Transfusion of RhD-Incompatible Blood Components in RhD-Negative Blood Marrow Transplant Recipients

Abstract

Background

Transfusion-dependent bone marrow transplant recipients are routinely transfused with ABO group and RhD-compatible blood components. However, because of the scarcity of RhD-negative blood components, particularly platelets, a policy was developed to transfuse RhD-positive blood components to RhD-negative patients during periods of shortage.

Methods

We reviewed the records of 78 RhD-negative patients with hematologic malignancies who received RhD-negative bone marrow and/or peripheral blood stem cells, from June 1995 to August 2000. The patients transfused with RhD-incompatible blood components were screened periodically for evidence of the development of red blood cell (RBC) alloimmunization.

Results

Three of 78 patients (4%) developed anti-D antibodies after receiving RhD-incompatible platelet transfusions. One of the patients developed evidence of anti-RhD antibodies after receiving 42 units of RhD-positive random donor platelets; the second patient developed such evidence after receiving 6 apheresis platelets and 2 infusions of intravenous immunoglobulin G (positive for anti-RhD). The third patient received 206 RhD-positive random donor platelets and 5 apheresis units. All patients were discharged from the hospital. The overall immunization rate was 4%. Six patients received Rh-incompatible packed RBCs and showed no evidence of neither anti-RhD nor any other anti-RBC antibodies. All 78 patients had received RhD-incompatible platelets throughout their engraftment period.

Conclusion

Transfusion of RhD-positive blood components to Rh-negative patients with hematologic cancers, who have received RhD-negative bone marrow and/or peripheral blood stem cells, are at low risk of developing RhD antibodies. These findings allow for a flexible strategy of blood component therapy support for this special patient population during periods of shortage.

Introduction

Aside from the ABO blood group system, Rh antigens, especially the D antigen, are the most clinically significant factors in alloimmunization that usually occur after exposure of RhD-negative individuals to RhD-positive blood components.[1-5] Patients with anti-RhD antibodies may be vulnerable to acute and delayed hemolytic transfusion reactions, which may lead to significant hemolysis, a drop in hemoglobin levels, and hemolytic disease of the newborn.[6-9] In a perfect world, RhD-negative patients would be able to receive blood components from RhD-negative donors. However, the availability of RhD-negative blood components is a practical problem for most transfusion services.[10,11]

The limited production of anti-RhD antibodies in patients with AIDS or cancer as well as cardiac and liver transplant recipients, who have either primary or secondary immunosuppression, has been described.[12,13] This low frequency of alloimmunization may be attributed to the reduced immune responsiveness of these patients.

Because of intensive bone marrow (BM) depression and improved survival in BM and peripheral blood stem cell (PBSC) transplant recipients, these patients are transfusion-dependent for a longer period of time. Logistic constraints often dictate that RhD-negative patients undergo transfusion with RhD-positive blood components.[14-17]

The present study was developed to evaluate the incidence of alloimmunization against the RhD antigen in RhD-negative patients with hematologic or other malignancies who have received BM or PBSC transplants from RhD-negative donors. This study was performed at the University of Texas MD Anderson Cancer Center, Houston, where we transfuse approximately 32,309 packed red blood cells (RBCs), 87,760 random-donor platelets 4878 single donor platelets 8958 units of fresh frozen plasma 549 granulocytes, and 1553 cryoprecipitate units annually.

Patients and Methods

From 1987 to 2001, we retrospectively reviewed the clinical and transfusion records of 78 RhD-negative patients. All of them had received allogeneic BM and/or PBSC transplants from RhD-negative donors.

None of the patients or donors had detectable anti-RhD antibodies before transplantation. Routine serologic testing for anti-RhD and other anti-RBC antibodies was performed with tube agglutination 3-cell screening (R₁R₁, R₂R₂, and rr phenotype; Immucor, Norcross, Georgia) every week until blood group conversion occurred, and as clinically indicated thereafter. Patients were not given anti-RhD-specific immunoglobulin following the RhD-incompatible transfusions.[18] All patients received myeloablative regimens and graft-vs-host treatment when applicable, following different MD Anderson Cancer Center protocols.

We recorded the patient's age, diagnosis, blood type ABO and Rh, date of BM and/or PBSC transplant, date of anti-RhD antibody detection, and number and type of all blood components received, including granulocytes, packed RBCs, platelets, fresh frozen plasma, and cryoprecipitates.[19-22]

Results

The 78 RhD-negative patients, 50 with leukemia, 22 with lymphoma, 2 with solid tumors, 2 with melanoma, 1 with myeloma, and 1 with aplastic anemia, received BM and/or PBSC from RhD-negative related and unrelated donors. The patients received 6136 units of different blood components. The RhD-incompatible blood components consisted of 18 granulocytes, 20 packed RBCs, 585 single-donor platelets, 4168 random donor platelets, 289 units of fresh frozen plasma, and 250 cryoprecipitate units. All blood components were leukoreduced with a Sepacell PLS-10A filter for platelets and Sepacell filter for RBCs (Baxter HealthCare Corpo Fenwal Division, Deerfield, Illinois). All blood components were also irradiated at 2500 cGy for 174 seconds.

