Stella T Chou
VerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 1996–2026
About
Stella T Chou, M.D., is an Associate Professor of Pediatrics (Hematology) at the Children's Hospital of Philadelphia. Her clinical expertise includes Pediatric Hematology, Transfusion Medicine, and transfusion therapy in sickle cell disease. Her research focuses on regenerative blood cellular therapy, the mechanisms of normal human hematopoietic development, and how these processes are disrupted in hematologic diseases. Dr. Chou's laboratory uses induced pluripotent stem cells (iPSCs) and primary human cells to model blood diseases and develop customized iPSCs with rare blood group antigen combinations as renewable sources of red cells. Her translational work has been at the forefront of integrating molecular technologies into clinical transfusion medicine and developing novel tools to improve red cell therapy, especially for individuals with sickle cell disease. She investigates mechanisms of hematopoietic development, the role of genetic modifiers in pediatric hematologic diseases, and aims to improve red blood cell therapy through innovative approaches such as creating genetically matched blood products. Dr. Chou has contributed to understanding the genetic factors influencing blood transfusions and has been involved in creating customized blood cells for transfusion support, with ongoing research into the genetic matching of blood group loci to prevent alloimmunization.
Research topics
- Medicine
- Internal medicine
- Genetics
- Biology
- Cell biology
- Immunology
- Cancer research
Selected publications
Rare antigen‐negative red blood cells from pluripotent stem cells for precision transfusion medicine
Transfusion · 2026-04-24
articleOpen accessSenior authorCorrespondingBACKGROUND: Blood bank identification of antibodies against high-prevalence antigens remains a challenge due to the scarcity of antigen-negative reagent red cells sourced from blood donors. The MAM antigen, encoded by EMP3, is one such antigen associated with red cell alloimmunization and hemolytic disease of the fetus and newborn. STUDY DESIGN AND METHODS: We used CRISPR-Cas9 gene editing to generate an EMP3 knockout (EMP3KO) induced pluripotent stem cell (iPSC) line from a type O, Rh null parent line, enabling production of rare MAM-negative red blood cells. Since a prior study suggested that loss of EMP3 may enhance erythroid proliferation, we hypothesized that EMP3KO could both yield a rare reagent cell and potentially improve erythroid expansion to support scalable production. Transcriptomic analysis allowed us to further investigate the effect of EMP3 loss in late erythroblasts. RESULTS: EMP3KO cells differentiated efficiently into erythroid cells, showing >95% CD235/CD71 co-expression and orthochromatic erythroblast morphology. Compared to unedited cells, no proliferative advantage was observed, contrasting with prior non-isogenic cell models. Agglutination assays confirmed complete loss of MAM antigen and demonstrated the diagnostic utility for identifying MAM antibodies. Transcriptomic profiling of EMP3KO erythroblasts revealed expression of key erythroid genes, as well as regulators of proliferation and heme metabolism, was comparable to the parent line. DISCUSSION: This study demonstrates that iPSC technology combined with gene editing can generate rare antigen-negative RBCs for immunohematology applications. Beyond MAM, this platform offers a strategy to create additional rare RBC phenotypes, advancing precision transfusion medicine and improving antibody identification against high-prevalence antigens.
Blood Red Cells & Iron · 2026-02-05
articleOpen accessSenior authorF0B7 Rh and K-matched red cell units from racially similar donors minimizes foreign antigen exposure to 1.6 per transfusion for patients with SCD F0B7 Among 35 antigens, 22% of units from self-declared Black donors had no foreign antigen exposure to the recipient with SCD. Patients with sickle cell disease (SCD) have an elevated risk for alloimmunization due to frequent transfusions and antigenic disparities with donors. Extended antigen matching beyond Rh (CcEe) and Kell (K) can reduce alloimmunization but is not broadly applied due to logistic and economic challenges. Red cell antigen exposures may be minimized when donor and patient populations are from similar racial and ethnic backgrounds. This study assessed alloantigen exposure across 35 antigens in patients with SCD receiving transfusions from donors self-identifying as Black or Hispanic. Seven hundred units transfused to 28 chronically transfused patients were genotyped using a single nucleotide polymorphism-based assay. Combining Rh and K-matching with donor unit selection from racially similar populations, patients were exposed to an average of 1.6 antigens per transfusion, compared to the previously reported 3.5 exposures per transfusion across the same 35 antigens using a general donor inventory. Among 514 units transfused to Black recipients from Black donors, 22% had no foreign antigen exposure of 35 antigens. The most frequent alloantigen exposures were Jk b , S, and Do a . One clinically significant anti-Jk b formed during the study. These findings suggest combining donor unit selection with blood group genotyping may improve compatibility and transfusion safety for high-risk populations.
