Severe Painful Crises Research Articles

Association of Clinical and Paraclinical Factors with Pain Crisis Severity in Sickle-Thalassemia Patients in Iran

Objectives: This study aimed to evaluate the effects of several factors, including hospitalization frequency, inflammatory and hemolytic markers, and the numbers of blood transfusions and crises, on the severity of pain crises in sickle-thalassemia patients. Methods: Of all patients visiting hematologists in university-affiliated hospitals and clinics, only 75 sickle cell disease (SCD) and sickle-thalassemia patients met the inclusion criteria for this study. Disease severity was measured based on pain crises per year and laboratory markers, including hemolytic and inflammatory indicators, outpatient or inpatient status, the number of hospital admissions, and the number of blood units transfused over one year. Results: In sickle cell patients, a significant correlation was observed between hospital admission and WBC (0.01), ALP (0.001), MCHC (0.001), ferritin (0.021), and ESR (0.006). Additionally, pain crises were positively correlated with transferrin saturation (TS) (+0.28) and the number of transfused blood units (+0.49) and negatively correlated with Hb (-0.30) and total iron binding capacity (TIBC) (-0.23). Blood unit transfusions showed a positive correlation with serum iron (+0.44), RDW (+0.36), ferritin (+0.39), pain crises (+0.49), and TS (+0.49), along with a negative correlation with Hb (-0.75) and MCHC (-0.33). When categorizing pain crises into two groups, patients experiencing more frequent crises generally exhibited lower hemoglobin levels and a higher number of blood units transfused. Hemoglobin also showed a significant negative correlation with lactate dehydrogenase (LDH) level in both groups: -0.604 (P = 0.005) in patients with ≥ 3 crises per year and -0.368 (P = 0.006) in patients with < 3 crises per year. Patients with hemoglobin levels of 7.5 or higher tended to maintain an LDH level below 1000. Among patients referred with pain crises, hemoglobin was negatively correlated with hemolytic markers such as LDH (-0.41) and retic (-0.29). Conclusions: Hemoglobin and LDH can serve as follow-up markers, as they are routinely measured in all sickle cell patients and, in this study, hemoglobin levels of 7.5 or higher and LDH levels below 1000 were associated with fewer and less severe pain crises. Regular monitoring of hemolytic markers may help in pain crisis prevention, as this study found that hemolytic crises frequently coincided with pain crises. Further research is needed to provide conclusive evidence in this area.

Navigating the nexus of personalized medicine and healthcare management: Advancing paediatric pain management modalities in sickle cell disease through thematic analysis for ages 1–12

ABSTRACT Sickle cell disease (SCD) affects millions of people and is a significant public health concern due to the severe pain crises it causes, often requiring emergency care and leading to hospitalization. Effective pain management strategies are crucial to improving the quality of life of children with SCD, particularly those aged 1 to 12 years, who are especially vulnerable. This study evaluates the effectiveness and suitability of various healthcare management strategies, with a specific focus on pain management modalities for this paediatric population. Through a thematic analysis of 36 articles from major healthcare databases, five key themes were identified: cognitive behavioral therapy (CBT) and complementary alternative medicine (CAM), digital and technological pain management methods, pain medications, individualized pain plans and enhancement strategies aimed at improving protocols. The findings highlight critical opportunities to advance pain management approaches and address current care gaps. The study underscores the importance of integrating parents and caregivers into the care process and addressing health inequalities that affect treatment outcomes. Evidence reveals that existing research on paediatric SCD pain management remains inadequate, and future studies are urgently needed to establish clear guidelines that improve treatment efficacy and translate into actionable evidence-based practices for this vulnerable population.

Urinary Biomarkers for the Assessment of Acute Kidney Injury of Pediatric Sickle Cell Anemia Patients Admitted for Severe Vaso-occlusive Crises.

Sickle cell nephropathy is a progressive morbidity, beginning in childhood, which is incompletely understood partially due to insensitive measures. We performed a prospective pilot study of pediatric and young adult patients with sickle cell anemia (SCA) to assess urinary biomarkers during acute pain crises. Four biomarkers were analyzed with elevations potentially suggesting acute kidney injury: (1) neutrophil gelatinase-associated lipocalin (NGAL), (2) kidney injury molecule-1, (3) albumin, and (4) nephrin. Fourteen unique patients were admitted for severe pain crises and were found to be representative of a larger SCA population. Urine samples were collected at the time of admission, during admission, and at follow-up after discharge. Exploratory analyses compared cohort values to the best available population values; individuals were also compared against themselves at various time points. Albumin was found to be moderately elevated for an individual during admission compared with follow-up ( P = 0.006, Hedge g : 0.67). Albumin was not found to be elevated compared with population values. Neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and nephrin were not found to be significantly elevated compared with population values or comparing admission to follow-up. Though albumin was found to be minimally elevated, further research should focus on alternative markers in efforts to further understand kidney disease in patients with SCA.

Sickle Cell Disease (SCD) Burden on Patients Treated With Hydroxyurea (HU): Results from the Real-World Assessment Survey for SCD in Saudi (ROARS)

The prevalence of SCD in the Kingdom of Saudi Arabia (KSA) is one of the highest in the world with up to 2.6% of the population affected. The Real-World Assessment Survey for Sickle Cell Disease in Saudi (ROARS) was conducted to evaluate the impact of SCD on the quality of life (QoL) of this population. Here, we present data on the QoL burden experienced by patients with SCD in KSA treated with hydroxyurea (HU). Between September and December 2021, patients in KSA with SCD (age: 5-65 years) were surveyed (caregivers were surveyed for patients 5-14 years) using structured, bilingual ROARS questionnaires (English/Arabic) through personal quantitative web-assisted telephone interviews. The survey includes the Patient-Reported Outcomes Measurement Information System (PROMIS) global health domain, a validated tool for assessing QoL among SCD patients and caregivers. The survey evaluated topics such as the impact of SCD on QoL, symptoms, impact of SCD on productivity at work/school, and treatment goals. A total of 1011 responses to the survey were collected; of these, 32.3% (n=327) of patients were currently being treated with HU (47% of adult and 17% of pediatric patients surveyed) and are the focus of this analysis. Amongst these patients, the median age (range) was 25 (5-83) years. Patients were responsible for reporting their SCD genotype: 58% of respondents were diagnosed with HbSS (n=189), 26% with HbSC (n=86), 2% with HbSβ0 thalassemia (n=8), and 5% with HbSβ+ thalassemia (n=15). Overall, 35% (adults, n=84; pediatric n=25) of patients in the eastern province were treated with HU, 27% (adult, n=71; pediatric, n=17) in the western province, 24% (adult, n=55; pediatric, n=24) in the southern province, and 14% (adult, n=29; pediatric, n=22) in the central province. Among HU-treated patients, 64% reported never ceasing/stopping treatment, 21% rarely ceased/stopped treatment and 15% of patients cease/stop treatment sometimes, often, or all the time. The most common reason for patients ceasing/stopping treatment was forgetting to take their medication (79%). Of patients who cease/stop treatment sometimes, often, or all the time (n=48), 17% of these stated that their medication was not available while 4% could not afford their medication. The mean (SD) number of VOCs reported by HU-treated patients in the 12 months prior to survey completion was 4.6 (4.09), while 32% (n=104) of these patients reported experiencing ≥5 VOCs in the same period. The most common SCD symptoms (other than VOCs) experienced by HU-treated patients were bone ache (reported by 92% of respondents), fatigue/tiredness (85%), headache (79%), anxiety (61%), joint stiffness (56%) and numbness/tingling (51%). Most HU-treated patients reported poor/fair or good health for all QoL metrics assessed (Figure 1). Almost half of patients (49%) reported that their SCD was impactful/extremely impactful on their emotional wellbeing. Of those treated with HU, 71% of patients reported that HU is effective in treating their SCD symptoms. However, 84% of patients report a desire for alternatives to their current pain management medication while 72% report concerns about the long-term side effects of HU. The most important treatment goals for these patients were improvement in quality of life (82%), improvement in overall symptoms (79%), and reduction in the number of severe pain crises and increase in the number of days free from severe pain crises (79%). A total of 48% of HU-treated patients were bothered by limitations in performing everyday activities; 48% and 55% of patients also reported that their SCD has prevented them from progressing in their career or education, respectively. Patients treated with HU reported missing a mean (SD) of 6.9 (10.4) hours of work in the 7 days prior to survey completion because of their SCD. Access to HU treatment continues to be a challenge, with approximately 70% of patients surveyed not receiving HU. Despite the observed clinical benefit in symptom control, patients receiving HU continue to experience disease burden including substantial impact on QoL and productivity at work/school (as evident from the treatment goals identified by patients). These data highlight the necessity of optimizing HU accessibility and treatment strategies to improve patient outcomes. These data also illustrate the need for novel therapeutic options and management strategies for patients with SCD to target patient-reported treatment goals. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pseudoprogression and Sarcoidosis-like Phenomena after CART-Cells and Bispecific Antibodies in Multiple Myeloma

