History of drug use in allogeneic hematopoietic cell transplant recipients.

Allogeneic hematopoietic cell transplant (HCT) is a curative therapy for malignant and non-malignant blood diseases. Drug use may be associated with adverse outcomes. We performed a retrospective analysis to assess non-relapse mortality (NRM) and overall survival (OS) in HCT patients with drug use. The medical charts of 232 patients were reviewed. Recipients of matched unrelated donor (MUD) or matched related donor (MRD) transplants were included. Drug use was defined by either metabolic evidence or provider documentation prior to transplant. Transplants were MUD (n = 148) or MRD (n = 84). Median follow-up duration was 15.5 months. There were 35 (15%) patients in the drug use group and 197 (85%) patients in the control group; 49% and 60.4% were in remission at the time of transplant, respectively. In univariate analysis, drug use was associated with a 3-year cumulative incidence of NRM of 43% vs 29% for the control group (p = 0.048), and an HR of 1.75, (95% CI: 1.02-2.99). After controlling for age, sex, disease status, and graft type, drug use was associated with a hazard ratio (HR) of 1.6 (95% CI: 0.95-2.92) for NRM, and an HR 1.2 (95% CI: 0.74-1.94) for OS. Larger cohorts may be needed to further evaluate this association.

Short term efficacy of recombinant porcine factor VIII in patients with factor VIII inhibitors.

BACKGROUND: Antibodies against factor VIII (FVIII), seen in acquired (AHA) and congenital haemophilia A, lead to severe bleeding diatheses. Current first-line treatment includes bypass agents. Recombinant porcine sequence FVIII (rpFVIII) was developed as an alternative therapy. AIM: To describe our institutional experience with the use of rpFVIII. METHODS: A retrospective chart review of five patients treated with rpVIII between 2016 and 2019. RESULTS: Five patients (four AHA, one congenital haemophilia with inhibitors) were treated with rpFVIII. No patient had an adverse event during infusion. All patients initially exhibited a response evidenced by increased FVIII levels from baseline <1% to 81%-170%, normalization of the activated partial thromboplastin time (aPTT) and resolution of bleeding. However, all five patients were subsequently noted to have decreasing peak FVIII levels and aPTT prolongation, either within the initial treatment course or upon later re-administration. Resistance to rpFVIII was recognized after an average of 12.4 exposure days. Porcine FVIII inhibitor levels measured afterwards were present (detectable-170 Bethesda units) in all patients. Three out of four AHA subjects also developed an increase in the anti-human FVIII inhibitor titres after receiving rpFVIII. CONCLUSION: rpFVIII was safe and initially effective in all patients. However, its use is associated with development of an inhibitor to rpFVIII, decreasing its efficacy and duration of effect. Further, rpFVIII use may lead to an increase in patient anti-human FVIII inhibitor titres. A larger study is necessary to appropriately assess the incidence of these outcomes.

Complete Remission of Bone Metastases in Renal Cell Carcinoma with Nivolumab.

A 60-year-old female, who presented with abdominal discomfort, was noted to have an enhancing left renal mass, with central necrosis on a CT scan. She underwent radical nephrectomy and biopsy revealed clear cell renal cell carcinoma, Fuhrman grade 4. After 1.5 years of her surgery, she developed metastatic disease with pulmonary nodules and was started on sunitinib. She had disease progression with development of a new 8.2 x 7.6 cm expansile, lytic bony lesion with a complete destruction of the left scapula and 5th left rib lesion. She was treated with Nivolumab for three years. Scans revealed complete resolution of the left scapular metastasis, left rib lesion and the pulmonary nodules. The patient experienced no skeletal-related event (SRE), and no bisphosphonates or receptor activator of nuclear factor-kappa B ligand (RANKL) inhibitor was used. The patient remains in complete remission, three years out of treatment. This case highlights the importance of exploring this particular class of drugs for renal cell carcinoma (RCC) with bone metastasis.

Meta-analysis of randomized trials on percutaneous patent foramen ovale closure for prevention of migraine.

BACKGROUND: The role of percutaneous patent foramen ovale (PFO) closure for prevention of migraine is controversial. METHODS: We performed a computerised search of MEDLINE, EMBASE and COCHRANE databases through December 2017 for randomised trials evaluating PFO closure versus control in patients with migraine headaches (with or without aura). The main study outcome was the reduction in monthly migraine attacks after PFO closure compared with the control group. RESULTS: The final analysis included three randomised trials with a total of 484 patients. Reduction in monthly migraine attacks was higher in PFO closure compared with the control group (standardised mean difference-SMD = 0.25; 95% CI: 0.06-0.43; p = .01). There was higher reduction of monthly migraine days in PFO closure group compared with control group (SMD = 0.30; 95% CI: 0.08-0.53; p = .01). There was no statistically significant difference in complete resolution of migraine attacks (OR: 3.67; 95% CI: 0.66-20.41; p = .14) and in responders' rate (OR: 1.92; 95% CI: 0.76-4.85; p = .17) between PFO closure and control groups. In patients whose majority of migraine attacks are with aura, there was an observed reduction in migraine attacks in PFO closure compared with control groups (SMD = 0.86; 95% CI: 0.07-1.65; p = .03). CONCLUSION: PFO closure might be beneficial in migraine patients by reducing migraine attacks and migraine days, especially in patients whose majority of migraine attacks are with aura. However, those benefits were not associated with an improvement in responders' rate or complete resolution of migraine; raising concerns on the magnitude of clinical benefit of PFO closure in migraine prevention.