A 59-year-old male patient with myelofibrosis was referred for allogeneic stem cell transplantation. Three years prior to the referral (March 1996), the patient was diagnosed with myelofibrosis by bone marrow biopsy. At that time he had pancytopenia and 6–10 cm splenomegaly. He was initially treated with interferon but this was discontinued after 8 weeks due to falling blood counts. The patient was then begun on RBC transfusions. His initial antibody screen was negative (July 1996). In August 1996, the patient was noted to have a weak cold agglutinin and positive direct antiglobulin test. The direct antiglobulin test was positive for both IgG and C3 with a nonspecific eluate. Over the next 24 months, the patient received a total of 24 units of packed RBCs. In August 1998, an antibody screen revealed the presence of anti-C, Kell (K), and the weak cold agglutinin. Repeat antibody screen after several additional transfusions showed anti-C, E, K, and the weak cold agglutinin. In October 1998, a further antibody screen demonstrated an additional anti-Kpb. Red cell phenotype revealed that the patient was negative for C, E, K, Kpb. From October 1998 until December 1999, the patient did not receive any red cell transfusions due to concerns about alloantibodies. He did receive several courses of methylprednisolone that decreased his transfusion requirements but did not raise the patient's hemoglobin above 8 g/dl. During this time, antibodies to C, E, Kpb, K continued to be positive (2+). In January 2000, due to progressive disease, the patient was begun on Rituximab 375 mg/m2 i.v. once weekly for 4 weeks in an effort to clear the alloantibodies. Five weeks later, the patient was found to have no evidence of antibodies or cold agglutinins by direct and indirect antiglobulin tests. In February 2000, the patient underwent umbilical cord blood transplantation. Due to significant GI bleeding, the patient received 70 units of packed RBCs after the transplant. All red blood cell units were positive for one or more of the previously noted antigens. The patient expired 70 days after transplant from vancomycin-resistant enterococcal sepsis. There were no obvious effects of Rituximab on the transplant. GVHD (grade I), and infections were not significantly different than the expected. Engraftment of cord units was delayed until 65 days post transplant. This delay was attributed to the patient's massive splenomegaly rather than the Rituximab since other patients with splenomegaly have delayed engraftment with umbilical cord blood cells.
Shortly after treatment with interferon, this patient developed a cold agglutinin titer that was noted on both direct and indirect antiglobulin testing. This is a known complication of interferon therapy.1 Previous reports document that cold agglutinins are responsive to Rituximab.2,3 However, after multiple transfusions, the patient developed multiple red cell alloantibodies. The presence of the anti-Kpb made transfusions very difficult since this antigen is expressed by >99% of the population. Based on reports that Rituximab could clear antibodies associated with cold agglutinins, this patient was treated with standard doses of Rituximab. Within 5 weeks of initiation of Rituximab therapy, all antibodies and cold agglutinins were cleared. The timing of this clearance is not unlike the rapid response that can be seen in ITP. The patient received 70 RBC transfusions over the next 2 months. He did not show any signs of overt hemolysis or transfusion reactions despite receiving units of RBCs that were positive for C, E, Kell and Kpb. At no time did his antibody screen turn positive. However, it should be noted that the patient was treated with a combination of fludarabine, melphalan, and anti-thymocyte globulin in preparation for his umbilical cord blood transplant. This regimen was administered within 2 weeks of his negative antibody screen. The contribution of the chemotherapy to the long-term clearance of the RBC antibodies is unknown. It appears that Rituximab can lead to clearance of RBC alloantibodies in the multiply transfused patient and allow transfusions with antigen-positive RBC units.
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