Director Transfusion Medicine Boston Children’s Hospital Boston, Massachusetts
Proposed Session Description: The emergence of gene therapy for sickle cell disease (SCD) has underscored the role of red blood cell (RBC) transfusion, not only in chronic disease management and acute prophylaxis, but as preparative intervention supporting hematopoietic stem cell mobilization, apheresis collection, and pre-transplant conditioning for cell and gene therapy (CGT). Patients with SCD present physiologic and immunohematologic complexities that influence mobilization, starting material quality, and downstream cellular manufacturing performance.
Transfusion can meaningfully impact each phase of the gene therapy journey. Yet sustaining multi-month transfusion regimens remains challenging for blood centers and clinically complex for alloimmunized patients. This session presents a precision-based transfusion framework integrating intraprocedural kinetic data with clinical outcomes to optimize RBC exchange practice, reduce blood product utilization, and expand CGT access.
Components
1. Preparative Transfusion Regimens and Stem Cell Mobilization in SCD Examines how structured preparative transfusion regimens influence the hematopoietic stem cell compartment, including the quantity and quality of CD34+ cells available for collection. The presentation will establish the case for metric driven, precision transfusion practice as a determinant of mobilization and collection success.
2. HbS Kinetics during RBCX and the Tailored Precision Approach Novel intraprocedural data characterize HbS depletion kinetics during RBCX, demonstrating a diminishing returns curve with disproportionate donor cell loss in later exchange phases. These findings support a tailored exchange strategy in which fewer RBC units achieve clinically meaningful HbS targets. Applications include optimization of prep transfusion regimens for gene therapy and refinement of RBCX protocols.
3. Alloimmunization as a Barrier to Curative Therapy and Strategies for Mitigation Alloimmunization represents a significant impediment to RBCX and eligibility for gene therapy or allogeneic transplantation in SCD. This component examines how efficient lower-volume RBCX strategies may reduce antigen exposure, attenuate alloimmunization risk, decrease demand for serologically compatible blood , and improve access to transformative CGT.
Learning Objectives:
Describe the physiologic rationale for preparative RBC transfusion in the context of stem cell mobilization and collection for gene therapy in SCD
Interpret intraprocedural HbS depletion kinetics and apply a tailored RBCX approach to clinical practice
Identify how alloimmunization limits access to curative therapies and discuss approaches to mitigate this risk through optimized transfusion practice
