Immunohematology and Transfusion Support of a Patient with Acute Myeloid Leukemia and an Anti-Vel

Background

Transfusion support of cancer patients presenting with red blood cell (RBC) antibodies against high-incidence antigens is a challenge for hospital-based Transfusion Services. For patients with antibodies against the high-frequency Vel antigen, only 0.0004% of blood donors will be Vel antigen-negative. Anti-Vel is notorious for looking like a benign, cold-reactive IgM antibody or a "high-titer, low-avidity" antibody; however, Vel-antibodies can fix complement at body temperatures and can cause severe hemolytic transfusion reactions. The immunohematology workup and RBC transfusion support are reported for a patient who developed an anti-Vel and other RBC antibodies during chronic transfusion therapy for myelodysplastic syndrome, with progression to acute myeloid leukemia. She was also evaluated for hematopoietic stem cell transplantation (HSCT).

Methods

Immunohematologic workups were performed at a regional immunohematology reference laboratory. Since the patient had a positive autocontrol and a positive direct antiglobulin test (DAT), allogeneic adsorptions were performed at 37°C using R₁R₁, R₂R₂ and rr RBC reagents. Adsorbed plasma and eluates from adsorbed RBCs were then tested for alloantibody detection using manual tube method at both LISS and PEG reactivity. In preparation for possible HSCT, RBC alloantibody titers and monocyte monolayer assay (MMA) were performed. All samples were collected with pediatric phlebotomy tubes whenever possible.

Results

The patient was a 66 year old woman with a myelodysplastic syndrome that transformed to acute myeloid leukemia (AML) with complex karyotype a year later. The RBC reference workup identified alloantibodies reacting to the high-incidence Vel antigen as well as low-incidence Yt(b) and C^w antigens. The patient's plasma was non-reactive with three of four Vel-negative (-) cells, whereas the reactive cell was C^w positive (+) and Yt(b+). Two allo-adsorptions were performed to remove anti-Vel. Upon repeat testing, anti-C^w was identified by LISS indirect antiglobulin test. Eluate from adsorbing RBCs was reactive with Vel- and Yt(b+) cells, suggesting presence of anti-Yt^b. In preparation for HSCT, anti-Vel and anti-C^w were titered at 0 and 64, respectively. MMA for anti-Vel ranged at 0.2-2% (normal <3%). Nevertheless, the hospital-based Transfusion Service provided rare ABO/Rh Vel- C^W- Yt(b-) crossmatch-compatible RBC to minimize the potential for stimulating anti-Vel, which might compromise a Vel+ HSCT. The patient required about 1 RBC unit per week to maintain hemoglobin above 4.5 g/dL. The Transfusion Service coordinated a search for antigen-negative RBCs with a national rare donor program, allowing at least 4 rare RBC units to be available at all times. Over an 18-month time period, the patient received 62 RBC Vel- units: 45 out of 62 (73%) were C^w- and 17 were C^w-unscreened but C-. Later in the patient's course, her transfusion rate increased to 2 RBC units per week. Because insufficient Vel- units were available within the USA, an international search by a rare donor program identified Vel- donors in Europe. FDA approval was obtained to import the rare units. She received 2 units from Spain and 2 units from Switzerland. Her leukemia progressed, and transfusion support was discontinued.

Conclusion

Coordination between hospital-based Transfusion Service, hematologists, and rare donor programs is required for rare RBC transfusion support in patients with antibodies against high-incidence antigens. A transfusion threshold of 4.5 g/dL may be tolerated when availability of rare RBC units is limited.