Sickle cell disease (SCD) patients have a higher incidence of certain cancers, but no studies have determined the impact of cancer on survival among SCD patients. SCD patients (n = 6423), identified from state-wide hospitalisation data, were linked to the California Cancer Registry (1988-2014). Multivariable Cox proportional hazards regression was used to examine survival. Among SCD patients, a cancer diagnosis was associated with a 3-fold increased hazard of death. Compared to matched cancer patients without SCD, SCD was associated with worse overall survival, but not cancer-specific survival, suggesting that SCD cancer patients should be treated with similar therapeutic intent. Abstract source Full text

Objective: Growing literature has documented the clinical utility of neuropsychological evaluations for predicting functional outcomes, including reduced healthcare service utilization, in a variety of clinical samples. The present study investigates the relationship between the integration of clinical neuropsychology services into an existing outpatient sickle cell clinic and frequency of emergency department (ED) visits and hospitalizations for pain crises. Method: Participants included 144 adults diagnosed with sickle cell disease (SCD) who either underwent neuropsychological evaluation (NP+), including interview, neuropsychological testing, and feedback, or treatment as usual (NP-). Medical records were reviewed for a two-year period, one year prior to study enrollment (pre-assessment) and one year post-study enrollment (post-assessment), to track the number of ED visits and hospitalizations related to sickle cell pain crises. Results: When examining pain crises ED visits prior to and following neuropsychological evaluation, there was a significant decrease in ED visits for the NP + group, but no change for the NP - group. No significant changes in pain crises hospitalizations were observed for the NP + and NP - groups. For the NP + group, the decreased incidence of pain crises ED visits and hospitalizations was associated with an estimated total cost savings of $994,821. Discussion: Results highlight that integration of neuropsychology services into an existing outpatient sickle cell clinic may reduce healthcare costs, particularly use of pain crises ED services, for adults with SCD. Abstract source

Sickle cell trait (SCT) is unique among the carrier states that are identified during newborn screening. Unlike other heterozygous states for rare recessive diseases, SCT is exceedingly prevalent throughout regions of the world, making sickle cell disease one of the most common monogenetic diseases worldwide. Because of this high frequency, reproductive counseling is of paramount importance. In addition, unlike other carrier states, SCT appears to be a risk factor for several clinical complications such as extreme exertional injury, chronic kidney disease, and venous thromboembolism. Increasing knowledge about these clinical outcomes can help inform genetic counseling recommendations. Expanding research and clinical efforts are needed to ensure that the promises of modern and precision medicine can be delivered to the millions of SCT carriers and their children. Abstract source Full text

Objective: To compare pregnancy outcomes in women with sickle cell disease from recent deliveries with a similar group delivered earlier. Methods: During a 12-year period (2005-2016), data from pregnant women with hemoglobin SS or SC were collected from three university medical centers and compared with earlier studies (1979-2003) involving similar patients. The primary endpoints were maternal complications during pregnancy and newborn outcomes. Results: There were 278 patients in the control group (1979-2003) compared with 150 patients in the study group (2005-2016). Women in the study group were older (P < 0.0001) and of less parity (P =0.0001), and complications of preterm delivery, preeclampsia, and having a transfusion were similar between the two groups (P = 0.45, 0.95, and 0.49, respectively). Pain crises were more common in the study group (P = 0.02) as was cesarean section (P < 0.0001), but there was a reduction in pulmonary complications (P = 0.0002). Maternal mortality was uncommon (control group [N=4] vs study group [N=3], P = 0.40). Newborn statistics revealed a similar gestational age at delivery (37 weeks), and the incidence of intrauterine growth restriction, as well as 5-minute Apgar score <7 did not differ by group (P = 0. 91, 0.85, and 0.16, respectively). Infants in the study group were heavier on average by approximately 220 g (P = 0.02), whereas the neonatal death rate was low (control group [N=1], study group [N=2] P = 0.60). Conclusions: Recent pregnancy outcome statistics in women with sickle cell disease have not changed through the years. Innovative strategies to improve maternal and newborn outcomes among such patients are needed. Abstract source Full text

Background: Hydroxyurea is an effective treatment for sickle cell anemia, but few studies have been conducted in sub-Saharan Africa, where the burden is greatest. Coexisting conditions such as malnutrition and malaria may affect the feasibility, safety, and benefits of hydroxyurea in low-resource settings. Methods: We enrolled children 1 to 10 years of age with sickle cell anemia in four sub-Saharan countries. Children received hydroxyurea at a dose of 15 to 20 mg per kilogram of body weight per day for 6 months, followed by dose escalation. The end points assessed feasibility (enrollment, retention, and adherence), safety (dose levels, toxic effects, and malaria), and benefits (laboratory variables, sickle cell-related events, transfusions, and survival). Results: A total of 635 children were fully enrolled; 606 children completed screening and began receiving hydroxyurea at a mean (±SD) dose of 17.5±1.8 mg per kilogram per day. The retention rate was 94.2% at 3 years of treatment. Hydroxyurea therapy led to significant increases in both the hemoglobin and fetal hemoglobin levels. Dose-limiting toxic events regarding laboratory variables occurred in 5.1% of the participants, which was below the protocol-specified threshold for safety. During the treatment phase, 20.6 dose-limiting toxic effects per 100 patient-years occurred, as compared with 20.7 events per 100 patient-years before treatment. As compared with the pretreatment period, the rates of clinical adverse events decreased with hydroxyurea use, including rates of vaso-occlusive pain (98.3 vs. 44.6 events per 100 patient-years; incidence rate ratio, 0.45; 95% confidence interval [CI], 0.37 to 0.56), nonmalaria infection (142.5 vs. 90.0 events per 100 patient-years; incidence rate ratio, 0.62; 95% CI, 0.53 to 0.72), malaria (46.9 vs. 22.9 events per 100 patient-years; incidence rate ratio, 0.49; 95% CI, 0.37 to 0.66), transfusion (43.3 vs. 14.2 events per 100 patient-years; incidence rate ratio, 0.33; 95% CI, 0.23 to 0.47), and death (3.6 vs. 1.1 deaths per 100 patient-years; incidence rate ratio, 0.30; 95% CI, 0.10 to 0.88). Conclusions: Hydroxyurea treatment was feasible and safe in children with sickle cell anemia living in sub-Saharan Africa. Hydroxyurea use reduced the incidence of vaso-occlusive events, infections, malaria, transfusions, and death, which supports the need for wider access to treatment. Abstract source Full text

