding; Karyopharm: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tolremo: Membership on an entity's Board of Directors or advisory committees. Koschmieder: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Karthos: Other: Travel support; Shire: Honoraria, Other; CTI: Membership on an entity's Board of Directors or advisory committees, Other; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Geron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Alexion: Other: Travel support; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees, Other; Abbvie: Other: Travel support; Image Biosciences: Other: Travel support; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; AOP Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding. Panse: Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Grunenthal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Apellis Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Isfort: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel reimbursement; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel reimbursement; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an e
AbstractList Introduction: Telomere biology disorders (TBD) are caused by mutations affecting proper telomere maintenance resulting in premature telomere shortening. Telomere length (TL) assessment is currently being used for screening and diagnosis of TBD of which Dyskeratosis congenita (DKC) is the most prominent TBD subtype typically found in children and adolescents. In adults, TBDs are characterized by a broad spectrum of more “cryptic” diverging mono- or oligosymptomatic clinical manifestations such as bone marrow failure (BMF), hepatopathy or interstitial lung disease (ILD). However, despite growing general clinical awareness and exertion of improved TL screening strategies, insufficient data are available about the clinical course of adult, late-onset TBDs. Here, we present a series of 41 consecutive adult TBD cases from 2014 to 2021 identified through the Aachen Telomeropathy registry. Methods and Patients: Median follow-up of the cohort was 2.0 (range 0-6.2) years. In 39/41 patients TBD diagnosis was established based on coexistence of the following three criteria: 1.) Identification of pathogenic variant in a known TBD-related gene via next-generation panel sequencing (NGS) or sequential whole exome sequencing (WES). 2.) The presence of prematurely shortened TL below the 1% percentile (39/41) or 5% percentile (2/41) in the lymphocyte gate detected by flow-FISH and 3.) the presence of BMF or ILD as predominant clinical manifestation. In 2 out of 41 cases, WES did not identify a definitive pathogenic variant. Here, diagnosis of TBD was established due to short telomere below the 1% percentile, BMF and the presence of typical DKC stigmata, other TBD symptoms and a positive family history. Results: Mean age of our cohort was 35.9 ± 17.6 years. 49% (n=20) of patients were females. Results of the genetic screening revealed heterozygous pathogenic variants in TERC (n=14) and TERT (n=11) as the most frequent variants, followed by RTEL1 (n=6), TIN2 (n=1), CTC1 (n=1) and DKC1 (n=1). Homozygous or compound heterozygous pathogenic variants were found for CTC1 (n=2), NHP2 (n=2) or TCAB1 (n=1). 46% (n=19) of patients had a positive family history. BMF was the most frequent symptom with 93% (n=38) presenting with leukopenia, 78% (n=32) with anemia and 76% (n=31) with thrombocytopenia. ILD was suspected/confirmed clinically in 44% (n=18), hepatopathies in 29% (n=12) and cancer in 12% of the patients in past medical history (n=5, liposarcoma, breast cancer, Hodgkin lymphoma, diffuse large B-cell lymphoma, endometrial cancer). Symptoms of the typical DKC triad (leukoplakia, nail dystrophy, abnormal skin pigmentation) were observed in 41% (n=17). Of those, 76% (13/17) presented with only one or two clinical signs. Based on past medical history, the onset of first TBD manifestation was observed at a mean age of 26.9 ± 18.3 years. Time from first symptom observed to the diagnosis of TBD was 8.2 ± 9.5 years. 22% (n=9) patients died during follow-up with mean time of 11.7 ± 10.1 years from first manifestation of TBD to death. Regarding treatment, 39% (n=16) were listed for allogeneic stem cell transplantation (allo Tx), but only 38% (6/16) of these eventually received allo Tx. Immunosuppressive therapy with ATG and CSA was carried out in 12% (n=5) of the patients with no patient responding to treatment. Eltrombopag was given in 5% of cases (n=2) without response. 