bims-sicedi Biomed News
on Sickle cell disease
Issue of 2025–05–25
seven papers selected by
João Conrado Khouri dos Santos, Universidade de São Paulo
  1. Dynamics of neutrophil phenotype and function in sickle cell disease.
  2. Comparing Absolute Neutrophil Counts of Children With Sickle Cell Disease With and Without the Duffy Null Phenotype.
  3. Impact of Voxelotor on Red Blood Cell Exchange Therapeutic Procedures: Evaluation of Multi-Institutional Procedure Data.
  4. Sickle hemoglobinopathy research in Zimbabwe and Zambia: setting up an international sickle cell disease registry.
  5. Comparison of Regimens Used for Allogeneic Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease.
  6. Safety of Hydroxyurea in Pregnancy: A Systematic Review of the literature.
  7. Physical activity, vaso-occlusive crises and pain in patients with sickle cell anaemia in Senegal.
  1. Front Immunol. 2025 ;16 1591283
    Dynamics of neutrophil phenotype and function in sickle cell disease.
    Aafke E Gaartman, Lydian A de Ligt, Boukje M Beuger, Anton T J Tool, Martijn Veldthuis, Taco W Kuijpers, Rob van Zwieten, Bart J Biemond, Robin van Bruggen, Erfan Nur.
       Introduction: While sickle cell disease (SCD) is primarily acknowledged as an erythrocyte disorder, emerging evidence suggests a role for altered neutrophil phenotype and function in SCD pathophysiology and disease severity. Given the conflicting findings in previous studies, we performed a comprehensive exploration of neutrophil characteristics in SCD patients during steady state and vaso-occlusive crisis (VOC), as well as in response to therapeutic interventions.
    Methods: Neutrophil phenotype was assessed by flow cytometry and functional properties were evaluated by measurement of neutrophil adhesion and reactive oxygen species (ROS) production.
    Results: A total of 49 SCD patients (of whom 19 during both steady state and VOC) along with 16 healthy ethnicity-matched and 30 non-matched controls, were included in the study. Differences were observed between neutrophils from patients compared to controls and between control groups. Neutrophil phenotype was more activated in SCD patients compared to non-matched controls. Neutrophil adhesion was increased in steady-state SCD patients compared to both ethnicity-matched and non-matched controls.
    Discussion: While neutrophil phenotype in SCD patients differed from non-matched controls, in contrast to earlier studies, the differences in neutrophil phenotype between SCD patients and ethnicity-matched controls were modest. In vitro neutrophil adhesion was higher in SCD patients than in ethnicity-matched and non-matched controls. Potential explanations for the discrepancies between earlier findings and our study are the large variation in neutrophil phenotypes between individuals, methodological variability between studies and differences in the time interval between blood sample collection and the measurements.
    Keywords:  hemolysis; neutrohil aging; neutrophil activation; neutrophil adhesion; neutrophil phenotype; reactive oxygen species; sickle cell disease
    DOI:  https://doi.org/10.3389/fimmu.2025.1591283
  2. Pediatr Blood Cancer. 2025 May 19. e31794
    Comparing Absolute Neutrophil Counts of Children With Sickle Cell Disease With and Without the Duffy Null Phenotype.
    Nate Goldfarb, Joseph Stanek, Joseph Walden, Melissa J Rose, Kathleen Nicol, Anthony Villella, Jennifer Young, Susan Creary.
      While nonpathogenic, the Duffy null phenotype (DN) lowers circulating neutrophils. DN is common among youth with sickle cell disease (SCD), but its implications on absolute neutrophil counts (ANC) and hydroxyurea over time are unclear. Our retrospective review found that all children who were not receiving hydroxyurea had stable ANC through age 9 years, but those with DN had lower mean ANC starting at 6 years of age. Among hydroxyurea users, ANC increased over time, regardless of DN status, suggesting opportunities to optimize hydroxyurea. Future studies of hospitalized and older individuals are needed to further examine DN's impact on people with SCD.
    Keywords:  outcomes research; sickle cell anemia; sickle cell disease
    DOI:  https://doi.org/10.1002/pbc.31794
  3. J Clin Apher. 2025 Jun;40(3): e70033
    Impact of Voxelotor on Red Blood Cell Exchange Therapeutic Procedures: Evaluation of Multi-Institutional Procedure Data.
    Sally Campbell-Lee, Ming Jin, Lisandro Fortuny, Daniel Sop, Suzanne Thibodeaux, Susan D-Roseff.
