bims-sicedi 2025-06-01 papers

bims-sicedi

Biomed News

on Sickle cell disease

Issue of 2025–06–01
ten papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo

The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial.
Mean Corpuscular Hemoglobin Modulates HbF/F-Cell and Clinical Response to Gene Therapy and Hydroxyurea in Sickle Cell Disease.
Real world analysis of long-term eff icacy of isovolemic red cell exchange in sickle cell disease: a single center experience.
Real-world assessment of acute red cell exchange for stroke in sickle cell disease.
Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial.
A series of Sickle cell disease-associated inflammatory bowel diseases: high prevalence of colonic involvement and primary sclerosing cholangitis.
Primary Stroke Screening and Hydroxyurea Treatment for Sickle Cell Anemia in Pediatric Healthcare Settings in East and Central Africa: A Narrative Review of Capacity Gaps and Opportunities.
Platelet-to-Neutrophil ratio as a predictor of risk of complications in sickle cell disease: a valuable insight for resource-limited settings.
Determining the FY*BES Allele in Iranian Sickle Cell Disease Patients to Enhance Matching Blood Transfusion.
Guidelines for the management of emergencies and critical illness in pediatric and adult patients with sickle cell disease.

Br J Clin Pharmacol. 2025 Jun;91(6): 1865-1872

The feasibility of pharmacokinetic-based dosing of hydroxyurea for children with sickle cell anaemia in Uganda: Baseline results of the alternative dosing and prevention of transfusions trial.

Alexandra Power-Hays, Ruth Namazzi, Min Dong, Caroline Kazinga, Charles Kato, Sadat Aliwuya, Kathryn McElhinney, Andrea L Conroy, Adam Lane, Chandy John, Alexander A Vinks, Teresa Latham, Robert O Opoka, Russell E Ware.

  Pharmacokinetic (PK)-guided dosing of hydroxyurea for children with sickle cell anaemia (SCA) could optimize dosing and improve outcomes, but its feasibility has not been demonstrated in low-resource settings where the majority of affected children live. Alternative Dosing And Prevention of Transfusions (ADAPT) is a prospective trial evaluating blood transfusions and the feasibility of determining PK-guided, hydroxyurea maximum tolerated doses (MTD) for children with SCA in Uganda, using portable high-performance liquid chromatography (HPLC) and a novel PK software programme (HdxSim). ADAPT enrolled 106 participants, and 100% completed PK testing. PK-guided doses were generated for 78%, of which 38% were within the protocol-defined range. Accurately, measuring serum hydroxyurea concentrations via HPLC and the potential for hydroxyurea degradation impacted the feasibility. Ensuring that people with SCA globally have access to hydroxyurea is imperative, and improving treatment strategies requires ongoing innovation including PK-guided dosing. ADAPT is registered at ClinicalTrials.gov (NCT05662098).

Keywords:  HPLC < drug analysis; clinical pharmacology; haematology; paediatrics; pharmacokinetics

DOI:  https://doi.org/10.1111/bcp.70071
Am J Hematol. 2025 May 28.

Mean Corpuscular Hemoglobin Modulates HbF/F-Cell and Clinical Response to Gene Therapy and Hydroxyurea in Sickle Cell Disease.

Martin H Steinberg, Abdullah Kutlar, Paola Sebastiani.



Keywords:  HPFH; heterocellular HbF; pancellular HbF; red cell indices; stress erythropoiesis

DOI:  https://doi.org/10.1002/ajh.27729
Blood Transfus. 2025 May 22.

Real world analysis of long-term eff icacy of isovolemic red cell exchange in sickle cell disease: a single center experience.

Nikhil Vojjala, Rishab Prabhu, Janaka Ss Liyanage, Dipen Kumar Modi, Jay Yang, Andrew Kin, Indryas Woldie, Asif Alavi, Vijendra Singh.

DOI: https://doi.org/10.2450/BloodTransfus.1009
Br J Haematol. 2025 May 25.

Real-world assessment of acute red cell exchange for stroke in sickle cell disease.

Samuel R Wilson, Denis Noubouossie, Jane A Little, Matthew S Karafin.

