Abstract
BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19.
METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting.
RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively).
CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.
Original language | English |
---|---|
Article number | 116 |
Pages (from-to) | 116 |
Journal | JOURNAL OF HEMATOLOGY & ONCOLOGY |
Volume | 15 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Dec 2022 |
Keywords
- Age
- Anticoagulation therapy
- Bleeding
- CLL
- COVID-19
- D-dimer
- LMWH
- Thromboprophylaxis
- Thrombosis
Access to Document
Other files and links
Cite this
- APA
- Author
- BIBTEX
- Harvard
- Standard
- RIS
- Vancouver
}
In: JOURNAL OF HEMATOLOGY & ONCOLOGY, Vol. 15, No. 1, 116, 01.12.2022, p. 116.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19
T2 - a study of ERIC, the European Research Initiative on CLL
AU - Antic, Darko
AU - Milic, Natasa
AU - Chatzikonstantinou, Thomas
AU - Scarfò, Lydia
AU - Otasevic, Vladimir
AU - Rajovic, Nina
AU - Allsup, David
AU - Alonso Cabrero, Alejandro
AU - Andres, Martin
AU - Baile Gonzales, Monica
AU - Capasso, Antonella
AU - Collado, Rosa
AU - Cordoba, Raul
AU - Cuéllar-García, Carolina
AU - Correa, Juan Gonzalo
AU - De Paoli, Lorenzo
AU - De Paolis, Maria Rosaria
AU - Del Poeta, Giovanni
AU - Dimou, Maria
AU - Doubek, Michael
AU - Efstathopoulou, Maria
AU - El-Ashwah, Shaimaa
AU - Enrico, Alicia
AU - Espinet, Blanca
AU - Farina, Lucia
AU - Ferrari, Angela
AU - Foglietta, Myriam
AU - Lopez-Garcia, Alberto
AU - García-Marco, José A
AU - García-Serra, Rocío
AU - Gentile, Massimo
AU - Gimeno, Eva
AU - da Silva, Maria Gomes
AU - Gutwein, Odit
AU - Hakobyan, Yervand K
AU - Herishanu, Yair
AU - Hernández-Rivas, José Ángel
AU - Herold, Tobias
AU - Itchaki, Gilad
AU - Jaksic, Ozren
AU - Janssens, Ann
AU - Kalashnikova, Olga B
AU - Kalicińska, Elżbieta
AU - Kater, Arnon P
AU - Kersting, Sabina
AU - Koren-Michowitz, Maya
AU - Labrador, Jorge
AU - Lad, Deepesh
AU - Laurenti, Luca
AU - Fresa, Alberto
AU - Levin, Mark-David
AU - Mayor Bastida, Carlota
AU - Malerba, Lara
AU - Marasca, Roberto
AU - Marchetti, Monia
AU - Marquet, Juan
AU - Mihaljevic, Biljana
AU - Milosevic, Ivana
AU - Mirás, Fatima
AU - Morawska, Marta
AU - Motta, Marina
AU - Munir, Talha
AU - Murru, Roberta
AU - Nunes, Raquel
AU - Olivieri, Jacopo
AU - Pavlovsky, Miguel Arturo
AU - Piskunova, Inga
AU - Popov, Viola Maria
AU - Quaglia, Francesca Maria
AU - Quaresmini, Giulia
AU - Reda, Gianluigi
AU - Rigolin, Gian Matteo
AU - Shrestha, Amit
AU - Šimkovič, Martin
AU - Smirnova, Svetlana
AU - Špaček, Martin
AU - Sportoletti, Paolo
AU - Stanca, Oana
AU - Stavroyianni, Niki
AU - Te Raa, Doreen
AU - Tomic, Kristina
AU - Tonino, Sanne
AU - Trentin, Livio
AU - Van Der Spek, Ellen
AU - van Gelder, Michel
AU - Varettoni, Marzia
AU - Visentin, Andrea
AU - Vitale, Candida
AU - Vukovic, Vojin
AU - Wasik-Szczepanek, Ewa
AU - Wróbel, Tomasz
AU - Segundo, Lucrecia Yáñez San
AU - Yassin, Mohamed
AU - Coscia, Marta
AU - Rambaldi, Alessandro
AU - Montserrat, Emili
AU - Foà, Robin
AU - Cuneo, Antonio
AU - Carrier, Marc
AU - Ghia, Paolo
AU - Stamatopoulos, Kostas
