Kooperativer Bibliotheksverbund

In: Current Oncology, MDPI AG, Vol. 30, No. 7 ( 2023-07-14), p. 6699-6707

Abstract: Background: The landscape of systemic therapies for advanced non-melanoma skin cancers has been revolutionized by the advent of immunotherapy. Cemiplimab is the only immune checkpoint inhibitor (ICI) approved by the European Medicine Agency for recurrent/metastatic cutaneous squamous cell carcinoma (cSCC). Its excellent efficacy outcomes are achieved due to its good tolerability profile. The drug-related hypersensitivity reaction (HSR) is a well-known issue in oncology, but it is rarely reported in respect to immune checkpoint inhibitors. Cemiplimab is among the agents with the best infusion tolerability profiles. Clinical practice guidelines in this field are lacking. Results: We report on the successful management of a severe infusion reaction induced by Cemiplimab in a patient with cSCC based on a desensitization protocol, which led to adequate treatment delivery and prolonged clinical benefit. A review of the available literature on HSR rates and its management with ICIs, and on drug desensitization (DD) protocols and their efficacy, was conducted to highlight the limited knowledge on this topic and its importance. Conclusion: Our experience highlights the need for a DD protocol in order to improve the treatment of HSRs, particularly when elicited by an immunotherapy agent, preventing treatment discontinuation and preserving its efficacy.

Type of Medium: Online Resource

ISSN: 1718-7729

URL: Article

DOI: 10.3390/curroncol30070491

Language: English

Publisher: MDPI AG

Publication Date: 2023

detail.hit.zdb_id: 2270777-3

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1130-1130

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: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Hexal: Other: Travel reimbursement; Mundipharma: Other: Travel reimbursement; Amgen: Other: Travel reimbursement; Roche: Other: Travel reimbursement; Alexion: Other: Travel reimbursement. Brummendorf: Bristol Myers: Research Funding; Janssen: Honoraria; Novartis: Honoraria, Patents & Royalties, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Repeat Diagnostics: Research Funding; Takepart Media: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-153630

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-7-4)

Abstract: The management of patients with chronic myeloid leukemia (CML) has been revolutionized by the introduction of tyrosine kinase inhibitors (TKIs), which induce deep molecular responses so that treatment can eventually be discontinued, leading to treatment-free remission (TFR) in a subset of patients. Unfortunately, leukemic stem cells (LSCs) often persist and a fraction of these can again expand in about half of patients that attempt TKI discontinuation. In this study, we show that presence of myelofibrosis (MF) at the time of diagnosis is a factor associating with TFR failure. Fibrotic transformation is governed by the action of several cytokines, and interestingly, some of them have also been described to support LSC persistence. At the cellular level, these could be produced by both malignant cells and by components of the bone marrow (BM) niche, including megakaryocytes (MKs) and mesenchymal stromal cells (MSCs). In our cohort of 57 patients, around 40% presented with MF at diagnosis and the number of blasts in the peripheral blood and BM was significantly elevated in patients with higher grade of MF. Employing a CML transgenic mouse model, we could observe higher levels of alpha-smooth muscle actin (α-SMA) in the BM when compared to control mice. Short-term treatment with the TKI nilotinib, efficiently reduced spleen weight and BCR::ABL1 mRNA levels, while α-SMA expression was only partially reduced. Interestingly, the number of MKs was increased in the spleen of CML mice and elevated in both BM and spleen upon nilotinib treatment. Analysis of human CML-vs healthy donor (HD)-derived MSCs showed an altered expression of gene signatures reflecting fibrosis as well as hematopoietic support, thus suggesting MSCs as a potential player in these two processes. Finally, in our cohort, 12 patients qualified for TKI discontinuation, and here we observed that all patients who failed TFR had BM fibrosis at diagnosis, whereas this was only the case in 25% of patients with achieved TFR, further supporting the link between fibrosis and LSC persistence.

