Hypoxic Storage Could Extend Red Blood Cell Life, Thereby Reduce Transfusion Frequency in Hematologic Malignancies

Steven L. Spitalnik, MD

Improvements in blood storage that extend the life of red blood cells (RBCs) will ultimately allow patients with hematologic malignancies to receive fewer transfusions less often, according to Steven L. Spitalnik, MD. This is the aim of a new storage system from Hemanext, which stores RBCs under hypoxic conditions, to reduce the oxidative stress on the stored RBCs.

“The concept behind Hemanext is to take our understanding of red cell storage biology and use that to hopefully make a better product, where we understand the dosage better, we understand the activity better, and the patient get better outcomes,” Spitalnik said. “The data to date suggests that it is true, and that at the outage we have more red cells circulating, and they circulate longer. Particularly in the chronic transfusion setting, this should lead to fewer transfusions and a better quality of life for our patients.”

In an interview with OncLive^®, Spitalnik, co-director of laboratory of transfusion biology, professor of pathology and cell biology, and vice-chairman of laboratory medicine at Columbia University Medical Center, discussed the evolution of RBC storage and the potential impact the Hemanext storage technique could have for patients with hematologic malignancies.

OncLive^®: What is the current standard for blood storage? What developments have we seen in those methods?

Spitalnik: Currently, the Hemanext product relates only to RBC storage. The way we currently store RBCs is similar to what we have been doing for the last 30 to 40 years. Whole blood is collected from volunteer donors, the plasma and platelets are removed by centrifugation, and the remaining red cells are resuspended in a preservative solution and stored in the refrigerator. The major advances over the last 30 to 40 years have been to change the preservative solution to improve it. Blood can now be stored in the United States for 6 weeks, whereas when I started my residency, it was probably 3 or 4 weeks. This is because of improvements in understanding RBC metabolism.

[Another] major change over the last 40 years or so has been the advent of leukoreduction to remove any remaining white blood cells from the donor red cell product. That has also improved the recipient’s response and decreased the number of transfusion reactions and problems from RBC transfusions.

With this in mind, what does the Hemanext product provide? What is the benefit of hypoxic blood for patients?

There is a lot of published evidence to support the idea that the reason we store RBC for only 6 weeks is because they undergo oxidative stress during the storage process in the refrigerator. This oxidative stress damages primarily the red cell membrane, and therefore, decreases the storage quality over time. The Hemanext approach is to store the RBCs under hypoxic conditions, with the expectation that it would reduce the oxidative stress on the stored RBCs, and that indeed seems to be true. The major effect of the storage lesion, where we think that oxidative stress is the primary etiologic cause, is to damage the RBCs so that they get cleared rapidly from the circulation.

Under current FDA standards, at the storage outdate, which is now 6 weeks in the United States, approximately 75% or more of the transfused red blood cells need to be circulating 24 hours later. This means that up to 25% of the transfused red blood cells have been cleared and are no longer circulating 24 hours later. Most of that clearance happens in the first hour or 2 post-transfusion. With the newest preservative solutions, that average red cell survival is approximately 85%. This mean that at outdate, 85% of the red cells are still circulating 24 hours later, and 15% are not. We can imagine that as RBCs get stored, we are giving a lower dose than we think. There are potential consequences from the red cells that are cleared in terms of alloimmunization or iron biology.

The idea behind the Hemanext product is to improve the red cell storage quality, so that even at 6 weeks of storage, significantly more than 85% of the transfused red cells will be circulating. The whole goal is to make a better product so that more red cells are circulating and there is less iron deposition. Particularly in the setting of chronic transfusion, such as sickle cell disease, beta thalassemia, or MDS, ideally we could get by with fewer transfusions over a period of time. This would be better for the patient in terms of being transfused less and having to come to an outpatient setting less frequently. [Additional benefits include] decreases in iron overload, decreases in risk of alloimmunization, and getting the same outcome with fewer transfusions.

What is the goal of this product?

Red cells are similar to drugs, and many of us have been trying for years to make transfusion biology and transfusion products more similar to pharmacological products and pharmacological interventions. We would never want to give a chemotherapeutic agent or any other kind of drug that is only 85% good. Whatever dose we give the patient, we want it to be 100% good. We want it to be pure, and we want to understand what is in [the drug]. We want to understand the pharmacokinetics and pharmacodynamics of the drug. Many of us have the same goal for RBC transfusions and platelet transfusions.