Introduction: CAR T-cell therapy is establishing itself as a new standard of care in relapsed and refractory multiple myeloma (RRMM). Yet, there are a number of open issues including the lack of data on optimal follow-up assessments post CAR T therapy. Appreciating the high incidence of extramedullary lesions and patchy disease patterns seen in the RRMM setting, whole body 18F-Fluorodeoxyglucose (FDG) PET/CT imaging is increasingly used. Whether FDG is the best tracer in this setting has yet to be determined, as the technique is being based not only on the quantification of increased glucose uptake by tumor cells but also by others such as inflammatory cells. A phenomenon linked to this issue is pseudoprogression, which refers to an increase in the target lesion size due to influx of immune cells that may be misinterpreted as disease relapse. Pseudoprogression is a well-known event after checkpoint blockade therapy, seen in up to 10% of patients with solid cancers. Whether myeloma patients treated with CAR T or bispecific antibodies are at risk for pseudoprogression is, to the best of our knowledge, unknown. Methods: We present a case study of a RRMM patient who experienced pseudoprogression twice during his course of disease treatment that included BCMA CAR T cells Idecabtagene vicleucel and GPRC5DxCD3 bispecific antibody talquetamab. We performed a comprehensive molecular analysis including single cell RNAseq from bronchoalveolar lavage as well as PET imaging using the three PET tracers 18F-FDG, 68Ga-DOTATOC, and 68Ga-Pentixafor (binds to CXCR4) to unravel the biology underlying pseudoprogression in this case. Results: A 61-year-old Caucasian male was diagnosed with biopsy-proven pulmonary MM and treated with BCMA targeting CAR T cells in his 4th line of therapy. Ten days after CAR T infusion, the patient started violent coughing and a FDG-PET revealed full resolution of focal bone lesions but disseminated FDG uptake at the lung and mediastinal lymph nodes reminiscent to sarcoidosis. We performed a PET using 68Ga-DOTATOC that usually detects sarcoidosis with high sensitivity and specificity, which was negative. Negative results were also seen for 68Ga-Pentixafor, which is an alternative tracer to FDG in the detection of MM. Bronchoalveolar lavage (BAL) along with endobronchial ultrasound guided biopsy was done, showing noncaseating granuloma formation in the biopsy without evidence of residual MM cells. Single cell RNA-seq on the BAL sample revealed CD4-positive T cells exhibiting simultaneous expression of genes associated with Th1 T-cells (TBX21, CXCR3, IFNG, TNF) and genes associated with Th17 T-cells (RORC, IL23R, CCR6, CCL20, KLRB1), indicative for a Th1-polarized Th17 phenotype. Furthermore, these cells expressed IL4I1, ABCB1, and CSF210-12 , while IL17A, IL17B, IL17E (IL25), and or IL17F was not expressed, highlighting presence of Th17.1 cells. This cell type has been described to be pro-inflammatory and pathogenic and implicated in several auto-immune diseases, including sarcoidosis. Together, our data suggest a non-infectious, Th17.1 T-cell driven sarcoidosis-like auto-immune phenomenon located in the lungs following anti-BCMA CAR T-cell therapy. Respiratory symptoms completely resolved following high-dose inhalative steroids. The patient relapsed from complete remission (CR), and FDG PET showed the known sarcoidosis-like pulmonary changes, but also revealed a number of new soft-tissue lesions, suspicious for extramedullary relapse. In contrast to the previous scans, these lesions were CXCR4 positive, suggesting a role of using multiple PET tracers in this setting. Later, the patient was enrolled on a trial investigating talquetamab. One week after dosing, the patient experienced severe pain crisis and a diffusion-weighted MRI revealed increase in size of multiple extramedullary lesions, but no new lesions. M- protein levels were decreasing at that time suggesting either mixed response or pseudoprogression. The patient was treated with painkillers and all lesions disappeared on a follow-up scan 6 weeks later, confirming pseudoprogression, and he is in an ongoing CR for 6 months at the time of writing. Conclusion: We present two educating episodes of pseudoprogression in one patient following immune oncology drugs in MM. While one event was transient and self-limiting, the pulmonary manifestations were similar to sarcoidosis and required treatment with steroids.