  Cerebrovascular accidents (CVA) are one of the most devastating complications in sickle cell disease (SCD). Chronic transfusion therapy has been established for primary and secondary prevention of CVA in SCD, resulting in a notable reduction in CVA incidence. For individuals with SCD presenting with CVA, the impact of acute management on neurological outcomes is not well studied. Herein, we examine the neurological outcomes of 29 children and adults with SCD who received acute red cell exchange (RCE) as primary therapy for neurological events at a single institution. Twelve (41%) individuals had a prior history of CVA, and 12 (41%) were on chronic transfusions. Among 13 adults, 3 (23%) had a history of diabetes and 4 (31%) had a history of hypertension. One adult (7.7%) received thrombolytic therapy; the remainder were ineligible due to age, timing of presentation, intracranial haemorrhage or transient symptoms. Higher post-RCE haematocrit was associated with decreased odds of death or persistent neurological symptoms at hospital discharge (OR 0.69, 95% CI: 0.45-0.94, p = 0.017). Optimal acute management of adults living with SCD presenting with CVA remains an understudied yet important topic. Future prospective studies may determine how best to tailor acute management to improve neurological outcomes.

Keywords:  red cell exchange; sickle cell disease; stroke; thrombolytics

DOI:  https://doi.org/10.1111/bjh.20170
Nat Med. 2025 May 26.

Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial.

Michael Grimley, Stella M Davies, Archana Shrestha, Amy Shova, Monika Asnani, Michael Kent, Farzana Sayani, Charles T Quinn, Omar Niss, Carolyn Lutzko, Parinda A Mehta, Pooja Khandelwal, Courtney Little, Sharat Chandra, Sydney Felker, Mengna Chi, Theodosia A Kalfa, Jennifer Knight-Madden, Paritha I Arumugam, Kristie N Ramos, Scott Witting, Teresa Latham, Frederic D Bushman, Punam Malik.

Autologous transplantation of gene-modified cells for treatment of sickle cell disease has involved myeloablative conditioning with associated cytopenias and toxicities. We report results of seven patients treated in a first-in-human phase 1/2 study for sickle cell disease using reduced-intensity conditioning transplant of autologous hematopoietic stem cells genetically modified with a lentiviral vector (GbGM), with 2-7 yr of follow-up. GbGM encodes a modified γ-globin gene that expresses a potent anti-sickling fetal hemoglobin, HbFG16D. The primary study objectives were safety (occurrence of adverse events and duration of neutropenia and thrombocytopenia) and feasibility of treatment. Primary feasibility endpoints of collection of at least 8 × 106 CD34+ cells per kg body weight, successful transduction of a minimum of 4 × 106 CD34+ cells per kg body weight and the number of subjects with an average vector copy number of >0.01 copies per cell 1 yr after infusion were met. A median of 4 collections (range, 4-8) were needed to achieve the target cell dose, and all products achieved the target vector copy number. There were 503 adverse events in the seven patients throughout the study period, the most common being grade 2-3 vaso-occlusive crisis. Median duration of grade 4 thrombocytopenia was 5 d and of grade 4 neutropenia was 8 d. All seven patients exhibited sustained HbFG16D expression and >80% reduction in severe vaso-occlusive events (secondary endpoints). The clinical trial was terminated after infusion of the seventh patient as the predetermined primary endpoints were met and industry funding was complete. Larger trials are warranted to evaluate the benefits of reduced-intensity conditioning. ClinicalTrials.gov registration number: NCT02186418 .

DOI: https://doi.org/10.1038/s41591-025-03662-2
Clin Res Hepatol Gastroenterol. 2025 May 23. pii: S2210-7401(25)00093-2. [Epub ahead of print] 102615

A series of Sickle cell disease-associated inflammatory bowel diseases: high prevalence of colonic involvement and primary sclerosing cholangitis.

Julien Kirchgesner, Jeremy Augustin, Thomas Bazin, Pamela Freiha, Alexandre Nuzzo, Philippe Seksik, Iradj Sobhani, Pablo Bartolucci, Mathieu Uzzan.

   OBJECTIVE: Co-occurrence of Sickle Cell Disease (SCD) and Inflammatory Bowel Diseases (IBD) has been scarcely reported. Our aim was to explore the intersection between SCD and IBD, focusing on the impact of SCD on the natural course of IBD and drug safety.
METHODS: We conducted a multicenter retrospective case-control study including consecutive patients diagnosed with IBD and SCD. Each IBD patient with SCD was matched with up to 4 IBD patients without SCD. Matching criteria were IBD type, sex, date of birth, length of follow-up and year of diagnosis. The primary outcome was a complicated IBD course.
RESULTS: 125 IBD patients were studied, including 24 SCD. 23/24 SCD patients had colonic involvement. 33.3% had concomitant primary sclerosing cholangitis (PSC) compared to 1% of controls (p<0.001). Survival without a complicated IBD course was estimated at 58.7% (CI95[49.6-69.5]) at 5 years for non-SCD patients, as compared to 63.3% (CI95[45.7-87.6]) for SCD patients SCD (p=0.36). The survival without the need of advanced therapy was estimated at 66.1% (CI95[57.3-76.2]) at 5 years for non-SCD patient, and at 78.2% (CI95[63-97.2]) in SCD patients (p=0.45) Regarding treatment safety, 26.3% of patients with SCD and 13.5% of controls experienced adverse events with biologics (p=0.17). There was one reported vaso-occlusive crisis associated with thiopurines.
CONCLUSION: Patients with SCD and IBD displayed a distinctive phenotype with constant colonic involvement and high prevalence of PSC.

