Prognostic Value Of Red Blood Cell and Platelet Transfusion In Elderly Patients With Aggressive Lymphoma Receiving First Line Immunochemotherapy: An Analysis Of The Lysa LNH 03-6B Study
Authors: Delarue Richard , Tilly Herve , Salles Gilles Andre , Thieblemont Catherine , Bologna Serge , Ghesquieres Herve , Hermine Olivier , Haioun Corinne , Bosly Andre 
Published: October 2019

Abstract

Introduction
There are some evidences that blood transfusions, either red blood cell (RBC) or platelet, could impact survival of patients affected with various medical conditions. Mechanisms are largely unknown but immune dysfunction, storage duration, cytokines or iron releases could be involved. These concerns led to the publication of revised guidelines with a more restrictive approach for RBC and platelet transfusions in various conditions, mostly surgery and emergency. However, less was known for cancer patients receiving therapy with a curative attempt.

Methods
The phase III randomized LNH 03-6B protocol included elderly patients from 60 to 80-year with untreated diffuse large B-cell lymphoma and an age-adjusted International Prognostic Index (aaIPI) of 1 or more. Patients were randomized between 8 cycles of R-CHOP given every 2 or 3 weeks (Delarue et al. Lancet Oncol 2013) and between a prophylactic treatment with Darbepoetin alfa in order to maintain hemoglobin level between 13 and 14 g/dL and an usual management of chemotherapy-induced anemia. In both arms, RBC and platelet transfusions were given according to physician decision without predefined threshold, but analysis of current practices showed that most patients were transfused with RBC for grade 3 or more anemia and with platelet for grade 4 thrombocytopenia.

Results
A total of 602 patients were included in the study and 599 have been analyzed for safety issues. Overall, 236 patients received at least one RBC transfusion (39%) with a higher incidence in the R-CHOP14 group (47% versus 31%, p=0.0001) and 60 patients (10%) received at least one platelet transfusion. Comparing with the whole study population, patients who were transfused presented with more aggressive baseline characteristics including percentage of patients with an aaIPI of 2 or 3 (72% versus 58%). Occurrence of RBC transfusion was associated with a worse outcome regarding progression-free (HR: 0.696, 95%CI: 0.547-0.885, p=0.0031) and overall survival (HR: 0.544, 95%CI: 0.414-0.714, p=<0.0001). Moreover, the number of episode of red blood cell transfusion (0 vs. 1-2 vs. >2) was also associated with PFS and OS. Occurrence of platelet transfusion was also associated with worse PFS (HR: 2.658, 95%CI: 1.922-3.677, p<0.0001) and OS (HR: 3.257, 95%CI: 2.302-4.608, p<0.0001), with an impact of the number of episode (0 vs. 1 vs. >1). In a multivariate analysis including LDH level, ECOG performans status and β2-microglobulin level, RBC and platelet transfusions were both predictive for overall survival (HR: 1.575, 95%CI: 1.158-2.143, p=0.0038 and HR: 2.608, 95% CI: 1.736-3.917, p<0.0001). Finally, no adverse event was associated with transfusion.

Conclusion
In elderly patients who received a first line immunochemotherapy for aggressive B-cell lymphoma, occurrence of transfusions as well as the number of blood products transfused appear to be significantly and independently associated with lower survival rates. These results suggest a direct effect of transfusion and will prompt us to explore possible mechanistic explanations in animal models and to validate this hypothesis in others cancer populations.

Disclosures:
No relevant conflicts of interest to declare.