Immunotherapy: the good, the bad, the ugly, and the really ugly

Abstract

http://onlinelibrary.wiley.com/doi/10.1111/trf.15033/full

Human red blood cell stroma: an alternative to traditional allogeneic adsorption methods

“…Because the stroma can be frozen for at least 2 years, large aliquots could be prepared by reference laboratories or blood banks and distributed to smaller institutions and transfusion services for use in investigations of patients having autoantibodies. Also, as more immunotherapeutics become available for clinical use that cross‐react with human RBCs where the RBC antigen has relatively high antigen site density, such as anti‐CD47 (Hu5F9‐G4), the use of alloadsorption to investigate underlying alloantibodies in these instances is the preferred approach . Having pre‐prepared human stroma as an adsorbing agent will reduce the average testing time to resolve these cases.…”

Two case reports involving therapeutic monoclonal anti‐CD47 (Hu5F9‐G4), it's effect on compatibility testing and subsequent selection of components for transfusion

“…While they aim to target malignant cells, due to the nature of the reactions involved and target molecules, these TMAbs may also interfere with compatibility testing in the blood bank, which can delay provision of blood components. 1,2 The humanized anti-CD47 TMAb Hu5F9-G4 is currently being used in a number of clinical trials. Hu5F9-G4 is a novel anti-CD47 monoclonal IgG4 antibody under evaluation in six studies in the United States and United Kingdom.…”

A stressful predicament for blood bankers!

“…Monoclonal immunotherapeutic drugs are becoming an effective way to attack certain cancers and other conditions. Some of these antibodies recognise red blood cells (RBCs) as well as their intended cancer cell targets and can create considerable havoc in transfusion services when trying to provide compatible blood for transfusion to those patients who are receiving these medications . Anti‐CD38 (daratumumab; DARA) is one example that has been used for a few years now and is FDA approved for use in multiple myeloma patients; unfortunately, it causes panagglutination in serologic tests .…”

“…Some of these antibodies recognise red blood cells (RBCs) as well as their intended cancer cell targets and can create considerable havoc in transfusion services when trying to provide compatible blood for transfusion to those patients who are receiving these medications . Anti‐CD38 (daratumumab; DARA) is one example that has been used for a few years now and is FDA approved for use in multiple myeloma patients; unfortunately, it causes panagglutination in serologic tests . The good news is that these serologic reactions are relatively weak (1+ to 2+), and various ways have been reported around the anti‐CD38 panagglutination, enabling elucidation of potentially clinically significant underlying alloantibodies .…”

“…CD47 acts, presumably, as a signal to monocyte‐macrophages to not phagocytose the cells, and anti‐CD47 can block the “don't eat me” signal and allow cells to be phagocytosed. When anti‐CD47 is administered to certain cancer patients, it is given at very high dosage, which creates huge problems for transfusion services during their serologic evaluations related to type and screen and provision of compatible blood . In the paper by Reyland et al, in this issue of Transfusion Medicine , the authors present two case studies of patients who are receiving anti‐CD47.…”