Blood Red Cells & Iron · 2026-03-01
articleOpen accessSenior author• Isovolemic hemodilution red cell exchange (IHD-RCE) can reduce donor red cell requirements when > 4 RBC units per RCE are needed. • IHD-RCE may increase donor red cell requirements in pediatric patients with total blood volumes ≤ 3500mL compared to standard-RCE Chronic red blood cell (RBC) transfusions are essential for sickle cell disease (SCD) management, but the cumulative demand for donor RBCs strains blood supplies and increases risks of iron overload and alloimmunization. Isovolemic hemodilution red cell exchange (IHD-RCE) is a two-step procedure designed to reduce RBC requirements, but its effectiveness remains unclear, particularly in pediatric patients. We conducted a retrospective cohort study of 45 children and young adults with SCD, each receiving standard-RCE followed by IHD-RCE, comparing within-patient RBC utilization between RCE types. Inclusion required ≥6 consecutive standard-RCEs and ≥6 consecutive IHD-RCEs within a year of each other. Across 2,667 RCE procedures, paired analyses demonstrated both standard and IHD-RCE required a median of 1.2 RBC units per liter of total blood volume (TBV; P = .3017). Adjusted analyses showed that IHD-RCE increased RBC requirements for patients with TBV ≤3500mL. Although not statistically significant, IHD-RCE offered modest RBC savings in patients with TBV >4500 mL. Stratified analysis showed IHD-RCE related savings only for patients requiring > 4 RBC units per transfusion before transitioning from standard-RCE to IHD-RCE ( P = .0186). These findings challenge the assumption that IHD-RCE universally reduces donor blood needs. In patients with low TBV or RBC needs, IHD-RCE does not reduce, and may even increase RBC utilization. Our findings underscore the importance of individualized transfusion strategies, especially during growth and puberty, as not all patients benefit from IHD-RCE.
Red cell antibody and antigen patterns in patients with sickle cell disease: A multi‐center analysis
Transfusion · 2026-04-12
articleBACKGROUND: Red cell alloimmunization complicates sickle cell disease (SCD) management despite current widespread prophylactic Rh/K matching in the United States (US). Regional antibody patterns remain poorly characterized. STUDY DESIGN AND METHODS: We conducted a retrospective analysis of 2965 SCD patients from 9 US sites (2010-2022). All hospitals prophylactically match for Rh and K antigens. Each site collected demographics, antigen status, antibody histories, and antibody screen results from their laboratory information system. RESULTS: Overall antibody prevalence was 29.7% with dramatic institutional variation (17.9%-56.0%). Alloantibody prevalence was 27.5%. Most autoantibody-positive patients (74.23%) also had alloantibodies, identifying a high-risk population. A third of patients with positive antibody histories had negative screens. Pediatric patients showed markedly different antibody profiles than adults. Hospitals' antibody patterns clustered by patient age rather than geography. Rh and K antibodies were the most common and also most likely to co-occur, followed by S, Fya, and Jkb antibodies. Antibodies against Jsa (1.82%), V (1.75%), and Kpa (1.69%) were more prevalent than anti-Jka (1.28%). Despite regional antibody variation, antigen frequencies remained overall consistent. In antigen-antibody pairwise comparisons, 3.15% were antigen-negative and antibody-positive reflecting alloimmunization; 0.47% were both antibody- and antigen-positive, suggesting partial/variant antigens. DISCUSSION: Substantial institutional variation in antibody prevalence suggests need for site-specific approaches to testing and prophylactic matching. High co-occurrence of auto- and alloantibodies, antibody immunogenicity patterns, and antigen-antibody discordances support the need for further research and consideration of refined testing and/or matching strategies beyond the current Rh and K standard.
