LEUKOCYTE-REDUCED TRANSFUSION THERAPY

Joseph E. Kiss, M.D., Medical Director

Blood Program and Apheresis/Outpatient Services

INTRODUCTION

Large numbers of donor leukocytes are present in cellular blood components, which includes whole blood, packed red blood cells (RBC), and platelets.  These “passenger” leukocytes are responsible for several complications associated with blood transfusions, including febrile non-hemolytic transfusion reactions, platelet refractoriness due to alloimmunization to human leukocyte antigens (HLA), and the transmission of certain cell-associated viruses, especially cytomegalovirus (CMV).  Advances in biotechnology have resulted in the development of filters capable of depleting residual leukocytes to levels below the specific thresholds needed to prevent these complications.

FILTRATION TECHNOLOGY

Three “generations” of blood filters are currently in use.  The first-generation filters are the standard 170-micron clot screen filters attached to the administration set used for all blood components.  A second-generation filter, or microaggregate blood filter (10 to 40 micron MABF), removes the granulocyte/platelet microaggregates, which form in stored RBC units.  Although useful, this technology is much less efficient for white blood cell removal (less than 1 log) than the third generation filters (2 to 3 log removal) currently available.  The ultrafine synthetic fibers incorporated into these newer filters creates a meshwork that removes donor leukocytes by a combination of barrier retention and direct adsorption.  Recent American Association of Blood Banks (AABB) Standards have established a maximum leukocyte content for prevention of febrile transfusion reactions to be <5 x 10⁶ WBCs/unit.  If used according to the manufacturer’s directions, these levels can be reliably achieved.

However, technical difficulties in using the filters at the bedside, such as employing excessively high flow rates or pressures or improper flushing of the filters, can impair efficacy of leukocyte removal.  This concern has prompted some to perform filtration only in the blood bank, where standard quality control procedures can be routinely maintained.

CLINICAL USAGE

Prevention of recurrent (i.e., two or more) non-hemolytic febrile transfusion reactions is readily accomplished using leukocyte-depleted blood components.  Third-generation filtration has largely supplanted the less efficient methods of leukocyte removal formerly used such as cell washing, use of MABF’s, and centrifugation (typically less than one log removal).

Alloimmunization to HLA antigens is a major cause of refractoriness to platelet transfusion in multi-transfused hematology/oncology patients.  The development of HLA antibodies is also problematic for certain organ transplant candidates such as those in need of kidney or cardiac transplantation.  In five randomized trials using leukocyte-depleted red cells and platelets in leukemia/oncology patients, the development of HLA antibodies was reduced from 13 to 50 percent in control subjects to 6 to 20 percent in the treatment groups.  Thus, there was an overall 50 percent reduction in the incidence of alloimmunization.  At present, the decision to use filtered blood products in the routine prevention of alloimmunization should be based on the incidence and morbidity of this complication in defined patient populations.

In general, multi-transfused hematology/oncology patients and selected transplant candidates are most likely to benefit. 

Evidence is mounting that current leukocyte filtration methods are very effective in preventing transfusion-transmitted CMV infections.  Like other major human herpes viruses, CMV is found exclusively in leukocytes.  To date, studies that have examined the incidence of CMV transmission using filtered, CMV-untested blood components have found no cases of CMV seroconversion or clinical disease in over 184 patients.  This can be compared with a frequency of 75/303 (25%) in control patients receiving standard blood components.

Results from a large prospective study directly comparing CMV seronegative blood products with filtered, CMV unscreened components are expected within the next year.  Until then, evidence of efficacy is sufficient to consider the use of filtered RBC or platelets as an alternative to CMV-seronegative products when such products are not available for transfusion.  The major argument against routine use of bedside filtration for this purpose is the uncertainty of adequate leukocyte reduction as mentioned above.

POTENTIAL FUTURE APPLICATIONS

A recent study has demonstrated that the immunosuppressive effects associated with blood transfusion can be prevented by leukocyte depletion.  This finding may have important implications in regard to post-operative infections and the risk of tumor recurrence after cancer surgery.

Evidence that allogeneic leukocytes can stimulate HIV-1 replication and secondary dissemination in vitro has prompted a clinical study as to whether leuko-depleted blood transfusions can impact the clinical course of HIV in infected patients.

Lastly, a new method known as pre-storage leukocyte filtration now permits 3 to 4-log leukocyte reduction in a closed system, so that an inventory of leukocyte-reduced red cells can be readily available for transfusion.  There seems little doubt that over the next few years the use of leukocyte reduced blood components will expand as promising clinical studies are confirmed and as technology improves.

Copies of the Transfusion Medicine Update can be obtained by contacting Deborah Small at (412) 209-7320 or
by e-mail:  dsmall@itxm.org.