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Ann Thorac Surg 2000;69:350
© 2000 The Society of Thoracic Surgeons
Discussion
DR JOHN H. CALHOON (San Antonio, TX): My thanks to Dr Pham and his colleagues from Pittsburgh on a nicely presented series, which should cause us all to reevaluate our lung transplant practice. One question to Dr Pham, about a manuscript and presentation that was very complete and well done, why do you think there was a difference in the biopsy incidence of obliterative bronchiolitis and the incidence of true bronchiolitis obliterans syndrome?
The other question would center around, where do we go from here? What do you think the optimum time of donor marrow transfusion would be? How would you best augment the engraftment? Would you use cytolytics, consider total lymphoid irradiation, the amount of infusion and/or, as I mentioned, its timing?
I would like to thank Dr Pham and his colleagues for this presentation and its contribution to our Society and profession.
DR FREDERICK L. GROVER (Denver, CO): I would like to particularly thank Dr Pham for his many years of contributions to the literature, and to our knowledge in the area of transplantation tolerance and chimerism. I think the most distressing part of taking care of lung transplant patients is the 30% to 50% incidence of the development of chronic obliterative bronchiolitis, which often leads to death, and any light that can be shed in this area is obviously very important.
I was particularly interested in those patients who received bone marrow infusion, but failed and later developed evidence of chronic rejection or obliterative bronchiolitis. Did those specific patients show decreased reactivity or did they not keep sustained chimerism?
And finally, how practical is the use of this? What percentage of patients will ultimately consent for infusion of the bone marrow?
Again, thank you very much.
DR PHAM: Thank you very much, Dr Calhoon for your kind comments. As I have presented, the incidence of bronchiolitis obliterans syndrome which is diagnosed by the clinical criteria is lower, but it does not reach statistical significance. As you know, bronchiolitis obliterans syndrome, is diagnosed based on the reduction in the FEV1. It reflects a global picture of the lung function, and it may be more sensitive than the histological data from the transbronchial biopsy, in which sampling errors undoubtedly play a role.
The second question is about the future direction of this study. I presented these data as an interim report of a pilot study to assess the safety issue of this procedure. Any time one infuses unmodified bone marrow into a patient, especially in a lung transplant recipient who has a high number of passenger leukocytes, one is concerned about the development of graft-versus-host disease, which has been reported by the liver transplant group at the University of Miami. Therefore, we proceed very cautiously. We first show that it can be safely done, and then we escalate our conditioning regimen slowly.
Doctor Camillo Ricordi and associates at the University of Miami had shown a survival advantage in liver recipients who received multiple infusion of donor bone marrow versus those who received single infusion. Based on these data, we currently have initiated the multiple bone marrow infusion protocol in lung recipients.
Another approach is to escalate the conditioning regimen of the recipient. However, as one escalates the conditioning regimen, one increases the risk of graft-versus-host disease. Recently, Dr Suzanne Ildstad and her associates had demonstrated a population of cells, facilitating cells (FC), in the bone marrow that facilitate the engraftment of BM stem cells without causing graft-versus-host disease. By combining facilitating cells and bone marrow stem cells infusion, low dose total body irradiation, and conventional immunosuppression, one may achieve better bone marrow engraftment with minor risk of graft-versus-host disease. This protocol is being evaluated at several centers by Dr Ildstad and associates.
I am grateful for Dr Grover’s kind comments. Patients who have chronic rejection lost their chimerism earlier than others. The major difficulty with this protocol was to obtain consent for donor bone marrow. In our organ procurement area, we were able to get bone marrow from 30% to 50% of cadaveric solid organ donors. Outside our area, the rate of getting donor bone marrow is less than 5%. I think with more public education, the rate of bone marrow donation in cadaveric donors will increase.
I would like to thank the Society for the opportunity to present this paper.
Related Article
Ann. Thorac. Surg. 2000 69: 345-350.
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