Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study.

ABSTRACT: During the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%). A total of 149 patients from 43 participating centers were enrolled: 74.1% male, median age 75 years, 75.2% Eastern Cooperative Oncology Group status of 0 to 1, 36.2% high-risk, and 8.9% autologous transplant candidates. All patients received ≥1 cycle ibrutinib (median, 8 cycles), 39.0% with rituximab. Grade ≥3 toxicity occurred in 20.3%, and 33.8% required dose reductions/delays. At 15.6-month median follow-up, 41.6% discontinued ibrutinib, 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2%, respectively. ORR was 77.3% (low risk) vs 59.0% (high risk) (P = .05) and 78.7% (ibrutinib-rituximab) vs 64.9% (ibrutinib; P = .13). Median progression-free survival (PFS) was 26.0 months (all patients); 13.7 months (high risk) vs not reached (NR) (low risk; hazard ratio [HR], 2.19; P = .004). Median overall survival was NR (all); 14.8 months (high risk) vs NR (low risk; HR, 2.36; P = .005). Median post-ibrutinib survival was 1.4 months, longer in 41.9% patients receiving subsequent treatment (median, 8.6 vs 0.6 months; HR, 0.36; P = .002). Ibrutinib with or without rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.

Bombay phenotype (Oh ) and high-titer anti-H in pregnancy: two case reports and a review of the literature.

BACKGROUND: Antenatal cases of Bombay-phenotype (Oh ) individuals and hemolytic disease of the fetus and newborn (HDFN) are not well described in the literature. We present two case reports of high-titer anti-H in pregnant Oh individuals and their serologic investigation, clinical management, and subsequent outcomes. We describe current published cases detailing pregnancy in Oh individuals, to add to the evidence base for clinical decision making and management of pregnancy. STUDY DESIGN AND METHODS: We describe two case reports of high-titer anti-H in pregnancy in Oh individuals. We summarize published cases to date, to inform clinical decision making and antenatal management in individuals with the Bombay phenotype. RESULTS: Of the case reports described, neither were affected by HDFN due to anti-H. Antibody titers were high in both cases (immunoglobulin G titer scores, 512 and 4000, respectively) and would be expected to cause some degree of HDFN, a surprising finding. Regular mean cerebral artery Doppler ultrasound was normal. Patient blood management (PBM) techniques ensured that the patient's hemoglobin (Hb) levels were monitored and maintained. Transfusion intervention was not required, with minimal blood loss recorded at birth in both cases. CONCLUSION: High-titer anti-H in Oh pregnancies may, in rare cases, cause HDFN, but evidence suggests that this may not be the case in all pregnancies. We recommend a multidisciplinary approach, with prompt referral to a fetomaternal medicine unit, combined with PBM strategies, and a planned delivery with the provision of rare-phenotype units (if available and if indicated) on standby.

Synthesis of ultrasmall magnetic iron oxide nanoparticles and study of their colloid and surface chemistry.

Colloidal nanoparticles of Fe(3)O(4) (4 nm) were synthesized by high-temperature hydrolysis of chelated iron (II) and (III) diethylene glycol alkoxide complexes in a solution of the parent alcohol (H(2)DEG) without using capping ligands or surfactants: [Fe(DEG)Cl(2)](2-) + 2[Fe(DEG)Cl(3)](2-) + 2H(2)O + 2OH(-) → Fe(3)O(4) + 3H(2)DEG + 8Cl(-) The obtained particles were reacted with different small-molecule polydentate ligands, and the resulting adducts were tested for aqueous colloid formation. Both the carboxyl and α-hydroxyl groups of the hydroxyacids are involved in coordination to the nanoparticles' surface. This coordination provides the major contribution to the stability of the ligand-coated nanoparticles against hydrolysis.

Turbulent times--the experiences of a college president.

The past president of The Royal College of Surgeons of England recounts difficulties arising during his 3-year term of office 1998-2001. These included prolonged hostile media and public criticism of surgeons and surgery as well as unexpected College interaction with government in regard to problems with the National Health Service.