      Hemoglobin S (HbS) polymerization inhibitor drugs such as voxelotor can result in a split peak in HbS as well as additional peaks with hemoglobin A in quantitative methods of HbS measurement. It is unclear how these results should be used to make transfusion decisions. The goal of this study is to compare RBC exchange (RBCX) replacement volumes calculated with HbS-Vox + HbS versus HbS alone. Patients aged 15-58 years who had variant hemoglobin quantitation performed for clinical care purposes with evidence of voxelotor treatment (split peak in HbS and/or additional peaks with hemoglobin A) were identified by investigator review of variant hemoglobin quantitation test results from the clinical laboratory. The RBCX replacement volume calculated with HbS% total (RBCX volume HbS% total) was compared to the RBCX replacement volume calculated with HbS unmod% (RBCX volume HbS unmod%) in each case. The mean difference between RBCX volume total HbS% and RBCX volume HbS% unmod is 398 mL with 95% CI (198, 598) and RBCX volume total HbS is significantly different from RBCX volume HbS unmod (p value = 0.0006). If the HbS total is not used to calculate RBCX replacement volumes in patients taking voxelotor, there is a significantly lower amount of RBC that would be ordered, which would lead to higher HbS after RBCX. Additional studies regarding the role of transfusion in such patients are necessary.
    Keywords:  calculation; complexes; drug; hemoglobin; quantitation; sickle; transfusion
    DOI:  https://doi.org/10.1002/jca.70033
  4. Front Med (Lausanne). 2025 ;12 1484763
    Sickle hemoglobinopathy research in Zimbabwe and Zambia: setting up an international sickle cell disease registry.
    Patience Kuona, Gwendoline Q Kandawasvika, Catherine Chunda-Liyoka, Ian M Ruredzo, Pauline M Sambo, Pamela Gorejena-Chidawanyika, Hamakwa M Mantina, Takudzwa J Mtisi, Cynthia Phiri, Lawson Chikara, Natasha M Kaweme, Exavior Chivige, Jombo Namushi, Tendai C Maboreke, Uma Athale, Collen Masimirembwa.
      Majority of the 500,000 children born with sickle cell disease (SCD) annually are born in Africa. SCD contributes significantly to morbidity and mortality. This is worsened by the reduced access to therapeutic plus preventive care and limited health outcomes data. To address these challenges, we aim to develop and manage a standardized electronic SCD registry, establish consistent standards of care (SoC) for patients, improve the SCD research and biobanking capacity in Zimbabwe and Zambia. This five-year program employs a multi-pronged approach that include infrastructure and skilled manpower capacity building of SCD clinics, registry, biobanking, cohort and implementation science research studies to improve SCD treatment outcomes. We are collaborating with the SickleInAfrica consortium (Ghana, Mali, Nigeria, Tanzania, Uganda, and South Africa), the African Institute of Biomedical Sciences and Technology (AiBST) and St Jude's Children Research Hospital. We have established the SCD registry in Zimbabwe and Zambia for children and adult patients enrolling 1796 (45%) of the targeted 4,000 participants as of March 2024. We are participating in SickleInAfrica consortium research activities, training health workers and educating SCD patient communities on SoC. This collaboration with African researchers, policymakers, health workers, and SCD patient communities will improve uptake of SCD SoC and increase our research capacity.
    Keywords:  Africa; SickleInAfrica; Zambia; Zimbabwe; cohort; registry; sickle cell disease; standards of care
    DOI:  https://doi.org/10.3389/fmed.2025.1484763
  5. Transplant Cell Ther. 2025 May 14. pii: S2666-6367(25)01168-6. [Epub ahead of print]
    Comparison of Regimens Used for Allogeneic Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease.
    Daniel Prior, Jingchen Liang, Yanhong Deng, Niketa Shah, Aron Flagg, Lakshmanan Krishnamurti.
       BACKGROUND: Prior analyses have reported on the impact of different donor types and conditioning regimen intensities on outcomes for patients with sickle cell disease (SCD) who undergo hematopoietic cell transplantation (HCT), and demonstrated superior outcomes using an HLA-matched related donor (MRD). However, the impact of conditioning regimen intensity on outcomes remains unclear, with conflicting findings across studies. In addition, the lack of data on comparative outcomes of different approaches to conditioning and graft-versus-host disease (GVHD) prophylaxis for allogeneic HCT for SCD remains a gap in the field.
    OBJECTIVE: To compare outcomes for SCD patients who have received HLA-matched related donor (MRD) HCT for SCD using different HCT regimens.
    STUDY DESIGN: We examined de-identified records of MRD HCT for SCD on patients transplanted between 1991 and 2022 in the United States and submitted to the CIBMTR. We compared the most common transplant regimens in the registry, which included TBI 300/400 cGy + sirolimus + anti-thymocyte globulin (ATG)/alemtuzumab (Hsieh et al. 2014); Busulfan/Fludarabine + CNI/methotrexate (MTX) + ATG/alemtuzumab (Krishnamurti et al. 2019); Fludarabine/Melphalan + CNI/MTX + ATG/alemtuzumab (King et al. 2015); and Busulfan/Cyclophosphamide (CY) + CNI /MTX/prednisone + ATG/alemtuzumab (Walters et al. 1996).