Keywords:  N/A

DOI:  https://doi.org/10.1016/j.clinre.2025.102615
Public Health Rev. 2025 ;46 1608359

Primary Stroke Screening and Hydroxyurea Treatment for Sickle Cell Anemia in Pediatric Healthcare Settings in East and Central Africa: A Narrative Review of Capacity Gaps and Opportunities.

Teresa Smith Latham, Katarzyna Czabanowska, Suzanne Babich, Faith Yego-Kosgei, Lisa M Shook, Russell E Ware.

   Objectives: Sickle cell anemia (SCA) is associated with increased morbidity and mortality and impacts resource-limited settings with limited capacity for diagnosis and treatment. This review provides context for the magnitude of the problem, describes screening methods to prevent stroke, and factors that impact outcomes.
Methods: A narrative review was conducted. Topics included background information on SCA, its clinical characteristics, complications including primary stroke, and available treatment options. Social, economic, and political factors in East and Central Africa were described.
Results: A total of 37 publications were categorized into four themes: morbidity and mortality of SCA in sub-Saharan Africa; TCD screening for risk of primary stroke in children; treatment of children with SCA in resource-limited settings; and approaches to capacity gaps.
Conclusion: SCA represents a public health problem in sub-Saharan Africa. TCD screening with hydroxyurea treatment can improve outcomes and prevent primary stroke. Multiple barriers exist, including limited diagnostic screening, inconsistent availability of and access to hydroxyurea, and knowledge gaps. These barriers are influenced by social, economic and policy factors that can be addressed to build capacity and improve outcomes.

Keywords:  capacity building; hydroxyurea; resource-limited settings; sickle cell anemia; stroke

DOI:  https://doi.org/10.3389/phrs.2025.1608359
Ann Hematol. 2025 May 24.

Platelet-to-Neutrophil ratio as a predictor of risk of complications in sickle cell disease: a valuable insight for resource-limited settings.

Chilota Efobi, Nnanna Ukpai, Onyinye Ezinne Eze, Bruno Basil.

Sickle cell disease (SCD) presents significant clinical challenges, particularly in resource-limited settings where early identification of high-risk patients remains difficult, necessitating the use of simple, cost-effective biomarkers to improve risk stratification and guide timely interventions. This study investigates the potential of platelet-to-neutrophil ratio (PNR) to serve as a predictor for risk of specific SCD complications in a population of Nigerian patients. This hospital-based cross-sectional analytical study was conducted over 7 months and included a total of 73 adult patients with haemoglobin SS genotype in a steady state. Data on socio-demographics, medical history, clinical characteristics, and laboratory parameters, including platelet-to-neutrophil ratio (PNR) were obtained. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 25. Comparative statistical analyses, binary logistic regression, and receiver operating characteristic (ROC) curve evaluations were performed to determine the predictive value of PNR for risk of SCD complications. Patients with avascular necrosis (AVN) had significantly lower median PNR values compared to those without the condition (151.0 IQR: 311.2 vs. 77.5 IQR: 61.0, p = 0.004). Multivariate logistic regression analysis identified PNR as an independent predictor of AVN (p = 0.034, OR = 1.003, 95% CI: 1.000-1.006), with an ROC-derived optimal cutoff of 96.6 yielding a sensitivity of 69.6% and specificity of 76.5% (AUC = 0.733, p = 0.004). This study reveals that RNR demonstrates reasonable potential as a predictor of AVN in Nigerian SCD patients and could serve as an easily accessible biomarker for SCD risk stratification, particularly in resource-limited settings. Further studies are needed for validation of its clinical utility and possible integration into SCD management protocols.

DOI: https://doi.org/10.1007/s00277-025-06419-6
Int J Hematol Oncol Stem Cell Res. 2025 Jan 01. 19(1): 1-6

Determining the FY*BES Allele in Iranian Sickle Cell Disease Patients to Enhance Matching Blood Transfusion.

