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Complete Sustained Response of a Refractory, Post-Transplantation, Large B-Cell Lymphoma to an Anti-CD22 Immunotoxin
- Adrian M. Senderowicz, MD;
- Ellen Vitetta, PhD;
- Donna Headlee, RN;
- Victor Ghetie, PhD;
- Jonathan W. Uhr, MD;
- William D. Figg, PharmD;
- Richard M. Lush, PhD;
- Maryalice Stetler-Stevenson, MD, PhD;
- Glenn Kershaw, MD;
- Douglas W. Kingma, MD;
- Elaine S. Jaffe, MD; and
- Edward A. Sausville, MD, PhD
- From the National Cancer Institute, National Institutes of Health, Bethesda, Maryland; University of Massachusetts Medical Center, Worcester, Massachusetts; and University of Texas Southwestern Medical Center, Dallas, Texas. Grant Support: Extramural portions of the study were supported by National Institutes of Health grants CA28149 and CA41081. Requests for Reprints: Edward A. Sausville, MD, PhD, Developmental Therapeutics Program, National Cancer Institute, Executive Plaza North, Suite 843, 6130 Executive Boulevard, Rockville, MD 20852. Current Author Addresses: Dr. Senderowicz and Ms. Headlee: Medicine Branch, Division of Clinical Science, National Cancer Institute, National Institutes of Health, Building 10, Room 12N226, 9000 Rockville Pike, Bethesda, MD 20892.
Glossary
CD19, CD20, CD21, CD22: B-cell surface markers frequently expressed on the surface of B-cell tumors. The immunotoxin used in our patient is directed against CD22.
EBER-1: Epstein-Barr encoded RNA.
Immunotoxin: A drug formed by chemical linkage of an antibody to a toxin.
RFB4-dgA: The immunotoxin used in our patient; it consists of the murine monoclonal antibody RFB4, which is linked to the deglycosylated A-chain of ricin, a plant toxin.
Vascular leak syndrome: A side effect of immunotoxin treatment that consists of nontargeted damage to endothelial cells and manifests as hypoalbuminemia and edema in its mild form.
Transplant recipients have an increased risk for post-transplantation lymphoproliferative diseases associated with Epstein-Barr virus. The incidence of such diseases is 1% in recipients of kidney transplants, 2.4% in recipients of heart or heart and lung transplants, 1% in recipients of liver transplants, and 0.6% in recipients of pancreas transplants [1]. Morphologic criteria distinguish at least three types of lymphoproliferative diseases: polyclonal B-cell or plasma cell hyperplasia; polymorphic B-cell hyperplasia and lymphoma, which are usually monoclonal; and monomorphic B-cell lymphoma [2, 3]. Particularly in polyclonal forms of disease, a decrease in the intensity of immunosuppressive therapy (for example, a decrease in the cyclosporine dose) with or without antiviral treatment leads to long-term clinical improvement [2]. If decreased immunosuppression as a therapeutic strategy is not successful, patients may receive chemotherapy; these patients, however, have a poor prognosis. The optimal management of patients whose disease progresses after chemotherapy is unknown [1].
An immunotoxin is formed when an antibody directed toward a tumor cell is chemically linked with a toxin, such as ricin. The antibody targets the toxin to the neoplastic cell, where it is internalized, inhibits protein synthesis, and results in the death of tumor cells [4]. We describe a patient who …