15% (n=6) received androgen treatment with danazol as the most frequently used drug in five of the six reported cases. All patients showed a response at least in one hematological lineage. Conclusions: Our data support the notion that despite the recent progress in screening and genetic diagnostics, late-onset TBD is still frequently underdiagnosed with several years from first manifestation of disease to diagnosis. Implementation of routine screening for TBD might improve the rate of correct TBD diagnosis and could help to avoid ineffective treatments. Beier: Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Other: Travel reembursement; Alexion: Speakers Bureau. Roeth: Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Kira: Consultancy, Honoraria; Bioverativ, a Sanofi company: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Apellis Pharmaceuticals: Consultancy, Honoraria; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria. Platzbecker: AbbVie: Honoraria; Novartis: Honoraria; Celgene/BMS: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Geron: Honoraria. Radsak: Novartis: Consultancy, Honoraria, Other: e.g. travel support; JAZZ: Other: e.g. travel support; Takeda: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria, Other: e.g. travel support; Daiichi Sankyo: Consultancy, Honoraria, Other: e.g. travel support; Astellas: Other: e.g. travel support; Incyte: Consultancy, Honoraria; Corat: Consultancy, Honoraria; Cogent Biosciences: Consultancy, Honoraria; TEVA: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; Amgen: Other: e.g. travel support; Abbvie: Other: e.g. travel support. Schafhausen: Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Swedish Orphan Biovitrum AB: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Corbacioglu: Gentium/Jazz Pharmaceuticals: Consultancy, Honoraria. Heuser: AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; BergenBio: Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer Pharma AG: Research Funding; Astellas: Research Funding; Karyopharm: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tolremo: Membership on an entity's Board of Directors or advisory committees. Koschmieder: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Karthos: Other: Travel support; Shire: Honoraria, Other; CTI: Membership on an entity's Board of Directors or advisory committees, Other; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Geron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Alexion: Other: Travel support; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees, Other; Abbvie: Other: Travel support; Image Biosciences: Other: Travel support; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; AOP Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding. Panse: Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Grunenthal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Apellis Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Isfort: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel reimbursement; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel reimbursement; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an e
Abstract Introduction: Telomere biology disorders (TBD) are caused by mutations affecting proper telomere maintenance resulting in premature telomere shortening. Telomere length (TL) assessment is currently being used for screening and diagnosis of TBD of which Dyskeratosis congenita (DKC) is the most prominent TBD subtype typically found in children and adolescents. In adults, TBDs are characterized by a broad spectrum of more "cryptic" diverging mono- or oligosymptomatic clinical manifestations such as bone marrow failure (BMF), hepatopathy or interstitial lung disease (ILD). However, despite growing general clinical awareness and exertion of improved TL screening strategies, insufficient data are available about the clinical course of adult, late-onset TBDs. Here, we present a series of 41 consecutive adult TBD cases from 2014 to 2021 identified through the Aachen Telomeropathy registry. Methods and Patients: Median follow-up of the cohort was 2.0 (range 0-6.2) years. In 39/41 patients TBD diagnosis was established based on coexistence of the following three criteria: 1.) Identification of pathogenic variant in a known TBD-related gene via next-generation panel sequencing (NGS) or sequential whole exome sequencing (WES). 2.) The presence of prematurely shortened TL below the 1% percentile (39/41) or 5% percentile (2/41) in the lymphocyte gate detected by flow-FISH and 3.) the presence of BMF or ILD as predominant clinical manifestation. In 2 out of 41 cases, WES did not identify a definitive pathogenic variant. Here, diagnosis of TBD was established due to short telomere below the 1% percentile, BMF and the presence of typical DKC stigmata, other TBD symptoms and a positive family history. Results: Mean age of our cohort was 35.9 ± 17.6 years. 