Objectives: The complement component 5 (C5) inhibitor ravulizumab demonstrated non-inferiority to eculizumab following 26 weeks of treatment in complement inhibitor-naïve and complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH; studies 301 and 302, respectively). This study aims to describe the results of both studies from 27 weeks to 2 years.Methods: Patients (N = 441) continued to receive ravulizumab throughout the extension period. Efficacy endpoints included lactate dehydrogenase (LDH) normalization, transfusion avoidance and fatigue score (FACIT-F). Safety analyses were also performed.Results: From 27 weeks to 2 years, improvements in LDH levels were maintained in both study populations. Transfusion avoidance was maintained in 81.9% (study 301) and 85.6% (study 302) of patients, and FACIT-F scores remained stable. Ravulizumab was well tolerated, and the incidence of adverse events (AEs) were similar between patients of both studies. Incidence of serious AEs deemed related to ravulizumab treatment was low (<3%).Conclusions: This study reports, to date, the longest period of follow-up in over 400 patients with PNH treated with ravulizumab (662 patient-years). Long-term, ravulizumab demonstrated durable efficacy and was well tolerated, highlighting the importance of C5 inhibitors as the mainstay of PNH treatment.
BackgroundThe evolution of molecular studies in myeloproliferative neoplasms (MPN) has enlightened us the understanding of this complex disease consisting of polycythaemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The epidemiology is well described in the western world but not in Asian countries like Malaysia.Materials and methodsThis retrospective national registry of MPN was conducted from year 2009 to 2015 in Malaysia.ResultsA total of 1010 patients were registered over a period of 5 years. The mean age was 54 years with male predominance. The ethnic distribution revealed that Chinese had a relatively high weighted incidence proportion (43.2%), followed by Indian (23.8%), Malay (15.8%) and other ethnic groups (17.2%). The types of MPN reported were 40.4% of ET (n = 408), 38.1% of PV (n = 385), 9.2% of PMF (n = 93), 3.1% of hypereosinophilic syndrome (HES) (n = 31) and 7.9% of unclassifiable MPN (MPN-U) (n = 80). Splenomegaly was only palpable clinically in 32.2% of patients. The positive JAK2 V617F mutation was present in 644 patients with 46.6% in PV, 36.0% in ET, 9.0% in PMF, and 7.4% in MPN-U, and had significantly lower haemoglobin (p < 0.001), haematocrit (p < 0.001) and white blood cells (WBC) (p < 0.001) than those with negative mutation. Significant differences in platelet and WBC count were detected in ethnic groups and MPN sub-types. There were more arterial thrombosis events seen in those with JAK2 V617F mutation as compared to venous thrombosis events (23.1% vs 4.4%). The bleeding rate was only 6.6%. Among the risk factors, previous thrombosis, old age (≥ 60 years) and hypertension were significantly correlated to positive JAK2 V617F mutation. The arterial thrombosis event is associated with higher presenting HB, HCT and PLT while the bleeding event is associated with lower presenting HB, HCT but higher PLT. The presence of JAK2 V617F mutation is associated with higher risk of arterial thrombosis.ConclusionChinese ethnicity is associated with higher rates of MPN. The history of thrombosis, age ≥ 60 years and hypertension are risk factors that can be correlated to JAK2 V617F mutation. This study is instrumental for policy makers to ensure preventive strategies can be implemented in future.
Vitamin B12 defi ciency and folate defi ciency are common causes of macrocytic anaemia and both are important for many cellular processes. These defi ciencies could be due to inadequate dietary intake, impaired absorption or drug ingestion. We present an interesting case of pancytopenia with microangiopathic haemolytic anaemia (MAHA) and intracranial bleeding (ICB) due to combined vitamin B12 and folate defi ciency, mimicking thrombotic thrombocytopenic purpura (TTP). Case presentationA 47-year-old male was admitted to the haematology ward for fatigue, persistent frontal headache and left upper-quadrant abdominal pain that had lasted one week. He was diagnosed with diffuse large B-cell lymphoma (DLBCL) which was treated with six cycles of dose-adjusted EPOCH-rituximab regimen. An end of treatment positron emission tomography (PET) scan reported no active fl uorodeoxyglucose (FDG) uptake, consistent with disease in remission. He had a history of jejunal resection at the age of 42 for bowel ischaemia with unknown aetiology and defaulted surgical follow-up. He was on treatment for type 2 diabetes mellitus and hypertension.Physical examination revealed scleral icterus, pallor and excess weight. There was an old midline laparotomy scar on the abdomen. Other physical and neurological examination fi ndings were unremarkable. The initial laboratory study (Table 1) showed white blood cell (WBC) count of 3.4 x 109/l, haemoglobin (Hb) of 76g/l platelet count of 67 x 109/l, mean corpuscular volume (MCV) of 91.2fl and reticulocyte count of 10.4%. He had indirect hyperbilirubinemia 62μmol/l and markedly raised lactate dehydrogenase (LDH) 9894U/l. Peripheral blood fi lm (PBF) reported anisopoikilocytosis, polychromasia, ovalocytes, spherocytes, numerous teardrop and fragmented red cells, thrombocytopenia (Figure 1) and hypersegmented neutrophils. His Coomb's test was negative, consistent with non-immune haemolytic anaemia. Coagulation profi le, renal, liver and thyroid function tests Vitamin B12 deficiency and folate deficiency are common causes of macrocytic anaemia and both are important for many cellular processes. These de ciencies could be due to inadequate dietary intake, impaired absorption or drug ingestion. We present a case of a 47-year-old male with a history of diffuse large B-cell lymphoma (DLBCL) who was admitted for fatigue, persistent frontal headache and left upper-quadrant abdominal pain. Further investigation showed that he had pancytopenia with microangiopathic haemolytic anaemia (MAHA) and intracranial bleeding (ICB). Serum vitamin B12 and folate were later found to be low and a diagnosis of combined vitamin B12 and folate de ciency mimicking thrombotic thrombocytopenic purpura (TTP) was made. The patient responded well to vitamin B12 and folate replacement.
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