    RESULTS: For pediatric MRD HCT, EFS rates were highest with the Krishnamurti et al. (3-year EFS 94%, 95% CI 88, 100) and lowest with the Hsieh et al. regimen (3-year EFS 57%, 95% CI 25, 100, p<0.001). Rates of chronic GVHD were lowest in the Hsieh et al. cohort (3-year rate 0%) and highest in the King et al. cohort (3-year rate 20.4%, 95% CI 13.2, 28.8, p=0.040). For adult MRD HCT, EFS rates were similar between the Hsieh et al. and Krishnamurti et al. regimens, while cGVHD was significantly lower in the Hsieh et al. cohort..
    CONCLUSIONS: These real-world data have the potential to inform shared decision-making in MRD HCT for SCD. Pediatric patients had the highest EFS rates using myeloablative conditioning regimens, while non-myeloablative conditioning resulted in the lowest EFS rates. Adult patients had similar event-free survival using myeloablative and non-myeloablative conditioning regimens, with less GVHD following non-myeloablative regimens.
    Keywords:  Sickle cell disease; conditioning regimen; hematopoietic cell transplantation; matched related donor
    DOI:  https://doi.org/10.1016/j.jtct.2025.05.004
  6. J Obstet Gynaecol Can. 2025 May 15. pii: S1701-2163(25)00164-1. [Epub ahead of print] 102924
    Safety of Hydroxyurea in Pregnancy: A Systematic Review of the literature.
    Ruqaiya Al Sulaimani, Natalie Zitoun, Hessah Alothman, Janine R Hutson, Facundo Garcia-Bournissen.
       INTRODUCTION: Hydroxyurea (HU) is an antimetabolite drug used to manage several hematological conditions, including chronic myeloid leukemia (CML) and sickle cell disease (SCD). Animal studies and limited human data have raised concern that HU exposures in pregnancy may increase the risk of congenital malformations or abnormal fetal growth. Although the quality of evidence is low, it has been recommended that HU is discontinued at least 3 months prior to conception.
    METHODS: We systematically reviewed all published studies up to July 2024 describing pregnancy and neonatal outcomes following HU exposure during pregnancy.
    RESULTS: A total of 329 articles went through title and abstract screening, which resulted in 54 articles undergoing full-text review, and 15 articles were finally eligible for data extraction. These 15 studies included in the review, published between 1993-2023, comprised 7227 pregnancies, with 567 pregnancies (7.8%) exposed to HU. Patient ages ranged from 17 to 45 years. Most patients had SCD (n = 502), followed by CML (n = 26), essential thrombocythemia (n = 24), and chronic myeloid splenomegaly (n = 2). In 13 cases, the underlying disease was not specified. Timing of exposures to HU varied from conception till throughout pregnancy. Neither teratogenic nor hematologic effects on the fetus were observed in these cases.
    CONCLUSION: Pregnancy risks associated to HU are lower than anticipated. Use of HU in pregnancy may be justified considering the significant risks associated to untreated conditions such as SCD.
    DOI:  https://doi.org/10.1016/j.jogc.2025.102924
  7. Br J Haematol. 2025 May 19.
    Physical activity, vaso-occlusive crises and pain in patients with sickle cell anaemia in Senegal.
    Mor Diaw, Mame Saloum Coly, Keyne Charlot, Matthieu Gallou-Guyot, Motohiko Miyachi, Tsukasa Yoshida, Macoura Gadji, Saliou Diop, Blaise Felix Faye, Arame Mbengue, Abdoulaye Samb, Sarah Skinner, Elie Nader, Brigitte Ranque, Philippe Connes, Julien Tripette.
      Acute physical exercise may trigger vaso-occlusive crises (VOC) in patients with sickle cell anaemia (SCA), creating uncertainty around physical activity (PA) recommendations. This cross-sectional study examined the relationships between PA, VOC and steady-state pain in 104 Senegalese male patients with SCA. PA was objectively measured over 5 weeks, recording daily steps and time spent in different PA intensities (expressed in metabolic equivalent of task, MET). VOC occurrence was tracked, and steady-state days excluded VOC days plus 2 days before and after. Pain frequency and intensity on steady-state days were recorded via diaries, and blood viscosity was measured. Ninety-eight patients (29 ± 8 years old) completed the study, averaging 9611 ± 4040 steps/day, with 293 ± 108, 64 ± 69 and 28 ± 32 min in ≥1.5, ≥3.0, and ≥6.0 MET PA respectively. Median daily step count and PA duration were not associated with VOC occurrence. However, higher step counts and more time in ≥1.5 and ≥6.0 MET PA correlated with lower pain frequency and intensity (on steady-state days) and lower blood viscosity. These findings suggest that PA may benefit patients with SCA, but further research is needed to establish guidelines.
    Keywords:  activity tracker monitor; pain; physical activity; sickle cell anaemia; vaso‐occlusive crisis
    DOI:  https://doi.org/10.1111/bjh.20150
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