bims-sicedi 2026-01-25 papers

Pediatr Blood Cancer. 2026 Jan 19. e70143

Liquid Hydroxyurea (Xromi) for Children With Sickle Cell Anemia: A New Solution Compounding Existing Problems.

Keywords: drug access; sickle cell disease; social determinants of health

DOI: https://doi.org/10.1002/1545-5017.70143

Blood Adv. 2026 Jan 21. pii: bloodadvances.2025018529. [Epub ahead of print]

Apohemoglobin-Haptoglobin Complex is a Therapeutic Against Vaso-Occlusive Crisis: Scavenging of Hemoglobin and Heme.

Carlos Jose Munoz, Ivan S Pires, Daniela Lucas, Cynthia R Muller, Jacinda Martinez, Srila Gopal, Andre F Palmer, Pedro Cabrales.

Sickle cell disease (SCD) leads to vaso-occlusive episodes (VOEs) releasing cell-free hemoglobin (Hb) and heme that drive oxidative stress, inflammation, and microvascular dysfunction. Current treatments for VOEs remain limited with no targeted therapies addressing these hemolytic byproducts. This study investigated the potential of an apohemoglobin-haptoglobin (ApoHb-Hp) complex (protein scavenger of both Hb and heme) versus haptoglobin (Hp) (scavenger of only Hb), in transgenic SCD mice exposed to hypoxia-reoxygenation. Briefly, HbSS-Townes mice instrumented with a dorsal skinfold window chamber received ApoHb-Hp (150 mg/kg), Hp alone (150 mg/kg), or an equal volume of saline vehicle, groups were compared to HbAA controls. At the same dose ApoHb-Hp had reduced Hb-binding capacity compared to Hp alone, but it possessed heme-binding capacity from the associated apoHb moiety. Despite the reduced Hb-binding capacity, ApoHb-Hp produced significantly greater protective effects than Hp alone. During hypoxia, ApoHb-Hp preserved >90% of baseline arteriolar and venular flow, while untreated and Hp-treated mice exhibited >50% reductions. Functional capillary density (FCD) at 72 hours post-hypoxia declined by 80% in untreated mice and 44% in Hp-treated mice, but only 27% in ApoHb-Hp-treated mice. Pulmonary inflammation was significantly lower in ApoHb-Hp-treated mice compared to Hp-treated mice, with reduced numbers of macrophages (15 ± 2 vs. 18 ± 3), neutrophils (5 ± 1 vs. 7 ± 1), and lymphocytes (18 ± 4 vs. 20 ± 3). The increased effectiveness of ApoHb-Hp, is due to its unique dual-scavenging mechanism. This addresses both Hb and heme toxicity, which each contribute to the pathophysiology of SCD. These findings indicate that the ApoHb-Hp complex is a promising therapeutic option for SCD.

DOI: https://doi.org/10.1182/bloodadvances.2025018529

Paediatr Anaesth. 2026 Jan 20.

Perioperative Outcomes and Sickle Cell Crisis in Children With Sickle Cell Disease: A Retrospective Observational Study.

Max M Feinstein, Ling Guo, Anthony Habib, May Hua, Guohua Li, Caleb Ing.

BACKGROUND: Sickle cell disease (SCD) is an inherited hemoglobinopathy affecting approximately 100 000 Americans, disproportionately affecting Black individuals. Sickling of hemoglobin S red blood cells due to conditions in the perioperative period including hypoxemia, hypothermia, surgical stress, and pain can reduce organ perfusion and lead to adverse outcomes including pain crisis, acute chest syndrome, and stroke.
AIMS: This study evaluates perioperative outcomes and risk factors for sickle cell crisis in children with SCD undergoing common inpatient surgical procedures.
METHODS: A retrospective cohort was created using the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) 2003-2019. Hospital admissions for children < 18 years of age undergoing a selected group of surgical procedures (cholecystectomy, appendectomy, congenital cardiac surgery, and posterior spinal fusions) commonly requiring inpatient stay were included. Diagnoses and procedures were identified using ICD-9/ICD-10 codes. Perioperative outcomes included post-operative length of stay (LOS), blood transfusions, hematologic, and infectious complications. Children with SCD were compared to those without SCD using multivariable Poisson regression to adjust for surgical procedure and sociodemographic, clinical, and hospital characteristics.
RESULTS: Of 5 75 005 children studied, 2357 (0.4%) had SCD. Relative to children without SCD, those with SCD had a longer post-operative LOS (adjusted incidence rate ratio [aIRR]: 1.29; 95% CI [1.26-1.32], p < 0.001). Children with SCD hospitalized for a surgical procedure were also more likely to receive a blood transfusion (adjusted risk ratio [aRR]: 13.1; 95% CI [12.1-14.2], p < 0.001). Significantly increased associated risks of hematologic and infectious complications, however, were not observed. Of children with SCD, 17.5% experienced a sickle cell crisis during hospitalization. The odds of sickle cell crisis in non-elective admissions were more than three times as high as in elective admissions (aOR 3.36; 95% CI [2.46-4.60], p < 0.001). Children with sickle cell crisis had a longer post-operative hospital stay (aIRR: 1.58; 95% CI [1.49-1.67]) than those without a crisis.
CONCLUSIONS: The perioperative course in children with SCD was associated with longer postoperative length of stay and higher blood transfusion rates relative to those without SCD undergoing similar surgical procedures. Perioperative sickle cell crisis was present in more than one out of six admissions, more common in non-elective admissions, and is associated with excess length of stay.

