This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kohler, P. C. Articles by Sondel, P. M. Search for Related Content PubMed PubMed Citation Articles by Kohler, P. C. Articles by Sondel, P. M.

In Vitro Analysis of Donor Bone Marrow following Monoclonal Antibody Treatment for the Prevention of Acute Graft versus Host Disease¹

Departments of Human Oncology [P. C. K., B. E., J. A. H., P. M. S.], Pediatrics [C. E., J. L. F., M. E. T., R. H., P. M. S.], Genetics [P. C. K., P. M. S.], and Medicine [M. B.], University of Wisconsin, Madison, Wisconsin 53792, and the Department of Surgery [R. B.], University of California-Los Angeles, Los Angeles, California 90024

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality following bone marrow transplantation. The in vitro removal of the GVHD-causing T-lymphocytes from donor marrow is one approach which could control this complication. Treatment of the donor bone marrow with lectins and erythrocyte-forming rosette depletion, anti-T-cell antisera or monoclonal antibodies are methods currently being tested to accomplish this.

CT-2 is an immunoglobulin monoclonal antibody specific for the T-cell erythrocyte-forming rosette receptor. Bone marrow from 23 consecutive donors was treated in vitro with CT-2 and complement, prior to infusion, as a potential means of controlling GVHD. Surface marker analysis using erythrocyte-forming rosetting, and OKT-3 and OKT-11 monoclonal antibodies on paired samples of treated and untreated marrow demonstrated a mean depletion to 1% of the original number of T-cells. Proliferative responses to alloantigens and mitogens as well as cytotoxic and natural killer cell function were tested and found to be markedly reduced. Despite these effects on T-lymphocytes, viable hematopoietic stem cell colonies were retained.

Clinical results following the in vitro T-lymphocyte depletion of donor bone marrow for the 8 histocompatible and 15 nonhistocompatible bone marrow transplantation are reported. Prompt engraftment with minimal GVHD, despite no posttransplant GVHD prophylaxis, was seen in seven of the matched patients. In the nonhistocompatible bone marrow transplantation, failure of engraftment occurred in 11 patients. Grades III–IV GVHD were seen in two of the four patients that engrafted despite good T-lymphocyte depletion. No predictive correlation could be found between the in vitro analysis of marrow following CT-2 treatment and clinical outcome.

¹ This research was supported by Grants CH-237 of the American Cancer Society, RO1-CA32685 of the NIH, the University of Wisconsin Graduate School Research Committee and Department of Pediatrics, The Ryan Corporation, Molecular Medicine, Inc., and Hybridoma Diagnostics, Inc.

² Human Oncology-Medical Genetics Fellow; supported in part by Grant GM07131 of the NIH. To whom requests for reprints should be addressed.

³ Junior Clinical Faculty Fellows of the American Cancer Society.

⁴ G. L. and J. A. Hartford Foundation Fellow and a Scholar of the Leukemia Society of America.

Received 6/21/85. Revised 5/ 1/86. Accepted 6/30/86.