This study sought to examine if modern medical evaluations including newborn screening and early diagnosis along with better methods of disease control have improved rates of hearing loss in children with sickle cell disease (SCD). Audiometric and medical data for patients with SCD was obtained from the AudGen Database and analyzed for the presence of hearing loss, type of hearing loss, severity of hearing loss, and correlation with comorbid conditions. Children with sickle cell trait (SCT) were used as a comparison group. A total of 189 patients with SCD and 244 patients with SCT had sufficient audiologic data available. Hearing loss was present in 62% of children with SCD and 50% of children with SCT in the study population. Patients with SCD were significantly more likely than those with SCT to have a sensorineural component to their hearing loss (P<0.001, odds ratio: 2.41 [1.53 to 3.79]) and to have severe or profound hearing loss (P=0.02, odds ratio: 4.00 [1.14 to 14.04]). The true prevalence of hearing loss in children with SCD has not been established as routine screening is not being performed. Routine auditory testing should be done for these children to detect this loss before it impacts development. Abstract source

Dr. Orkin is David G. Nathan Distinguished Professor of Pediatrics at Harvard Medical School. Dr. Orkin completed his medical graduation from Harvard Medical School in 1972, followed by postdoctoral research at the National Institutes of Health and clinical training in pediatrics and hematology-oncology at Children's Hospital Boston and DFCI, where he joined the faculty in 1978. He is currently a Howard Hughes Medical Institute Investigator and was elected to the 2019-2020 Council of the National Academy of Medicine. Over the past decade, his laboratory has defined critical nuclear regulators of hematopoiesis. His work on the molecular pathology of inherited blood disorders also greatly improved the diagnosis and treatment of these conditions. Stuart Orkin's research focuses on stem cell biology, particularly the development and function of the blood system, the relationship between cancer and stem cells, and the mechanisms responsible for self-renewal of stem cells and the switch from fetal to adult hemoglobin.   Representative Publications: Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype Mathematical modeling of erythrocyte chimerism informs genetic intervention strategies for sickle cell disease Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing Medicine. Sickle cell disease at 100 years DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease Online profile

When she was growing up in St. Petersburg, Florida, Brandi Abernethy was so often sick from her illness that school officials demanded she be home-schooled through her middle and high school years. But Abernethy didn’t let that put a damper on her academic or civic achievements—or, for that matter, her social life. She graduated a semester early, all the while volunteering for her local Sickle Cell Association—at one point becoming the “poster child,” raising awareness about the disease throughout the community. She’s now fulfilling her dream to become a hematology-oncology nurse while raising her four-year-old son. Related story

Objective: Sickle cell disease (SCD) is a lifelong condition characterized by pain, which is associated with reduced health-related quality of life (HRQL). Data suggest that patients with SCD vary in how they cope and their neurocognitive abilities. This study aimed to characterize executive functioning and pain coping styles in children with SCD experiencing a range of pain frequency (i.e., chronic, episodic, and asymptomatic) and to examine whether executive functioning mediates the relationship between pain coping and HRQL. Method: Participants included 100 children and adolescents with SCD between the ages of 8 and 18 years (M = 13.53, SD = 2.8) and their parents who were recruited during outpatient SCD clinic visits in a children's hospital. Children completed questionnaires related to pain experience and pain coping. Parents completed questionnaires about demographic information, their child's executive functioning, and HRQL. Results: Pain intensity, executive dysfunction, and engagement in emotion-focused coping (i.e., internalizing/catastrophizing and externalizing) predicted poor HRQL. In addition, engagement in emotion-focused coping predicted executive dysfunction. Multivariate analysis of covariance revealed executive functioning did not differ based on pain frequency; however, executive functioning was a significant mediator that helped explain the relationships between distraction and emotion-focused coping techniques on HRQL. Conclusion: Findings support that executive functioning is an important factor in understanding the relationship between pain coping and HRQL in youth with SCD. Future research is warranted to examine the potential impact of executive functioning on the utility of interventions targeting adaptive pain coping in youth with SCD. Abstract source Full text

This interview study documented how individuals with sickle cell disease make decisions about who to talk with concerning their illness based on psychological and interpersonal issues that are important to them. Reasons for sickle cell disease disclosure to specific persons were self-related (receiving support, venting feelings), other-related (educating others about sickle cell disease, forewarning others about sickle cell disease-related problems, someone asked for information about the disease), or situational (mostly focusing on another person being physically close or available to talk to). Reasons for sickle cell disease nondisclosure to specific persons were self-related (fear of rejection, being stereotyped, maintaining privacy) or other-related (lack of support, not worrying someone). Abstract source Full text