49% (n=20) of patients were females. Results of the genetic screening revealed heterozygous pathogenic variants in TERC (n=14) and TERT (n=11) as the most frequent variants, followed by RTEL1 (n=6), TIN2 (n=1), CTC1 (n=1) and DKC1 (n=1). Homozygous or compound heterozygous pathogenic variants were found for CTC1 (n=2), NHP2 (n=2) or TCAB1 (n=1). 46% (n=19) of patients had a positive family history. BMF was the most frequent symptom with 93% (n=38) presenting with leukopenia, 78% (n=32) with anemia and 76% (n=31) with thrombocytopenia. ILD was suspected/confirmed clinically in 44% (n=18), hepatopathies in 29% (n=12) and cancer in 12% of the patients in past medical history (n=5, liposarcoma, breast cancer, Hodgkin lymphoma, diffuse large B-cell lymphoma, endometrial cancer). Symptoms of the typical DKC triad (leukoplakia, nail dystrophy, abnormal skin pigmentation) were observed in 41% (n=17). Of those, 76% (13/17) presented with only one or two clinical signs. Based on past medical history, the onset of first TBD manifestation was observed at a mean age of 26.9 ± 18.3 years. Time from first symptom observed to the diagnosis of TBD was 8.2 ± 9.5 years. 22% (n=9) patients died during follow-up with mean time of 11.7 ± 10.1 years from first manifestation of TBD to death. Regarding treatment, 39% (n=16) were listed for allogeneic stem cell transplantation (allo Tx), but only 38% (6/16) of these eventually received allo Tx. Immunosuppressive therapy with ATG and CSA was carried out in 12% (n=5) of the patients with no patient responding to treatment. Eltrombopag was given in 5% of cases (n=2) without response. 15% (n=6) received androgen treatment with danazol as the most frequently used drug in five of the six reported cases. All patients showed a response at least in one hematological lineage. Conclusions: Our data support the notion that despite the recent progress in screening and genetic diagnostics, late-onset TBD is still frequently underdiagnosed with several years from first manifestation of disease to diagnosis. Implementation of routine screening for TBD might improve the rate of correct TBD diagnosis and could help to avoid ineffective treatments. Disclosures Beier: Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Other: Travel reembursement; Alexion: Speakers Bureau. Roeth: Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Kira: Consultancy, Honoraria; Bioverativ, a Sanofi company: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Apellis Pharmaceuticals: Consultancy, Honoraria; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria. Platzbecker: AbbVie: Honoraria; Novartis: Honoraria; Celgene/BMS: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Geron: Honoraria. Radsak: Novartis: Consultancy, Honoraria, Other: e.g. travel support; JAZZ: Other: e.g. travel support; Takeda: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria, Other: e.g. travel support; Daiichi Sankyo: Consultancy, Honoraria, Other: e.g. travel support; Astellas: Other: e.g. travel support; Incyte: Consultancy, Honoraria; Corat: Consultancy, Honoraria; Cogent Biosciences: Consultancy, Honoraria; TEVA: Consultancy, Honoraria; Otsuka: Consultancy, Honoraria; Amgen: Other: e.g. travel support; Abbvie: Other: e.g. travel support. Schafhausen: Blueprint Medicines: Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Swedish Orphan Biovitrum AB: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Corbacioglu: Gentium/Jazz Pharmaceuticals: Consultancy, Honoraria. Heuser: AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; BergenBio: Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer Pharma AG: Research Funding; Astellas: Research Funding; Karyopharm: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tolremo: Membership on an entity's Board of Directors or advisory committees. Koschmieder: Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Karthos: Other: Travel support; Shire: Honoraria, Other; CTI: Membership on an entity's Board of Directors or advisory committees, Other; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Geron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Alexion: Other: Travel support; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees, Other; Abbvie: Other: Travel support; Image Biosciences: Other: Travel support; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; AOP Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding. Panse: Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai: Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Grunenthal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Apellis Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Isfort: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel reimbursement; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel reimbursement; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honorari
Author Radsak, Markus P.