Daily Users of Marijuana with Sickle Cell Disease Report More Severe Pain Crisis Yet Have Similar Rates of Admission to Non-Users

▪Introduction: Pain in sickle cell disease (SCD) starts as episodes of recurrent pain and progresses to chronic pain with age. Pain is typically treated with opioids which are often insufficient. One reason for this may be that opioids likely do not effectively treat neuropathic or inflammatory pain in SCD. Cannabinoids, such as marijuana, alleviate neuropathic pain and reduce inflammation. Our SCD patients report marijuana improves their pain and studies in murine models of SCD show cannabinoids reduce mast cell activation, inflammation, and hyperalgesia. Medical marijuana is now legal in 28 states and 4 of them list SCD as a qualifying condition. However, there are minimal data on the use of marijuana in SCD. Thus, we performed a pilot study of adults with SCD who use daily marijuana. Our hypothesis was that daily marijuana users would have worse pain scores from non-daily users which drives their drug use. Our secondary hypotheses were that daily marijuana users may have decreased levels of opioid use, hospital utilization, quality of life measures (QoL) or inflammation.Methods: We conducted a cross-sectional pilot study of adults living with SCD who do and do not use daily marijuana. Subjects were enrolled at scheduled clinic visits, any subject not at their heathy baseline was excluded. Subjects were asked if they had used marijuana in the past 30 days, reasons for use, and rate of use. Subjects who reported daily use were compared to those who used less often or reported no marijuana use. Our primary outcome was pain as defined by Adult Sickle Cell Quality of Life measurement information system (ASCQ-Me) pain domains. ASCQ-Me has separate domains for pain crisis frequency, pain crisis severity, and 7-day pain interference which allows for measurement of both crisis pain and chronic pain. Our secondary outcomes were differences in hospital utilization, opioid use, QoL measures included in ASCQ-ME: sleep, stiffness, social impact and emotional impact, Patient Reported Outcome Measurement Information System domains for nausea and anxiety, and inflammation as demonstrated by WBC and platelet counts, C reactive protein (CRP), markers of mast cell and neutrophil activation and endothelial damage. Hospital utilization (total annual admissions and emergency room visits) was assessed by medical record review over a one-year period (1/1/2016 to 12/31/2016). Weekly opioid use was estimated by review of dispensed prescriptions using the Connecticut Prescription Monitoring Program converted into average weekly oral morphine equivalents. Flow cytometry was performed for levels of: neutrophils and activated neutrophils, monocytes, non-classical and inflammatory monocytes, circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs). The R statistical software program was used to perform t-tests and Wilcoxon rank-sum tests where normality was not met to compare daily users to non-daily users. Significance was set at p<0.05.Results: We enrolled 29 subjects,16 (55%) of whom reported marijuana use in the past 30 days and of those 6 (21%) reported daily marijuana use. Pain relief was endorsed as a reason for marijuana use in 93% of users and 100% of daily users. There was no difference in mean age (32.0 SD 8.6 vs 32.4 SD 12.6 years p=1.0) or gender (% female: 67 vs 52% p=0.7) between groups. Daily marijuana users had higher pain crisis severity scores (61.7 vs 50.0 p=0.03). There was no significant difference in scores for pain crisis frequency, pain interference, or other QoL measures (Table). Daily users had similar median annual admissions and emergency room visits to non-daily users (1.0 (IQR 0.25-1.0) vs 2.0 (IQR 0 - 5.0) admissions p=0.3; 1.0 (IQR 0.25-1.75) vs 0 (IQR 0-1.5) ED visits p=0.6) and used similar doses of weekly opioids (274.5 [IQR 91.5-3447.9] vs 28.6 [IQR 3.03-135.6] mg weekly po morphine equivalents p=0.5). There were no differences in CRP, CBC, CECs or EPCs, or in levels of all neutrophils and monocytes types.Conclusion: In our pilot study, we found daily marijuana users reported more severe pain crisis, but had similar rates of hospital utilization and similar amounts of opioids dispensed. We posit that patients with more severe pain crisis may use daily marijuana to effectively treat their pain allowing them to have similar hospital and opioid utilization to those with less severe pain. Larger prospective studies should be performed to test these hypotheses. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

CRISPR/Cas9 Gene-Edited Hematopoietic Stem Cell Therapy for Sickle Cell Disease

Sickle cell disease (SCD) is a life-threatening hereditary disorder that affects thirty million individuals worldwide. The disease results from a single amino acid change in the β-globin gene, which causes polymerization of hemoglobin and deformation of red blood cells, leading to vaso-occlusion, severe pain crisis, multi-organ dysfunction, and ultimately reduction of lifespan in affected individuals. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative therapy for SCD, yet its success is limited by donor availability and high risk of graft-versus-host disease. Increasing expression of fetal γ-globin in adults is an accepted therapeutic strategy for treating SCD. Supporting this approach are GWAS studies that have identified genetic loci, including within the BCL11A gene, that are associated with elevated fetal hemoglobin (HbF) and mitigated disease severity. Leveraging CRISPR/Cas9 genome editing technology, we aim to develop a safe and curative therapy by autologous, genome-modified HSCT leading to sustained generation of HbF-containing, functional red blood cells. Guide RNAs (gRNAs) targeting the erythroid-specific enhancer region of the BCL11A gene were assayed in CD34+ hematopoietic stem and progenitor cells (HSPCs), and one gRNA was selected for in vivo evaluation based on editing efficiency and functional potency. We achieved approximately 80% target site editing in human CD34+ HSPCs and 65% in CD34+CD38-CD90+CD45RA-CD49f+ defined LT-HSCs. Potential off-target editing sites were identified by two approaches: in silico prediction and unbiased oligo insertion method. These sites were then directly interrogated in HSPCs by targeted PCR amplification and NGS analysis, and to date our selected gRNA had zero validated off-target sites. In addition, HSPC composition was not altered following electroporation of ribonucleoprotein complex, and cells were capable of in vitro expansion and multi-lineage differentiation as measured by CFU assays. Upon in vitro differentiation into the erythroid lineage, edited cells demonstrated ~40% reduction in BCL11A mRNA with a corresponding two-fold increase in γ-globin transcript, translating to a 30-40% increase in HbF positive cells. Most importantly, when CD34+ cells derived from SCD patients were gene-edited and differentiated into erythroid cells, a similar editing efficiency and increase in HbF positive cells was observed. To evaluate whether gene editing alters the self-renewal, engraftment or lineage differentiation capacity of HSCs, gene-edited HSPCs were transplanted into NOD- scid IL2rγnull (NSG) mice to assess reconstitution of the hematopoietic system. Mice displayed 30-40% human CD45+ cell engraftment and multi-lineage reconstitution at 16 weeks following transplantation. When long-term engrafted bone marrow cells were harvested from the recipients and differentiated into erythroid cells in vitro, gene-edited bone marrow cells produced significantly higher numbers of HbF positive cells compared to mock-edited bone marrow cells. These data support the development of autologous genome-modified HSPC transplantation as a novel cell therapy for SCD. DisclosuresYu:Novartis Institutes for BioMedical Research: Employment. Liu:Novartis Institutes for BioMedical Research: Employment. Curran:Novartis Institutes for BioMedical Research: Employment. Zhang:Novartis: Employment. Snead:Novartis: Employment. Schmedt:Novartis: Employment. Yang:Novartis Institutes for BioMedical Research: Employment. Lin:Novartis: Employment. Tschantz:Novartis Institutes for BioMedical Research: Employment. Quinn:Novartis Institutes for BioMedical Research: Employment. Russ:Novartis: Employment. Clarkson:Novartis: Employment. Janiak:Novartis: Employment. Stewart:Intellia Therapeutics: Employment. Mulumba:Intellia Therapeutics: Employment. Lescarbeau:Intellia Therapeutics: Employment. Murray:Intellia Therapeutics: Employment. Seitzer:Intellia Therapeutics: Employment. Strapps:Intellia Therapeutics: Employment. Huang:Intellia Therapeutics: Employment. Sloan:Intellia Therapeutics: Employment. Mickanin:Novartis: Employment. Klickstein:Novartis: Employment. Stevenson:Novartis: Employment.

