{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:13:21Z","timestamp":1790230401982,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T00:00:00Z","timestamp":1486080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In recent years, there have been major advances in the treatment of chronic lymphocytic leukemia (CLL) particularly since the development of novel therapeutic agents, mostly \u201cbiological drugs.\u201d One of the obvious advantages of these agents is the decreased rate of infectious complications occurring during the course of therapy, compared to the use of standard immuno\u2010chemotherapy regimens. Here, we describe 3 patients with CLL and 1 with mantle cell lymphoma who developed severe life\u2010threatening pneumonias, during monotherapy with ibrutinib. The first case was a 70\u2010year\u2010old woman with relapsed CLL who developed bilateral pneumonia with hypoxia 1\u00a0week after starting ibrutinib. She did not respond to broad\u2010spectrum antibiotics and was treated empirically with trimethoprim\u2010sulphamethoxazole and improved. In the second case, we describe a 76\u2010year\u2010old woman with relapsed CLL who developed recurrent pneumonia after 3\u00a0years of treatment with ibrutinib. Presuming that ibrutinib was the cause of pneumonitis with secondary infection, it was stopped with subsequent improvement. The third patient a 67\u00a0year\u2010old man died because of severe bilateral necrotizing pneumonia due to invasive aspergillosis and mucormycosis with pulmonary hemorrhage. The fourth patient with relapsed mantle cell lymphoma died because of severe bilateral pneumonia, caused by pseudomonas and candida, despite receiving appropriate antibiotics. From this experience, we hypothesize that the etiology of severe pneumonia associated with ibrutinib treatment is probably multifactorial, involving factors like preexisting immune\u2010suppression, drug induced pneumonitis and infections. We suggest that patients with CLL or other lymphoproliferative disorders with suspected pneumonia during monotherapy with ibrutinib should be very carefully evaluated and need to undergo complete diagnostic workup to establish an exact diagnosis. Understanding which patients with CLL or lymphoma treated with kinase inhibitors are at a higher risk for developing pulmonary complications could be one of the important future challenges, when selecting the best available therapy for these patients.<\/jats:p>","DOI":"10.1002\/hon.2387","type":"journal-article","created":{"date-parts":[[2017,2,3]],"date-time":"2017-02-03T11:07:07Z","timestamp":1486120027000},"page":"349-354","source":"Crossref","is-referenced-by-count":31,"title":["Severe pneumonia associated with ibrutinib monotherapy for CLL and lymphoma"],"prefix":"10.1002","volume":"36","author":[{"given":"Natalia","family":"Kreiniz","sequence":"first","affiliation":[{"name":"Hematology Unit Bnai Zion Medical Center  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Bejar","sequence":"additional","affiliation":[{"name":"Pathology Department Bnai Zion Medical Center  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Polliack","sequence":"additional","affiliation":[{"name":"Hematology Department Hadassah University Hospital and Hebrew University Medical School  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-8612","authenticated-orcid":false,"given":"Tamar","family":"Tadmor","sequence":"additional","affiliation":[{"name":"Hematology Unit Bnai Zion Medical Center  Haifa Israel"},{"name":"The Ruth and Bruce Rappaport Rappaport Faculty of Medicine Technion  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,3]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.3816\/CLM.2009.n.071"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.696"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443903"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215637"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.796049"},{"issue":"16","key":"e_1_2_5_7_1","first-page":"1594","article-title":"Ibrutinib for chronic lymphocytic leukemia","volume":"374","author":"Burger JA","year":"2016","journal-title":"N Engl J 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an overview of toxicities associated with ibrutinib and idelalisib in patients with chronic lymphocytic leukemia","volume":"8","author":"Falchi L","year":"2016","journal-title":"Mediterr J Hematol Infect Dis"}],"container-title":["Hematological 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