Keywords: anesthesia; pediatrics; sickle cell; surgery

DOI: https://doi.org/10.1002/pan.70130

Blood Adv. 2026 Jan 22. pii: bloodadvances.2025017413. [Epub ahead of print]

Bone marrow transplantation for sickle cell disease using post-transplantation cyclophosphamide and 400 cGy TBI.

Marti Goldenberg, Ravi Varadhan, Christopher J Gamper, Kenneth R Cooke, Alexander J Ambinder, Heather J Symons, Lydia H Pecker, Richard J Jones, Robert A Brodsky, Javier Bolaños-Meade.

Reduced intensity conditioning (RIC), haploidentical donors, and post-transplantation cyclophosphamide (PTCy) have overcome many barriers associated with bone marrow transplantation (BMT) for sickle cell disease (SCD). However, initial approaches had high graft failure rates. Our preliminary data suggested increasing the total body irradiation (TBI) dose from 200 to 400 cGy could improve engraftment. This study included SCD patients aged 2-70 undergoing BMT from November 2014 - January 2025. The regimen included anti-thymocyte globulin, fludarabine, cyclophosphamide, and single fraction 400 cGy TBI. Graft-vs-host disease (GVHD) prophylaxis included PTCy, mycophenolate mofetil, and sirolimus. Outcomes measured were disease-free survival (DFS), graft failure, overall survival (OS), and GVHD incidence. Forty-three patients (median age 23) were transplanted. Thirty-four (79%) had >2 indications for BMT and all had >2 SCD comorbidities. Five-year OS probability was 95.5% (CI 0.87 - 1.0) at a median follow-up of 2.43 years. DFS probability at 2 years was 94.5% (CI 0.87 - 1.0) with only 2 (5%) graft failures. Two patients died late (2.5 and 6 years) after BMT. The cumulative incidence of grades 3-4 acute GVHD was 2.4% (CI 0 - 0.07) and moderate-severe chronic GVHD was 7.3% (CI 0 - 0.15). Median time to discontinuation of immunosuppression was 354 days. Of the 27 female patients, 12 had return of menses and/or normalized gonadal function. RIC haploidentical BMT with 400 cGy maintained a low toxicity profile, provides high rates of durable engraftment, and may preserve fertility. This regimen expands the availability of curative therapy for severe SCD. NCT00489281.

DOI: https://doi.org/10.1182/bloodadvances.2025017413

Kidney360. 2026 Jan 21.

Kidney Function Decline in Sickle Cell Disease: Associations with Renin Angiotensin System Inhibitors.

Kabir O Olaniran, Alecia C Nero, Orson W Moe, Robert D Toto, S Susan Hedayati.

BACKGROUND: Sickle cell disease (SCD) is associated with accelerated kidney function decline, with no proven effective therapies. We examined the associations between treatment with renin-angiotensin system inhibitors (RASi) and eGFR decline in SCD.
METHODS: This 2-center observational study used electronic health record data of adult, Black patients with SCD (by hemoglobin electrophoresis) and ≥1 year follow-up between 2010-2024. We compared incident RASi users (exposure) to no treatment (reference). We created 1:1 propensity score-matched cohorts, balancing on demographics, vital signs, comorbidities, medications, and laboratory values. The primary endpoint was the difference in the mean change in eGFR per year, analyzing only chronic slopes (≥90 days post-index date) using linear mixed models on the matched cohorts. Sensitivity analyses were performed excluding patients with missing albuminuria and excluding low-dose RASi. Effect modification by SCD-modifying therapies was also examined.
RESULTS: Matched cohorts identified were primary analysis (358 patients), excluding missing albuminuria data (262 patients), and excluding low dose RASi (270 patients). All cohorts achieved optimal standardized mean differences < 0.2. After multivariable adjustment, there was no significant difference in eGFR decline between RASi and the reference in the primary cohort (-0.15 mL/min/year; 95% confidence interval [CI], -1.67 to +1.36; p = 0.84), the sensitivity analysis cohort excluding missing albuminuria data (+0.89 mL/min/year; 95% CI, -0.86 to +2.63; p = 0.32) and the sensitivity analysis cohort excluding low dose RASi (+0.78 mL/min/year; 95% CI, -1.12 to +2.67; p = 0.42). All p values for interaction terms between RASi and SCD-modifying therapies in all models were > 0.05.
CONCLUSIONS: In this large, real-world cohort of patients with SCD, RASi use was not associated with slowed eGFR decline. These findings underscore the limitations of observational data and highlight the urgent need for prospective trials to identify effective GFR-preserving therapies for this high-risk population.

DOI: https://doi.org/10.34067/KID.0000001116