Sickle cell disease and the adherence to guidelines for the use of blood transfusions in Duhok, Kurdistan, Iraq

Background and objective: One of the important health problems in Duhok city, Iraqi Kurdistan Region, is sickle cell disease. Blood transfusion remains a significant therapeutic intervention in patients with sickle cell disease that reduces complications related to vaso-occlusions. This study aimed to assess compliance to guidelines for the use of blood transfusionsin Duhok, Kurdistan, Iraq. Methods: This is a cross-sectional study that included 135 patients with sickle cell disease registered at Jeen center of pediatric hematological diseases in Duhok, Kurdistan, Iraq. Between April 1st and July 31st, 2019, 205 medical visits of sickle cell disease were registered. Every patient was evaluated to record the clinical setting and explanations behind visiting and indications for transfusion. Results: Of 135 patients,65.9% had sickle cell anemia (HbSS disease), 33.3% had sickle beta thalassemia, and one patient (0.7%) had Sickle/D disease. A total of 205 medical visits of sickle cell disease were registered with 84 blood transfusion decisions. The most common indicated guideline reasons for transfusion were symptomatic anemia and acute hemolytic crisis with a drop of hemoglobin &gt;2 g/dl below steady state hemoglobin and severe painful crisis only accounted for 38.1%. Conclusion: In this study of patients with sickle cell disease, most blood transfusions were not indicated according to the transfusion guidelines (British Committee for Standards in Haematology – BCSH, 2017). Keywords: Transfusion guidelines for sickle cell disease (BCSH 2017); Sickle cell disease; Iraq.

Evaluation of sleep quality and restless legs syndrome in adult patients with sickle cell anemia.

To determine the prevalence of poor sleep quality and RLS in adult patients with sickle cell anemia (SCA). The second aim was to identify the risk factors for RLS and impairment of sleep quality in SCA patients. Patients at least 18years old, with hemoglobin electrophoresis confirmation of sickle cell disease, were included. Restless legs syndrome was diagnosed according to the International Restless Legs Syndrome Study Group criteria. The sleep quality of the patients was determined using the Pittsburgh Sleep Quality Index (PSQI) scale. The Epworth Sleepiness Scale (ESS) was used to assess excessive daytime sleepiness. Of 72 patients enrolled in the study, the median totalPSQI score was 5 (R 1-17). The totalPSQI score was significantly associated with increased age and number of acute severe or extremely severe painful crises during the previous year (p< 0.001, r= 0.45; p= 0.013, r= 0.291 respectively). Of 72 patients, 13 (18%) had RLS and 11 (15%) had excessive daytime sleepiness. The presence of RLS was significantly associated with increased age (p= 0.004). The presence of RLS was not associated with fetal hemoglobin, hemoglobin, hematocrit, or ferritin levels (p> 0.05 for all). The prevalence of RLS among this sample ofadult patients with sickle cell anemia was much higher than that previously reported for the general Turkish population. The presence of RLS was an important cause of sleep disturbance in theseadult patients with SCA.

Phytomedicines (medicines derived from plants) for sickle cell disease.

Sickle cell disease, a common recessively inherited haemoglobin disorder, affects people from sub-Saharan Africa, the Middle East, Mediterranean basin, Indian subcontinent, Caribbean and South America. It is associated with complications and a reduced life expectancy. Phytomedicines (medicine derived from plants in their original state) encompass many of the plant remedies from traditional healers which the populations most affected would encounter. Laboratory research and limited clinical trials have suggested positive effects of phytomedicines both in vivo and in vitro. However, there has been little systematic appraisal of their benefits. This is an updated version of a previously published Cochrane Review. To assess the benefits and risks of phytomedicines in people with sickle cell disease of all types, of any age, in any setting. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, the International StandardRandomised Controlled Trial NumberRegister (ISRCTN), the Allied and Complimentary Medicine Database (AMED), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Dates of most recent searches: Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Trials Register: 17 March 2020; ISRCTN: 19 April 2020; AMED: 18 May 2020; ClinicalTrials.gov: 24 April 2020; and the WHO ICTRP: 27 July 2017. Randomised or quasi-randomised trials with participants of all ages with sickle cell disease, in all settings, comparing the administration of phytomedicines, by any mode to placebo or conventional treatment, including blood transfusion and hydroxyurea. Both authors independently assessed trial quality and extracted data. Three trials (212 participants) of three phytomedicines: Niprisan® (also known as Nicosan®), Ciklavit® and a powdered extract of Pfaffia paniculata were included. The Phase IIB (pivotal) trial suggests that Niprisan® may be effective in reducing episodes of severe painful sickle cell disease crisis over a six-month period (low-quality evidence). It did not appear to affect the risk of severe complications or the level of anaemia (low-quality evidence). The single trial of Cajanus cajan (Ciklavit®) reported a possible benefit to individuals with painful crises, and a possible adverse effect (non-significant) on the level of anaemia (low-quality evidence). We are uncertain of the effect of Pfaffia paniculata on the laboratory parameters and symptoms of SCD (very low-quality of evidence). No adverse effects were reported with Niprisan® and Pfaffia paniculata (low- to very low-quality evidence). While Niprisan® appeared to be safe and effective in reducing severe painful crises over a six-month follow-up period, further trials are required to assess its role in managing people with SCD and the results of its multicentre trials are awaited. Currently, no conclusions can be made regarding the efficacy of Ciklavit® and the powdered root extract of Pfaffia paniculata in managing SCD. Based on the published results for Niprisan® and in view of the limitations in data collection and analysis of the three trials, phytomedicines may have a potential beneficial effect in reducing painful crises in SCD. This needs to be further validated in future trials. More trials with improved study design and data collection are required on the safety and efficacy of phytomedicines used in managing SCD.

Daily Cannabis Users with Sickle Cell Disease Show Fewer Admissions than Others with Similar Pain Complaints.

Introduction: Previous studies have shown that cannabis use is common in adults with sickle cell disease (SCD), and that many patients report using cannabis to treat pain. Methods: We performed a cross-sectional study of adults with SCD and compared daily users of cannabis with others using validated patient-reported measures of pain and quality of life as well as opioid and health care utilization. Results: Daily cannabis users with SCD had worse pain episode severity scores than others (56.7 vs. 48.8, p=0.02) yet had 1.8 fewer annual admissions (p=0.01) and 1.2 fewer annual emergency room (ER) visits (p=0.01), and similar amounts of opioids dispensed to others after matching for age, gender, SCD genotype, hydroxyurea use, and pain impact scores. Conclusions: We show that people with SCD with more severe pain crisis are more likely to use daily cannabis, yet have lower rates of hospital admission and ER use as compared with others with similar disease severity and pain impact. Randomized controlled trials should be performed.

Blood Transfusion Frequency and Indications in Yemeni Children with Sickle Cell Disease.

