The BTK (Bruton's tyrosine kinase) inhibitor ibrutinib is associated with an increased risk of bleeding. A previous study reported defects in collagen- and adenosine diphosphate (ADP)-dependent platelet responses when ibrutinib was added ex vivo to patient samples. Whereas the collagen defect is expected given the central role of BTK in glycoprotein VI signaling, the ADP defect lacks a mechanistic explanation. In order to determine the real-life consequences of BTK platelet blockade, we performed light transmission aggregometry in 23 patients receiving ibrutinib treatment. All patients had reductions in collagen-mediated platelet aggregation, with a significant association between the degree of inhibition and the occurrence of clinical bleeding or bruising (P=0.044). This collagen defect was reversible on drug cessation. In contrast to the previous ex vivo report, we found no in vivo ADP defects in subjects receiving standard doses of ibrutinib. These results establish platelet light transmission aggregometry as a method for gauging, at least qualitatively, the severity of platelet impairment in patients receiving ibrutinib treatment.

Patients with hematological malignancy are likely to have symptom control needs similar to those with metastatic cancer. Because such symptom burden appears to affect those at all phases of illness, comprehensive symptom assessment is suggested throughout. The introduction of palliative care services during times of increased symptom burden may assist hematologists and other carers in the management of their patients' distress and quality of life.

Current evidence suggests that patients with hematological malignancies less frequently access palliative care services, and for those who do, this tends to occur later in their illness than their counterparts with solid malignancies. These patients are also more likely to die in hospital following escalating interventions. This approach to care that considers palliative care referral after most treatments are exhausted has implications for the quality of palliative care intervention possible. An episodic approach engaging palliative care according to needs rather than prognosis may be more valuable. The successful integration of palliative care into the care of hemato-oncological patients requires recognition by palliative care physicians of the particular issues encountered in care, namely, the difficulty in individual prognostication; ongoing therapeutic goals of curability or long term survival; the technical nature and complications of treatment; the speed of change to a terminal event; the need for pathology testing and transfusion of blood products as death approaches; the potentially reversible nature of intercurrent events such as infection; and the long relationships that develop between patients and their hematologists. Meanwhile, hematologists should be aware of the benefits of palliative care earlier in an illness trajectory and that palliative care does not equate to terminal care only. This review summarizes current practices and barriers to referral, and suggests recommendations for collaborative care and further research in the palliation of hemato-oncological patients. In doing so, it highlights to palliative care and hematology physicians how successful integration of their disciplines may improve their care of these patients.

Summary The ratio of osteoprotegerin [OPG, tumour necrosis factor receptor superfamily, member 11b (TNFRSF11B)] to receptor activator of nuclear factor κB ligand [RANKL, tumour necrosis factor (ligand) superfamily, member 11 (TNFSF11)] in bone is critical for the regulation of bone remodelling. Myeloma cells can home to bone, triggering increased RANKL and decreased OPG expression by stromal cells, leading to osteolysis. Whether myeloma cells contribute directly to the pool of RANKL or OPG in bone has been contentious. Here we provide evidence of RANKL expression by reverse transcription polymerase chain reaction and in situ hybridization, demonstrating transcripts encoding both the membrane‐bound and secreted forms of RANKL in five human multiple myeloma cell lines (LP‐1, NCI‐H929, OPM‐2, RPMI8226, U266) and myeloma cells purified from bone marrow aspirates of myeloma patients. We demonstrated that RANKL encoding mRNAs are translated to protein by antibody detection of RANKL. In vitro assays showed that myeloma cells induced bone marrow derived mononuclear cells to differentiate into adherent tartrate‐resistant acid phosphatase positive multinucleated cells, indicative of the formation of functional osteoclasts. This differentiation could also be achieved with passaged myeloma media alone, implicating secreted products. Finally, we provide evidence that the differentiation observed is at least in part the result of myeloma cell expression of RANKL. We therefore conclude that myeloma cells can directly contribute to the pool of RANKL in bone.

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