Tirabrutinib hydrochloride for B-cell lymphomas.

Bruton tyrosine kinase (BTK) plays an important role in the B-cell receptor (BCR) signaling pathway by mediating proliferation, migration and adhesion in B-cell malignancies. Therefore, the components of BCR signaling, especially BTK, are considered to be attractive therapeutic targets. Ibrutinib, a first-in-class BTK inhibitor, has been approved for the treatment of several types of B-cell malignancies worldwide. However, ibrutinib has off-target activities on non-BTK kinase that are related to adverse effects or might translate into clinical limitations. To overcome these limitations, more specific BTK inhibitors are needed. Tirabrutinib hydrochloride (tirabrutinib) is a potent, highly selective, irreversible oral inhibitor of BTK. Tirabrutinib irreversibly and covalently binds to BTK in B cells and has demonstrated effective in vitro cytotoxicity in many types of B-cell malignancies and in vivo antitumor activity in mouse models. Here, we provide a comprehensive review of the preclinical and clinical activity of tirabrutinib, a drug approved in Japan for relapsed or refractory primary central nervous system lymphoma and all lines of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma.

Prolonged lymphocytopenia after bendamustine therapy in patients with relapsed or refractory indolent B-cell and mantle cell lymphoma.

This corrects the article DOI: 10.1038/bcj.2015.86.

The significant impact of acute kidney injury on CKD in patients who survived over 10 years after myeloablative allogeneic SCT.

There are no well-defined studies of chronic kidney disease (CKD) among long-term survivors after hematopoietic SCT. A retrospective longitudinal study was conducted to characterize CKD in 77 subjects that had undergone myeloablative allogeneic SCT, all of whom had their serum creatinine (Cr) levels followed-up during the 10-year period after SCT. Their mean (range) survival time was 14.4 (10.5-20.2) years. CKD was defined as a persistent decrease in the Cr-based estimated glomerular filtration rate to below 60 mL/min/1.73 m². Acute kidney injury (AKI) was defined as an increase in Cr within the first 100 days after SCT, and its severity was classified into three stages according to the AKIN criteria. Kaplan-Meier and Cox proportional hazards regression analyses evaluated the association between AKI and the incidence of CKD. The cumulative incidence of CKD increased over time and reached 34% at 10 years. After adjusting for known risks for post-SCT CKD, each AKIN stage was strongly associated with the incidence of CKD. The incidence of CKD probably increases over time among subjects who are alive at >10 years after SCT. This study places a new emphasis on AKI as an important risk factor for CKD in post-SCT subjects.

Mortality and medical morbidity beyond 2 years after allogeneic hematopoietic stem cell transplantation: experience at a single institution.

Long-term follow-up data on patients who underwent allogeneic hematopoietic stem cell transplantation in our institution between 1990 and 2007 were evaluated for mortality and morbidity beyond 2 years post-transplantation. Follow-up data were obtained annually from medical records or by mail to the relevant hospitals, or to the patients themselves. In total, 369 patients survived more than 2 years, but 72 patients died thereafter. Relapse was the most common cause of death, followed by pulmonary complications and infections. Second malignancy was the cause of death in seven patients. Chronic kidney disease was one of the most serious complications, and seven patients needed regular dialysis or kidney transplantation. Hypertension and diabetes were reported in 19 and 11.2% patients, respectively. Second malignancies were observed in 14 patients beyond 2 years after transplantation, and the oral mucosa, tongue, esophagus and colon were the main organs involved. We recommend that physicians caring for allogeneic hematopoietic stem cell transplant patients should at a minimum examine kidney function and gastrointestinal tract for secondary malignancy, in addition to hematological status. Such information will be useful for optimizing outcomes through the detection and prevention of complications.