Rosa Ruchlemer1, Ronen Ben-Ami2, Maskit Bar-Meir3, Jennifer R Brown4, Marion Malphettes5, Rogier Mous6, Sanne H Tonino7, Carole Soussain8, Noelie Barzic9, Julia A Messina10, Preetesh Jain11, Regev Cohen12, Brian Hill13, Stephen P Mulligan14, Marcel Nijland15, Yair Herishanu16, Ohad Benjamini17, Tamar Tadmor18, Koh Okamoto19, Benjamin Arthurs20, Batsheva Gottesman21, Arnon P Kater7, Munir Talha22, Barbara Eichhorst23, Maya Korem24, Naama Bogot25, Fransien De Boer26, Jacob M Rowe27, Tamar Lachish28. 1. Department of Hematology, Shaare-Zedek Medical Center, affiliated with the Hebrew University Medical School, Jerusalem, Israel. 2. Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Infectious Diseases Unit, Shaare-Zedek Medical Center, affiliated with the Hebrew University Medical School, Jerusalem, Israel. 4. Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. 5. Department of Immunology, Saint Louis Hospital, Paris, France. 6. UMC Cancer Center, Hematologie, University Medical Center Utrecht, Utrecht, the Netherlands. 7. Department of Hematology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam University Medical Centers, Amsterdam, the Netherlands. 8. Institut Curie-Site de Saint-Cloud, Hematologie, Saint-Cloud, France. 9. Centre Hospitalier Lyon-Sud, Lyon, France. 10. Department of Medicine, Duke University, Durham, NC, USA. 11. Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA. 12. Infectious Diseases Unit, Laniado Hospital, Netanya, Israel. 13. Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Center, Cleveland, OH, USA. 14. Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia. 15. Department of Hematology, University Medical Centre Groningen, Groningen, the Netherlands. 16. Department of Hematology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 17. Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Ramat Gan, Israel. 18. Department of Hematology, Bnai Zion Medical Center, Haifa, Israel. 19. Division of Infectious Diseases, Rush University Medical Center, affiliated with the University of Tokyo Hospital, Chicago, IL, USA, Japan. 20. Division of Pulmonary & Critical Care Medicine, Veterans Affairs Portland Health Care System, Oregon Health & Science University, Portland, OR, USA. 21. Meir Medical Center, Kfar Saba, Israel. 22. Leeds Teaching Hospitals, NHS Trust, Leeds, UK. 23. University of Cologne, Cologne, Germany. 24. The Infectious Diseases Unit, Hadassah Medical Center, affiliated with Hebrew University Medical School, Jerusalem, Israel. 25. CT Institute, Shaare-Zedek Medical Center, affiliated with Hebrew University Medical School, Jerusalem, Israel. 26. Ikazia Hospital Rotterdam, Rotterdam, the Netherlands. 27. Department of Hematology, Shaare-Zedek Medical Center, Jerusalem, Israel. 28. Infectious Diseases Unit, Shaare-Zedek Medical Center, affiliated with Hebrew University Medical School, Jerusalem, Israel.
Abstract
BACKGROUND: Invasive fungal diseases (IFD) are life-threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. OBJECTIVES: Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. METHODS: Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non-Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. RESULT: Thirty-five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1-540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. CONCLUSIONS: The prevalence of IFD among chronic lymphocytic leukaemia/non-Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib-associated IFD.
BACKGROUND:Invasive fungal diseases (IFD) are life-threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. OBJECTIVES: Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. METHODS: Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non-Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. RESULT: Thirty-five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1-540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. CONCLUSIONS: The prevalence of IFD among chronic lymphocytic leukaemia/non-Hodgkin lymphomapatients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib-associated IFD.
Authors: Arthur L Shaffer; James D Phelan; James Q Wang; DaWei Huang; George W Wright; Monica Kasbekar; Jaewoo Choi; Ryan M Young; Daniel E Webster; Yandan Yang; Hong Zhao; Xin Yu; Weihong Xu; Sandrine Roulland; Michele Ceribelli; Xiaohu Zhang; Kelli M Wilson; Lu Chen; Crystal McKnight; Carleen Klumpp-Thomas; Craig J Thomas; Björn Häupl; Thomas Oellerich; Zachary Rae; Michael C Kelly; Inhye E Ahn; Clare Sun; Erika M Gaglione; Wyndham H Wilson; Adrian Wiestner; Louis M Staudt Journal: Blood Cancer Discov Date: 2021-09-14
Authors: Jeremy A W Gold; Seda S Tolu; Tom Chiller; Kaitlin Benedict; Brendan R Jackson Journal: Clin Infect Dis Date: 2022-08-25 Impact factor: 20.999
Authors: Emily M Eichenberger; Jennifer Saullo; Danielle Brander; Shih-Hsiu Wang; John R Perfect; Julia A Messina Journal: Med Mycol Case Rep Date: 2019-12-05