Summary. The characteristics of severe neutropenia with a delayed onset following administration of rituximab have been evaluated in 53 consecutively treated patients. All but one patient received rituximab for the treatment of non‐Hodgkin's lymphoma. Eight episodes of grade 4 neutropenia were detected between 1 and 5 months after rituximab, when administered alone on five occasions, and on three occasions in combination with chemotherapy, where neutrophil counts had recovered prior to the development of neutropenia. In three episodes, the patients presented with sepsis. Development of neutropenia did not correlate with either the presence of detectable disease or the administration of further treatment. Neutropenia was associated with selective depletion of neutrophil precursors in all but one episode, where it was associated with generalized bone marrow hypoplasia. All episodes developed after a period of either normal or mildly depressed neutrophil counts following treatment with rituximab, and persisted for between several days and several months, before undergoing spontaneous recovery in four instances, and after administration of filgrastim in the remainder. Episodes of neutropenia were associated with disordered immune status manifested by lymphopenia and hypogammaglobulinaemia, raising the possibility that either disturbance of the balance of lymphocyte subsets or an immune dyscrasia induced by rituximab resulted in the development of this type of neutropenia.

Protein kinase C-beta II (PKC-beta II) expression has been reported to indicate inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based chemotherapy. This study compared prognostic significance of immunohistochemically determined PKC-beta II expression in de novo DLBCL treated with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy with and without rituximab. Outcomes were assessed in 80 consecutive patients, 48 treated with CHOP, and 32 with rituximab plus CHOP (R-CHOP). PKC-beta II expression correlated with inferior overall survival (OS) and progression-free survival (PFS) in CHOP-treated patients with low-risk International Prognostic Index (IPI) disease (0-2 adverse factors), but not in the overall patient group unstratified by IPI. PKC-beta II expression correlated with inferior OS and PFS in R-CHOP-treated patients unstratified by IPI status. Immunohistochemically demonstrated PKC-beta II expression thus identified patient subgroups where alternative treatment strategies may confer superior outcome. We now report that PKC-beta II expression has prognostic significance not only for CHOP therapy in low-risk IPI disease, but also for all patients receiving CHOP plus rituximab.

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Background Direct acting oral anticoagulants (DOAC) are now commonly prescribed medications. Urgent reversal of their anticoagulant effect is sometimes required in emergency situations. In Australia, a specific reversal agent for factor Xa (FXa)‐inhibitor DOAC is not available. Instead, two non‐specific haemostatic agents, activated prothrombin complex concentrate (aPCC) and 3 factor‐prothrombin complex concentrate (3F‐PCC), are used off‐label despite a paucity of evidence for their effectiveness or safety. Aims To provide further insight into the efficacy and safety of 3F‐PCC and aPCC for the reversal of the anticoagulant effect of FXa inhibitor DOACs. Methods We conducted a single‐centre retrospective cohort study to investigate the use of aPCC and 3F‐PCC for patients on FXa‐inhibitor DOAC who present with a significant bleeding event or who require urgent surgery. The primary outcome was haemostatic efficacy according to prespecified criteria. Safety outcomes included the thromboembolic event rate and all‐cause mortality during the hospital admission. Results A total of 51 patients was included in the study (36 patients who had a spontaneous bleeding event and 15 non‐bleeding patients who required urgent perioperative management). Thirty‐one patients received aPCC and 20 patients received 3F‐PCC. Haemostasis was adjudicated as effective in all assessable patients (n = 50; 100%). Thromboembolic events occurred in three patients who received aPCC and one patient who received 3F‐PCC. All‐cause mortality was 7.8% (four patients). Conclusions Both aPCC and 3F‐PCC are useful adjuncts for the management of patients who require urgent reversal of the anticoagulant effect of FXa‐inhibitor DOAC. However, the risk of thromboembolism in this patient group requires careful consideration. Prospective, comparator studies are needed along with the development of guidelines that reflect the availability of haemostatic agents in Australia.