Theodore A. Gooley

Clinical trials and methods of data analysis in stem cell transplantation.

The Clinical Research Division at the FHCRC performs more stem cell transplants than any other institution in the world. The first transplant in Seattle was done in 1969, and currently roughly 450 transplants are done yearly. These facts put the FHCRC in a unique position to conduct both small- and large-scale clinical trials designed to address some of the most important and interesting questions that face the transplantation community today. The large volume of data generated from past transplants also provides a rich database from which information can be used to generate hypotheses and to monitor progress made in the field.

In recent years, many dose-finding studies have been designed within the Clinical Division with the goal of determining whether of not an effective dose of a treatment can be found such that the dose appears both safe and efficacious. This is in contrast to the more standard Phase I setting where one may be concerned only with safety and not efficacy. One such example is selective depletion of T cells in the donor marrow, where it is desired to find a dose of T cells that is associated with acceptable rates of graft failure while at the same timebeing associated with acceptable rates of severe graft-versus-host disease.

With the advent of the National Marrow Donor Program, use of alternative donors is becoming more commonplace for patients who lack a suitable family-member donor. It has beenshown in certain diseases that the time from diagnosis to transplant is an important prognostic factor in predicting outcome after transplantation and that outcome is adversely affected by donors who fail to share certain HLA antigens with the patient. A decision often needs to be made by both patient and physician whether to get transplanted early with a less-than-optimal donor or to wait longer in the hope of finding a more suitable donor. We are currently in the process of dealing with these and related issues for patients with chronic myeloid leukemia who receive a transplant from an unrelated donor.

The prevention and treatment of fungal and viral infections continues to be a problem following stem cell transplantation due to the immunocompromised condition of the patient. We have completed several randomized, controlled trials in recent years, and others are currently underway. These trials have led to significant progress in the prevention and treatment of certain infections, and the resultsof past and current clinical trials continue to shape strategies used to deal with such complications.