Type of Medium: Online Resource

ISSN: 1663-9812

URL: Article

URL: Article

URL: Article

URL: Article

URL: Article

DOI: 10.3389/fphar.2023.1212392

DOI: 10.3389/fphar.2023.1212392.s001

DOI: 10.3389/fphar.2023.1212392.s002

DOI: 10.3389/fphar.2023.1212392.s003

DOI: 10.3389/fphar.2023.1212392.s004

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2023

detail.hit.zdb_id: 2587355-6

SSG: 15,3

In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 17 ( 2021-08-27), p. 9306-

Abstract: Age is a major risk factor for severe outcome of the 2019 coronavirus disease (COVID-19). In this study, we followed the hypothesis that particularly patients with accelerated epigenetic age are affected by severe outcomes of COVID-19. We investigated various DNA methylation datasets of blood samples with epigenetic aging signatures and performed targeted bisulfite amplicon sequencing. Overall, epigenetic clocks closely correlated with the chronological age of patients, either with or without acute respiratory distress syndrome. Furthermore, lymphocytes did not reveal significantly accelerated telomere attrition. Thus, these biomarkers cannot reliably predict higher risk for severe COVID-19 infection in elderly patients.

Type of Medium: Online Resource

ISSN: 1422-0067

URL: Article

DOI: 10.3390/ijms22179306

Language: English

Publisher: MDPI AG

Publication Date: 2021

detail.hit.zdb_id: 2019364-6

SSG: 12

In: Respirology, Wiley, Vol. 27, No. 3 ( 2022-03), p. 226-235

Abstract: The pulmonary phenotypes of 31 patients with interstitial lung disease (ILD) and heterozygous poly(A)‐specific ribonuclease ( PARN ) mutations in this cohort were heterogeneous, but idiopathic pulmonary fibrosis was the most frequent diagnosis. Haematological and hepatic features were less frequent than in patients affected with telomerase reverse transcriptase ( TERT )‐ or telomerase RNA component ( TERC )‐associated ILDs.

Type of Medium: Online Resource

ISSN: 1323-7799 , 1440-1843

URL: Issue

URL: Article

DOI: 10.1111/resp.v27.3

DOI: 10.1111/resp.14195

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 2010720-1

In: British Journal of Haematology, Wiley, Vol. 193, No. 3 ( 2021-05), p. 669-673

Abstract: Dyskeratosis Congenita (DKC) is a systemic disorder caused by mutations resulting in impaired telomere maintenance. Clinical features include bone marrow failure and an increased risk of developing hematological malignancies. There are conflicting data whether androgen derivatives (AD) can elongate telomeres in vivo and whether AD treatment enhances the risk of gaining myelodysplastic syndrome‐related mutations. Seven TERC or TERT ‐mutated DKC patients underwent AD treatment. All patients revealed hematological response. Telomere length of lymphocytes and granulocytes increased significantly and no MDS‐related mutations were detected. Pending longer follow‐up, treatment with AD seems to represent an efficient and safe therapy for DKC patients.

Type of Medium: Online Resource

ISSN: 0007-1048 , 1365-2141

URL: Issue

URL: Article

DOI: 10.1111/bjh.v193.3

DOI: 10.1111/bjh.16997

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 1475751-5

In: British Journal of Surgery, Oxford University Press (OUP), Vol. 106, No. 2 ( 2019-01-08), p. e73-e80

Abstract: The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally.

Type of Medium: Online Resource

ISSN: 0007-1323 , 1365-2168

URL: Article

DOI: 10.1002/bjs.11025

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2019

detail.hit.zdb_id: 2006309-X

In: International Journal of Dermatology, Wiley, Vol. 60, No. 6 ( 2021-06), p. 778-780

Type of Medium: Online Resource

ISSN: 0011-9059 , 1365-4632

URL: Issue

URL: Article

DOI: 10.1111/ijd.v60.6

DOI: 10.1111/ijd.15393

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 2020365-2

In: International Journal of Dermatology, Wiley, Vol. 52, No. 11 ( 2013-11), p. 1367-1368