Three patients (4%) developed anti-RhD antibodies, and the exact binomial 95% confidence interval for this estimate was 0.80% to 10.83%. None of the other patients developed any detectable antibodies against RBCs during the follow-up period, including 6 patients who received RhD-incompatible packed RBCs.[23-29]

The first patient with anti-RhD antibodies, a 63-year-old man with a history of follicular cell lymphoma and blood type A, was Rh-negative and received a PBSC transplant from an A Rh-negative donor. Anti-D and anti-C antibodies developed 10 days after transplantation. He received 12 units of A Rh-negative packed RBCs and 30 units of A Rh-positive random donor platelets in the 3 months before detection of the anti-D antibodies.

The second patient was a 72-year-old man with a history of chronic lymphocytic leukemia and splenectomy, with blood type A Rh-negative, who received an allogeneic BM transplant from an O Rh-negative donor. Anti-D and anti-E antibodies developed 9 months after transplantation; the patient received 19 units of O Rh-negative packed RBCs, 7 units of A Rh-positive single-donor platelets, and 53 units of Rh-incompatible random donor platelets during the 9 months before detection of the antibodies.

The third patient, a 32-year-old woman with a history of chronic lymphocytic leukemia and blood type O, was Rh-negative and received an allogeneic BM transplant from an O Rh-negative donor. Anti-D antibodies developed 4 months after transplantation; the patient received 16 units of O Rh-negative packed RBCs, 5 units of Rh-positive single-donor platelets, and 206 units of Rh-positive random-donor platelets in the 4 months before detection of the antibodies.

All patients tolerated well the transplants and blood transfusions. They were discharged from the hospital for outpatient follow-up.

Discussion

RhD antigen is a potent immunogen. Anti-D antibodies, in fact, develop in more than 80% of Rh-negative volunteers given RhD-positive packed RBCs. ABO group antigens are present on platelets, but RhD antigens are not expressed.

Previous studies examining the incidence of RhD alloimmunization, secondary to RhD-incompatible platelet transfusion in immunosuppressed cancer patients receiving chemotherapy, showed that the frequency of RhD alloimmunization ranged from 0% to 19%. However, these studies were carried out at a time when platelet units were more heavily contaminated with RBCs.[30,31]

Recent developments in platelet apheresis and blood-component-processing technology have led to a contamination of less than 0.1 mL of RBCs per platelet unit, resulting in a significant reduction in the incidence of RhD alloimmunization. Patients with impaired immunity, coupled with the immunosuppressive effect of their treatments, have significantly reduced ability to mount an effective response to antigenic stimuli, including the RhD antigen.

More recent studies showed a low incidence of RhD alloimmunization in patients with hematologic malignancies. However, there was a significant increase in the susceptibility of patients with nonhematologic malignancies to alloimmunization after RhD-incompatible transfusions.

Anti-D antibodies are virtually never observed in RhD-negative recipients of hemopoietic cell grafts from RhD-positive donors, although they developed in some RhD-positive patients who received RhD-negative hemopoietic cell grafts. The recipient's residual RBCs may stimulate the donor's engrafted lymphocytes; this usually starts about 6 months after stem cell transplantation.[32-36]

McLeod and colleagues[31] reported that despite the profound immunosuppression associated with autologous BM transplantation, alloimmune response to D-positive RBCs in platelet concentrates can occur in some D-negative recipients. In our institution in which large numbers of PBSC and BM transplants are performed, such patients are usually transfusion-dependent. Because of the scarcity of RhD-negative blood components, in particular, platelets, policy was enacted to transfuse RhD-incompatible platelets in these patients.

The aim of the present study was to evaluate the outcome of this policy and report the incidence of alloimmunization against the RhD antigen in this group of patients.

We found an incidence of RhD alloimmunization of 4% in the 78 RhD-negative multitransfused participants. Only 3 patients had anti-D antibodies; their age range was 32-72 years. Two of them were males and one was female ; 2 of the patients had chronic lymphocytic leukemia, whereas one had lymphoma. They received 30, 60, and 211 units of RhD-incompatible platelet units, respectively. All 3 patients were discharged from the hospital in good status and with no reported complications.

In conclusion, we found that immunosuppressed BM and/or PBSC transplant recipients are not likely to have anti-D antibodies, as an anti-D response developed in only 3 of 78 patients (4%). This result is of great practical value in allocating blood components during periods of blood shortage.

Our study suggests that transfusion of RhD-incompatible blood components to immunosuppressed PBSC recipients with hematologic or nonhematologic cancers may be without significant clinical consequence. These findings are beneficial for institutions in which inventory constraints demand the administration of large numbers of RhD-incompatible platelets.