Mina Samadi Ivriq, Arezoo Oodi, Saeed Mohammadi, Bijan Keikhaei-Dehdazi, Moharram Ahmadnezhad, Sahar Jolharnejad.

  Background: Duffy antibodies play a significant role in hemolytic transfusion reactions and hemolytic disease of the fetus and newborn, Duffy(FY) blood group genotyping an essential part of transfusion medicine. The purpose of this study was to assess the importance of Duffy (FY) DNA typing in conducting transfusion compatibility testing and improving Red Blood Cell matching during transfusion. Materials and Methods: In this study, 135 blood samples from SCD patients from the Southwest of Iran were included. All samples were tested with Anti-Fya and Anti-Fyb using the hemagglutination technique, and 64 samples with the fy(a+b-) and fy(a-b-) phenotypes were genotyped using DNA sequencing methods. Results: The prevalence of alloimmunization in this population was 13.04%. fy(a-b+) was the most common phenotype (37/135, 27.4%), followed by fy(a+b-) (35/135, 26%), fy(a+b+) (34/135, 25.2%); and fy(a-b-) (29/135, 21.4%). Among the 64 fy(a+b-) and fy(a-b-) samples, 40 (62.5%) patients had FY*BES allele. 21 out of 40 samples were FY*BES/FY*BES, 17 were FY*A/FY*BES, and 2 were FY*B/FY*BES. Conclusion: The prevalence of GATA-1 mutation (FY*BES allele), in fy(a-b-) and fy(a+b-) patients was reported 62.5%. Therefore, it is possible to use the genotypic information as a database to facilitate the process of searching and supplying better-matched blood transfusion.

Keywords:  Duffy; FY*BES allele; Sickle cell disease

DOI:  https://doi.org/10.18502/ijhoscr.v19i1.17818
Ann Intensive Care. 2025 May 29. 15(1): 74

Guidelines for the management of emergencies and critical illness in pediatric and adult patients with sickle cell disease.

Armand Mekontso Dessap, Stephane Dauger, Mehdi Khellaf, Maite Agbakou, Sophie Agut, François Angoulvant, Jean-Benoît Arlet, Cécile Aubron, Florent Baudin, Florence Boissier, Nicolas Bounaud, Pierre Catoire, Jérôme Cecchini, Djamila Chaiba, Anthony Chauvin, Richard Chocron, Benedicte Douay, Delphine Douillet, Narcisse Elenga, Olivier Flechelle, Ségolène Gendreau, Sybille Goddet, Jeremy Guenezan, Anoosha Habibi, Claire Heilbronner, Bérengère Koehl, Pierrick Le Borgne, Philippe Le Conte, Annick Legras, Michael Levy, Bernard Maitre, Mathieu Oberlin, Mehdi Oualha, Nicolas Peschanski, France Pirenne, Corinne Pondarre, Jérôme Rambaud, Keyvan Razazi, Geoffroy Rousseau, Aurélie Schirmann, Isabelle Thuret, Ruddy Valentino, Guillaume Voiriot, Barbara Villoing, Marion Grimaud, Sandrine Jean.

Forty-two questions were evaluated concerning management of emergencies and critical illnesses in paediatric and adult patients with sickle cell disease. The assessment covered the following areas: patient referral, vaso-occlusive crisis, acute chest syndrome, transfusion therapy, and priapism. The patient referral category included guidelines for admission to intensive care unit and management at specialized reference centers. The vaso-occlusive crisis topic encompassed pain management, hydration, incentive spirometry, and target oxygen saturation levels. For acute chest syndrome, the focus areas included imaging techniques such as lung ultrasound, computed tomography scans, and echocardiography; treatment with systemic corticosteroids; non-invasive ventilation; prophylactic and therapeutic anticoagulation; and procalcitonin and antibiotic therapy. The section on transfusion therapy addressed indications and methods of transfusion, as well as the diagnosis and prediction of delayed hemolytic transfusion reactions. A total of 45 recommendations were proposed, including 14 specific to adults, 13 specific to pediatrics, and 18 applicable to both adults and children, along with three therapeutic algorithms. The Grade of Recommendation Assessment, Development, and Evaluation (GRADE) methodology was adhered to throughout the process. Sixteen recommendations were based on a low level of evidence (GRADE 2+ or 2-), while 26 were based on evidence that could not be classified under the GRADE system and were therefore considered expert opinions. Finally, for three aspects of sickle cell disease management, the experts concluded that no reliable recommendations could be made based on the current state of knowledge. The recommendations and therapeutic algorithms received strong agreement from the experts.

DOI: https://doi.org/10.1186/s13613-025-01479-3