Blood · 2025-11-03
articleOpen accessSenior authorAbstract Introduction: Human developmental hematopoiesis is a complex process occurring in sequential waves at different embryonic sites. This process yields both differentiated blood cells essential for embryonic development and hematopoietic stem cells (HSCs) necessary for lifelong blood cell production. There are at least two main hematopoietic programs during embryogenesis: a transient primitive wave that primarily generates myelo-erythroid progenitors in the yolk sac, and a definitive wave occurring in the aorta-gonad-mesonephros region which produces progenitors with expanded lineage potential and the first transplantable HSCs. A challenge in generating HSCs from induced pluripotent stem cells (iPSCs) is that many current methods recapitulate early developmental stages only, failing to produce transplantable HSCs and limiting their application for in vivo studies. We have previously shown that we can recapitulate fetal erythropoiesis using a protocol that produces definitive hematopoietic cells. Red cells generated with this method primarily produce fetal globin and are functionally distinct from primitive erythroblasts. Here, we adapted this method to a serum-free 3D culture system to produce definitive hematopoietic stem progenitor cells (HSPCs) from iPSCs to 1) evaluate long-term engraftment via xenotransplantation and 2) model a preleukemic disorder of fetal origin, transient abnormal myelopoiesis (TAM), which affects ~20% of neonates with Trisomy 21 (T21) and is associated with mutations in the key hematopoietic transcription factor GATA1. Methods We designed a serum-free 3D culture system that directs mesodermal commitment through Wnt pathway activation by manipulating developmental cues through retinoic acid signaling and shear stress. We transplanted 24 NBSGW mice with 1.2-2 million iPSC-derived HSPCs using 3 distinct wildtype (WT) lines and experimental batches. The 3D definitive differentiation was assessed using isogenic T21 iPSCs with wild type GATA1 or the truncated isoform lacking the N-terminus, GATA1s. Results Long-term repopulation was achieved up to 20 weeks post-transplant in the bone marrow (BM) of all engrafted mice (mean = 3.9±11.7% human HLA-ABC+) and in the peripheral blood of 16/24 mice. In mice with the highest level of engraftment (>10%), we detected human HSCs as well as myeloid, lymphoid, erythroid and megakaryocyte precursors in the BM, indicating complete hematopoietic reconstitution. Human CD34+ cells recovered from the graft retained multilineage potential in colony forming assays. Importantly, no leukemia or teratomas were observed in any of the transplanted mice. To assess whether this definitive iPSC culture protocol could faithfully model the fetal blood disorder TAM, we generated definitive HSPCs from T21/wtGATA1 and T21/GATA1s iPSCs. Both T21 lines generated budding HSPCs at day 15; however, the percentage of CD34+CD45+ HSPCs was lower compared to euploid controls (60.5% of WT ±12.9 for T21, and 64.5% of WT ± 0.06 for T21/GATA1s). In addition, at day 15 we observed a significant CD41+CD42b+ megakaryocyte population in both trisomy lines, consistent with the disease phenotype and that was not previously observed with our primitive hematopoietic differentiation protocols. Compared to WT controls, we observed a 2.3-fold and a 4.2-fold increased megakaryocyte population from T21/wtGATA1 and T21/GATA1s iPSCs, respectively. T21/GATA1s HPSCs also showed aberrant morphology with megakaryocytic and blast-like features. Conclusions These studies show that our serum-free 3D culture system can generate iPSC-derived HSPCs that can engraft immunodeficient mice, reconstitute different blood lineages, and persist for 20 weeks. Using a T21/TAM iPSC model, we found an enhanced megakaryocyte population in T21/wtGATA1 consistent with a phenotype we observed with primary human fetal liver hematopoiesis, but not with iPSC-derived primitive hematopoietic progenitors. Thus, T21/GATA1s definitive HSPCs recapitulate the enhanced megakaryopoiesis consistent with TAM in vitro. Ongoing xenotransplant experiments will help elucidate the interaction of trisomy 21 and GATA1s and provide a novel in vivo model to study and treat human hematological diseases.
P691: Genetic testing for inherited red blood cell disorders: Diagnostic yield and clinical utility
Genetics in Medicine Open · 2025-01-01
articleOpen accessInherited Red Blood Cell Disorders (IRBCD) in children and young adults are a heterogenous group of disorders caused by underlying genetic defects affecting various cellular aspects of red blood cell structure and function. These defects commonly involve enzymatic pathways, cell membrane structure and elasticity, and ribosomal proteins. Clinical symptoms include anemia, reticulocytopenia or reticulocytosis, jaundice and splenomegaly, and are often accompanied by other features such as congenital anomalies.
Emerging Considerations in Transfusion Medicine
Clinics in Laboratory Medicine · 2025-12-30
articleSenior authorCorrespondingStem Cell Reports · 2025-07-17 · 1 citations
articleOpen accessSenior authorTrisomy 21 (T21) is associated with baseline erythrocytosis, thrombocytopenia, neutrophilia, transient abnormal myelopoiesis (TAM), and myeloid leukemia of Down syndrome (ML-DS). TAM and ML-DS blasts harbor mutations in GATA1, resulting in the exclusive expression of the truncated isoform GATA1s. Germline GATA1s mutations in individuals without T21 cause congenital cytopenias, typically without a leukemic predisposition. To dissect the developmental effects of T21 and GATA1s, we used a combination of isogenic human induced pluripotent stem cells, primary human fetal and neonatal cells, and single-cell transcriptomics to interrogate hematopoietic progenitors differing only by chromosome 21 and/or GATA1 status. Both T21 and GATA1s induced early lineage skewing, and trajectory analysis revealed that GATA1s altered the temporal regulation of lineage-specific transcriptional programs, disrupting cell proliferation and maturation irrespective of chromosomal context. These studies uncovered unexpected heterogeneity and lineage priming in early, multipotent hematopoietic progenitors and identified transcriptional and functional maturation blocks linked to GATA1s.
