Current Issues in 
July-September 2002

Spontaneous Loss or Reactivation of Atypical RBC Alloantibodies in Cancer Patients

By Aida Narvios


Cancer patients have an increased risk of red blood cell (RBC) alloimmunization as a consequence of long-term chronic RBC transfusion support (1). However, spontaneous loss of RBC alloantibodies in the progression of the disease process in these patients is not typically expected.

Antibody identification is a critical step in the laboratory workup for a patient having positive RBC alloantibody screening. This ensures that a patient can receive an infusion of crossmatched compatible units. Occasionally, some patients demonstrate an apparent loss or reactivation of alloantibodies. This phenomenon is not currently well understood in cancer patients, however. Therefore, we conducted a retrospective analysis of patients showing loss or reappearance of significant RBC alloantibodies.

Materials and Methods

A review of patient files in the Transfusion Service at The University of Texas M. D. Anderson Cancer Center was conducted from June 2001 to May 2002. All patients having clinically significant RBC alloantibodies were included in the study. Antibody screening was performed according to the standard operating procedures of the Transfusion Service. The patients' clinical information, including their transfusion history in our institution and other hospitals, was investigated. Their clinical history, including use of medications and interventions, was also reviewed. A total of 25 patients were included in the study. One patient was excluded because the anti-D antibody was passively acquired through the administration of RhD immune globulin (human). The characteristics of these patients are listed in Table 1.


Table 1. Baseline Characteristics of the 25 Study Patients*



Age range (years)


Sex (%)  




Diagnosis (%)  












    Aplastic anemia


    Hodgkin's lymphoma




    Breast cancer


    Synovial sarcoma


    Gastric cancer


    Rectal cancer




 *MDS, myelodysplastic syndrome; AML, acute myelogenous leukemia; CML, chronic myelogenous leukemia; ALL, acute lymphocytic leukemia; CLL, chronic lymphocytic leukemia; RAEB-T, refractory anemia with excess blast transformation; MFH, malignant fibrohistiocytoma.



RBC alloantibody loss was observed in all 25 patients. Thirteen (52%) of the patients had a history of loss of only one alloantibody, while 12 (48%) patients had loss of multiple alloantibodies. The frequency of loss of these antibodies is shown in Table 2. The highest incidence was seen in the Rh system, especially with anti-E. This was followed by the Kell system, in particular, anti-K. Antibodies in the Kidd and Duffy systems were also noted. In spite of the extensive workup performed in the Transfusion Service, some of the antibodies could not be identified. All of the patients received an infusion of 2 to 126 units of crossmatched compatible packed red blood cells or least incompatible packed red blood cells. The medications that these patients received were not similar. Finally, only two allogeneic bone marrow recipients qualified for this study.


Table 2. Incidence of RBC Alloantibody Loss



Rh system  










Kell system  


Kidd system  




Duffy system  


Unidentified antibodies




The atypical alloantibodies that we identified in this study have the potential to cause a hemolytic transfusion reaction. The presence of Rh antibodies usually results from a blood transfusion or pregnancy. In addition, anti-K is highly immunogenic and can cause both immediate and delayed reactions, Duffy system antibodies are known to react only with red cells that have a double dose of the antigen, and Kidd system antibodies are notorious in developing an anamnestic response to the antigen (2). Individual alloantibody characteristics should be considered in the evaluation of serum antibody screening results, which is inconsistent with analyzing the patient's history. This will assist technologists and pathologists in the choice of laboratory workup.

Prior studies indicated that the patient's disease state can affect the development of alloantibodies. For example, patients having lymphocytic leukemia often fail to make RBC alloantibodies irrespective of the type of chemotherapy they receive (3-6). One study also found that acute myelogenous leukemia patients have a low rate of RBC alloantibody formation (3). Furthermore, studies found the following incidences of alloantibody formation in patients having the respective diagnoses: acute myelogenous leukemia, 16% (4); aplastic anemia, 11% (4); chronic myelogenous leukemia, <15 % (4); hemoglobinopathy, 29% (4); gastrointestinal bleeding, 11% (7); and renal failure, 14% (7). Also, bone marrow transplant recipients have a low rate of RBC alloimmunization (8). The highest rates of RBC alloimmunization occur in patients having myelodysplastic syndrome, autoimmune hemolytic anemia, or cirrhosis (3).

Certain drugs may affect RBC alloimmunization. For instance, patients who have received a blood transfusion and azidothymidine treatment apparently have a low rate of RBC alloimmunization (9). Reactivation of an RBC alloantibody has also been described following granulocyte colony-stimulating factor treatment (10).

Finally, maintaining accurate, complete patient records and information on known RBC alloantibodies both inside and outside the institution is essential to preventing hemolytic transfusion reactions (7,11-13).

In conclusion, we have shown that RBC alloantibodies can be lost or undetected at some point of a patient's disease progression or regression. These are significant alloantibodies that can cause a hemolytic transfusion reaction, thereby jeopardizing the life of the patient. A careful review of the transfusion history of every patient is recommended. At this time, we cannot identify whether certain chemotherapeutic agents cause this phenomenon. Therefore, more studies like this one are needed.


  1. Hundric-Haspl Z, Jurakovac-Loncar N, Grgicevic D, Balijia M. Alloimmunizations following blood transfusions. Acta Med Croatica 48:193-197, 1994.
  2. AABB Technical Manual, 14th edition, Chapter 4, p. 306.
  3. Seyfried H, Walewski I. Analysis of immune response to red cells antigens in multi-transfused patients with different diseases. Mater Med Pol 22:21-25, 1990.
  4. Blumberg N, Peck K, Ross K, Avila E. Immune response to chronic red blood cell transfusion. Vox Sang 44:212-217, 1983.
  5. Schonewille H, Haak HL, van Zijl AM. Alloimmunization after blood transfusion in patients with hematologic and oncologic disease. Transfusion 39:763-771, 1999.
  6. Blumberg N, Ross K, Avila E, Peck K. Should chronic transfusions be matched for antigens other than ABO and Rho(D)? Vox Sang 47:205-208, 1984.
  7. Lasky LC, Rose RR, Polesky HF. Incidence of antibody formation and positive direct antiglobulin tests in a multitransfused hemodialysis population. Transfusion 24;198-200, 1984.
  8. Abou-Elella AA, Camarillo TA, Allen MB, Barclay S, Pierce JA, Holland HK, Wingard JR, Bray RA, Rodey GE, Hillyer CD. Low incidence of red cell and HLA antibody formation by bone marrow transplant patients. Transfusion 35:931-935, 1995.
  9. Calverly D, Haley L, Ballem P. Red blood cell alloimmunization in transfused patients on AZT. Br J Haematol 78:248-250, 1991.
  10. Norol F, Bonin P, Charpentier F, Bierling P, Beaujean F, Cartron JP, Bories D, Kuentz M. Apparent reactivation of red cell alloantibody in a healthy individual after G-CSF administration. Br J Haematol 103:256-258, 1998.
  11. Ramsey G, Smietana SJ. Long-term follow-up testing of red cell alloantibodies. Transfusion 34:122-124, 1994.
  12. Havemann H, Lichtiger B. Identification of previous erythrocyte alloimmunization and the type and screen at a large cancer center: A 4-year retrospective review. Cancer 69:252-255, 1992.
  13. Lichtiger B, Perry-Thornton E. Hemolytic transfusion reactions in oncology patients: Experience in a large cancer center. J Clin Oncol 2:438-442, 1984.

Return to main menu

Volume 10, Number 3
Copyright 2002 The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Newsletter homepage URL: