Ibrutinib for mantle cell lymphoma at first relapse: a United Kingdom real-world analysis of outcomes in 211 patients.

Ibrutinib is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL) and clinical trial data supports use at second line compared to later relapse. We aimed to investigate outcomes and tolerability for ibrutinib when given second line in a real-world setting. Our multicentre retrospective analysis included 211 R/R MCL patients, median age 73 years, receiving ibrutinib second-line within the United Kingdom's National Health Service. Overall response to ibrutinib was 69% (complete response 27%). The median progression-free survival (PFS) was 17·8 months (95% CI 13·1-22·2) and median overall survival (OS) 23·9 months (95% CI 15·0-32·8). Drug-related adverse event led to dose reduction in 10% of patients and discontinuation in 5%. In patients with progressive disease, accounting for 100 of 152 patients stopping ibrutinib, 43% received further systemic therapy. Post-ibrutinib rituximab, bendamustine and cytarabine (R-BAC) showed a trend toward improved survival compared to alternative systemic treatments (post-ibrutinib median OS 14·0 months, 95% CI 8·1-19·8, vs. 3·6 months, 95% CI 2·6-4·5, P = 0·06). Our study confirms the clinical benefit and good tolerability of ibrutinib at first relapse in a real-world population. Patients progressing on ibrutinib had limited survival but outcomes with R-BAC in select patients were promising.

Vitamin D deficiency and its correction in children with sickle cell anaemia.

Vitamin D deficiency is common in sickle cell anaemia (SCA, HbSS), although its significance and optimal means of correction are unknown. We conducted an audit to assess the clinical significance of 25-hydroxy vitamin D (25-OHD) deficiency in children with SCA and to evaluate two methods of vitamin D supplementation. We audited 25-OHD levels in 81 children with SCA and looked for statistical associations with biochemical, haematological and clinical parameters. In a separate group of regularly transfused children with SCA, we compared changes in 25-OHD blood concentrations following treatment with either high-dose intramuscular ergocalciferol (n = 15) or 4 days of high-dose oral cholecalciferol (n = 64). Ninety-one percent of children with SCA had 25-OHD levels <20 µg/L. The 25-OHD levels were negatively correlated with increasing age (P < 0.001) but showed no significant relationship to laboratory measurements, transcranial Doppler velocities or hospital attendance. Both intramuscular ergocalciferol and oral cholecalciferol supplementations resulted in increases of 25-OHD blood concentration to normal levels. The mean dose of ergocalciferol was greater than that of cholecalciferol (7,729 versus 5,234 international units (IU)/kg, P < 0.001), but the increment in 25-OHD levels was significantly greater in the oral cholecalciferol group (6.44 versus 2.82 (ng/L)/(IU/kg), P < 0.001). Both approaches resulted in vitamin D sufficiency for about 120 days. Increased 25-OHD concentration was significantly associated with increased serum calcium concentration. Vitamin D deficiency is very common in SCA and can be effectively corrected with high-dose intramuscular ergocalciferol or 4 days of high-dose oral cholecalciferol. Prospective, randomised studies are needed to assess the clinical value of vitamin D supplementation.

Extramedullary haematopoiesis in a patient with myelofibrosis.

Megakaryocytes are large multilobulated precursor cells which usually reside within the bone marrow and give rise to platelets. There have been rare occurrences where they have been found in peripheral blood and extramedullary tissues in conditions where the underlying mechanisms of the bone marrow have been affected. This case report discusses an unusual presentation of a man with myelofibrosis who was found to have megakaryocytes in his ascitic fluid. We have highlighted the images showing utility of combination of traditional staining methods and immunohistochemistry in combating this diagnostic dilemma.

The recognition of oral manifestations of haematological disease saves lives: a case report.

Background: Acute Leukaemias are haematological disorders characterised by the proliferation of immature white blood cells in the bone marrow and/or peripheral blood. Oral manifestations of leukaemia are common and may be the first sign of the disease. The clinical presentation of these Acute Leukaemias may include neutropenic sepsis, hyperviscocity and coagulopathy which confer a potential morbidity and mortality. Clinicians must be able to recognise this pattern of presentation. Case report: We report a 34-year-old female who was referred to the Oral and Maxillofacial Surgery department with acute dental pain and pericoronitis. She subsequently had a simple dental extraction but re-presented with a bleeding socket that did not respond to local treatment. Investigation of this led to a diagnosis of Acute Promyelocytic Leukemia (APL). She was admitted under the care of the haematology team for urgent, life-saving, treatment. Conclusions: Early diagnosis and treatment of the Acute Leukaemias can be life saving. The oral manifestations of disease are common and may be the first sign. Clinicians must be able to recognise this pattern of presentation and arrange urgent investigation and specialist management. Clinical/CPD relevance: This case report discusses leukaemia and highlights the important role General Dental Practitioners can play in early diagnosis. We frame a safe approach to managing these patients in a typical case. Whilst this disease subtype is rare, the learning points can be universally applied.

Case report of idiopathic pulmonary haemosiderosis in a child with recurrent chest infections.

Idiopathic pulmonary haemosiderosis (IPH) is a rare condition that usually presents as a triad of haemoptysis, iron deficiency anaemia and pulmonary infiltrates. We report a case of IPH diagnosed in a 7 year old boy who had recurrent hospital admissions with severe chest infections and haemoptysis from his first few months of life. He was found to have microcytic hypochromic anaemia, diffuse infiltrate shadowing on his chest X-ray (CXR) and ground-glass opacification on his computed tomogram (CT). Perl's Prussian blue staining of his bronchoalveolar lavage fluid revealed haemosiderin-laden macrophage infiltration. After exclusion of infective, cardiac, immunological and glomerular causes, he was diagnosed with idiopathic pulmonary haemosiderosis. He has since been treated intermittently with steroids, which have failed to control his symptoms fully.