Transfusion · 2025-07-16 · 1 citations
reviewOpen accessThe Association for the Advancement of Blood and Biotherapies (AABB) Clinical Transfusion Medicine Committee (CTMC) includes experts from various backgrounds in clinical transfusion medicine (TM). This committee conducts yearly assessments of significant developments in TM for the AABB Board of Directors. Beginning in 2018, these assessments have been summarized and published in the journal Transfusion, establishing an educational resource for practitioners in TM. What follows is a synopsis of key advancements derived from publications in calendar year 2024. CTMC members selected notable English-language publications relevant to TM from calendar year 2024. While all attempts were made to be comprehensive, our approach was not a systematic review with structured search methodology, nor did we formally evaluate evidence certainty. Specialists (2–3 CTMC members per topic) summarized key publications within their respective areas of interest, occasionally including contextual references. Each summary underwent independent review and editing by at least two CTMC members. The first and senior authors compiled these summaries and edited them for length and content to assemble the final manuscript. A meta-analysis of 80 studies covering 176 million transfusions found higher estimates of TRALI with active surveillance compared to passive surveillance.1 Pooled TRALI estimates among the active surveillance studies were 0.17/10,000 (95% confidence intervals [CI]: 0.03–0.43) s (RBCs), 0.31/10,000 (95%CI: 0.22–0.42) for platelets, and 3.19/10,000 (95%CI: 0.09–10.66) for plasma. Studies using passive surveillance estimates reported TRALI rates an order of magnitude lower, 0.02–0.10/10,000, depending on the component. Passive surveillance methods underreport TRALI, but the benefits of large-scale active surveillance must be weighed against potential costs. MiPLATE, a prospective, multicenter, randomized noninferiority trial of riboflavin and UV-light treated apheresis platelets (MIRASOL®, Terumo Blood and Cell Technologies, Lakewood, CO) versus conventional apheresis platelets in plasma showed increased days with World Health Organization (WHO) grade ≥2 bleeding in the MIRASOL® arm (1.7 vs. 0.6 days in the conventional arm, relative risk [RR] 2.79, 95% CI 1.67–4.67).2 This failed to meet the prespecified noninferiority margin of 1.6, and the trial was stopped for futility. Patients in the MIRASOL® arm required more platelet transfusions (RR = 1.22, 95% CI 1.05–1.41) and had a greater risk of platelet refractoriness. CRISP-HS, a prospective, phase 2, randomized, open-label trial evaluated CSP in 200 traumatically injured, non-pregnant patients at risk of bleeding and requiring large-volume transfusion.3 Participants were randomized to receive either a single CSP unit stored up to 14 days or usual care. The principal clinical outcome of 24-h mortality was seen in 6 patients in the CSP arm and 10 patients in the usual-care arm (difference −4.3%, 95% CI −12.8% to 3.5%). Only 47 (48%) participants in the usual-care arm received a platelet transfusion, at a median of 56 min after the average CSP transfusion. The possible prolonged storage time and safety of CSPs warrant further investigation; several trials are ongoing. A test targeting rRNA and DNA for the major causative agents of malaria (Plasmodium falciparum, Plasmodium knowlesi, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax) is the first NAT licensed by the FDA for screening whole blood donations.4 The test is highly sensitive (100% sensitivity at 3-5-fold the limit of detection) and specific (100% with 95% CI 99.982%–100%).4 While pathogen reduction technology (PRT) is considered effective for P. falciparum mitigation, it is not yet available for RBC components. Current screening is limited to the donor history questionnaire, which identifies donors with a history of malaria or those who have visited or lived in malaria-endemic areas. This current strategy defers 50,000 to 160,000 donors/year, but still fails to capture all asymptomatically infected donors, which has resulted in 13 transfusion-transmitted malaria cases from 2000 to 2021.5 Other recently developed tests include the new Brazilian NAT PLUS HIV/HBV/HCV/Malaria (Bio-Manguinhos/Fiocruz) kit, which can detect Plasmodium species in plasma samples and is sufficiently sensitive to detect subpatent infections.7 In addition, a second highly sensitive and specific rRNA-based test for Plasmodium species received a CE mark but has not been implemented for routine blood donor screening and is not available in the United States.8 A propensity-matched retrospective cohort analysis of surgical patients with iron deficiency anemia from the TriNetX Research Network compared preoperative treatment with IV iron (n = 77,179) or with RBC transfusions (n = 77,179).9 Preoperative iron was associated with lower postoperative mortality (RR, 0.63, 95% CI, 0.60–0.66), lower postoperative