Do Blood Transfusions Cause Pulmonary Complications Following Hematopoietic CELL Transplantation?
Authors: Solh Melhem , Morgan Shanna , Mc Cullough Jeffrey , Shanley Ryan , Weisdorf Daniel J. 
Published: November 2019

Abstract

Introduction
Transfusion of blood products is an essential component of the hematopoietic cell transplantation (HCT) process. Blood transfusions mainly platelets and plasma, carry several risks including, but not limited to, acute and delayed lung injury, especially in critically ill patients. The effect of transfusions on lung complications post HCT has not been previously investigated. We studied 215 adult allogeneic HCT recipients at the University of Minnesota and examined the association between transfusion of blood components and development of lung complications post HCT.
Methods
215 consecutive adult allogeneic HCT recipients were retrospectively analyzed for blood product utilization. Patients without lung complications were used as a control group and those with any lung complication prior to day 180 post HCT were the study cohort. Blood utilization was quantitated as the total number of transfusion episodes and the number of transfusion episodes per week divided into three time intervals: day 0-30, day 31-60, and day 61-180 after HCT. Transfusions were analyzed as density (episodes or units per week). Lung complication data was collected from the transplant database and merged with the transfusion data. The effects of transfusion density and other factors on the odds of ever having a lung complication were modeled using multivariable logistic regression.
Results
195 patients were included in the analysis and 20 were excluded, mostly due to incomplete data. 113 (58%) of the patients developed lung events prior to day 180 post HCT. Of the 113 patients with lung events, 81 (72%) were related to infectious causes. The study group with pulmonary complications and controls had similar baseline demographic characteristics (age, gender, CMV serostatus, disease and disease risk and donor source). Six months survival was significantly lower in the lung complications group (52%) versus the controls (78%) p=0.01. Patients who developed lung events received more transfusions including: episodes per week during the first month following HCT (median 4.3 (range x-y) vs. 2.7 (x-y) for controls); platelet units per week (3.5 (range x-y) vs. 2.0 (x-y)); and RBC units per week (1.8 (x-y) vs. 1.4 (x-y)); p <0.01 for all. Transfusion episodes increased significantly in the week following each lung event compared to the preceding week (7.1 (range x-y) versus 5.5 (x-y); p=0.04). In multivariate analysis, the presence of any lung complication, use of an umbilical cord graft and occurrence of chronic GVHD were each independently associated with increased number of transfusion episodes post HCT. Table 1 shows factors that were significantly associated with increased blood utilization up to day 180.
Conclusion
These data suggest that transfusion of more blood products is associated with lung complications and their use increases after the lung events. Limiting use of blood components in the post HCT period is recommended, potentially to reduce the risks of lung events.

Table 1: Risk factors for Transfusion episodes/week from day 1-180 post HCT All Transfusion Episodes RBC Units Platelet Units Risk factor Relative transfusion density P-value Relative density P-value Relative density P-value Control group 1.0 1.0 1.0 ARDS/IPS 4.1 <.01 3.7 <.01 3.5 <.01 DAH 4.3 <.01 4.7 <.01 5.7 <.01 Bacterial pneumonia 2.6 <.01 2.7 <.01 3.1 <.01 Pulmonary edema 2.6 <.01 3.4 <.01 2.9 <.01 Female 1.0 1.0 1.0 Male 0.9 0.36 1.0 0.83 1.0 0.86 Reduced intensity conditioning 1.0 1.0 1.0 Myeloablative with TBI 1.4 0.02 1.2 0.20 1.7 <.01 Myeloablative without TBI 1.8 0.05 1.6 0.14 1.3 0.66 CMV serostatus Recipient+ 1.0 1.0 1.0 CMV R-/Donor- 0.7 0.03 0.9 0.48 0.6 0.05 CMV R-/D+ 1.2 0.39 1.0 0.91 1.2 0.55 Sibling donor 1.0 1.0 1.0 Unrelated Adult donor 0.9 0.70 0.8 0.60 0.6 0.40 Unrelated umbilical cord blood donor 1.7 <.01 1.8 <.01 2.0 <.01 Standard risk disease 1.0 1.0 1.0 High risk disease 1.2 0.19 1.3 0.04 1.2 0.47
Abbreviations
ARDS/IPS: Adult respiratory distress syndrome/Idiopathic pneumonia syndrome; DAH: Diffuse alveolar hemorrhage; NOS: not otherwise specified; TBI: total body irradiation; CMV: cytomegalovirus.

Disclosures
No relevant conflicts of interest to declare.