Beier, Fabian
Platzbecker, Uwe
Hinze, Claas
Panse, Jens
Egle, Alexander
Koschmieder, Steffen
Brummendorf, Tim H
Tometten, Mareike
Vieri, Margherita
Roeth, Alexander
Schafhausen, Philippe
Heuser, Michael
Maurer, Angela
Kurth, Ingo
Isfort, Susanne
Kricheldorf, Kim
Kirschner, Martin
Kreuter, Michael
Wilk, C. Matthias
Corbacioglu, Selim
Meyer, Robert
Halfmeyer, Insa
Chromik, Jörg
Hoechsmann, Britta
Author_xml – sequence: 1
  givenname: Fabian
  surname: Beier
  fullname: Beier, Fabian
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 2
  givenname: Mareike
  surname: Tometten
  fullname: Tometten, Mareike
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 3
  givenname: Martin
  surname: Kirschner
  fullname: Kirschner, Martin
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 4
  givenname: Insa
  surname: Halfmeyer
  fullname: Halfmeyer, Insa
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 5
  givenname: Margherita
  surname: Vieri
  fullname: Vieri, Margherita
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 6
  givenname: Kim
  surname: Kricheldorf
  fullname: Kricheldorf, Kim
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 7
  givenname: Angela
  surname: Maurer
  fullname: Maurer, Angela
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 8
  givenname: Alexander
  surname: Roeth
  fullname: Roeth, Alexander
  organization: Department of Hematology and Stem Cell Transplantation, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
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  givenname: Uwe
  surname: Platzbecker
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  organization: Department of Hematology, Cellular Therapy and Hemostaseology, University Hospital Leipzig, Leipzig, Germany
– sequence: 10
  givenname: Markus P.
  surname: Radsak
  fullname: Radsak, Markus P.
  organization: Department of Internal Medicine III, University Medical Center, Johannes Gutenberg-University of Mainz, Mainz, Germany
– sequence: 11
  givenname: Philippe
  surname: Schafhausen
  fullname: Schafhausen, Philippe
  organization: Department of Oncology, Hematology and BMT, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
– sequence: 12
  givenname: Selim
  surname: Corbacioglu
  fullname: Corbacioglu, Selim
  organization: Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany
– sequence: 13
  givenname: Britta
  surname: Hoechsmann
  fullname: Hoechsmann, Britta
  organization: University of Ulm and Institute of Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service and University Hospital Ulm, Institute of Transfusion Medicine, Ulm, Germany
– sequence: 14
  givenname: C. Matthias
  surname: Wilk
  fullname: Wilk, C. Matthias
  organization: Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland
– sequence: 15
  givenname: Claas
  surname: Hinze
  fullname: Hinze, Claas
  organization: Department of Pediatric Rheumatology and Immmunology, University Hospital Münster, Münster, Germany
– sequence: 16
  givenname: Jörg
  surname: Chromik
  fullname: Chromik, Jörg
  organization: Medical Clinic II, Hematology, Hemostaseology, Medical Oncology, Rheumatology, Infectious Disease, University Hospital Frankfurt, Frankfurt, Germany
– sequence: 17
  givenname: Alexander
  surname: Egle
  fullname: Egle, Alexander
  organization: 3rd Medical Dept. with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University, Salzburg, Austria
– sequence: 18
  givenname: Michael
  surname: Heuser
  fullname: Heuser, Michael
  organization: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
– sequence: 19
  givenname: Michael
  surname: Kreuter
  fullname: Kreuter, Michael
  organization: Center for interstitial and rare lung diseases, pneumology and respiratory critical care medicine, University of Heidelberg, Thoraxklinik, Heidelberg, Germany
– sequence: 20
  givenname: Ingo
  surname: Kurth
  fullname: Kurth, Ingo
  organization: Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany
– sequence: 21
  givenname: Steffen
  surname: Koschmieder
  fullname: Koschmieder, Steffen
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 22
  givenname: Jens
  surname: Panse
  fullname: Panse, Jens
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 23
  givenname: Robert
  surname: Meyer
  fullname: Meyer, Robert
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
– sequence: 24
  givenname: Susanne
  surname: Isfort
  fullname: Isfort, Susanne
  organization: Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany
– sequence: 25
  givenname: Tim H
  surname: Brummendorf
  fullname: Brummendorf, Tim H
  organization: Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, University Hospital Aachen, Aachen, Germany
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Snippet Introduction: Telomere biology disorders (TBD) are caused by mutations affecting proper telomere maintenance resulting in premature telomere shortening....
Abstract Introduction: Telomere biology disorders (TBD) are caused by mutations affecting proper telomere maintenance resulting in premature telomere...
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Title Clinical Presentation of Patients with Adult Late-Onset Telomere Biology Disorders - Results from the Aachen Telomeropathy Registry
URI https://dx.doi.org/10.1182/blood-2021-153630
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