N1 - Funding Information: L.S. received advisory boards fees from AbbVie and Janssen; educational activity AstraZeneca. DA received funding to attend symposia from Gilead and Bayer. MA received advisory boards fees from AbbVie, AstraZeneca, Janssen-Cilag; travel support from AbbVie and Novartis. RC received speaker fees from Roche, Janssen, AbbVie, AstraZeneca, Celgene, BMS, Kite, and Takeda; advisory board fees from Janssen, AbbVie, Celgene, BMS, Kite, Takeda, Incyte, Kyowa-Kirin, and ADCT; travel and accommodation expenses from Roche, Janssen, AbbVie, Celgene, BMS, Kite, Takeda, and Pfizer; research grant from Pfizer. MC received honoraria from AbbVie, Gilead, Janssen, and AstraZeneca. LS received advisory boards fees from AbbVie, BeiGene and Janssen; educational activity AstraZeneca. BE received consulting or advisory boards fees from Janssen, Roche, Novartis, AbbVie, Gilead, Celgene, ArQule, AstraZeneca, Oxford Biomedica (UK), and BeiGene; speaker / speaker’s bureau fees from Janssen, Gilead, Roche, AbbVie, Novartis, Celgene, Adaptive Biotechnologies, BioGene, and AstraZeneca; research support / research funding from Janssen, Gilead, Roche, AbbVie, BeiGene, and AstraZeneca; travel, accommodations, expenses from Janssen, Roche, Novartis, AbbVie, Gilead, and Celgene. MF received honoraria from Abbvie, Janssen, Gilead. JAG-M received honoraria for advisory board and speaker´s bureau from Mundipharma, Glaxo, AbbVie, Roche, Gilead, AstraZeneca, and Janssen; research support from Hoffman-La Roche, AbbVie, and Janssen. RG-S received educational grants from AbbVie, Janssen, and Novartis. EG received travel grants, honoraria as a consultant and/or speaker bureau for Janssen-Cilag, Roche, and AbbVie. MGDS received honoraria for consultancy/advisory boards with Roche, Janssen Cilag, Gilead, AbbVie, and BMS; research Grant from Gilead, and AstraZeneca. YH received honoraria from AbbVie, Janssen, AstraZeneca, Roche and Medison, outside the submitted work. JAH received honoraria and advisory boards fees from Janssen, AbbVie, AstraZeneca, Roche, Beigene, Gilead, and BMS-Celgene. OJ received honoraria from AbbVie, Janssen, and Roche. AK received honoraria from Janssen, BMS, Astra Zeneca, Roche/Genentech; research money from Janssen, BMS, AstraZeneca, and Roche/Genentech. SK received Travel grant from Celgene; research funding from Janssen, Roche/Genentech, and AbbVie. LL received honoraria for advisory board and lecturing from Janssen, Gilead, AbbVie, Roche, and AstraZeneca. M-DL received advisory board and travel expenses from AbbVie, Janssen, Takeda, and Roche. AG received speaker’s bureau fees from Roche, Janssen, AbbVie, Celgene, Fresenius, Novonordisk; advisory board participation fees from Janssen, and AbbVie; travel and accommodation expenses from Roche, Janssen, and AbbVie. MoMa received speaker bureau fees from Amgen, honoraria as a consultant from Gilead. JM received honoraria and travel grants from AbbVie, Janssen, Roche, Gilead, and Takeda. JAHR received honoraria and advisory boards fees from Janssen, Abbvie, AstraZeneca, Roche, Beigene, Lilly, Gilead, and BMS-Celgene. MD received honoraria from AbbVie, Janssen, Astra-Zeneca, and Novartis. FRM received research funding from Gilead; advisory board participation fees from AbbVie, Gilead, Janssen, AstraZeneca, Takeda, and Roche; speakers bureau fees from Gilead, Janssen, and AbbVie. TM received honoraria from AbbVie, Janssen, AstraZeneca, Gilead, Roche, and Alexion; advisory board participation fees from AbbVie, AstraZeneca, Janssen, Alexion, Morphosys, and Sunesis. RM received honoraria from Janssen, AbbVie, and AstraZeneca. MAP received advisory board participation fees from