Type of Medium: Online Resource

ISSN: 0011-9059 , 1365-4632

URL: Issue

URL: Article

DOI: 10.1111/ijd.2013.52.issue-11

DOI: 10.1111/ijd.12087

Language: English

Publisher: Wiley

Publication Date: 2013

detail.hit.zdb_id: 2020365-2

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1217-1217

Abstract: Introduction: Dyskeratosis Congenita (DKC) is caused by mutations in genes related to telomere maintenance resulting in prematurely shortened telomeres. Clinically, classical DKC is characterized by mucocutaneous abnormalities, bone marrow failure and other variable features such as lung or liver fibrosis. In adults, mono- or oligosymptomatic DKC is typically presenting with a clinically more heterogeneous and often cryptic picture without classical symptoms of DKC. Data on immunodeficiency as a predominant symptom in DKC patients is limited. The common variable immunodeficiency (CVID) represents a heterogenous group of disease with no universally accepted definition. Typically, patients show hypogammaglobulinaemia and impaired vaccine response. In most cases the genetic basis of CVID remains unknown and to date, the disease is primarily via exclusion of other reasons for hypogammaglobulinaemia. In this study, we aimed to retrospectively analyze the frequency and characteristics of adult patients with altered telomere maintenance (manifesting themselves as "cryptic DKC") within a well-defined cohort of patients with clinical findings of CVID. Materials and Methods: 200 patients of the Freiburg registry of adult CVID patients underwent whole-exome sequencing (WES). Diagnosis of CVID was established based on the recommendations of the European Society of Immune Deficiencies. Retrospectively, all patients were screened for mutations/variants in the following DKC causing genes: TERT, RTEL1, DKC1, NHP2, TERC, NOP10, TCAB1, TIN2 and CTC1. Screening identified 23 patients (age: 45 +/- 13 years; mean +/- S.D.) with mutations/polymorphisms in these genes. All identified variants were heterozygous. One patient showed polymorphisms in three different genes. To analyze the functional consequences on telomere maintenance, telomere length (TL) of peripheral blood mononuclear cells (PBMCs) were analyzed via MM-Q-PCR in all 23 patients. Furthermore, Flow-FISH analysis of lymphocytes as well as granulocytes was carried out in 22 and 14 patients, respectively. Results: TL analysis measured with MM-Q-PCR showed in most of the 23 patients shortened TL compared to an age-matched control group. We measured premature TL shortening below the 1% percentile in 44% (10/23) and below the 10% percentile in 52% (12/23). TL determined via flow-FISH showed TL in lymphocytes below the 10% percentile in 64% (14/22) and below 1% in 27% (6/22). WES revealed 24 polymorphisms/mutations in RTEL1 (n=5), TERT (n=3), NHP2 (n=6), DKC1 (n=8) and CTC1 (n=2). Based on bioinformatic prediction, 78 % (19/24) of all polymorphisms were classified as likely benign variants. Two patients with pathogenic mutations were identified: One 30 year old patient with previously described pathogenic TERT mutation (c.1234C 〉 T, p.His412Tyr) was identified showing lymphocyte and granulocyte TL with flow-FISH between the 1% and 10% percentile and below the 1% percentile using MM-Q-PCR. One 23 year old patient with a bioinformatic predicted pathogenic mutation in RTEL1 (c.2313_2315delAGA, p.Glu771del) showed TL in flow-FISH and MM-Q-PCR below the 1% percentile. Of note, this patient developed few years after initial CVID diagnosis severe interstitial lung disease. Three patients were identified with possible DKC showing variants of unknown significance in the RTEL1 (41 years: c.380G 〉 A, p.Arg127Gln) and TERT (65 years: c.3257G 〉 A, p.Arg1086His and 42 years: c.1843G 〉 A, p.Ala615Thr) gene having both TL in lymphocytes/granulocytes (flow-FISH) and leukocytes (MM-Q-PCR) below the 5% percentile. Conclusions: Clinical signs of immunodeficiency can be a rare first manifestation of cryptic/late-onset DKC in adult patients. We found out that at least 1% of all patients with CVID syndrome is caused by mutations typically found in DKC. Our data adds a further important clinical manifestation to the broad clinical spectrum of cryptic DKC. In return, awareness of CVID as a possible first manifestation of cryptic DKC can improve patient management. TL analysis in addition to genetic work-up provides a valuable tool to identify DKC as underlying disease of CVID and other disorders characterized by impaired replicative potential. Disclosures Brümmendorf: Ariad: Consultancy; Merck: Consultancy; University Hospital of the RWTH Aachen: Employment; Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy. Beier:Novartis: Honoraria; Repeat Dx: Other: Partner.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-128915

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7