A comparison between erythrocytapheresis and venesection for the treatment of JAK2-mutated polycythaemia.

BACKGROUND: JAK2-mutated polycythaemia vera (PV) is associated with reduced survival because of thrombotic events and haematological disease transformation. Therapeutic venesection has traditionally been used to lower haematocrit, but the technique of erythrocytapheresis has emerged over the last decade. AIM: To compare erythrocytapheresis with venesection as treatment for PV by assessing medical efficacy and financial viability. METHODS: One hundred sixteen patients with PV who received red cell depletion therapy at Barwon Health between 2014 and 2021 were identified. The haematocrit drop after each session, interval between treatment times and number of sessions required to achieve a haematocrit <0.45 were compared with an independent t test. Thrombosis rates were compared with Pearson's chi-squared test. Cost-funding analysis was done by assessing the Weighted Inlier Equivalent Separation and National Weighted Activity Unit funding models. RESULTS: Patients treated with erythrocytapheresis achieved a greater haematocrit drop each treatment session (0.075 vs 0.03, P < 0.01), required fewer sessions to achieve a haematocrit <0.45 (1 vs 4, P < 0.01) and experienced fewer thrombotic complications (8.7% vs 32.1%, P = 0.02) than those treated with venesection. Cost-funding analysis demonstrated that erythrocytapheresis was more financially viable with a surplus of AU$297 per session compared to a deficit of AU$176 with venesection. Even if funding for venesection is increased, the cost of erythrocytapheresis may be mitigated by a lower number of procedures required per year (3.8 vs 5.3, P < 0.01). CONCLUSIONS: Erythrocytapheresis is more efficacious than venesection for the treatment of PV and is accompanied by rapid reductions in haematocrit and reduced thrombotic complications.

Indium-labelled autologous platelet sequestration studies predict response to splenectomy in immune thrombocytopenia: an Australian experience.

BACKGROUND: Splenectomy is an effective intervention in primary immune thrombocytopenia (ITP). Attempts to define pre-clinical predictors of platelet response to splenectomy are inconsistent. Based on international studies defining the likelihood of platelet response using platelet sequestration, patients with relapsed/refractory ITP being considered for splenectomy at a regional Australian hospital were assessed with 111 indium-labelled autologous platelet sequestration (ILAPS) studies. AIMS: To audit the use of ILAPS in an Australian setting and define its role in predicting response to splenectomy. METHODS: A retrospective review of all patients referred for an ILAPS study at a regional hospital was performed. Results for each patient were expressed as an 'R' value (spleen/ liver uptake ratio) to quantify the platelet sequestration pattern and outcome post-splenectomy, based on platelet counts. RESULTS: A total of 45 patients was identified: 13 underwent splenectomy and 32 were medically managed. Patients with favourable ILAPS scans (pure or predominant splenic sequestration) demonstrated a superior response post-splenectomy (100% overall response rate (ORR); 83.5% complete remission (CR)) compared with those with unfavourable ILAPS scans (mixed or pure hepatic sequestration) (71.4% ORR; 57.1% CR) over 12 months. CONCLUSIONS: The use of ILAPS in the Australian setting is feasible and this experience confirms larger international studies demonstrating its utility as a predictor of response to splenectomy in ITP. An unfavourable ILAPS scan could be considered a negative predictor of response prompting consideration for other emerging ITP treatments such as thrombopoietin-receptor agonists or B-cell depleting therapy such as Rituximab.

Phase 3 study of subcutaneous bortezomib, thalidomide, and prednisolone consolidation after subcutaneous bortezomib-based induction and autologous stem cell transplantation in patients with previously untreated multiple myeloma: the VCAT study.

Efficacy and safety of bortezomib-based consolidation following ASCT were investigated in newly diagnosed multiple myeloma patients from Australia, Korea, and China. Patients received three cycles of bortezomib-cyclophosphamide-dexamethasone induction followed by high-dose therapy/ASCT, then were randomized (1:1) to consolidation with TP (thalidomide 100 mg/d for ≤12 months/until disease progression; prednisolone 50 mg on alternate days indefinitely/until disease progression; n = 100) or VTP (subcutaneous bortezomib 1.3 mg/m2 every 2 weeks for 32 weeks, plus TP; n = 103). The hypothesized difference in CR + VGPR rate (after ≤12 months consolidation therapy) was not met. The rate of CR + VGPR was numerically higher with VTP versus TP; however, this was not statistically significant (85.7% versus 77.1%; rate difference 8.6%; 95% confidence interval -2.3%-19.5%; p = .122). Secondary efficacy outcomes were similar between treatment arms. Addition of bortezomib to TP consolidation was associated with limited additional toxicity but did not significantly improve efficacy versus TP.

FLORID NEOVASCULARIZATION OF THE RETINA IN A DIABETIC PATIENT UNDERGOING INDUCTION AND CONSOLIDATION THERAPY FOR ACUTE PROMYELOCYTIC LEUKEMIA.

PURPOSE: To report on a 39-year-old gentleman with a background of Type 2 diabetes mellitus who was diagnosed with acute promyelocytic leukemia (APL), which was treated by all-trans retinoic acid (ATRA), and subsequently developed bilateral neovascularization of the disk (NVD). METHODS: Ophthalmic examination and investigation including fundus photography and fluorescein angiography. RESULTS: Three months after commencement of ATRA therapy, the patient was found to have florid bilateral NVD with adjacent preretinal and intraretinal hemorrhages. Fundus fluorescein angiography was undertaken and NVD was confirmed in both eyes, which was significantly greater than expected for the extent of disease secondary to diabetic retinopathy. As a result of the fluorescein angiography findings, we believe ATRA-mediated upregulation of vascular endothelial growth factor may be the etiology of the NVD. Literature review shows some in vitro studies, which describe ATRA-induced upregulation of vascular endothelial growth factor in ocular tissues. The patient was managed successfully by cessation of ATRA and a single intravitreal injection of bevacizumab in each eye. CONCLUSION: Acute promyelocytic leukemia treated with ATRA may result in upregulation of vascular endothelial growth factor in retinal tissues. Subsequent development of NVD may occur; however, this resolves well by cessation of ATRA and intravitreal injection of bevacizumab. We recommend that all patients undergoing treatment with ATRA for acute promyelocytic leukemia be monitored by an ophthalmologist.

A retrospective audit of the use of Prothrombinex-HT for refractory bleeding following adult cardiac surgery.

OBJECTIVE: To review the frequency of use, possible efficacy and safety profile of Prothrombinex-HT (CSL Bioplasma, Melbourne, VIC) in treatment of patients with microvascular bleeding refractory to standard measures after cardiothoracic surgery. METHODS: A retrospective chart review was performed of 60 consecutive cardiothoracic surgical patients who received Prothrombinex-HT between February and August 2003. Data collected included baseline demographic information, nature and complexity of surgery, preoperative medications, baseline haematological parameters and evidence of clinically significant prothrombotic complications. Consumption of blood products, haematological parameters and mediastinal bleeding rates before and after administration of Prothrombinex-HT were documented in 22 patients who received Prothrombinex-HT in the ICU. RESULTS: No major prothrombotic complications were noted in the series of 60 patients. Two patients had superficial thrombophlebitis. Blood product consumption and haematological parameters were markedly reduced after administering Prothrombinex-HT. CONCLUSIONS: Use of Prothrombinex-HT was not associated with significant prothrombotic complications. Limited evidence of its efficacy suggests that it should be further evaluated in the setting of cardiothoracic surgery.