Key Points High-resolution matching for HLA-A, -B, -C, and -DRB1 is required for optimal survival in myeloablative-unrelated donor transplantation. HLA-DPB1 nonpermissive mismatches should be avoided in otherwise matched transplants to minimize overall mortality.

Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia.

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PURPOSE Cardiovascular adverse events (CVAEs) can occur during proteasome inhibitor (PI) therapy. We conducted a prospective, observational, multi-institutional study to define risk factors and outcomes in patients with multiple myeloma (MM) receiving PIs. PATIENTS AND METHODS Patients with relapsed MM initiating carfilzomib- or bortezomib-based therapy underwent baseline assessments and repeated assessments at regular intervals over 6 months, including cardiac biomarkers (troponin I or T, brain natriuretic peptide [BNP], and N-terminal proBNP), ECG, and echocardiography. Monitoring occurred over 18 months for development of CVAEs. RESULTS Of 95 patients enrolled, 65 received carfilzomib and 30 received bortezomib, with median 25 months of follow-up. Sixty-four CVAEs occurred, with 55% grade 3 or greater in severity. CVAEs occurred in 51% of patients treated with carfilzomib and 17% of those treated with bortezomib ( P = .002). Median time to first CVAE from treatment start was 31 days, and 86% occurred within the first 3 months. Patients receiving carfilzomib-based therapy with a baseline elevated BNP level higher than 100 pg/mL or N-terminal proBNP level higher than 125 pg/mL had increased risk for CVAE (odds ratio, 10.8; P < .001). Elevated natriuretic peptides occurring mid–first cycle of treatment with carfilzomib were associated with a substantially higher risk of CVAEs (odds ratio, 36.0; P < .001). Patients who experienced a CVAE had inferior progression-free survival (log-rank P = .01) and overall survival (log-rank P < .001). PI therapy was safely resumed in 89% of patients, although 41% required chemotherapy modifications. CONCLUSION CVAEs are common during PI therapy for relapsed MM, especially with carfilzomib, particularly within the first 3 months of therapy. CVAEs were associated with worse overall outcomes, but usually, discontinuation of therapy was not required. Natriuretic peptides were highly predictive of CVAEs; however, validation of this finding is necessary before uniform incorporation into the routine management of patients receiving carfilzomib.

Silent cerebral infarcts (SCIs) are the most commonly recognized cause of neurologic injury in patients with sickle cell anemia (SCA), identified in $20% of children. In children with SCA, SCIs are associated with an average 5 full-scale IQ point decrement, 1 poor academic performance, 2 and future overt strokes. 3 Recently, Bernaudin et al 4 reported that in children with SCA, the cumulative risk for SCI was 19.2% by age 8 years, 32.4% by age 14 years, and 39.1% by age 18 years. Very little is known about the prevalence of SCI in adults with SCA. We tested the hypothesis that the prevalence of SCI was significantly .39% in patients .18 years old with SCA.Due to the high age-dependent prevalence of SCI in children and adolescents with SCA, associated deficits in neuropsychometric performance, 5 the association of SCI with future overt stroke, 5 and the impact of these associated morbidities on health care outcomes in adults with SCA, including adherence to complex instructions associated with management of chronic illness, we elected to obtain, as part of routine clinical practice, magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) scans of the brain in adults with SCA. If SCI or cerebral vasculopathy is found via neuroimaging, we refer these adults for cognitive testing, neurology consultation, or both. We completed a retrospective chart review of adults with SCA (hemoglobin SS or hemoglobin S b zero [Sb 0 ] thalassemia) followed in the comprehensive sickle cell disease clinic, with surveillance MRI and MRA of the brain performed as part of standard-of-care assessment for SCI from 2011 to 2013. The cerebral MRIs and MRAs were rereviewed by 2 board-certified neuroradiologists for the purpose of this study. Consensus findings were recorded including presence of cerebral infarcts ($3 mm on T2-weighted images in 2 imaging planes), 6 intracerebral hemorrhage, aneurysms, 7,8 and cerebral vasculopathy 9,10 according to prior established criteria for MRI and MRA. If no neurologic concerns were reported in the medical record and the neurologic examination was normal, infarcts were judged to be silent. STATA version 13 (StataCorporation, College Station, TX) was used for all analyses. Patient characteristics were described by median and interquartile range (IQR) for continuous measures and by number and percent for categorical measures. A 2-sided P # .05 was considered statistically significant. This study was approved by the Vanderbilt University Institutional Review Board as a retrospective cohort analysis.The study population included 121 adults with SCA (hemoglobin SS or Sb 0 thalassemia) out of ;200 individuals with sickle cell disease that were followed in the clinic. Of these 121 individuals, 69 unselected adults underwent neuroimaging with brain MRI. Nine adults with SCA and overt strokes were excluded. The final study population included 60 adults with SCA and neuroimaging. Of note, a total of 52 individuals were excluded because they did not have neuroimaging, primarily because of failure...