morbidity (RR, 0.76, 95% CI, 0.75–0.78), higher hemoglobin concentration (10.1 ± 1.8 g/dL vs. 9.4 ± 1.7 g/dL, p = .001), and fewer postoperative RBC transfusions (RR, 0.30, 95% CI, 0.29–0.31). The authors concluded that iron supplementation can improve patient outcomes, reduce blood utilization, and avoid the associated risks and costs of transfusion. Three multicenter RCTs—HEMOTION, TRAIN, and SAHARA—evaluated liberal versus restrictive RBC transfusion strategies in neurocritically ill adults.10-12 These studies varied in the hemoglobin thresholds defining liberal and restrictive strategies, type of neurologic injury, and primary neurologic outcome measure. In the HEMOTION trial, which included 722 patients with traumatic brain injury (TBI), a liberal transfusion strategy (hemoglobin ≤10 g/dL) was compared with a restrictive one (hemoglobin ≤7 g/dL).10 The liberal strategy did not significantly reduce the risk of unfavorable neurologic outcome at 6 months (overall RR, 0.93, 95% CI 0.83–1.04). Similarly, the SAHARA trial, involving 725 patients with aneurysmal subarachnoid hemorrhage (SAH), found no significant difference between a liberal transfusion strategy (hemoglobin ≤10 g/dL) versus a restrictive one (hemoglobin ≤8 g/dL) on the risk of unfavorable neurologic outcome at 12 months (risk ratio, 0.88; 95% CI, 0.72–1.09; p = .22).12 However, the TRAIN trial, which included 820 patients with several forms of acute brain injury (59% with TBI, 23% with SAH, 18% with intracerebral hemorrhage [ICH]), did identify a benefit to the liberal transfusion strategy (hemoglobin <9 g/dL) compared with a restrictive one (hemoglobin <7 g/dL) on neurologic outcomes at 6 months (adjusted RR, 0.86 [95% CI, 0.79–0.94]; p = .002).11 Although two trials showed no statistically significant difference, point estimates favored liberal strategies in all three trials. A future evidence synthesis could further inform transfusion strategy decisions for this patient group, if feasible. The HeLiX trial of 1245 participants with liver resection found no difference in RBC transfusion, intraoperative blood loss, or total estimated blood loss over 7 days; however, TXA was associated with more significant perioperative complications.13 In the STOP-MSU trial with 201 participants, TXA within 2 h of ICH symptom onset did not reduce hematoma expansion compared with placebo.14 In TREATT with 616 participants, TXA (IV or oral) did not reduce WHO grade ε2 bleeding or mortality in patients receiving chemotherapy or hematopoietic stem-cell transplantation for hematological malignancies.15 In an RCT of 530 patients with acute factor Xa inhibitor-associated ICH, andexanet alfa reduced ICH expansion on imaging, but had more arterial thrombotic events compared with standard of care.16 Although the control group included non-standardized use of prothrombin complex concentrate (PCC), there were similar 30-day mortality and functional outcomes. Trials with standardized use of PCC and longer-term clinical outcomes are needed to compare andexanet alfa versus PCC.17 UNITY was an international, open-label, phase 2 study of nipocalimab for hemolytic disease of the fetus and newborn (HDFN).18 Nipocalimab blocks the neonatal Fc receptor, preventing transplacental IgG transfer. This study enrolled pregnant women with prior severe fetal anemia, stillbirth, or HDFN-related placental pathology who had a critical anti-D or anti-K titer, carried a D-positive or K-positive fetus, and had no current treatment with intravenous immunoglobulin or plasmapheresis. Participants received IV nipocalimab (30 or 45 mg/kg) from 14 to 35 weeks' gestation. Live births occurred in 12 of 13 pregnancies with a median gestational age of 36 weeks and 4 days. Of the 12 live-born infants, 1 required one exchange transfusion and one simple transfusion, and 5 infants required only simple transfusions. Maternal samples and cord blood showed decreased alloantibody titers and IgG levels. Nipocalimab shows early promise as an important treatment for HDFN, though larger studies are needed. A multisite study evaluated RH genotypes and RBC alloimmunization rates in 342 chronically transfused patients with SCD.19 Despite serologic prophylactic antigen matching, RBC alloimmunization remained problematic and varied across sites (range 5%–41%). Genotyping using BeadChip arrays confirmed 33% with RHD and 57% with RHCE variant alleles in this cohort. No difference in anti-D, anti-C, or anti-E antibody formation was observed between individuals with variant versus conventional antigen expression. This study highlights the variability in alloimmunization rates in a population for which prophylactic Rh and K matching is widespread; a molecular approach might be necessary to further reduce alloimmunization rates in transfused SCD patients. A multicenter prospective study evaluated next-generation sequencing-based quantitative cell-free fetal (cff) DNA for fetal antigen genotyping in alloimmunized pregnancies at 120 US