Rheologic Assessments of Sickle Cell Patients Post Allogeneic Hematopoietic Cell Transplant

Abstract

<h3>Introduction</h3> Red blood cell (RBC) rheology is markedly abnormal in sickle cell disease (SCD) and is associated with clinical complications. Even fully oxygenated, sickle RBC are less deformable than those of HbAA or HbAS individuals; upon deoxygenation, deformability further declines. The goal of any cell-based therapy of curative intent should be to normalize SCD RBC rheology. We propose to functionally assess a series of post-allogeneic hematopoietic cell transplant (alloHCT) patients (pts) with SCD using rheological biomarker measurements of deformability and sickling to determine if the rheology has been normalized. <h3>Methods</h3> Blood from 6 SCD pts post-alloHCT were analyzed using an ektacytometer with oxygenscan (Lorrca) to measure RBC deformability (elongation index EI), under a range of pO₂ (150-0 mmHg). EImax is the deformability of the oxygenated sickle RBC; EImin is the deformability of deoxygenated RBCs. The point of sickling (PoS) is the pO₂ at which RBC deformability rapidly declines. Reference ranges were generated using n=45 HbSS samples age 2-21, on hydroxyurea, chronic transfusion, or untreated; n=14 HbAS, and n=43 HbAA. <h3>Results</h3> Figure 1 shows measurements obtained on 5 pts post alloHCT with a range of donor chimerism, as well as typical values for HbAA, HbAS, and HbSS. Pts 1 and 3 exhibit normal rheology; both were transplanted with an HbAA donor, had high chimerism and no detectable HbS. Pt 2 had 40% whole blood chimerism and hbS < 50%, yet their plot resembles that of untransplanted HbSS. Pts 5 and 6 exhibit rheology in the HbAS range; they have intermediate chimerism from an AS donor. Pt 2 is the only subject with values in the HbSS range, and the only subject with SCD symptoms. Clinical details and biomarker values for all 6 analyzed are in Table 1, as well as ranges of rheological values for HbSS and HbAS pts generated in the Sheehan and Shevkoplyas labs. <h3>Conclusions</h3> Current HCT evaluation depends on chimerism and hemoglobin profiles, and do not assess RBC function. Using the Lorrca with oxygenscan, we identified a post-alloHSCT patient with rheological values consistent with an HbSS patient despite donor chimerism >20% and HbS <50% thought sufficient for cure from an HbAA donor. Our results suggest that this functional analysis may help with management post-alloHCT and may be essential in assessing new gene-based therapy approaches to curing pts with SCD.