A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx-SCD, n 5 199), and 64 non-Tx-SCD subjects to describe the frequency of ironrelated morbidity and mortality. Subjects recruited from 31 centers in the US, Canada or the UK were similar with respect to age (overall: 25 ± 11 years, mean ± SD) and gender (52% female). We found that Tx-SCD subjects were hospitalized more frequently compared with Thal or non-Tx-SCD (P < 0.001). Among those hospitalized, Tx-SCD adult subjects were more likely to be unemployed compared with Thal (RR 5 1.6, 95% CI 1.0-2.5) or nonTx-SCD (RR 5 3.1, 95% CI 1.3-7.3). There was a positive relationship between the severity of iron overload, assessed by serum ferritin, and the frequency of hospitalizations (r 5 0.20; P 5 0.009). Twenty-three deaths were reported (6 Thal, 17 Tx-SCD) in 23.5 ± 10 months of follow-up. Within the Tx-SCD group, those who died began transfusion (25.3 vs. 12.4 years, P < 0.001) and chelation therapy later (26.8 vs. 14.2 years, P 5 0.01) compared with those who survived. The unadjusted death rate in Thal was lower (2.2/100 person years) compared with that in Tx-SCD (7.0/100 person years; RR 5 0.38: 95% CI 0.12-0.99). However, no difference was observed when age at death was considered. Despite improvements in therapy, death rate in this contemporary sample of transfused adult subjects with Thal or SCD is 3 times greater than the general US population. Long term follow-up of this unique cohort of subjects will be helpful in further defining the relationship of chronic, heavy iron overload to morbidity and mortality. Am. J. Hematol. 82:255-265, 2007. V V C 2006 Wiley-Liss, Inc. Contract

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of Busulfan (13.2 mg/kg), Fludarabine (175 mg/m2) and Thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. Twenty-two patients (median age 22 years; range 17–36) were enrolled at 8 centers. Seventeen patients received marrow from an HLA-identical sibling donor and 5 patients received marrow from an 8/8 HLA-allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grade II-III acute GVHD (18%) and 6 developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1-year post-transplant. One patient who developed secondary graft failure survives disease-free after a second BMT. The one-year overall survival and event-free survival (EFS) are 91% (95% CI 68–98%) and 86% (95% CI, 63–95%), respectively, and 3-year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health-related quality of life were observed. The study satisfied the primary endpoint of 1-year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA-matched donor BMT with standard of care in adults with severe SCD (NCT02766465).

Patients with sickle cell disease frequently experience severe pain events that lead to unplanned healthcare utilization. Mobile health tools (mHealth) may help prevent these events by providing remote monitoring and self-management support. This article describes the feasibility of the Sickle cell disease Mobile Application to Record symptoms via Technology (SMART), an mHealth app developed to help sickle cell disease patients monitor and manage their day-to-day symptoms. Fifteen patients recorded their pain intensity using a paper visual analog scale (VAS) and then repeated this measurement using an electronic VAS pain measure on SMART. Patients continued using SMART to record clinical symptoms, pain intensity, location and perceived severity, and treatment strategies for at least 28 days. Patient median age was 29 years (range 16-54); 60.0% were male. There was a high intraclass correlation between pain measurements entered on the paper VAS and SMART on the iPhone and the iPad We found a strong association between patient perceived pain severity and pain intensity entries using SMART (b = 1.71; p < 0.01). Daily compliance with SMART entries was a mean 75.0%, with a high of 85.7% in week 1 and low of 57.9% in week 4; however, one-third (n = 5) of the patients were 100.0% compliant even in week 4. Patients who were over age 35 or used an iPad for the study had the highest compliance rates. This study showed that SMART is a useable and feasible method for monitoring daily pain symptoms among adolescents and adults with sickle cell disease-related pain.

The prevalence of objective insomnia assessed by polysomnography was higher than the prevalence of subjective insomnia according to DSM-IV-validated questionnaires. Clinical trials.gov ID: NCT00596713.