Janssen, AbbVie, Astra Zeneca, and Merck; speaker’s bureau fees from Janssen, AbbVie, AstraZeneca, Varifarma, and Merck. FMQ received advisory board participation fees from Astrazeneca, and Janssen; speakers bureau fees from AstraZeneca, and Janssen; consultant (but no fees) for Sandoz; travel accommodation from Amgen and Gentili. GR received consultancy fees and honoraria from Abbvie, AstraZeneca, and Janssen. MaMo received consultancy fees from Gilead srl. GMR received honoraria from AbbVie, Gilead, and Janssen; received research funding from Gilead. MS received consultancy fees, advisory board participation fees, travel grants, honoraria from Janssen, Gilead, Roche, AstraZeneca, AbbVie. MS received honoraria from AbbVie, AstraZeneca, Gilead, Janssen, and Roche. PS received funding from Gilead; advisory board participation fees from AbbVie and Janssen; honorarium AbbVie, Janssen, and AstraZeneca. SEA received speaker fees from Janssen, and Takeda. LT received advisory board participation fees from Janssen, Roche, AbbVie, Gilead, Takeda; research funding from Janssen, Roche, Takeda, and Gilead. EVDS received teaching activities fees from Amgen; speaker fees from Janssen. MV received advisory board participation fees from Janssen, Roche, Astra Zeneca, Beigene; speaker fees from Abbvie. AJ received consultancy fees from AstraZeneca, Janssen, Novartis, and Sanofi; advisory board participation fees from Astra Zeneca, Janssen, Sobi, Novartis, Sandoz, MSD, and Incyte, Beigene; speaker fees from Astra Zeneca, Janssen, Sobi, Incyte, Novartis, Abbvie, Amgen, Takeda, and Beigene. AE received honoraria and advisory boards fees from Janssen, Abbvie, Novartis, Biosidus and BMS-Celgene. AV received speaker’s bureau fees from Italfarmaco and Gilead; advisory board participation fees from Janssen and Takeda. CV received honoraria from Janssen. IM received speaker Fees from Janssen, Roche, Abbvie, Sandoz. FM received fees from Janssen, and Gilead. TW received research funding from Roche; honoraria for advisory board, and research funding from Janssen; honoraria, advisory board participation fees, and travel grant from AbbVie; speaker’s bureau fees from Gilead. TC, AK, GK, AAC, DA, MB, MBG, AC, SC, J-GC, CC-G, LDP, MRDP, GDP, CD, MD, DD, ME, MKM, LF, AF, MoF, MG, OG, YKH, TH, II, GI, OBK, EK, JLG, DL, EL, LM, RM, MaMa, MaMot, RN, JO, LO, MP, IP, VMP, GQ, RR, JGC, SS, GS, AS, OS, NS, TT, DTR, ST, MVG, EWS, MY, AR have no conflict of interest to disclose. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19.METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting.RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively).CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.
AB - BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19.METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting.RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively).CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.
KW - Age
KW - Anticoagulation therapy
KW - Bleeding
KW - CLL
KW - COVID-19
KW - D-dimer
KW - LMWH
KW - Thromboprophylaxis
KW - Thrombosis
UR - http://www.scopus.com/inward/record.url?scp=85137135373&partnerID=8YFLogxK
U2 - https://doi.org/10.1186/s13045-022-01333-0
DO - https://doi.org/10.1186/s13045-022-01333-0
M3 - Article
C2 - 36028857
SN - 1756-8722
VL - 15
SP - 116
JO - JOURNAL OF HEMATOLOGY & ONCOLOGY
JF - JOURNAL OF HEMATOLOGY & ONCOLOGY
IS - 1
M1 - 116
ER -