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Bendamustine-Associated Hemolytic Anemia

Pharmacy Practice Resident, West Virginia University Pharmaceutical Services, West Virginia University Hospitals, Morgantown, WV

Aaron Cumpston, PharmD

Blood and Marrow Transplant Clinical Specialist, West Virginia University Pharmaceutical Services, West Virginia University Hospitals

Abraham Kanate, MD

Fellow, West Virginia University Section of Hematology/Oncology, School of Medicine, West Virginia University

Scot C Remick, MD

Director, West Virginia University Section of Hematology/Oncology, Mary Babb Randolph Cancer Center, School of Medicine, West Virginia University

Reprints: Dr. Glance, West Virginia University Hospitals, 1 Medical Center Dr., Morgantown, WV 26506, fax 304/598-4073, lglance{at}sole.wvu.edu

OBJECTIVE: To report a case of probable bendamustine-related hemolytic anemia.

CASE SUMMARY: A 64-year-old white female had recently received treatment with bendamustine for stage III follicular lymphoma. After her fourth cycle, she was admitted to an outside facility with severe right upper quadrant pain across her back and findings consistent with obstructive jaundice. She was found to have pancytopenia and elevations in total bilirubin, alkaline phosphatase, and transaminase levels. A bone marrow biopsy showed no evidence of lymphoma and presence of megakaryocytes on 2 occasions. Upon transfer to West Virginia University Hospitals, her haptoglobin was found to be undetectable, total bilirubin 10.3 mg/dL (unconjugated bilirubin 4.9 mg/dL), reticulocyte count 21.4% (reticulocyte index 2%), alkaline phosphatase 1125 U/L, and lactate dehydrogenase 421 U/L. The peripheral smear showed evidence of spherocytes and very rare schistocytes. Based on these findings, the woman was diagnosed with hemolytic anemia secondary to bendamustine exposure. She was started on prednisone 1 mg/kg (60 mg) daily and, soon after, her platelets and hemoglobin stabilized.

DISCUSSION: Drug-induced hemolytic anemia is an acquired or extrinsic process that results in antibody-mediated red blood cell destruction. The patient was not taking any medications commonly associated with hemolytic anemia; however, her laboratory test results were consistent with hemolytic anemia. Based on bendamustine's structural similarity to fludarabine and fludarabine's association with causing hemolytic anemia, we considered exposure to bendamustine to be the most likely contributory factor for her diagnosis. According to the Naranjo probability scale, a probable likelihood was reflected in bendamustine causing the hemolytic anemia.

CONCLUSIONS: Continued monitoring of postmarketing data is necessary to correlate this occurrence of hemolytic anemia with bendamustine therapy.

Key Words: bendamustine, hemolytic anemia

Published Online, October 6, 2009. www.theannals.com, DOI 10.1345/aph.1M329