HBV reactivation in CLL patients with occult HBV infection treated with ibrutinib without viral prophylaxis

Innocenti, Idanna; Morelli, Francesca; Autore, Francesco; Corbingi, Andrea; Pasquale, Raffaella; Sorà, Federica; Pompili, Maurizio; Laurenti, Luca

doi:10.1080/10428194.2018.1523401

Cited by 18 publications

(14 citation statements)

References 9 publications

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“…Although infections have been linked to ibrutinib treatment, these are mostly bacterial and fungal infections 56,57 . However, there are reported cases showing the reactivation of hepatitis B virus (HBV) after ibrutinib treatment 58,59 . Because APOBEC3G can also inhibit HBV, our finding may provide new insights to the understanding of HBV reactivations with ibrutinib treatment where imbalances or deficiencies of APOBEC3 family members contribute to a deficient host response to infections.…”

Section: Discussionmentioning

confidence: 99%

B Cell Receptor Signaling Drives APOBEC3 Expression Via Direct Enhancer Regulation in Chronic Lymphocytic Leukemia B Cells

Wang

Yan

Boysen

et al. 2021

Preprint

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Constitutively activated B cell receptor (BCR) signaling is a primary biological feature of chronic lymphocytic leukemia (CLL). The biological events controlled by BCR signaling in CLL are not fully understood and need investigation. To make inroads we obtained blood samples from CLL patients before and after Bruton's tyrosine kinase inhibitors (BTKi) treatment and used them to study BCR signaling regulated genes. Here, by analysis of the chromatin states and gene expression profiles of CLL B cells from patients before and after BTKi ibrutinib treatment, we show that BTKi treatment leads to a decreased expression of APOBEC3 family genes in an enhancer regulation dependent manner. BTKi treatment reduces enrichment of enhancer markers (H3K4me1, H3K27ac) and chromatin accessibility at putative APOBEC3 enhancers. CRISPR-Cas9 directed deletion or inhibition of the putative APOBEC3 enhancers leads to reduced APOBEC3 expression. We further find that transcription factor NFATc1 couples BCR signaling with the APOBEC3 enhancer activity to control APOBEC3 expression. Importantly, enhancer regulated APOBEC3 expression contributes to replication stress in malignant B cells. We also demonstrate a novel mechanism for BTKi suppression of APOBEC3 expression via direct enhancer regulation in a NFATc1 dependent manner, implicating BCR signaling as a potential regulator of leukemic genomic instability.

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Section: Discussionmentioning

confidence: 99%

B Cell Receptor Signaling Drives APOBEC3 Expression Via Direct Enhancer Regulation in Chronic Lymphocytic Leukemia B Cells

Wang

Yan

Boysen

et al. 2021

Preprint

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“…Ibrutinib has primarily been associated with fungal infections [2,3], but reactivation of varicella zoster, hepatitis B, and chronic hepatitis E have also emerged as issues [2,5,6]. A single case of West Nile encephalitis has also been reported [9] in an ibrutinib patient, suggesting that ibrutinib may predispose to severe viral infections, perhaps through irreversible inhibition of ITK.…”

Section: Discussionmentioning

confidence: 99%

“…Invasive aspergillosis has been the most common serious infection, but other fungal pathogens (cryptococcosis, histoplasmosis, mucormycosis, and Pneumocystis jirovecii) have also been problematic [2][3][4]. Viral infections have also been an issue with the occurrence of zoster [2] as well as chronic hepatitis E and hepatitis B reactivation [5,6]. is report details an unusual case of herpes encephalitis occurring in an 86-year-old man receiving ibrutinib for Waldenstrom's macroglobulinemia.…”

Section: Introductionmentioning

confidence: 99%

HSV-1 Encephalitis in an Elderly Man Receiving Ibrutinib for Waldenstrom’s Macroglobulinemia

Wallace

2020

Case Reports in Infectious Diseases

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Ibrutinib is a major new addition to the therapeutic armamentarium for chronic lymphocytic leukemia, mantle cell lymphoma, Waldenstrom’s macroglobulinemia, and chronic graft versus host disease. Though ibrutinib has proven to be a revolutionary new small molecule agent, and has relatively minimal toxicity as compared to traditional chemotherapy, infections have emerged as a major complication of therapy. While fungal infections have been the most problematic (including CNS aspergillosis), zoster, hepatitis B reactivation, and chronic hepatitis E have been reported in association with ibrutinib therapy. This report describes a case of herpes encephalitis in an 86-year-old Waldenstrom’s patient receiving ibrutinib and speculates as to whether this late life encephalitis may have been related to ibrutinib.

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“…Combined with the patient's medical history, FCR chemotherapy, including fludarabine, cyclophosphamide and rituximab, was given at the first time. Prior to chemotherapy, our patient began to use anti HBV drugs due to occult hepatitis B virus Infection (anti-HBc anti-HBs were positive) (9). Meanwhile, hundreds of milliliters A B pleural effusion was drained continuously every day.…”

Section: Case Presentationmentioning

confidence: 99%

Complete resolution of chylothorax with ibrutinib in chronic lymphocytic leukemia: a case report

Cheng¹,

Huang²,

Wei³

et al. 2022

Ann Palliat Med

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Chylothorax is an infrequent pleural effusion often caused by traumatic or nontraumatic injury to the thoracic duct. Nontraumatic chylothorax caused by chronic lymphocytic leukemia (CLL) is rarely reported. Previous experience has implied that the main factor affecting the treatment of chylothorax is whether the anti-cancer treatment is effective. The patient diagnosed with chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) before the hospital admission, and not received any treatment.After four months, he had progressive dyspnea. Chest computed tomography (CT) scan showed bilateral pleural effusion with progressive lymphadenopathy, and massive chylous pleural effusion was drained by closed thoracic drainage. After a course of chemotherapy including fludarabine, cyclophosphamide and rituximab (FCR), the patient developed agranulocytosis and his pleural effusion was still abundant. After careful consideration, the patient refused to receive following chemotherapy and chose to take ibrutinib orally. Two months after oral ibrutinib, ultrasound examination showed that pleural effusion completely disappeared. In the next one year, the patient had a routine follow-up and was in good condition. To our knowledge, this is the first report of ibrutinib in the treatment of chylothorax associated with CLL. Ibrutinib provides a more palliative treatment for elderly CLL patients with chylothorax.

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HBV reactivation in CLL patients with occult HBV infection treated with ibrutinib without viral prophylaxis

Cited by 18 publications

References 9 publications

B Cell Receptor Signaling Drives APOBEC3 Expression Via Direct Enhancer Regulation in Chronic Lymphocytic Leukemia B Cells

B Cell Receptor Signaling Drives APOBEC3 Expression Via Direct Enhancer Regulation in Chronic Lymphocytic Leukemia B Cells

HSV-1 Encephalitis in an Elderly Man Receiving Ibrutinib for Waldenstrom’s Macroglobulinemia

Complete resolution of chylothorax with ibrutinib in chronic lymphocytic leukemia: a case report

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