sites.20 The study included 156 pregnant patients (15.4% Hispanic, 9% non-Hispanic Black, 65.4% non-Hispanic White, 4.5% Asian, 1.3% more than one ethnicity, and 4.5% unknown ethnicity) mean gestational age of 16.4 weeks (range 10–37 weeks). Cell-free fetal DNA analysis was performed as part of prenatal care and validated with neonatal buccal swabs in a blinded laboratory. Concordance between cff DNA and neonatal genotype was determined for K, E, C, c, Fya, and D antigens. The investigators identified 145 instances in which the fetus was antigen positive and 320 instances in which the fetus was negative, with perfect concordance between prenatal cff DNA and neonatal genotyping. Cell-free fetal DNA testing is a promising technique for improved prenatal diagnosis and management of HDFN. A study analyzing 6 million blood donations from the United Kingdom (UK) and Australia found significant risk factors for high anti-A or anti-B titers (defined as IgM titer ≥128 in this study, although high titer definitions can vary).21 Female and group O donors were more likely to have high titers, whereas group B donors had the lowest proportion of high titer isoagglutinins. High titer positivity decreased with increasing donor age. Australian donors (37%) had higher rates of high titer versus the UK donors (9%). No obvious seasonal variation in titers was observed in either country. In the UK, donors identifying as Black, Asian, other, or mixed ethnicity were approximately twice as likely to have high titers compared to White donors after controlling for ABO group and sex. The authors conclude that age, sex, and self-reported ethnic background are strong predictors of high anti-A and anti-B titers. In a post-hoc secondary analysis of the Transfusion of Prematures (TOP) RCT, 1690 ELBW infants were included (mean [SD] gestational age, 26.0 [1.5] weeks; 899 infants [53.2%] were female).22 After categorizing 4947 hazard periods (72 hours after transfusion) and 5813 control periods, 133 NEC cases were identified. Fifty-nine of these cases (44.4%) occurred during hazard periods. Baseline and clinical characteristics of infants with NEC during hazard periods did not differ from those of infants with NEC during control periods. The adjusted RR was 0.95 (95% CI, 0.68–1.32). The findings suggest that, among ELBW infants with the hemoglobin ranges occurring in the TOP trial, exposure to RBC transfusions was not temporally associated with a higher risk of NEC during 72-h posttransfusion periods. An observational cohort study and secondary analysis of the Preterm Erythropoietin Neuroprotection Trial evaluated 819 infants (429 [52.4%] male; mean [SD] gestational age, 25.5 [1.1] weeks), 245 (30%) who received at least one platelet transfusion during initial hospitalization.23 The primary outcome of death or severe NDI occurred in 46.5% (114 of 245) of infants transfused with platelets and 13.9% (80 of 574) of untransfused infants. After adjusting for propensity score, gestational age at birth, and trial treatment group, death or severe NDI was more common after platelet transfusion (adjusted odds ratio 2.43, 95% CI, 1.24–4.76). Platelet transfusion in extremely preterm infants may be associated with increased risk of death or severe NDI at 2 years' corrected age. The underlying mechanisms remain unknown. An international prospective observational cohort study across 64 NICUs in 22 European countries examined RBC transfusion in 1143 preterm infants (<32 weeks' gestation).24 Overall RBC transfusion prevalence rate during postnatal days 1–28 was 3.4 transfusion days per 100 admission days, with considerable variation across countries, only partly explained by patient mix. By day 28, 36.5% (95% CI, 31.6%–41.5%) of infants had received at least one transfusion. Most transfusions (82.8%) were given based on defined hemoglobin thresholds. Pre-transfusion hemoglobin levels per study threshold were below the restrictive thresholds implemented in ETTNO in 324 of 729 transfusions (44.4%) and TOP in 265 of 729 (36.4%).25, 26 Conversely, they were between restrictive and liberal thresholds in 352 (48.3%) and 409 (56.1%) of transfusions, respectively. An international steering committee, parent representatives, and stakeholder organization member panel provide a clinical practice guideline recommending restrictive RBC transfusion strategy, with moderate certainty of evidence, for preterm neonates with less than 30 weeks' gestation.27 The group reviewed evidence from a systematic review of 6 RCTs including 3483 participants to compare high versus low hemoglobin-based thresholds. The findings suggest lower hemoglobin thresholds likely result in little to no difference in key short-term and long-term outcomes. Consequently, the guideline recommends a restrictive transfusion strategy, with specific hemoglobin thresholds based on postnatal age and respiratory support requirements. For instance, during postnatal weeks 1, 2, and 3 or more, the recommended hemoglobin thresholds