Background Blood transfusion is an essential component in the care of patients with sickle cell disease (SCD), but it might be associated with serious acute and delayed complications. This study was aimed to describe red cell transfusion patterns and indications among hospitalized SCD children in a low-resource setting. Patients and Methods. A retrospective, descriptive study of all children (≤16 years) with SCD who received blood transfusion therapy during their hospital admissions in the pediatric department at Al-Sadaqa Teaching Hospital in Aden, Yemen, for a period of one year. Results Out of 217 hospitalized children with SCD, 169 (77.9%) were transfused and received 275 RBC transfusion episodes. The mean age of transfused children was 6.9 ± 4.6 years and 103 (60.9%) were males, with a male/female ratio of 1.6 : 1 (p=0.004). Hemoglobin (Hb) levels were significantly lower in the transfused than in the nontransfused (Hb 5.5 ± 1.5 vs. 7.7 ± 1.5 g/dL, p=0.03). Pretransfusion Hb levels were ˂7.0 g/dL in 86.2% and ˂5.0 g/dL in 39.3% of patients. Single transfusion was given to 122 (72.2%) and 5 or more transfusions in 9 (4.15%) of patients on different occasions. Simple (top-up) transfusion was used in all transfusion events. Commonest indications for transfusion were anemic crises (41.1%), vasoocclusive crises (VOC) (13.8%), VOC with anemic event (11.3%), acute chest syndrome (8.7%), and stroke (7.3%). Conclusion Intermittent blood transfusion remains a common practice for the management of children with acute SCD complications. Main indications were acute anemic crises, severe pain crises, ACS, and stroke. In limited resource settings, such as Yemen, conservative transfusion policy appears to be appropriate.

Assessing Feasibility of a Focused Geriatric Assessment in Older Adults with Sickle Cell Disease to Address Functional Risk Factors for Morbidity and Mortality

Background During the last five decades the life expectancy for people living with sickle cell disease (SCD) has improved markedly, with median survival of 61 years in recent cohorts enrolled from academic centers. Older adults with SCD (defined herein as age ≥ 50 years) make up 13% of the adult population at four major academic medical health systems in North and South Carolina. As this population continues to grow, more data are needed to guide medical management appropriate to their needs, as a lifetime of vaso-occlusion often leads to functional decline and premature development of complications seen in geriatric populations. There are no validated assessment tools and interventions to improve physical function in older adults with SCD. In this study we evaluated the feasibility of a focused geriatric assessment (FGA) for older adults with SCD. Methods Twenty adults with SCD ≥ 50 years old were enrolled in a prospective cohort study. Measures previously validated in the oncology FGA were included and enriched with additional physical and cognitive functional measures. Activity monitoring was performed for 7 days using the Actigraph wT3X-BT, and biomarkers were collected at each study visit (baseline, 10-20 days after a hospitalization [for those who experienced a hospitalization during the study period] and 12-month after baseline). The primary endpoint was the proportion of subjects who complete the assessment. Secondary endpoints were duration of the FGA, proportion who completed the activity monitoring and lab collection, and acceptability. Results Twenty-one of 25 older adults approached for the study consented. Nearly all (20/21, 95%) completed the FGA. One was removed after missed study visits. The median duration of the assessment was 97 minutes (range 73-175 minutes), and there were no adverse events. The mean age was 57 years (range 50-71), 50% (10) were female, 30% (6) were on disability and 50% (10) were working. 45% (9) were former smokers but only 5% (1) were current smokers (Table). On the acceptability survey, 95% (19) reported the length of the assessment as appropriate. 10% (2) subjects reported a portion of the Montreal Cognitive Assessment (MoCA) as difficult. No subject found the questions upsetting, and 2 subjects reported that they would remove redundant questions. All subjects had a Karnofsky Performance Score of at least 80% and were able to complete activities of daily living. A third (35%) had been admitted in the last 6 months, and most (75%) had had severe pain crises at home that limited their activity. 40% (8) had &amp;gt; 4 severe crises at home in the last 6 months. The mean usual gait speed was 1.14 m/sec (range 0.90-1.50) (Figure). Mean Timed Up and Go (TUG) was 10.1 seconds (range 7.7-14.0). Two (10%) subjects had a TUG consistent with increased fall risk (≥ 12 seconds). Mean grip strength of the dominant hand was 39 kg (range 22-54 kg) for males and 25 kg (range 20-34 kg) for females, which is 38% and 43% lower than expected for age and gender. Mean six-minute walk (6MW) was 465m for males and 499m for females, which is 22% and 4% lower than expected for age/gender/height/weight. In the 17 subjects with heart rate recovery (HRR) recorded after 6MW, the mean HRR at 1 minute (HRR1) was 20 bpm (range 0-46). 31% of tested subjects had a HRR1 consistent with impaired HRR (12 bpm or fewer). HRR negatively correlated with age (HRR1 B=-1.1; 95% CI -0.2 - -2; p&amp;lt;0.05). Half of the subjects had mild cognitive impairment (MoCA score &amp;lt; 26). MoCA scores correlated with literacy testing (B= 0.39; 95% CI 0.10-0.68; p=0.02). The first 12 subjects wore the activity monitor 6 days (range 4-8 days) for an average of 15 hours a day. Average activity was sedentary for 7 hours (47%), light 7.5 hours (50%), and moderate 1 hour (7%) per day. There was a median of 7070 steps/day. Conclusions We found FGA to be feasible, acceptable, and safe. The duration of the FGA in our population was 3 times longer than the FGA for oncology. One of our most remarkable findings is that the older adults with SCD in this study have a physical function similar to non-SCD adults over the age of 80. They also demonstrate impaired HRR, an independent predictor of mortality in the elderly. After completion of the 12-month follow-up assessments, we will develop a briefer assessment to be evaluated in a larger study. Future steps will be to determine if FGA can predict outcomes such as risk of hospitalization and mortality and to develop interventions to improve these outcomes. Disclosures Strouse: Global Blood Therapeutics: Consultancy.

