Overall Survival in Hematopoietic Stem Cell Transplantation Is Not Correlated with Age of Red Cells Transfused Pre- and Post-Transplantation
Authors: Aung Fleur M. , Bassett Roland L , Lichtiger Benjamin , Freireich Emil J. , Khouri Issa F 
Published: October 2019

Abstract
Red blood cells undergo biochemical and morphologic changes during storage and the time-dependent changes known as “storage lesions” are well documented. These changes have raised concerns that stored older red cells (RBC) could increase the patient’s mortality risk. The primary aim of blood storage has been to extend the storage life of RBCs with the use of additive storage solutions. However, the clinical consequences of transfusion of newer versus older red cells remain unclear for Hematopoietic stem cell transplant (HSCT) patients.
Objectives
The primary objective of this retrospective study was to analyze the association of aged RBCs and ICU admission, short-term and long-term survival and the association between overall survival with the number of RBCs transfused up to D+100 post-transplant.
Methods:
Study Design
The study design was approved by the MDACC Institutional Review Board. The 2008-2009 Blood Bank records were reviewed for HSCT patients. All transfused RBC data pre-transplant (D-100 to D-1) and post-transplant (D0 to D+100) was included without exclusion of patients who received a mixture of different ages of RBCs. The age of RBCs transfused was categorized into two groups: <14/>14 days and < 28/ > 28 days of age. The patients were categorized into ICU vs. Non-ICU patients. A further categorization of the non-ICU patients was made by number of RBCS received post-transplant: 0-5, 6-10 and >11 RBCS.
Definition
Age of Red cells
A patient was defined as having aged red blood cells (RBC) pre-transplant if he/she received at least one RBC that was >14 days old. A separate definition of aged red blood cells categorized patients as having received at least one unit that was >28 days old. This categorization was repeated for post-transplant RBCs at both 14 and 28 days.
Statistical Analysis:
Fisher’s exact test was used to compare ICU rates between patients who did and did not receive aged RBCs. The Kaplan-Meier was used to estimate the distribution of overall survival (OS) from the date of transplant, and distributions were compared using the log-rank test. Analyses are performed for all patients, and then repeated for the subset of patients with AML.
Results:
397 HSCT patients (229 [58%] males: 168 [42%] females), median 52 years (range 2-74) received median 3 RBCs (range 0-44) pre-transplant and 8 RBCs (range 0-111) post-transplant. 252 (63.5%) patients received peripheral hematopoietic progenitor cells, 262 (66%) patients received an ABO mismatched graft and the majority 297 (75%) was Caucasian. The diagnoses were as follows: AML (47%), ALL (42%), CLL (12%), CML (7%), Lymphoma (19%), Myeloma (2%), Aplastic Anemia (1%), and other non-hematologic disorders (1%). There were 73 (18%) patients (41 [56%] male:32 [44%] female, median 54 years [range 14-74] admitted to the ICU with a median stay 37 days (range 1-64) post-transplant who received 438 (median 3 [range 0-30]) RBCs pre-transplant and 1475 ( median 18 [range 2-73]) RBCs post-transplant. The 324 (72%) non-ICU patients (188[58%] male: 136 [42%} female, median 52 years [range 2-72]) received 1869 RBCs (median 3 [range 0-44]) pre-transplant and 3348 RBCS (median 7 [range 0-112]) post-transplant.
When the age of the RBCS transfused to ICU vs. Non-ICU patients pre-and post-transplant was analyzed there was statistical significance noted (p=0.002) between age of RBCs (< 14/>14 days) transfused post-transplant and ICU stay.
For the 324 non-ICU patients, as worse survival was noted in those who received more red cell transfusion with strong evidence of a difference between patients who received 0-5 RBCS vs.6-10 RBCS vs. >11 RBCS (p=0.001). The median overall survival is 3.4 years for 136 (42%) patients who received 0-5 RBCs vs. 3.1 years for 72 (22%) patients who received 6-10 RBCs vs. 0.7 years for 116 (36%) patients who received > 11 RBCs post-transplant. Of the 73 ICU patients, 2 (3%) are alive (post-transplant day 1819 and 1981) vs. 134 (41%) non-ICU patients, median 1561 (range 175-2203) post-transplant day. The cause of death for the ICU patients was related to transplant related causes.
Conclusion:
Our findings reveal that the number of RBCs transfused had a correlation with overall survival rather than the age of the red cells transfused pre- and post-transplant. We were unable to confirm the conclusion reached by Wang et.al that newer blood if used exclusively may save lives based on published clinical experience.

Disclosures
No relevant conflicts of interest to declare.