for neonates on respiratory support are 11, 10, and 9 g/dL, respectively; for those on minimal or no respiratory support, the thresholds are 10, 8.5, and 7 g/dL, respectively. A survey of 22 US apheresis centers found that TPE was the most common procedure, followed by hematopoietic progenitor cell collections and RBC exchanges.28 CAR-T-cell collections were a consistent area of growth. The average nurse-to-patient ratio was 1.2, but the COVID-19 pandemic and increased cellular collections created staffing challenges for many programs due to the need for specialized staff. Gene therapy treatments, particularly for SCD, have further increased demand for cellular collections.29-31 Sufficient mobilization of hematopoietic stem cells (HSC) for patients with SCD is complicated by impaired bone marrow microenvironment, myelosuppressive effect of hydroxyurea (HU), and contraindication to granulocyte colony-stimulating factor (G-CSF). Response to plerixafor alone may be limited, necessitating multiple collection days to achieve the desired CD34 yield. In some cases, multiple stimulation/collection cycles, separated by at least 2–4 weeks, are necessary. Past trials have shown that HU discontinuation and pre-mobilization RBC exchange (an additional apheresis need) are beneficial.32 Nevertheless, during gene therapy clinical trials, 5–10% of participants could not be treated due to insufficient HSC yields.29, 30 ECP remains a treatment option for acute and chronic GVHD following allogeneic HSC transplantation;33 however, JAK inhibitors have changed treatment priorities. For acute GVHD, ruxolitinib is now the preferred second-line therapy for acute GVHD with ECP used in cases of severe disease or in combination with ruxolitinib.35 For chronic GVHD, ECP is still valuable in refractory cases, particularly for steroid-sparing benefits, though newer agents, like belumosudil and axatilimab, are expanding treatment alternatives.34, 35 A retrospective study compared 42 iTTP episodes treated with caplacizumab and immunosuppression alone versus standard therapy (TPE, corticosteroids, rituximab).36 There were no significant differences in time to platelet count normalization (median: 3 vs. 4 days), clinical response, or iTTP-related mortality. The TPE-free approach reduced hospital stays and intensive care unit admissions. Despite these findings, certain patients did require subsequent TPE, possibly due to concomitant disease such as infection. These findings suggest the potential for a paradigm shift in iTTP management. Two phase 3, single-group, open-label studies were reported of exagamglogene autotemcel (exa-cel, Vertex Pharmaceuticals Incorporated), a nonviral genetically modified hematopoietic stem cell therapy that reactivates fetal hemoglobin synthesis.37, 38 In a study of 44 patients with SCD with recurrent severe vaso-occlusive crises, of 30 patients with were from vaso-occlusive and all 30 did not require for vaso-occlusive for at least 12 In a study, patients with transfusion occurred in of 35 patients with with a mean total hemoglobin of gene therapy autotemcel a to genetically hematopoietic the of a modified hemoglobin A in patients with following therapy remains a but A a patient with multiple who developed following antigen analysis that the had the While have high this the need for long-term surveillance and improved to A study gene therapy for severe A promising participants received with the Patients who received significantly higher (median: compared with those participants remained from bleeding events over a median of 14 These findings the potential of HSC therapy as a treatment for an to In the FDA to the first therapy for or based on a multicenter, open-label, phase 2 clinical The study included patients with or who had received at least one prior The rate was among patients who received the recommended of to blood collection sites in showed lower rates of blood collections in with a higher proportion of = 95% CI p to blood may the blood and donor A panel of international experts defined a blood as a clinical demand for blood be in a and in at least of transfusion is White on three potential strategies, blood intraoperative and blood and challenges in the need for blood in these is a to from of and as for received from Terumo and The authors have no of to
Blood · 2025-11-03