PF744 SPECTRUM OF PARVOVIRUS B19 INFECTION IN CHILDREN WITH SICKLE CELL DISEASE: ATYPICAL PRESENTATIONS

Background:Human Parvovirus B19 (P‐B19) infection is known to cause aplastic crisis in sickle cell disease (SCD) patients. However, few studies have reported rare unusual complication of Parvovirus in SCD.Aims:To describe the demographic and clinical characteristics of Parvovirus B19 infection in hospitalized children with SCD admitted to Sultan Qaboos Universirty Hospital (SQUH) throughout the period (2009–2018), with special emphasis on atypical presentations.Methods:Descriptive retrospective study.Results:Out of 4688 admission episodes of pediatric patients with SCD throughout the duration of study, 108 patients (61 males &amp; 47 females) were diagnosed with Parvovirus B12 infection evidenced by positive PCR, with an age ranging from 18 months to 13.5 years. Parvovirus B19 infection accounts for 2.3% of the total admissions in our institution. It is the 4th commonest cause of hospitalizing children with SCD, just after painful crisis, acute chest syndrome, and fever without focus respectively. Out of the 108 cases, 94 children presented with isolated classical aplastic (erythroblastopenic) crisis, associated with variable grades of fever +/‐ joint pains. The majority of patients required transfusion once, although 20 of them needed twice or more transfusions. Atypical presentations were encountered in 14 patients (12.9%). The commonest is splenic sequestration coupled with aplastic crisis and marked reticulocytopenia (12 cases). The first two cases were siblings diagnosed in 2010. Since then, this complication has been increasingly recognized in our patients and we have noted a familial tendency to develop Parvovirus B19‐induced acute splenic sequestration, indicating a possible genetic predisposition to this complication, which is seen in our cohort in a much higher frequency compared to the published literature.Severe Parvovirus B19‐induced bone marrow failure was seen in a 7 year‐old male patient. This boy developed marked pancytopenia associated with protracted high grade fever, acute chest syndrome and severe painful crisis. The only positive culprit was Parvovirus B19 which was persistently positive with a very high viral load detected with PCR. He required multiple top ups &amp; exchange transfusions. Ultimately, Intravenous Immunoglobulins (IVIG) were administered to control his overwhelming viral infection, and he responded successfully. Another interesting case is a 5‐year‐old boy with SCD and G6PD deficiency. He presented with increasing anemia, jaundice and hemoglobinuria. All lab parameters were consistent with acute intravascular hemolysis, combined with suboptimal marrow response evidenced by reticulocytopenia. Coombs test and flow cytometry for Paroxysmal Nocutrnal Hemoglobinuria were negative. Parvovirus B19 PCR was positive in a significantly high copy number. The boy was diagnosed as a case of acute intravascular hemolytic anemia due to G6PD deficiency triggered by concomitant Parvovirus B19 infection which explains the reticulocytopenia. The patient required transfusion three times, then discharged uneventfully.Summary/Conclusion:Parvovirus B19 infection is common in children with SCD. Clinical presentations are not confined to classical aplastic crisis. High index of suspicion is needed to identify Parvovirus specially in cases presented with acute splenic sequestration. We recommend screening for Parvovirus in all cases presented with acute splenic seqestration coupled with suboptimal reticulocyte reponse. In severe refractory cases of Parvo infection, IVIG might be used as a salvage therapy.

Hydroxyurea Utilization Patterns Among Sickle Cell Disease Patients in the United States, US FDA Sentinel Database

Background: Hydroxyurea, an antineoplastic agent, was approved in 1998 to reduce the frequency of sickle cell crises in adult patients with sickle cell disease (SCD). More recently in 2017, hydroxyurea was also approved for pediatric patients, 2 years of age and older with sickle cell anemia and recurrent moderate to severe painful crises. Prior to this, hydroxyurea had been used in the United States (US) in pediatric patients with SCD without a labeled indication. This study investigated hydroxyurea utilization patterns among pediatric and adult patients with SCD in the US prior to the pediatric approval using administrative claims data in the Sentinel database sponsored by the US Food and Drug Administration.Methods: Data from 17 health plans contributing to the Sentinel Distributed Database were queried from January 1, 2000 through September 30, 2015. Eligible patients had a claim with a diagnosis of SCD in any care setting at any time during the query period. SCD was identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Patients were required to be enrolled in plans with both medical and drug coverage on the date of their SCD diagnosis. Patients who were dispensed hydroxyurea after diagnosis of SCD were identified as hydroxyurea users. Patients included in the sub-analysis evaluating hydroxyurea cumulative duration of therapy were required to be continuously enrolled with medical and drug coverage for at least 90 days prior to the initial hydroxyurea dispensing date, during which, gaps in coverage of up to 45 days were allowed. For this sub-analysis, follow-up began on the day of the first valid hydroxyurea dispensing and continued until the first occurrence of any of the following: 1) disenrollment; 2) death; 3) the end date of the data provided by each Data Partner; 4) the end of the last hydroxyurea exposure episode; or 5) the end of the query period. Cumulative duration of hydroxyurea therapy was calculated by summing days' supplies from outpatient pharmacy hydroxyurea dispensings for each patient. Results were stratified by age group (≤1, 2-5, 6-11, 12-17, 18-49, and 50+ years) and race.Results: A total of 95,606 patients with SCD were identified during the query period. Roughly half of patients (46.8%) were adults 18-49 years of age. Thirty-two percent (n= 30,900) were ≥50 years of age and 20.9% (n= 19,950) were ≤17 years of age. The study population included 40.3% African-American and 15.9% White patients. Race was unknown for 42.6% of the study population. Among pediatric SCD patients ≤1, 2-5, 6-11 and 12-17 years of age, hydroxyurea was dispensed to 4.1%, 7.7%, 16.5% and 16.0% of patients respectively. Among adults 18-49 years and ≥50 years, 18.4% and 4.7% respectively were dispensed hydroxyurea. The majority of pediatric hydroxyurea users were dispensed hydroxyurea for ≥ 325 days cumulatively. The median [inter quartile range] number of days of cumulative hydroxyurea exposure among patients ≤1, 2-5, 6-11, 12-17, 18-49 and 50+ years were 422 [139, 789], 420 [157, 836], 462 [156, 1145], 328 [120, 877], 204 [65, 505] and 253 [88, 599] days respectively.Conclusions: Although hydroxyurea was not approved for pediatric use in the US until 2017, for the period January 1, 2000 through September 30, 2015, the proportion of pediatric SCD patients 6-11 years and 12-17 years and adult SCD patients 18-49 years of age who were dispensed hydroxyurea were similar in the FDA Sentinel database. Among patients dispensed hydroxyurea, the durations of cumulative exposure were generally higher among pediatric compared to adult patients with SCD. The higher cumulative hydroxyurea exposure duration among pediatric SCD patients may reflect greater tolerability and adherence to hydroxyurea treatment in this population among other reasons. While this analysis evaluated utilization patterns prior to hydroxyurea approval for pediatric SCD patients, further research to evaluate any changes in hydroxyurea use patterns after the pediatric labeling would be useful. DisclosuresNo relevant conflicts of interest to declare.

Outcome of Age-Adapted Approach to HLA-Identical Related Hematopoietic Stem Cell Transplantation in Severe Sickle Cell Disease: Saudi Experience