articleAbstract Background: The current treatment landscape for SCD is limited, and treatment options have associated risks and can be burdensome for patients. Red blood cell (RBC) transfusions are indicated to treat or prevent complications, like severe anemia, acute multi-organ failure, vaso-occlusive crises (VOC), acute chest syndrome (ACS), and stroke. However, every RBC transfusion administered carries risks, such as iron overload, alloimmunization, or delayed hemolytic transfusion reactions (DHTR) that can be life-threatening. Voxelotor is a treatment for SCD that inhibits the polymerization of sickle hemoglobin (Hb) and has shown clinical benefit on Hb levels, which may decrease the need for RBC transfusions. Pfizer voluntarily withdrew voxelotor from the market on September 25, 2024, due to emerging preliminary data that showed the benefit of voxelotor may no longer outweigh the risk. Objective: This observational study using claims data aimed to determine if treatment with voxelotor reduces RBC transfusion rates compared to matched controls not treated with voxelotor. Methods: This non-interventional, real-world study aimed to evaluate the effect of voxelotor on the reduction of RBC transfusion burden in patients with SCD ≥ 12 years of age in the US with at least two visits with a transfusion in the prior 365 days (baseline). The study period was November 25, 2018 - January 31, 2024. The study used the Komodo Healthcare Map (KHM) database linked to Claritas prescription data (proprietary voxelotor claims) and Quest Diagnostics lab data. The study population included patients with a new prescription claim for voxelotor (no use 365 days prior) in the exposed group, while the control (non-voxelotor) group included coarsened exact matched 1:4 (voxelotor to controls) patients who did not have a prescription claim for voxelotor. Propensity score (PS) matching using variable-ratio (1:2) greedy nearest neighbor matching with a caliper distance of 1% was used to balance baseline confounders between the two groups. Potential confounding covariates were assessed for balance using absolute standardized differences (ASD); covariates that remained imbalanced (ASD &gt; 0.1) after the matching process were adjusted for in outcome models. Patients were followed from the index date (matched voxelotor prescription date) until disenrollment, death, discontinuation of voxelotor, or the occurrence of exclusion criteria. To account for variable follow-up for each patient, outcomes were assessed as per-patient-per-year (PPPY). Results: After PS matching, the voxelotor and non-voxelotor groups consisted of 164 and 289 patients, respectively. The mean follow-up was 288 days in the voxelotor group and 333 days in the non-voxelotor group. The mean (SD) age of patients was 33.0 (16.0) years in the voxelotor group and 31.6 (15.4) years in the non-voxelotor group. The mean (SD) number of VOCs during the baseline period was 5.5 (5.4) in the voxelotor group and 5.6 (5.7) in the non-voxelotor group. The voxelotor and non-voxelotor groups were balanced with the majority of absolute standardized difference values for the covariates ≤ 0.1. The voxelotor group had 5.3 RBC transfusions PPPY at baseline and 3.4 RBC transfusions PPPY in follow-up for a reduction of 1.9 RBC transfusions PPPY, compared to the non-voxelotor group who had 5.5 RBC transfusions PPPY in baseline and 4.9 RBC transfusions PPPY in follow-up for a reduction of 0.6 RBC transfusions PPPY. The difference in the rate change was -1.3 RBC transfusions PPPY (95% CI: -2.1, -0.6; p&lt;0.001). In the voxelotor group, 61.6% experienced &gt;30% reduction in RBC transfusions between baseline and follow-up compared to 48.1% of the non-voxelotor group (odds ratio: 1.8; 95% CI: 1.2, 2.6). Additionally, 34.1% of the voxelotor group had no RBC transfusions during follow-up, compared to 29.1% in the non-voxelotor group (odds ratio: 1.3; 95% CI: 0.9, 1.9). Discussion: In individuals with SCD and a history of RBC transfusions, voxelotor led to a statistically significant reduction in RBC transfusions PPPY compared to matched controls in this real-world study using medical claims data. This study suggests that transfusion rate may be improved with voxelotor and further studies are needed to confirm these findings. The impact of voxelotor on other clinically relevant endpoints, such as VOCs, still needs to be evaluated.
Recent grants
RH genotype matched red cell transfusions for patients with sickle cell disease
NIH · $3.4M · 2019–2025
NIH · $7.3M · 2016–2025
NIH · $2.0M · 2020
NIH · $1.0M · 2016–2023
Understanding the complexity of gene dosage imbalance in Down syndrome
NIH · $3.4M · 2019–2024
Frequent coauthors
- 61 shared
Deborah L. French
- 60 shared
Mitchell J. Weiss
St. Jude Children's Research Hospital
- 42 shared
Connie M. Westhoff
New York Blood Center
- 33 shared
Christopher S. Thom
Children's Hospital of Philadelphia
- 31 shared
David F. Friedman
Children's Hospital of Philadelphia
- 27 shared
Paul Gadue
Children's Hospital of Philadelphia
- 24 shared
Kaoru Takasaki
Children's Hospital of Philadelphia
- 22 shared
Alyssa Gagne
Labs
Chou LaboratoryPI
Awards & honors
- Featured article in Am J Hum Genet (2022)
- Featured article in Blood (2018)
- Featured article in Blood Adv (2017)
- Featured article in J Clin Invest (2015)
- Featured article in Cell Stem Cell (2016)
- Resume-aware match score
- Save to shortlist
- AI-drafted outreach
See your match with Stella T Chou
PhdFit ranks faculty by your research interests, methods, and publications — grounded in their actual work, not templates.
- Free to start
- No credit card
- 30-second signup