▪Sickle cell disease (SCD) is one of the most common inherited disorders in Saudi Arabia with nearly 60,000 affected individuals (Alsultan et al. Ped. Transplant. 2016). Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment in SCD. A recent international survey showed excellent long-term survival of SCD patients after HLA-identical sibling HSCT; however, patients aged 16 years or older had higher risk of GVHD and mortality (Gluckman et al. Blood 2017). HLA-identical related HSCT in adult SCD patients using non-myeloablative (NMA) conditioning consisting of alemtuzumab, 300 cGy total body irradiation (TBI), and sirolimus was successful in establishing long term stable donor chimerism with minimal toxicity and GVHD (Hsieh et. al. JAMA 2014). In this study, we reviewed the outcome of SCD patients who underwent transplant at our institution using standard protocols (NMA regimen in patients ≥14 years and myeloablative regimen in < 14 years) to address whether age remains a risk factor that influences HSCT outcome in SCD.Children (<14 years) with severe SCD received myeloablative conditioning using one of two regimens: first regimen was cyclophosphamide (Cy) 200mg/kg, busulfan (Bu) 16mg/kg, and thymoglobulin (ATG) 10mg/kg and recently we use thiotepa 8mg/kg, Bu 16mg/kg, and fludarabine (Flu) 160mg/m2. Bu pharmacokinetics was performed to target AUC of 900-1350 µmol/L.min. GVHD prophylaxis included cyclosporine and methotrexate 10mg/m2 on day +1, +3, and +6. Bone marrow was the source of stem cells in all pediatric patients. Cyclosporine was continued during the first-year post HSCT and tapered slowly afterward based on donor chimerism. Adult patients (≥14 years) received hydroxyurea at maximum tolerated dose and hypertransfusion for 2-3 months with iron chelation if indicated prior to HSCT followed by NMA conditioning consisting of alemtuzumab (1mg/kg divided over 5 days on day -7 to -3) and TBI 300 cGy with testicular shielding in males on day -1. Sirolimus was used as GVHD prophylaxis starting day -2 and continued for at least one-year post HSCT with subsequent taper based on donor chimerism. Stem cells source was GCSF mobilized peripheral blood stem cells in all adult patients targeting cell dose of CD34 10X106/kg based on recipient weight. All SCD patients underwent exchange transfusion prior to HSCT to achieve HbS <30%. Hemoglobin was maintained between 9-11 g/dL and platelet count > 50,000/uL during HSCT. Supportive care included penicillin V, acyclovir, antifungal, and Pneumocystis jiroveci pneumonia prophylaxis. Levetiracetam was used as seizure prophylaxis. Strict monitoring of blood pressure and magnesium was performed. Graft failure and death from any cause were considered as events.A total of 51 patients with severe SCD were transplanted at our center, 17 children and 34 adults. Patient and transplant characteristics are summarized in Table. Indications for HSCT included recurrent severe pain crisis (n=33), stroke (n=14), avascular necrosis (n=2), sickle cell hepatopathy (n=1), and priapism (n=1). All patients engrafted successfully for both neutrophil and platelets. There was no acute or chronic GVHD among adult patients. Two pediatric patient had mild grade I acute GVHD in the skin that was controlled with topical treatment and none of pediatric patients had chronic GVHD. Three adult patients developed secondary graft failure on day 61, 170, and 225 post transplant with aplastic marrow in two patients despite full donor chimerism and autologous recovery in the third patient. Among the two patients who had aplastic anemia, one died secondary to sepsis and one underwent successful second transplant using cyclophosphamide, Flu, and ATG. Thirty-one adults have stable donor chimerism. Event free survival (EFS) at 2 years was 90% in adult patients and 100% in children (P=0.3). Overall survival (OS) at 2 years was 97% in adults and 100% in children (P=0.4). Median follow up duration was 416 days (range, 61-1256) in adults and 203 (range, 30-2505) days in children.We demonstrated that age-adapted approach in guiding the choice of conditioning regimen intensity in severe SCD is associated with excellent outcome and minimal risk of graft rejection, GVHD, and transplant-related mortality. This real world data is important to encourage patients and transplant physicians to consider this curative treatment. Longer follow up duration is needed to confirm our findings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Measurement of Sickle Cell Disease Symptoms from the Patient Perspective: Considerations for Clinical Trials

OBJECTIVES: Sickle cell disease (SCD), a group of inherited blood disorders, can impact multiple organs and can lead to variable clinical presentations. In addition to severe pain crises, patients may experience chronic symptoms (e.g. pain, tiredness). Assessing treatment benefit using a patient-reported outcome (PRO) measurement strategy can be critical for supporting clinical SCD research. We conducted qualitative research activities to inform considerations for PRO measurement strategies to assess daily chronic symptoms in regulated SCD clinical trials in patients 16 years and older.METHODS: Research activities aimed to identify the relevant and important signs/symptoms of SCD and determine their potential for measurement via existing PRO instruments. A literature review, meetings with clinical experts (N=5), and interviews with adolescent and adult SCD patients (N=20) were conducted. Trained researchers conducted semi-structured qualitative interviews. Results were analyzed to develop a synthesized SCD conceptual model describing the literature, expert, and patient perspectives of SCD.Five instruments used in SCD research were selected for review: Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-MeSM), Pediatric Quality of Life Inventory (PedsQL™) sickle cell disease module, the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue and Pediatric Pain Interference measures, and Scribe Sickle Cell Record of Daily Symptom Burden™ (SSCRDSB). Signs/symptoms in the SCD conceptual model were compared to those assessed in these instruments and measurement properties were reviewed. Considerations for concept selection (e.g. suitability of measuring a symptom via PRO instrument) and item development (e.g. selection of recall period) in developing a PRO measurement strategy were evaluated. Instruments developed to assess SCD concepts should have documented evidence of content validity (i.e., qualitative data confirming the instrument measures concepts important, relevant and understandable to the target patient population) and should include clear instructions, a short recall period, items that measure dimensions of importance to patients (e.g., symptom intensity), and well-defined response options that are sufficiently sensitive to detect change.RESULTS: Patients reported 22 signs/symptoms that they experienced generally with SCD and/or during pain episodes, which were largely endorsed by the literature and/or clinical experts. Pain was reported by all patients and tiredness was reported by 80.0% of patients; both were cited as the most important to improve with treatment. Patients reported 29 impacts of SCD across 9 domains.Across the 5 instruments, pain was the most frequently measured SCD symptom concept, measured in different ways by 3 instruments. None of the reviewed instruments assessed more than 5 of the signs/symptoms included in our SCD conceptual model with the SSCRDSB assessing the greatest number of signs/symptoms (n=5/22 concepts, 22.7%). The remaining 4 instruments assessed 3 or fewer of the signs/symptoms reported by patients. Physical impacts were the most frequently measured impact domain, assessed to varying degrees by all 5 instruments evaluated. The PedsQL™ SCD module assessed the greatest number of impact domains in our SCD conceptual model (n=7/9 domains, 77.8%). The reviewed instruments were determined to have limitations in the context of assessing SCD signs/symptoms daily as part of regulated clinical trials.CONCLUSIONS: The research activities conducted as part of this work suggest that (1) patients experience numerous SCD signs/symptoms regularly and intermittently and (2) existing instruments, while perhaps suitable for other contexts of use or in conjunction with other tools, may be inadequate for evaluating the most important symptoms in a way that can demonstrate treatment benefit when measured daily in regulated clinical research. A de novo instrument developed for these purposes may better assess treatment benefit from the patient perspective in the context of measuring variable SCD symptoms daily in a regulated clinical trial setting. DisclosuresOjo:Ironwood Pharmaceuticals: Employment. Litcher-Kelly:Ironwood Pharmaceuticals: Consultancy. Mazar:Ironwood Pharmaceuticals: Consultancy. Klooster:Ironwood Pharmaceuticals: Consultancy. Ollis:Ironwood Pharmaceuticals: Consultancy. Chaston:Ironwood Pharmaceuticals: Consultancy. Roeder:Ironwood Pharmaceuticals: Consultancy. Treadwell:Global Blood Therapeutics: Consultancy; Ironwood Pharmaceuticals: Consultancy; Pfizer: Consultancy. Reasner:Ironwood Pharmaceuticals: Employment, Equity Ownership.

Phytomedicines (medicines derived from plants) for sickle cell disease.

Sickle cell disease, a common recessively inherited haemoglobin disorder, affects people from sub-Saharan Africa, the Middle East, Mediterranean basin, Indian subcontinent, Caribbean and South America. It is associated with complications and a reduced life expectancy. Phytomedicines (medicine derived from plants in their original state) encompass many of the plant remedies from traditional healers which the populations most affected would encounter. Laboratory research and limited clinical trials have suggested positive effects of phytomedicines both in vivo and in vitro. However, there has been little systematic appraisal of their benefits. This is an update of a Cochrane Review first published in 2004, and updated in 2010, 2013, and 2015. To assess the benefits and risks of phytomedicines in people with sickle cell disease of all types, of any age, in any setting. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, the International StandardRandomised Controlled Trial NumberRegister (ISRCTN), the Allied and Complimentary Medicine Database (AMED), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP).Dates of most recent searches: Cochrane Cystic Fibrosis and Genetic Disorders Haemoglobinopathies Trials Register: 10 April 2017; ISRCTN: 26 July 2017; AMED: 24 August 2017; ClinicalTrials.gov: 02 August 2017; and the WHO ICTRP: 27 July 2017. Randomised or quasi-randomised trials with participants of all ages with sickle cell disease, in all settings, comparing the administration of phytomedicines, by any mode to placebo or conventional treatment, including blood transfusion and hydroxyurea. Both authors independently assessed trial quality and extracted data. Two trials (182 participants) and two phytomedicines Niprisan® (also known as Nicosan®) and Ciklavit® were included. The Phase IIB (pivotal) trial suggests that Niprisan® was effective in reducing episodes of severe painful sickle cell disease crisis over a six-month period (low-quality evidence). It did not affect the risk of severe complications or the level of anaemia (low-quality evidence). No serious adverse effects were reported. The single trial of Cajanus cajan (Ciklavit®) reported a possible benefit to individuals with painful crises (low-quality evidence), and a possible adverse effect (non-significant) on the level of anaemia (low-quality evidence). While Niprisan® appeared to be safe and effective in reducing severe painful crises over a six-month follow-up period, further trials are required to assess its role in the management of people with sickle cell disease and the results of its multicentre trials are awaited. Currently no conclusions can be made regarding the efficacy of Ciklavit®. Based on the published results for Niprisan® and in view of the limitations in data collection and analysis of both trials, phytomedicines may have a potential beneficial effect in reducing painful crises in sickle cell disease. This needs to be further validated in future trials. More trials are required on the safety and efficacy of phytomedicines used in managing sickle cell disease.

The Use of Marijuana and Hydroxyurea Among Sickle Cell Patients

ObjectiveSickle cell crises are a common, painful complication of sickle cell disease. These crises are treated in the emergency department with narcotic analgesia. However due to concerns about addiction, tolerance and side effects of pain medications, physicians specifically hematologists recommend the use of hydroxyurea as an alternative therapeutic medication for sickle cell patients. Hydroxyurea is the only FDA approved therapeutic medication proven to decrease the painful vasoocclusive process in sickle cell disease. Similarly, marijuana is being studied as an alternative in reducing pain in sickle cell disease. However, few have looked at the prevalence of hydroxyurea and marijuana use in sickle cell disease patients. We want to explore the prevalence of marijuana use among our hydroxyurea and non-hydroxyurea users.MethodWe developed a structured self-administered anonymous questionnaire that was provided to our adult sickle cell patients. One hundred and three (103) patients with HbSS, HbSC, HbSBetaThalassemia and HbSS disease with Alpha Thalassemia trait were consented and explained the purpose of the questionnaire. The questionnaire was administered in a private room in our clinic. The questionnaire focused on the following variables: (1) current regimen of their prescribed narcotic medication at steady state (2) current regimen of their prescribed narcotic medication during a moderate to severe pain crisis (3) use of Marijuana and Hydroxyurea during steady state and during a moderate to severe pain crisis (4) whether or not they were taking Hydroxyurea and the (5) physical effects of combining prescribed narcotic medication with illicit drug use. The questionnaire consisted of twenty-five (25) questions which took on average 10-15 minutes. The answers to the questionnaire were entered into REDCap (Research Electronic Data Capture). It is a secure, web-based application designed to support data capture for research studies, providing 1) an intuitive interface for validated data entry; 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for importing data from external sources. The data was analyzed using SPSS 23.0 (IBM Corp. Armonk, NY). Chi-square or Fisher exact testing was used to test the association between variables on the prevalence of cannabis use for pain management and other symptom relief and its side effects during self-administration in patients with sickle cell disease.ResultsOur analysis showed that fifty-one (51%) percent of the participants were females while forty-nine (49%) percent were males. Thirty-six (36%) percent of patients were between 25-34 years of age and the median age was 30 years. Thirty-three percent (33%) had a college degree or higher. Sixty percent (60%) of participants admitted to using marijuana at least once. Fifty-six percent (56%) of patients used both hydroxyurea and marijuana while forty-four percent (44%) of patients did not use hydroxyurea but used marijuana. Thirty percent (30%) of participants stated they used marijuana within the last 12 months to relieve symptoms associated with sickle cell disease. The main reasons for use were to increase appetite, improve sleep, mood and concentration, relieve stress and anxiety and alleviate pain. Eighty percent (80%) of participants stated that marijuana was not as effective in managing their sickle-related pain as hydroxyurea. There was no significant difference (p= 0.173) between the use of marijuana among hydroxyurea users and non-hydroxyurea users. Five percent(5%) of participants reported combining marijuana with prescribed narcotic medications to alleviate their sickle-related pain.ConclusionIn summary, our data showed that within the groups of hydroxyurea users and non-hydroxyurea users, there was no significant difference in the use of marijuana. Both groups use marijuana as much as the general population. However, the use of marijuana among our sickle cell patients was not solely dependent on pain control. Further studies need to be conducted to show any significant results between hydroxyurea and non-hydroxyurea users. DisclosuresNo relevant conflicts of interest to declare.

Demands and challenges for patients with sickle-cell disease requiring hematopoietic stem cell transplantation in Saudi Arabia.

Allogeneic HSCT is the only curative treatment for SCD. In this study, we estimated the number of Saudi patients with SCD who are candidates for HSCT. We used the presence of overt stroke, recurrent ACS, and frequent severe pain crisis as indications for HSCT. We calculated the frequencies of these complications among a Saudi SCD cohort of 376 patients with SCD, 250 from SW and 126 from Eastern (E) provinces. We found that 59 (23.6%) of SW patients were transplant candidates compared to 22 (17.4%) from E province. It is estimated that about 61000 patients with SCD live in Saudi Arabia. Thus, the projected number of Saudi patients with SCD who are candidates for HSCT is 10536 patients. Of those, 2148 are children. The burden of SCD on HSCT centers in Saudi Arabia is substantial and is difficult currently to meet the demand. We recommend recruiting/training more transplant physicians and nurses, expand current capacity of centers if feasible, and open new transplant centers to make HSCT a practical therapeutic option for patients with severe SCD in Saudi Arabia.